Zinc(Zn)is an essential micronutrient for both plants and humans.Zn deficiency is common in many paddy fields and reduces yield and grain Zn content(GZC).To accelerate breeding for improved GZC and Zn deficiency toler...Zinc(Zn)is an essential micronutrient for both plants and humans.Zn deficiency is common in many paddy fields and reduces yield and grain Zn content(GZC).To accelerate breeding for improved GZC and Zn deficiency tolerance(ZDT)rice varieties,it is important to identify genes regulating Zn homeostasis.In this study,a member of the Ser/Thr protein phosphatase family,LOC_Os07g48840(named as OsGZ7),was found to contributed to ZDT and GZC in rice.The expression of OsGZ7 in roots and shoots was inhibited by Zn deficiency and toxicity,but induced by iron(Fe),manganese(Mn),and copper(Cu)deficiency,as well as chromium toxicity.OsGZ7 localized to the cytoplasm and was expressed in all tissues during the tillering,flowering,and grain-filling stages,particularly in the leaf blade and leaf sheath.At the seedling stage,knockout of OsGZ7 enhanced ZDT and increased Zn accumulation in both roots and shoots.At the maturity stage,knockout of OsGZ7 enhanced GZC,while overexpression of OsGZ7 reduced GZC.RNA-seq analysis suggested that OsGZ7 might regulate Zn homeostasis by affecting metal binding,hormone signal transduction,and oxidoreductase activity.Taken together,our findings indicate that OsGZ7 contributes to ZDT and Zn accumulation in rice.展开更多
OBJECTIVE:To utilize the Traditional Chinese Medicine constitution(TCMC)as a complementary and alternative approach for early disease detection and treatment,with a focus on Yin and Yang deficiency constitutions,which...OBJECTIVE:To utilize the Traditional Chinese Medicine constitution(TCMC)as a complementary and alternative approach for early disease detection and treatment,with a focus on Yin and Yang deficiency constitutions,which serve as key references for disease prevention and management.METHODS:The dataset containing the data of Yin and Yang deficiency constitution was identified through the Gene Expression Omnibus database.This database was used for differential expression genes(DEGs)analysis and weighted gene co-expression network analysis(WGCNA),and the characteristic genes were then obtained in the dataset using a machine learning method.The hub genes of Yin and Yang deficiency constitution were obtained after analysis using the above three methods,and the hub genes were enriched and analyzed.Subsequently,the hub genes of Yin and Yang deficiency constitution were validated using external datasets.Receiver operating characteristic(ROC)analysis was used on each hub genes of the two groups to further understand their diagnostic performance.The mi RNA–lnc RNA-gene network was used to further analyze the hub genes.Immunoinfiltration and gene set enrichment analysis were performed on the shared hub genes.RESULTS:The GSE87474 dataset was used for DEGs analysis and WGCNA.Using machine learning analyses,we identified 15 and 14 hub genes for Yin and Yang deficiency constitutions,respectively.The results of enrichment analyses showed that Yin deficiency constitution was associated with interleukin-17 signaling pathway,whereas Yang deficiency constitution was associated with glycosaminoglycan biosynthesis–keratan sulfate.The validation dataset GSE56116 showed statistically significant data for s-adenosylmethionine sensor upstream of MTORC1(SAMTOR,also named C7orf60),cofilin 2(CFL2),cytohesin 1 interacting protein(CYTIP),G protein-coupled receptor 183(GPR183),hippocampus abundant transcript 1(HIAT1),kelch like family member 15(KLHL15),mitogen-activated protein kinase 6(MAPK6),and prostaglandin-endoperoxide synthase 2(PTGS2)in Yin deficiency and fucosyltransferase 8(FUT8),TATA-box binding protein associated factor,RNA polymerase I subunit D(TAF1D),zinc finger protein 24(ZNF24),MAPK6,and leptin receptor overlapping transcript like 1(LEPROTL1)in Yang deficiency.The ROC results indicated that these genes have diagnostic value.MAPK6 is a shared hub gene for Yin and Yang deficiencies.CONCLUSIONS:This study identified C7orf60,CFL2,CYTIP,GPR183,HIAT1,KLHL15,MAPK6,and PTGS2 in Yin deficiency and FUT8,TAF1D,ZNF24,MAPK6,and LEPROTL1 in Yang deficiency as potential biomarkers,providing insights into their pathogenesis.This theory not only guides the diagnostic approach in TCM but also extends its influence to various scientific research fields.展开更多
Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first t...Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell(MDCC-MSB-1)via oxidative stress-induced endoplasmic reticulum(ER)stress.We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days.The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities(T-AOC,CAT,and GSH-Px),accumulation of peroxides(H2O2 and MDA),significant upregulation of ER stress-relatedmarkers(GRP78,IER 1,PERK,EIF-2α,ATF4,and CHOP),a significant increase in iron ion levels,significant upregulation of pyroptosis-related gene(NLRP3,ASC,Caspase1,GSDMD,IL-18 and IL-1β),significantly increase ferroptosis-related genes(TFRC,COX2)and downregulate GPX4,HO-1,FTH,NADPH.In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results,demonstrating that the addition of antioxidant(NAC),ER stress inhibitor(TUDCA)and pyroptosis inhibitor(Vx765)alleviated oxidative stress,endoplasmic reticulum stress,pyroptosis,and ferroptosis.Overall,this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.展开更多
Deficiency or restriction of Zn absorption in soils is one of the most common micronutrients deficient in cereal plants. To investigate critical micronutrient interaction in zinc deficiency and zinc sufficient in soil...Deficiency or restriction of Zn absorption in soils is one of the most common micronutrients deficient in cereal plants. To investigate critical micronutrient interaction in zinc deficiency and zinc sufficient in soil, a factorial experiment based on completely randomized design (CRD) with three replications was conducted in 2023. Six wheat cultivars with different Zn efficiency were used. The cultivars were grown under Zn deficiency and adequate conditions. Results showed that in Zn deficiency conditions, with increasing Zn concentration in the roots, Fe concentrations were increased too, while the Cu and Mn concentrations decreased. In the same condition and with increasing Zn concentration in shoots, the concentrations of Fe and Mn decreased, while Cu were increased. However, by increasing Zn concentration, Fe, Cu, and Mn concentrations were increased in Zn deficiency condition in grains, as well as Zn sufficient conditions. RST (root to shoot micronutrient translocation) comparison of cultivars showed that in lack of Zn, the ability of translocation of Zn, Fe, and Mn in Zn-inefficient cultivar from root to shoot was higher than inefficient cultivar. In the same conditions, the capability of Zn-inefficient cultivar in Cu translocation from root to shoot was lower than other cultivars. In general, it seems that in Zn deficiency conditions, there are antagonistic effects among Zn, Cu and Mn and synergistic effects between Zn and Fe in the root. Also, in Zn sufficient conditions, there were synergistic effects among all studies micronutrients which include Zn, Fe, Cu, and Mn.展开更多
Objective To explore the clinical characteristics and methods for syndrome differentiation prediction,as well as to construct a predictive model for Qi deficiency and blood stasis syndrome in patients with acute ische...Objective To explore the clinical characteristics and methods for syndrome differentiation prediction,as well as to construct a predictive model for Qi deficiency and blood stasis syndrome in patients with acute ischemic stroke(AIS).Methods This study employed a retrospective case-control design to analyze patients with AIS who received inpatient treatment at the Neurology Department of The First Hospital of Hunan University of Chinese Medicine from January 1,2013 to December 31,2022.AIS patients meeting the diagnostic criteria for Qi deficiency and blood stasis syndrome were stratified into case group,while those without Qi deficiency and blood stasis syndrome were stratified into control group.The demographic characteristics(age and gender),clinical parameters[time from onset to admission,National Institutes of Health Stroke Scale(NIHSS)score,and blood pressure],past medical history,traditional Chinese medicine(TCM)diagnostic characteristics(tongue and pulse),neurological symptoms and signs,imaging findings[magnetic resonance imaging-diffusion weighted imaging(MRI-DWI)],and biochemical indicators of the two groups were collected and compared.The indicators with statistical difference(P<0.05)in univariate analysis were included in multivariate logistic regression analysis to evaluate their predictive value for the diagnosis of Qi deficiency and blood stasis syndrome,and the predictive model was constructed by receiver operating characteristic(ROC)curve analysis.Results The study included 1035 AIS patients,with 404 cases in case group and 631 cases in control group.Compared with control group,patients in case group were significantly older,had extended onset-to-admission time,lower diastolic blood pressure,and lower NIHSS scores(P<0.05).Case group showed lower incidence of hypertension history(P<0.05).Regarding tongue and pulse characteristics,pale and dark tongue colors,white tongue coating,fine pulse,astringent pulse,and sinking pulse were more common in case group.Imaging examinations demonstrated higher proportions of centrum semiovale infarction,cerebral atrophy,and vertebral artery stenosis in case group(P<0.05).Among biochemical indicators,case group showed higher proportions of elevated fasting blood glucose and glycated hemoglobin(HbA1c),while lower proportions of elevated white blood cell count,reduced hemoglobin,and reduced high-density lipoprotein cholesterol(HDL-C)(P<0.05).Multivariate logistic regression analysis identified significant predictors for Qi deficiency and blood stasis syndrome including:fine pulse[odds ratio(OR)=4.38],astringent pulse(OR=3.67),superficial sensory abnormalities(OR=1.86),centrum semiovale infarction(OR=1.57),cerebral atrophy(OR=1.55),vertebral artery stenosis(OR=1.62),and elevated HbA1c(OR=3.52).The ROC curve analysis of the comprehensive prediction model yielded an area under the curve(AUC)of 0.878[95%confidence interval(CI)=0.855-0.900].Conclusion This study finds out that Qi deficiency and blood stasis syndrome represents one of the primary types of AIS.Fine pulse,astringent pulse,superficial sensory abnormalities,centrum semiovale infarction,cerebral atrophy,vertebral artery stenosis,elevated blood glucose,elevated HbA1c,pale and dark tongue colors,and white tongue coating are key objective diagnostic indicators for the syndrome differentiation of AIS with Qi deficiency and blood stasis syndrome.Based on these indicators,a syndrome differentiation prediction model has been developed,offering a more objective basis for clinical diagnosis,and help to rapidly identify this syndrome in clinical practice and reduce misdiagnosis and missed diagnosis.展开更多
Brassica napus(oilseed rape)is sensitive to boron(B)deficiency and exhibits young leaf curling in response to low-B stress at the seedling stage,which leads to reduced photosynthesis and plant growth.So far,no gene ha...Brassica napus(oilseed rape)is sensitive to boron(B)deficiency and exhibits young leaf curling in response to low-B stress at the seedling stage,which leads to reduced photosynthesis and plant growth.So far,no gene has been identified to be involved in B deficiency induced leaf curling.Our previous results showed the transcription factor BnaA1.WRKY53 might be involved in B-deficiency tolerance.However,altered BnaA1.WRKY53 expression does not influence B concentration in shoot,root and leaf cell walls,which suggests Bna A1.WRKY53 might be involved in other biological processes.Indeed,phenotypic and anatomical analyses revealed that BnaA1.WRKY53 negatively regulated the leaf curling induced by leaf epinasty by suppressing the overexpansion of palisade cells under B deficiency.Further transcriptome enrichment analysis of differentially expressed genes(DEGs)between wild-type and BnaA1.WRKY53overexpression line showed auxin response pathway was enriched.In addition,Arabidopsis DR5::GFP auxin reporter line showed B deficiency caused predominant auxin signal accumulation in the adaxial side and concomitant adaxial cell expansion,which indicated that B deficiency may induce leaf curling by altering auxin distribution.Phytohormone quantification and gene expression analysis demonstrated that BnaA1.WRKY53 prevent auxin overaccumulation in leaves by suppressing auxin biosynthetic genes under B deficiency.Furthermore,exogenous 1-naphthlcetic acid(NAA)treatment experiments revealed that high auxin could induce leaf curling and BnaA1.WRKY53 expression.Overall,these findings demonstrate that auxin and the transcription factor BnaA1.WRKY53 synergistically regulate leaf curling to maintain an optimal leaf area under B deficiency,and provide novel insights into the resistance mechanisms against B-deficiency-induced leaf curling in oilseed rape.展开更多
BACKGROUND Patients with colorectal cancer(CRC)exhibiting microsatellite instability(MSI)-high generally demonstrate a favorable response to immunotherapy.In contrast,the efficacy of immunotherapy in microsatellite-st...BACKGROUND Patients with colorectal cancer(CRC)exhibiting microsatellite instability(MSI)-high generally demonstrate a favorable response to immunotherapy.In contrast,the efficacy of immunotherapy in microsatellite-stable(MSS)CRC patients is considerably restricted.This study sought to evaluate the effectiveness of immu-notherapy in MSS patients characterized by homologous recombination defi-ciency(HRD)as opposed to those with homologous recombination proficiency(HRP).AIM To investigate and compare the clinicopathological characteristics,treatment modalities,and outcomes between the HRD and HRP groups in CRC.METHODS Next-generation sequencing was performed on 268 CRC patients to identify tumor-associated genetic alterations and assess their HRD scores and MSI status.Patients with HRD-related gene alterations or an HRD score≥30 were classified into the HRD group,while the remaining patients were assigned to the HRP group.Clinical data,including staging and treatment regimens,were collected for analysis.Cox regression and Kaplan-Meier survival curves were employed to evaluate whether the HRD group demonstrated improved survival outcomes following immunotherapy treatment.RESULTS Among the 268 patients,64 were classified into the HRD group,which had a higher proportion of early-stage CRC diagnoses compared to the HRP group.Kaplan-Meier survival curves indicated significantly better survival rates in the HRD group compared to the HRP group across all cohorts,as well as among MSS patients treated with immunotherapy(P<0.05).CONCLUSION This study demonstrates that CRC patients with HRD have a more favorable prognosis and suggests that HRD status could serve as a predictive marker for immunotherapy response in MSS patients.展开更多
Background:Iron facilitates key biological functions underpinning sports performance,and up to 60%of female athletes experience iron deficiency.However,the effects of iron deficiency on sports performance in female at...Background:Iron facilitates key biological functions underpinning sports performance,and up to 60%of female athletes experience iron deficiency.However,the effects of iron deficiency on sports performance in female athletes is unclear,as are the degree of benefits of iron supplementation(FeSup).This study characterizes the effects of iron deficiency and FeSup on sports performance in high-level female athletes.Methods:Searches of the electronic databases MEDLINE,SPORTDiscus,Web of Science,Scopus,and CINAHL were performed in July 2023.Studies were included that evaluated the effects of iron deficiency or FeSup on sports performance in high-level(maximal oxygen uptake(VO2max)>45 mL/kg/min,or trained>5 h/week)iron deficient(ID)(serum ferritin(sFer)<40 mg/L)female athletes.Studies were assessed using a modified Downs and Black Quality Assessment Checklist.Results:A total of 23 studies comprising 669 athletes(age range:13-47 years)across 16 sports were included in the review.Iron deficiency negatively affects endurance performance by 3%-4%.However,endurance performance improved by 2%-20%when ID athletes were treated with 100 mg/day of elemental iron for up to 56 days via oral supplementation,or bi-daily via parenteral administration over 8-10 days.ID nonanemic athletes with low sFer stores may be predisposed to reduced maximal aerobic capacity.However,maximal aerobic capacity improved by 6%-15%following 16 mg/day-100 mg/day of elemental iron for 36-126 days.Isokinetic strength and anaerobic power performance may be impeded(-23%to+4%)among ID athletes,but the effect of FeSup on anaerobic power varied markedly(-5%to+9%)following 100 mg/day of elemental iron over 42-56 days,or 100 mg of elemental iron bi-daily over 8-10 days.The quality of studies was moderate(77%),ranging from low(57%)to high(100%).Moststudies(n=18)contained group sizes-20 athletes,thus limiting the likelihood of detecting significant effects(statistical power>0.80).Conclusion:High-level ID female athletes experience a negative impact on endurance performance,which can be improved by supplementing with»100 mg of elemental iron per day or bi-daily.The decrements in other performance parameters characterizing a range of sports coincide with the severity of iron deficiency.展开更多
Vitamin D deficiency is disproportionately prevalent among overweight and obese children,with conventional explanations such as poor dietary intake or reduced sun exposure offering only partial insight.Emerging eviden...Vitamin D deficiency is disproportionately prevalent among overweight and obese children,with conventional explanations such as poor dietary intake or reduced sun exposure offering only partial insight.Emerging evidence reveals a multifactorial pathophysiology,including sequestration of vitamin D in adipose tissue,altered hepatic metabolism,diminished bioavailability,and inflammationinduced resistance at the tissue level.These mechanisms contribute to a functional deficiency,wherein serum 25-hydroxyvitamin D levels may remain suboptimal despite adequate intake or sun exposure.Obesity-related alterations in vitamin Dbinding proteins,receptor expression,and pro-inflammatory signaling further compromise biological activity.Current diagnostic criteria and supplementation guidelines do not fully reflect these physiological complexities,leading to underdiagnosis and insufficient treatment.Personalized approaches-incorporating higher,body composition-adjusted dosing and consideration of inflammatory status-are emerging as promising strategies to restore sufficiency and improve metabolic outcomes.While preliminary evidence supports the safety and efficacy of high-dose supplementation in this population,pediatric-specific clinical trials are lacking.This review synthesizes current understanding of the pathophysiological mechanisms underlying vitamin D deficiency in pediatric obesity and emphasizes the need for individualized,evidence-based interventions to optimize vitamin D status and overall health.展开更多
Objective:Patients with homologous recombination deficiency(HRD)demonstrate distinct clinicopathological and prognostic features.However,standardised and clinically validated HRD detection methodologies specifically t...Objective:Patients with homologous recombination deficiency(HRD)demonstrate distinct clinicopathological and prognostic features.However,standardised and clinically validated HRD detection methodologies specifically tailored for non-small cell lung cancer(NSCLC)have yet to be established.Further research is needed to clarify the precise role and clinical implications of HRD in NSCLC.Methods:A cohort of 580 treatment-naive NSCLC patients was retrospectively enrolled.Comprehensive genomic profiling(CGP)was performed for all patients,and HRD status was evaluated using two genomic scar score(GSS)-based algorithms:a machine learning-based GSS(ML-GSS)and a continuous linear regression-based GSS(CLR-GSS).To assess the diagnostic performance(sensitivity and specificity)of the ML-GSS and CLR-GSS algorithms for HRD detection,immunohistochemical(IHC)staining was conducted for two HRD-related biomarkers:Schlafen 11(SLFN11)and RAD51.Survival analysis,including progression-free survival(PFS),along with multivariable Cox proportional hazards models,was performed to compare the prognostic value of the two HRD algorithms.Results:Among all patients,146(25.2%)and 46(7.9%)were classified as HRD-positive(HRD+)by ML-GSS and CLR-GSS,respectively.Using SLFN11 IHC expression as the reference standard,comparative analysis demonstrated that ML-GSS exhibited significantly higher sensitivity but lower specificity than CLR-GSS.This trend was consistently observed in RAD51 staining analysis.Compared to HRD-negative(HRD-)patients,MLGSS-defined HRD+cases displayed distinct clinicopathological and genomic features,including a higher prevalence of homologous recombination(HR)-related genes mutations,BRCA1/2 mutations,TP53 mutations,elevated tumor mutation burden(TMB),and increased copy number variations(CNVs).In contrast,CLR-GSSdefined HRD+patients were only enriched for BRCA1/2 mutations,TP53 mutations,and elevated TMB.Furthermore,ML-GSS-defined HRD+status was associated with significantly worse prognosis following first-line therapy compared to HRD-patients.Univariate and multivariable Cox analyses identified ML-GSS-defined HRD+and TP53 mutations as significant predictors and independent risk factors,respectively.No such associations were observed in the CLR-GSS-defined HRD+cohort.Conclusions:ML-GSS demonstrated superior performance to CLR-GSS in assessing chromosomal instability(CIN)and showed greater clinical utility.We recommend the ML-GSS algorithm as a robust and clinically validated tool for HRD/CIN evaluation in NSCLC.Furthermore,ML-GSS-defined HRD+status was identified as both a significant predictor and an independent risk factor.展开更多
Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECK...Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECKMATE-649,ORIENT-16,and KEYNOTE-859 trials,have markedly transformed the treatment paradigm for advanced gastric cancer(AGC)3-5.展开更多
The trace element selenium(Se)occurs naturally throughout the earth.Se deficiency has been linked to impaired breast health and other diseases in human and animals.Compared to severe Se deficiency,marginal dietary Se ...The trace element selenium(Se)occurs naturally throughout the earth.Se deficiency has been linked to impaired breast health and other diseases in human and animals.Compared to severe Se deficiency,marginal dietary Se deficiency accusers more frequently in low-Se regions.Therefore,to investigate the Se status and inflammatory response of the mammary gland under marginal dietary Se levels,an lipopolysaccharide(LPS)induced mouse mastitis model was established.Mice were fed with moderate Se diet(0.087 mg•kg^(-1) Se),adequate Se diet(0.15 mg•kg^(-1) Se)or excessive Se diet(1.5 mg•kg^(-1) Se)for 60 days.Se status and inflammatory factors were investigated.Results showed that the Se status of mammary gland correlated with dietary Se levels.Marginal Se deficiency exacerbated mammary tissue histopathology;increased the mRNA level of inflammatory genes tumor necrosis factor alpha(TNF-α),interleukin-1β(IL-1β)and cyclooxygenase-2(COX-2);and enhanced the phosphorylation of NF-κB p65 in mammary gland tissues.Supplementation of Se in diet higher than recommended levels reduced the inflammatory reaction of mammary glands in LPS-induced mastitis model and provided a protective effect.展开更多
Objective:To investigate whether differences exist in DNA fragmentation levels and protamine deficiency in the sperm of obese men compared to those of overweight and proven fertile,normal weight men and evaluate the a...Objective:To investigate whether differences exist in DNA fragmentation levels and protamine deficiency in the sperm of obese men compared to those of overweight and proven fertile,normal weight men and evaluate the alterations related to reproductive hormones,semen parameters and their association with body mass index(BMI).Methods:Participants in this observational study were divided into three groups based on their BMI:proven fertile,normal weight men(n=200);overweight men(n=200);and obese men(n=200).After 3 days of abstinence,seminal fluid was collected from all participants and analyzed.Blood samples were also collected on the same day for hormonal analysis.Sperm DNA fragmentation and protamine deficiency were also assessed.Results:A total of 600 men with a mean age of(34.3±7.9)2 years were included in the study.Obese males(BMI 30 kg/m or higher)exhibited significant reductions in semen volume,sperm concentration,total sperm motility percentage,progressive motility,non-progressive motility,and levels of total testosterone,follicle-stimulating hormone(FSH)and luteinizing hormone(LH)compared to overweight(BMI 25 to 29.9 kg/m2)and normal weight males(BMI 18.5 to 24.9 kg/m2)(P<0.001).Conversely,obese males showed a significant increase in prolactin level,sperm DNA fragmentation,and protamine deficiency compared to overweight and normal weight males(P<0.001).Significant negative correlations were demonstrated between BMI and sperm concentration,motility,total testosterone,FSH and LH(P<0.001),whereas prolactin,sperm DNA fragmentation and protamine deficiency were positively correlated with BMI(P<0.001).Conclusions:This study provides clear evidence that obesity contributes potentially to male infertility by inducing sperm DNA fragmentation and protamine deficiency,as well as negatively impacting reproductive hormones and semen quality.展开更多
BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)...BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)and GH deficiency(GHD).Irrespective of the presence of GHD,NS is a Food and Drug Administration-approved indication for recombinant-GH therapy.Few case reports of combined anterior pituitary hormone deficiency(CPHD)in NS have been reported.AIM To describe the clinico-biochemical characteristics of NS with CPHD and to assess the response to recombinant GH therapy.METHODS An ambispective case-control study was conducted to compare the clinicohormonal profile and response to recombinant-GH in pediatric patients with NS and CPHD and pediatric patients with NS but without CPHD.RESULTS Five children with NS and CPHD were compared to 6 patients with NS but without CPHD.The most common anterior pituitary hormone involvement in combination with GHD was adrenocorticotrophic hormone deficiency causing hypocortisolemia(n=3,60%),followed by hypogonadotropic hypogonadism and secondary hypothyroidism(n=1 each).Pituitary hypoplasia was seen in the magnetic resonance imaging of all patients with CPHD.Patients with NS and CPHD had lower standard deviation scores of height(-4.18 vs-2.52,P=0.009),bodyweight,and body mass index but a slightly better first year response to recombinant GH(9.2 vs 5.5,P=0.06).There were no differences in dysmorphisms and other anomalies between the two groups.Patients with NS and CPHD had a similar response to GH as patients with CPHD but without NS.One patient with NS and CPHD developed hypocortisolism after GH initiation.CONCLUSION Hypoplasia of the pituitary and GHD with involvement of other pituitary hormones may be seen in NS and may determine response to recombinant GH therapy.展开更多
The prevalence of iron deficiency anemia(IDA)remains high in infants,resulting in growth retardation,neurodevelopmental impairment,immunodeficiency and other irreversible injuries.Efficient and safe iron supplementati...The prevalence of iron deficiency anemia(IDA)remains high in infants,resulting in growth retardation,neurodevelopmental impairment,immunodeficiency and other irreversible injuries.Efficient and safe iron supplementation for infants has been the goal of recent research.This study aims to investigate the effect of encapsulated ferric pyrophosphate(FePP)on intestinal inflammation and gut microbiota in IDA suckling rats.Newborn Sprague-Dawley rats were gavaged with low and high doses of FePP and FeSO4(2 and 10 mg Fe/kg BW,respectively)during postnatal days 2-14,while the Ctrl group was gavaged with saline.Results showed that FePP supplementation was as effective as FeSO4 in promoting growth,alleviating anemia and restoring body iron levels.Both low and high doses of FePP could significantly down-regulate the expression of pro inflammatory cytokines in the colon to the level similar to that in the Ctrl group(P>0.05).However,the high dose of FeSO4 did not show a down-regulation effect.Compared with the Ctrl group,IDA caused a disturbance of gut microbiota composition in suckling rats,and FePP could restore this dysbiosis.Besides,FePP was more beneficial than FeSO4 in increasing the abundance of beneficial bacteria such as Bacteroides and Akkermansia.Spearman’s correlation analysis showed a correlation between gut microbiota and biochemical indicators such as iron status,pro-inflammatory cytokine expression,and oxidative stress level.Overall,these findings suggested that FePP could effectively improve IDA,and is more effective than FeSO4 in alleviating intestinal inflammation and regulating gut microbiota,which provides a basis for the application of new iron fortificant in infant formula.展开更多
Objective To elucidate the mechanism of Fuzheng Gankang Pill in treating combined allergic rhinitis and asthma syndrome(CARAS)with lung-spleen qi deficiency and wind-cold invading the lung syndrome using network pharm...Objective To elucidate the mechanism of Fuzheng Gankang Pill in treating combined allergic rhinitis and asthma syndrome(CARAS)with lung-spleen qi deficiency and wind-cold invading the lung syndrome using network pharmacology and molecular docking.MethodsThe active components and targets of the 13 herbs in Fuzheng Gankang Pill were retrieved from the TraditionalChinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and HERB.A“core herb-active component-target"network was constructed using Cytoscape to screen core components.CARAS disease targets were obtained from Genecards,NationalCenter for Biotechnology Information(NCBI),and Online Mendelian Inheritance in Man(OMIM).Targets related to the clinical phenotypes of CARAS with lung-spleen qi deficiency and wind-cold invading the lung syndrome were retrieved from the Traditional ChineseMedicineSyndrome Ontology and Multidimensional Quantitative Association Calculation Platform.The intersection of CARAS disease targets and syndromerelated targets yielded CARAS disease-syndrome targets.The intersection of Fuzheng Gankang Pill component-related targets and CARAS disease-syndrome targets provided“disease-syndrome-formula”intersection targets.These targets were uploaded to the STRING database for protein-protein interaction(PPI)network analysis,with topological analysis identifying key targets.Metascape was used for Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking validation was performed using AutoDock Vina 1.1.2.Results The 13 core herbs of Fuzheng Gankang Pill contain a total of 200 active ingredients and 289 related targets.There are 2,412 disease targets for CARAS and 735 corresponding disease targets for the main and secondary symptoms of lung-spleen qi deficiency and wind-cold invading the lung.Through the Venn diagram,a total of 35 intersecting targets were obtained for Fuzheng Gankang Pill,CARAS,and the combination of lung-spleen qi deficiency and wind-cold invading the lung syndrome.Quercetin,Polygonatum sibiricum flavonoids,β-sitosterol,baicalein,kaempferol,etc.,are core components.PPI network analysis found that tumor necrosis factor(TNF),prostaglandin-endoperoxide synthase 2(PTGS2),interleukin(IL)-1β,IL-6,transforming growth factor beta 1(TGFβ1),BCL2,etc.,are the core targets for the compound to exert therapeutic effects.GO enrichment analysis showed that the 13 core drugs of Fuzheng Gankang Pill mainly participate in key biological processes such as positive regulation of protein modification,response to hormones,and negative regulation of cell population proliferation through protein kinases in areas such as membrane rafts,membrane microregions,plasma membrane protein complexes,and receptor com-plexes.KEGG enriched a total of 30 signaling pathways.Molecular docking shows that active ingredients such as quercetin and kaempferol bind stably toTNF(binding energy≤-9.0 kcal·mol^(-1))and PTGS2(≤-8.5kcal·mol^(-1)).Conclusion Fuzheng Gankang Pill may regulate biological processes such as cell apoptosis,tissue remodeling,inflammatory response,and immune response by acting on core targets such as TNF and PTGS2 through its core components quercetin,baicalein,β-sitosterol,baicalein,and kaempferol,thereby exerting therapeutic effects on CARAS with lung-spleen qi deficiency and wind-cold invading the lung syndrome.展开更多
BACKGROUND Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases,stroke,and renal failure.Traditional Chinese Medicine(TCM)has been utilized for an extend...BACKGROUND Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases,stroke,and renal failure.Traditional Chinese Medicine(TCM)has been utilized for an extended period to address hypertension,with the syndrome known as Yin deficiency and Yang hyperactivity syndrome(YDYHS)frequently observed in individuals with elevated blood pressure.This syndrome is characterized by symptoms including dizziness,tinnitus,irritability,and insomnia,which are thought to result from an imbalance between Yin,representing the cooling and nourishing aspects,and Yang,denoting the active and warming aspects of the body.Despite the prevalent application of TCM in clinical settings,the metabolic mechanisms underlying the YDYHS in the context of hypertension remain inadequately elucidated.AIM To explore the differential plasma metabolites and associated pathways in hypertensive patients with YDYHS using gas chromatography-mass spectrometry(GC-MS)to elucidate the distinctive blood metabolite pattern in this patient population.METHODS GC-MS was used to analyze plasma samples from 51 hypertensive patients with YDYHS and 20 healthy controls.Chemometric methods,including principal component analysis and partial least squares discriminant analysis,were employed to identify potential biochemical patterns.Simultaneously,the high-quality Kyoto Encyclopedia of Genes and Genomes metabolic pathways database was used to identify associated metabolic pathways.Using variable importance in projection and receiver operating characteristic curve analyses,potential biomarkers were extracted to assess their clinical utility.RESULTS Metabolomic profiling of hypertensive patients with YDYHS identified 20 potential biomarkers(4-hydroxybenzoic acid,pectin,1,2,3-trihydroxybenzene,D-ribose,3-hydroxybutyric acid,quinic acid,L-lysine,oleic acid,2-hydroxybutyric acid,linoleic acid,citric acid,alpha-tocopherol,D-glucuronic acid,glycerol,N-acetyl-L-aspartic acid,betamannosylglycerate,indolelactic acid,L-glutamic acid,D-maltose,L-aspartic acid)and four metabolic pathways(linoleic acid metabolism;alanine,aspartate and glutamate metabolism;D-glutamine and D-glutamate metabolism;arginine biosynthesis).The identified differential metabolites may serve as potential biomarkers for distinguishing hypertensive patients with YDYHS from healthy controls.The area under the curve values ranged from 0.750 to 0.866.Receiver operating characteristic curve analysis showed that these differential metabolites can effectively classify hypertensive patients with YDYHS and healthy individuals.CONCLUSION The metabolomic analysis revealed a distinct blood metabolite pattern in hypertensive patients with YDYHS compared to the healthy control group,highlighting the potential role of the identified 20 biomarkers and four metabolic pathways in these patients.These findings may serve as an important material basis for understanding the occurrence and development of the disease,providing a scientific foundation for future clinical diagnosis.展开更多
Objective:As an age-related neurodegenerative disease,the prevalence of mild cognitive impairment(MCI)increases with age.Within the framework of traditional Chinese medicine,spleen-kidney deficiency syndrome(SKDS)is r...Objective:As an age-related neurodegenerative disease,the prevalence of mild cognitive impairment(MCI)increases with age.Within the framework of traditional Chinese medicine,spleen-kidney deficiency syndrome(SKDS)is recognized as the most frequent MCI subtype.Due to the covert and gradual onset of MCI,in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes.There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS(MCI-SKDS).Methods:This investigation enrolled 312 elderly individuals diagnosed with MCI,who were randomly distributed into training and test datasets at a 3:1 ratio.Five machine learning methods,including logistic regression(LR),decision tree(DT),naive Bayes(NB),support vector machine(SVM),and gradient boosting(GB),were used to build a diagnostic prediction model for MCI-SKDS.Accuracy,sensitivity,specificity,precision,F1 score,and area under the curve were used to evaluate model performance.Furthermore,the clinical applicability of the model was evaluated through decision curve analysis(DCA).Results:The accuracy,precision,specificity and F1 score of the DT model performed best in the training set(test set),with scores of 0.904(0.845),0.875(0.795),0.973(0.875)and 0.973(0.875).The sensitivity of the training set(test set)of the SVM model performed best among the five models with a score of 0.865(0.821).The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset.The DCA of all models showed good clinical application value.The study identified ten indicators that were significant predictors of MCI-SKDS.Conclusion:The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical;the model demonstrates good predictive value and clinical applicability,and the DT model had the best performance.展开更多
Objective:To observe the therapeutic effect of Moist Burn Ointment combined with rotating moxibustion on patients with pressure ulcers and deficiency of both Qi and blood.Methods:40 patients with pressure ulcers and d...Objective:To observe the therapeutic effect of Moist Burn Ointment combined with rotating moxibustion on patients with pressure ulcers and deficiency of both Qi and blood.Methods:40 patients with pressure ulcers and deficiency of both Qi and blood were randomly divided into two groups from July 2024 to November 2025.Group A received Moist Burn Ointment combined with rotating moxibustion,while Group B received Moist Burn Ointment only.Results:Group A showed better efficacy,wound healing time,dressing change frequency,satisfaction,PUSH score,and adverse reaction indicators compared to Group B(P<0.05).Conclusion:The combination of Moist Burn Ointment and rotating moxibustion in the treatment of patients with pressure ulcers and deficiency of both Qi and blood can shorten wound healing time,reduce dressing change frequency,and alleviate the degree of pressure ulcers,which is safe and efficient.展开更多
Metformin-induced vitamin B12 deficiency is a prevalent condition among pa-tients with type 2 diabetes mellitus.In recent years,a growing body of evidence has demonstrated the association between vitamin B12 deficienc...Metformin-induced vitamin B12 deficiency is a prevalent condition among pa-tients with type 2 diabetes mellitus.In recent years,a growing body of evidence has demonstrated the association between vitamin B12 deficiency and the onset,progression,and worsening of diabetic neuropathy(DNP)as well as its im-provement with supplementation in cases of deficiency.Major clinical guidelines for diabetes and DNP remain vague in their recommendations for B12 measu-rement and supplementation,and some guidelines do not address it at all.Given that vitamin B12 therapy is an economical,safe,and widely available treatment in most countries and supported by emerging evidence of its potential benefits,greater efforts should be made to promote systematic screening for vitamin B12 deficiency in all patients with DNP before establishing a definitive diagnosis as well as in patients with diabetes with risk factors for deficiency.Vitamin B12 deficiency should be treated in all affected patients,and supplementation should be considered in those with borderline levels when confirmatory diagnostic tests for deficiency are unavailable.Clinical guidelines should place greater emphasis on the recommendations for measuring and supplementing vitamin B12 in these patients.展开更多
基金supported by the National Key R&D Program of China(Grant No.2022YFE0139400)the National Natural Science Foundation of China(Grant No.31961143016)the Shenzhen Science and Technology Program,China(Grant No.JCYJ20200109150650397).
文摘Zinc(Zn)is an essential micronutrient for both plants and humans.Zn deficiency is common in many paddy fields and reduces yield and grain Zn content(GZC).To accelerate breeding for improved GZC and Zn deficiency tolerance(ZDT)rice varieties,it is important to identify genes regulating Zn homeostasis.In this study,a member of the Ser/Thr protein phosphatase family,LOC_Os07g48840(named as OsGZ7),was found to contributed to ZDT and GZC in rice.The expression of OsGZ7 in roots and shoots was inhibited by Zn deficiency and toxicity,but induced by iron(Fe),manganese(Mn),and copper(Cu)deficiency,as well as chromium toxicity.OsGZ7 localized to the cytoplasm and was expressed in all tissues during the tillering,flowering,and grain-filling stages,particularly in the leaf blade and leaf sheath.At the seedling stage,knockout of OsGZ7 enhanced ZDT and increased Zn accumulation in both roots and shoots.At the maturity stage,knockout of OsGZ7 enhanced GZC,while overexpression of OsGZ7 reduced GZC.RNA-seq analysis suggested that OsGZ7 might regulate Zn homeostasis by affecting metal binding,hormone signal transduction,and oxidoreductase activity.Taken together,our findings indicate that OsGZ7 contributes to ZDT and Zn accumulation in rice.
基金Supported by National Natural Science Foundation of China:Establishment and Validation of a High-throughput Screening System for Traditional Chinese Medicine Against Dry Eye Disease based on transforming growth factor-βand B-cell lymphoma-2(No.81574031)2023 Hunan Provincial Department of Education Scientific Research Project:Yiguanjian Decoction Regulates Th17/Treg Cell Balance and Its Intervention Mechanism in Dry Eye with Liver Yin Deficiency Syndrome(No.23A0300)。
文摘OBJECTIVE:To utilize the Traditional Chinese Medicine constitution(TCMC)as a complementary and alternative approach for early disease detection and treatment,with a focus on Yin and Yang deficiency constitutions,which serve as key references for disease prevention and management.METHODS:The dataset containing the data of Yin and Yang deficiency constitution was identified through the Gene Expression Omnibus database.This database was used for differential expression genes(DEGs)analysis and weighted gene co-expression network analysis(WGCNA),and the characteristic genes were then obtained in the dataset using a machine learning method.The hub genes of Yin and Yang deficiency constitution were obtained after analysis using the above three methods,and the hub genes were enriched and analyzed.Subsequently,the hub genes of Yin and Yang deficiency constitution were validated using external datasets.Receiver operating characteristic(ROC)analysis was used on each hub genes of the two groups to further understand their diagnostic performance.The mi RNA–lnc RNA-gene network was used to further analyze the hub genes.Immunoinfiltration and gene set enrichment analysis were performed on the shared hub genes.RESULTS:The GSE87474 dataset was used for DEGs analysis and WGCNA.Using machine learning analyses,we identified 15 and 14 hub genes for Yin and Yang deficiency constitutions,respectively.The results of enrichment analyses showed that Yin deficiency constitution was associated with interleukin-17 signaling pathway,whereas Yang deficiency constitution was associated with glycosaminoglycan biosynthesis–keratan sulfate.The validation dataset GSE56116 showed statistically significant data for s-adenosylmethionine sensor upstream of MTORC1(SAMTOR,also named C7orf60),cofilin 2(CFL2),cytohesin 1 interacting protein(CYTIP),G protein-coupled receptor 183(GPR183),hippocampus abundant transcript 1(HIAT1),kelch like family member 15(KLHL15),mitogen-activated protein kinase 6(MAPK6),and prostaglandin-endoperoxide synthase 2(PTGS2)in Yin deficiency and fucosyltransferase 8(FUT8),TATA-box binding protein associated factor,RNA polymerase I subunit D(TAF1D),zinc finger protein 24(ZNF24),MAPK6,and leptin receptor overlapping transcript like 1(LEPROTL1)in Yang deficiency.The ROC results indicated that these genes have diagnostic value.MAPK6 is a shared hub gene for Yin and Yang deficiencies.CONCLUSIONS:This study identified C7orf60,CFL2,CYTIP,GPR183,HIAT1,KLHL15,MAPK6,and PTGS2 in Yin deficiency and FUT8,TAF1D,ZNF24,MAPK6,and LEPROTL1 in Yang deficiency as potential biomarkers,providing insights into their pathogenesis.This theory not only guides the diagnostic approach in TCM but also extends its influence to various scientific research fields.
基金supported by the National Natural Science Foundation of China Regional Joint Innovation Fund (No.U22A20524)the Heilongjiang Province Natural Science Foundation Key projects (No.ZD2023C002).
文摘Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell(MDCC-MSB-1)via oxidative stress-induced endoplasmic reticulum(ER)stress.We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days.The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities(T-AOC,CAT,and GSH-Px),accumulation of peroxides(H2O2 and MDA),significant upregulation of ER stress-relatedmarkers(GRP78,IER 1,PERK,EIF-2α,ATF4,and CHOP),a significant increase in iron ion levels,significant upregulation of pyroptosis-related gene(NLRP3,ASC,Caspase1,GSDMD,IL-18 and IL-1β),significantly increase ferroptosis-related genes(TFRC,COX2)and downregulate GPX4,HO-1,FTH,NADPH.In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results,demonstrating that the addition of antioxidant(NAC),ER stress inhibitor(TUDCA)and pyroptosis inhibitor(Vx765)alleviated oxidative stress,endoplasmic reticulum stress,pyroptosis,and ferroptosis.Overall,this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.
文摘Deficiency or restriction of Zn absorption in soils is one of the most common micronutrients deficient in cereal plants. To investigate critical micronutrient interaction in zinc deficiency and zinc sufficient in soil, a factorial experiment based on completely randomized design (CRD) with three replications was conducted in 2023. Six wheat cultivars with different Zn efficiency were used. The cultivars were grown under Zn deficiency and adequate conditions. Results showed that in Zn deficiency conditions, with increasing Zn concentration in the roots, Fe concentrations were increased too, while the Cu and Mn concentrations decreased. In the same condition and with increasing Zn concentration in shoots, the concentrations of Fe and Mn decreased, while Cu were increased. However, by increasing Zn concentration, Fe, Cu, and Mn concentrations were increased in Zn deficiency condition in grains, as well as Zn sufficient conditions. RST (root to shoot micronutrient translocation) comparison of cultivars showed that in lack of Zn, the ability of translocation of Zn, Fe, and Mn in Zn-inefficient cultivar from root to shoot was higher than inefficient cultivar. In the same conditions, the capability of Zn-inefficient cultivar in Cu translocation from root to shoot was lower than other cultivars. In general, it seems that in Zn deficiency conditions, there are antagonistic effects among Zn, Cu and Mn and synergistic effects between Zn and Fe in the root. Also, in Zn sufficient conditions, there were synergistic effects among all studies micronutrients which include Zn, Fe, Cu, and Mn.
基金National Natural Science Foundation of China(U22A20377)Natural Science Foundation of Hunan Province of China(23C0168).
文摘Objective To explore the clinical characteristics and methods for syndrome differentiation prediction,as well as to construct a predictive model for Qi deficiency and blood stasis syndrome in patients with acute ischemic stroke(AIS).Methods This study employed a retrospective case-control design to analyze patients with AIS who received inpatient treatment at the Neurology Department of The First Hospital of Hunan University of Chinese Medicine from January 1,2013 to December 31,2022.AIS patients meeting the diagnostic criteria for Qi deficiency and blood stasis syndrome were stratified into case group,while those without Qi deficiency and blood stasis syndrome were stratified into control group.The demographic characteristics(age and gender),clinical parameters[time from onset to admission,National Institutes of Health Stroke Scale(NIHSS)score,and blood pressure],past medical history,traditional Chinese medicine(TCM)diagnostic characteristics(tongue and pulse),neurological symptoms and signs,imaging findings[magnetic resonance imaging-diffusion weighted imaging(MRI-DWI)],and biochemical indicators of the two groups were collected and compared.The indicators with statistical difference(P<0.05)in univariate analysis were included in multivariate logistic regression analysis to evaluate their predictive value for the diagnosis of Qi deficiency and blood stasis syndrome,and the predictive model was constructed by receiver operating characteristic(ROC)curve analysis.Results The study included 1035 AIS patients,with 404 cases in case group and 631 cases in control group.Compared with control group,patients in case group were significantly older,had extended onset-to-admission time,lower diastolic blood pressure,and lower NIHSS scores(P<0.05).Case group showed lower incidence of hypertension history(P<0.05).Regarding tongue and pulse characteristics,pale and dark tongue colors,white tongue coating,fine pulse,astringent pulse,and sinking pulse were more common in case group.Imaging examinations demonstrated higher proportions of centrum semiovale infarction,cerebral atrophy,and vertebral artery stenosis in case group(P<0.05).Among biochemical indicators,case group showed higher proportions of elevated fasting blood glucose and glycated hemoglobin(HbA1c),while lower proportions of elevated white blood cell count,reduced hemoglobin,and reduced high-density lipoprotein cholesterol(HDL-C)(P<0.05).Multivariate logistic regression analysis identified significant predictors for Qi deficiency and blood stasis syndrome including:fine pulse[odds ratio(OR)=4.38],astringent pulse(OR=3.67),superficial sensory abnormalities(OR=1.86),centrum semiovale infarction(OR=1.57),cerebral atrophy(OR=1.55),vertebral artery stenosis(OR=1.62),and elevated HbA1c(OR=3.52).The ROC curve analysis of the comprehensive prediction model yielded an area under the curve(AUC)of 0.878[95%confidence interval(CI)=0.855-0.900].Conclusion This study finds out that Qi deficiency and blood stasis syndrome represents one of the primary types of AIS.Fine pulse,astringent pulse,superficial sensory abnormalities,centrum semiovale infarction,cerebral atrophy,vertebral artery stenosis,elevated blood glucose,elevated HbA1c,pale and dark tongue colors,and white tongue coating are key objective diagnostic indicators for the syndrome differentiation of AIS with Qi deficiency and blood stasis syndrome.Based on these indicators,a syndrome differentiation prediction model has been developed,offering a more objective basis for clinical diagnosis,and help to rapidly identify this syndrome in clinical practice and reduce misdiagnosis and missed diagnosis.
基金supported by the National Natural Science Foundation of China(32002122,32372805)。
文摘Brassica napus(oilseed rape)is sensitive to boron(B)deficiency and exhibits young leaf curling in response to low-B stress at the seedling stage,which leads to reduced photosynthesis and plant growth.So far,no gene has been identified to be involved in B deficiency induced leaf curling.Our previous results showed the transcription factor BnaA1.WRKY53 might be involved in B-deficiency tolerance.However,altered BnaA1.WRKY53 expression does not influence B concentration in shoot,root and leaf cell walls,which suggests Bna A1.WRKY53 might be involved in other biological processes.Indeed,phenotypic and anatomical analyses revealed that BnaA1.WRKY53 negatively regulated the leaf curling induced by leaf epinasty by suppressing the overexpansion of palisade cells under B deficiency.Further transcriptome enrichment analysis of differentially expressed genes(DEGs)between wild-type and BnaA1.WRKY53overexpression line showed auxin response pathway was enriched.In addition,Arabidopsis DR5::GFP auxin reporter line showed B deficiency caused predominant auxin signal accumulation in the adaxial side and concomitant adaxial cell expansion,which indicated that B deficiency may induce leaf curling by altering auxin distribution.Phytohormone quantification and gene expression analysis demonstrated that BnaA1.WRKY53 prevent auxin overaccumulation in leaves by suppressing auxin biosynthetic genes under B deficiency.Furthermore,exogenous 1-naphthlcetic acid(NAA)treatment experiments revealed that high auxin could induce leaf curling and BnaA1.WRKY53 expression.Overall,these findings demonstrate that auxin and the transcription factor BnaA1.WRKY53 synergistically regulate leaf curling to maintain an optimal leaf area under B deficiency,and provide novel insights into the resistance mechanisms against B-deficiency-induced leaf curling in oilseed rape.
基金Supported by Natural Science Foundation of Guangdong Province,No.2021A1515011146 and No.2023A1515010785Key Areas Research and Development Programs of Guangdong Province,No.2023B1111050009.
文摘BACKGROUND Patients with colorectal cancer(CRC)exhibiting microsatellite instability(MSI)-high generally demonstrate a favorable response to immunotherapy.In contrast,the efficacy of immunotherapy in microsatellite-stable(MSS)CRC patients is considerably restricted.This study sought to evaluate the effectiveness of immu-notherapy in MSS patients characterized by homologous recombination defi-ciency(HRD)as opposed to those with homologous recombination proficiency(HRP).AIM To investigate and compare the clinicopathological characteristics,treatment modalities,and outcomes between the HRD and HRP groups in CRC.METHODS Next-generation sequencing was performed on 268 CRC patients to identify tumor-associated genetic alterations and assess their HRD scores and MSI status.Patients with HRD-related gene alterations or an HRD score≥30 were classified into the HRD group,while the remaining patients were assigned to the HRP group.Clinical data,including staging and treatment regimens,were collected for analysis.Cox regression and Kaplan-Meier survival curves were employed to evaluate whether the HRD group demonstrated improved survival outcomes following immunotherapy treatment.RESULTS Among the 268 patients,64 were classified into the HRD group,which had a higher proportion of early-stage CRC diagnoses compared to the HRP group.Kaplan-Meier survival curves indicated significantly better survival rates in the HRD group compared to the HRP group across all cohorts,as well as among MSS patients treated with immunotherapy(P<0.05).CONCLUSION This study demonstrates that CRC patients with HRD have a more favorable prognosis and suggests that HRD status could serve as a predictive marker for immunotherapy response in MSS patients.
文摘Background:Iron facilitates key biological functions underpinning sports performance,and up to 60%of female athletes experience iron deficiency.However,the effects of iron deficiency on sports performance in female athletes is unclear,as are the degree of benefits of iron supplementation(FeSup).This study characterizes the effects of iron deficiency and FeSup on sports performance in high-level female athletes.Methods:Searches of the electronic databases MEDLINE,SPORTDiscus,Web of Science,Scopus,and CINAHL were performed in July 2023.Studies were included that evaluated the effects of iron deficiency or FeSup on sports performance in high-level(maximal oxygen uptake(VO2max)>45 mL/kg/min,or trained>5 h/week)iron deficient(ID)(serum ferritin(sFer)<40 mg/L)female athletes.Studies were assessed using a modified Downs and Black Quality Assessment Checklist.Results:A total of 23 studies comprising 669 athletes(age range:13-47 years)across 16 sports were included in the review.Iron deficiency negatively affects endurance performance by 3%-4%.However,endurance performance improved by 2%-20%when ID athletes were treated with 100 mg/day of elemental iron for up to 56 days via oral supplementation,or bi-daily via parenteral administration over 8-10 days.ID nonanemic athletes with low sFer stores may be predisposed to reduced maximal aerobic capacity.However,maximal aerobic capacity improved by 6%-15%following 16 mg/day-100 mg/day of elemental iron for 36-126 days.Isokinetic strength and anaerobic power performance may be impeded(-23%to+4%)among ID athletes,but the effect of FeSup on anaerobic power varied markedly(-5%to+9%)following 100 mg/day of elemental iron over 42-56 days,or 100 mg of elemental iron bi-daily over 8-10 days.The quality of studies was moderate(77%),ranging from low(57%)to high(100%).Moststudies(n=18)contained group sizes-20 athletes,thus limiting the likelihood of detecting significant effects(statistical power>0.80).Conclusion:High-level ID female athletes experience a negative impact on endurance performance,which can be improved by supplementing with»100 mg of elemental iron per day or bi-daily.The decrements in other performance parameters characterizing a range of sports coincide with the severity of iron deficiency.
文摘Vitamin D deficiency is disproportionately prevalent among overweight and obese children,with conventional explanations such as poor dietary intake or reduced sun exposure offering only partial insight.Emerging evidence reveals a multifactorial pathophysiology,including sequestration of vitamin D in adipose tissue,altered hepatic metabolism,diminished bioavailability,and inflammationinduced resistance at the tissue level.These mechanisms contribute to a functional deficiency,wherein serum 25-hydroxyvitamin D levels may remain suboptimal despite adequate intake or sun exposure.Obesity-related alterations in vitamin Dbinding proteins,receptor expression,and pro-inflammatory signaling further compromise biological activity.Current diagnostic criteria and supplementation guidelines do not fully reflect these physiological complexities,leading to underdiagnosis and insufficient treatment.Personalized approaches-incorporating higher,body composition-adjusted dosing and consideration of inflammatory status-are emerging as promising strategies to restore sufficiency and improve metabolic outcomes.While preliminary evidence supports the safety and efficacy of high-dose supplementation in this population,pediatric-specific clinical trials are lacking.This review synthesizes current understanding of the pathophysiological mechanisms underlying vitamin D deficiency in pediatric obesity and emphasizes the need for individualized,evidence-based interventions to optimize vitamin D status and overall health.
基金supported by the National High Level Hospital Clinical Research Funding(No.BJ-2019-195)the National High Level Hospital Clinical Research Funding(No.BJ-2023-090)。
文摘Objective:Patients with homologous recombination deficiency(HRD)demonstrate distinct clinicopathological and prognostic features.However,standardised and clinically validated HRD detection methodologies specifically tailored for non-small cell lung cancer(NSCLC)have yet to be established.Further research is needed to clarify the precise role and clinical implications of HRD in NSCLC.Methods:A cohort of 580 treatment-naive NSCLC patients was retrospectively enrolled.Comprehensive genomic profiling(CGP)was performed for all patients,and HRD status was evaluated using two genomic scar score(GSS)-based algorithms:a machine learning-based GSS(ML-GSS)and a continuous linear regression-based GSS(CLR-GSS).To assess the diagnostic performance(sensitivity and specificity)of the ML-GSS and CLR-GSS algorithms for HRD detection,immunohistochemical(IHC)staining was conducted for two HRD-related biomarkers:Schlafen 11(SLFN11)and RAD51.Survival analysis,including progression-free survival(PFS),along with multivariable Cox proportional hazards models,was performed to compare the prognostic value of the two HRD algorithms.Results:Among all patients,146(25.2%)and 46(7.9%)were classified as HRD-positive(HRD+)by ML-GSS and CLR-GSS,respectively.Using SLFN11 IHC expression as the reference standard,comparative analysis demonstrated that ML-GSS exhibited significantly higher sensitivity but lower specificity than CLR-GSS.This trend was consistently observed in RAD51 staining analysis.Compared to HRD-negative(HRD-)patients,MLGSS-defined HRD+cases displayed distinct clinicopathological and genomic features,including a higher prevalence of homologous recombination(HR)-related genes mutations,BRCA1/2 mutations,TP53 mutations,elevated tumor mutation burden(TMB),and increased copy number variations(CNVs).In contrast,CLR-GSSdefined HRD+patients were only enriched for BRCA1/2 mutations,TP53 mutations,and elevated TMB.Furthermore,ML-GSS-defined HRD+status was associated with significantly worse prognosis following first-line therapy compared to HRD-patients.Univariate and multivariable Cox analyses identified ML-GSS-defined HRD+and TP53 mutations as significant predictors and independent risk factors,respectively.No such associations were observed in the CLR-GSS-defined HRD+cohort.Conclusions:ML-GSS demonstrated superior performance to CLR-GSS in assessing chromosomal instability(CIN)and showed greater clinical utility.We recommend the ML-GSS algorithm as a robust and clinically validated tool for HRD/CIN evaluation in NSCLC.Furthermore,ML-GSS-defined HRD+status was identified as both a significant predictor and an independent risk factor.
基金supported by The National Key Research and Development Program of China(Grant no.2021YFA0910100)Healthy Zhejiang One Million People Cohort(Grant no.K-20230085)+5 种基金Post-doctoral Innovative Talent Support Program(Grant no.BX2023375)Lingyan Project of Zhejiang Provincial Department of Science and Technology(Grant no.2025C02059)the National Natural Science Foundation of China(Grant nos.82304946,82473489,and 82403546)Natural Science Foundation of Zhejiang Province(Grant nos.LR21H280001,LGF22H160056,ZCLQN25H1602,and LMS25H160006)Medicine and Health Science Fund of Zhejiang Province Health Commission(Grant nos.2025KY047 and 2022KY658)Traditional Chinese Medicine Science and Technology Project of Zhejiang Provincial Health Commission(Grant no.2022ZA023).
文摘Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECKMATE-649,ORIENT-16,and KEYNOTE-859 trials,have markedly transformed the treatment paradigm for advanced gastric cancer(AGC)3-5.
基金Supported by the Natural Science Foundation of the Heilongjiang Province of China(C2016003)China Postdoctoral Science Foundation(2015M581415)Heilongjiang Postdoctoral Fund(LBH-Z15005)。
文摘The trace element selenium(Se)occurs naturally throughout the earth.Se deficiency has been linked to impaired breast health and other diseases in human and animals.Compared to severe Se deficiency,marginal dietary Se deficiency accusers more frequently in low-Se regions.Therefore,to investigate the Se status and inflammatory response of the mammary gland under marginal dietary Se levels,an lipopolysaccharide(LPS)induced mouse mastitis model was established.Mice were fed with moderate Se diet(0.087 mg•kg^(-1) Se),adequate Se diet(0.15 mg•kg^(-1) Se)or excessive Se diet(1.5 mg•kg^(-1) Se)for 60 days.Se status and inflammatory factors were investigated.Results showed that the Se status of mammary gland correlated with dietary Se levels.Marginal Se deficiency exacerbated mammary tissue histopathology;increased the mRNA level of inflammatory genes tumor necrosis factor alpha(TNF-α),interleukin-1β(IL-1β)and cyclooxygenase-2(COX-2);and enhanced the phosphorylation of NF-κB p65 in mammary gland tissues.Supplementation of Se in diet higher than recommended levels reduced the inflammatory reaction of mammary glands in LPS-induced mastitis model and provided a protective effect.
文摘Objective:To investigate whether differences exist in DNA fragmentation levels and protamine deficiency in the sperm of obese men compared to those of overweight and proven fertile,normal weight men and evaluate the alterations related to reproductive hormones,semen parameters and their association with body mass index(BMI).Methods:Participants in this observational study were divided into three groups based on their BMI:proven fertile,normal weight men(n=200);overweight men(n=200);and obese men(n=200).After 3 days of abstinence,seminal fluid was collected from all participants and analyzed.Blood samples were also collected on the same day for hormonal analysis.Sperm DNA fragmentation and protamine deficiency were also assessed.Results:A total of 600 men with a mean age of(34.3±7.9)2 years were included in the study.Obese males(BMI 30 kg/m or higher)exhibited significant reductions in semen volume,sperm concentration,total sperm motility percentage,progressive motility,non-progressive motility,and levels of total testosterone,follicle-stimulating hormone(FSH)and luteinizing hormone(LH)compared to overweight(BMI 25 to 29.9 kg/m2)and normal weight males(BMI 18.5 to 24.9 kg/m2)(P<0.001).Conversely,obese males showed a significant increase in prolactin level,sperm DNA fragmentation,and protamine deficiency compared to overweight and normal weight males(P<0.001).Significant negative correlations were demonstrated between BMI and sperm concentration,motility,total testosterone,FSH and LH(P<0.001),whereas prolactin,sperm DNA fragmentation and protamine deficiency were positively correlated with BMI(P<0.001).Conclusions:This study provides clear evidence that obesity contributes potentially to male infertility by inducing sperm DNA fragmentation and protamine deficiency,as well as negatively impacting reproductive hormones and semen quality.
文摘BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)and GH deficiency(GHD).Irrespective of the presence of GHD,NS is a Food and Drug Administration-approved indication for recombinant-GH therapy.Few case reports of combined anterior pituitary hormone deficiency(CPHD)in NS have been reported.AIM To describe the clinico-biochemical characteristics of NS with CPHD and to assess the response to recombinant GH therapy.METHODS An ambispective case-control study was conducted to compare the clinicohormonal profile and response to recombinant-GH in pediatric patients with NS and CPHD and pediatric patients with NS but without CPHD.RESULTS Five children with NS and CPHD were compared to 6 patients with NS but without CPHD.The most common anterior pituitary hormone involvement in combination with GHD was adrenocorticotrophic hormone deficiency causing hypocortisolemia(n=3,60%),followed by hypogonadotropic hypogonadism and secondary hypothyroidism(n=1 each).Pituitary hypoplasia was seen in the magnetic resonance imaging of all patients with CPHD.Patients with NS and CPHD had lower standard deviation scores of height(-4.18 vs-2.52,P=0.009),bodyweight,and body mass index but a slightly better first year response to recombinant GH(9.2 vs 5.5,P=0.06).There were no differences in dysmorphisms and other anomalies between the two groups.Patients with NS and CPHD had a similar response to GH as patients with CPHD but without NS.One patient with NS and CPHD developed hypocortisolism after GH initiation.CONCLUSION Hypoplasia of the pituitary and GHD with involvement of other pituitary hormones may be seen in NS and may determine response to recombinant GH therapy.
基金funded by the National Natural Science Foundation of China(32001676)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(CAST)(2022QNRC001).
文摘The prevalence of iron deficiency anemia(IDA)remains high in infants,resulting in growth retardation,neurodevelopmental impairment,immunodeficiency and other irreversible injuries.Efficient and safe iron supplementation for infants has been the goal of recent research.This study aims to investigate the effect of encapsulated ferric pyrophosphate(FePP)on intestinal inflammation and gut microbiota in IDA suckling rats.Newborn Sprague-Dawley rats were gavaged with low and high doses of FePP and FeSO4(2 and 10 mg Fe/kg BW,respectively)during postnatal days 2-14,while the Ctrl group was gavaged with saline.Results showed that FePP supplementation was as effective as FeSO4 in promoting growth,alleviating anemia and restoring body iron levels.Both low and high doses of FePP could significantly down-regulate the expression of pro inflammatory cytokines in the colon to the level similar to that in the Ctrl group(P>0.05).However,the high dose of FeSO4 did not show a down-regulation effect.Compared with the Ctrl group,IDA caused a disturbance of gut microbiota composition in suckling rats,and FePP could restore this dysbiosis.Besides,FePP was more beneficial than FeSO4 in increasing the abundance of beneficial bacteria such as Bacteroides and Akkermansia.Spearman’s correlation analysis showed a correlation between gut microbiota and biochemical indicators such as iron status,pro-inflammatory cytokine expression,and oxidative stress level.Overall,these findings suggested that FePP could effectively improve IDA,and is more effective than FeSO4 in alleviating intestinal inflammation and regulating gut microbiota,which provides a basis for the application of new iron fortificant in infant formula.
基金supported by Special Project of Traditional Chinese Medicine Scientific Research in Henan Province(2023ZY1024,2022ZY1144)Special COVID-19 Research Project of Traditional Chinese Medicine in Henan Province(2022ZYFY08)+1 种基金Traditional Chinese Medicine Culture and Management Research Project in Henan Province(TCM2023005)Basic Scientific Research Business Fund Project of Henan Integrative Medicine Hospital(2304025,2304015)。
文摘Objective To elucidate the mechanism of Fuzheng Gankang Pill in treating combined allergic rhinitis and asthma syndrome(CARAS)with lung-spleen qi deficiency and wind-cold invading the lung syndrome using network pharmacology and molecular docking.MethodsThe active components and targets of the 13 herbs in Fuzheng Gankang Pill were retrieved from the TraditionalChinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and HERB.A“core herb-active component-target"network was constructed using Cytoscape to screen core components.CARAS disease targets were obtained from Genecards,NationalCenter for Biotechnology Information(NCBI),and Online Mendelian Inheritance in Man(OMIM).Targets related to the clinical phenotypes of CARAS with lung-spleen qi deficiency and wind-cold invading the lung syndrome were retrieved from the Traditional ChineseMedicineSyndrome Ontology and Multidimensional Quantitative Association Calculation Platform.The intersection of CARAS disease targets and syndromerelated targets yielded CARAS disease-syndrome targets.The intersection of Fuzheng Gankang Pill component-related targets and CARAS disease-syndrome targets provided“disease-syndrome-formula”intersection targets.These targets were uploaded to the STRING database for protein-protein interaction(PPI)network analysis,with topological analysis identifying key targets.Metascape was used for Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking validation was performed using AutoDock Vina 1.1.2.Results The 13 core herbs of Fuzheng Gankang Pill contain a total of 200 active ingredients and 289 related targets.There are 2,412 disease targets for CARAS and 735 corresponding disease targets for the main and secondary symptoms of lung-spleen qi deficiency and wind-cold invading the lung.Through the Venn diagram,a total of 35 intersecting targets were obtained for Fuzheng Gankang Pill,CARAS,and the combination of lung-spleen qi deficiency and wind-cold invading the lung syndrome.Quercetin,Polygonatum sibiricum flavonoids,β-sitosterol,baicalein,kaempferol,etc.,are core components.PPI network analysis found that tumor necrosis factor(TNF),prostaglandin-endoperoxide synthase 2(PTGS2),interleukin(IL)-1β,IL-6,transforming growth factor beta 1(TGFβ1),BCL2,etc.,are the core targets for the compound to exert therapeutic effects.GO enrichment analysis showed that the 13 core drugs of Fuzheng Gankang Pill mainly participate in key biological processes such as positive regulation of protein modification,response to hormones,and negative regulation of cell population proliferation through protein kinases in areas such as membrane rafts,membrane microregions,plasma membrane protein complexes,and receptor com-plexes.KEGG enriched a total of 30 signaling pathways.Molecular docking shows that active ingredients such as quercetin and kaempferol bind stably toTNF(binding energy≤-9.0 kcal·mol^(-1))and PTGS2(≤-8.5kcal·mol^(-1)).Conclusion Fuzheng Gankang Pill may regulate biological processes such as cell apoptosis,tissue remodeling,inflammatory response,and immune response by acting on core targets such as TNF and PTGS2 through its core components quercetin,baicalein,β-sitosterol,baicalein,and kaempferol,thereby exerting therapeutic effects on CARAS with lung-spleen qi deficiency and wind-cold invading the lung syndrome.
基金Supported by the Projects of Design and Statistics of Clinical Trials in Traditional Chinese Medicine,No.A YXC2022-01-0110Exploring the Mechanism by which Pingyang Yuyin Granules Improve Hypertensive Kidney Injury Based on the'Balance'Theory of PPARγ/HGF and TGF-β1/Smads Signaling Pathways,No.Y2022ZR09.
文摘BACKGROUND Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases,stroke,and renal failure.Traditional Chinese Medicine(TCM)has been utilized for an extended period to address hypertension,with the syndrome known as Yin deficiency and Yang hyperactivity syndrome(YDYHS)frequently observed in individuals with elevated blood pressure.This syndrome is characterized by symptoms including dizziness,tinnitus,irritability,and insomnia,which are thought to result from an imbalance between Yin,representing the cooling and nourishing aspects,and Yang,denoting the active and warming aspects of the body.Despite the prevalent application of TCM in clinical settings,the metabolic mechanisms underlying the YDYHS in the context of hypertension remain inadequately elucidated.AIM To explore the differential plasma metabolites and associated pathways in hypertensive patients with YDYHS using gas chromatography-mass spectrometry(GC-MS)to elucidate the distinctive blood metabolite pattern in this patient population.METHODS GC-MS was used to analyze plasma samples from 51 hypertensive patients with YDYHS and 20 healthy controls.Chemometric methods,including principal component analysis and partial least squares discriminant analysis,were employed to identify potential biochemical patterns.Simultaneously,the high-quality Kyoto Encyclopedia of Genes and Genomes metabolic pathways database was used to identify associated metabolic pathways.Using variable importance in projection and receiver operating characteristic curve analyses,potential biomarkers were extracted to assess their clinical utility.RESULTS Metabolomic profiling of hypertensive patients with YDYHS identified 20 potential biomarkers(4-hydroxybenzoic acid,pectin,1,2,3-trihydroxybenzene,D-ribose,3-hydroxybutyric acid,quinic acid,L-lysine,oleic acid,2-hydroxybutyric acid,linoleic acid,citric acid,alpha-tocopherol,D-glucuronic acid,glycerol,N-acetyl-L-aspartic acid,betamannosylglycerate,indolelactic acid,L-glutamic acid,D-maltose,L-aspartic acid)and four metabolic pathways(linoleic acid metabolism;alanine,aspartate and glutamate metabolism;D-glutamine and D-glutamate metabolism;arginine biosynthesis).The identified differential metabolites may serve as potential biomarkers for distinguishing hypertensive patients with YDYHS from healthy controls.The area under the curve values ranged from 0.750 to 0.866.Receiver operating characteristic curve analysis showed that these differential metabolites can effectively classify hypertensive patients with YDYHS and healthy individuals.CONCLUSION The metabolomic analysis revealed a distinct blood metabolite pattern in hypertensive patients with YDYHS compared to the healthy control group,highlighting the potential role of the identified 20 biomarkers and four metabolic pathways in these patients.These findings may serve as an important material basis for understanding the occurrence and development of the disease,providing a scientific foundation for future clinical diagnosis.
基金funded by the National Natural Science Foundation of China(No.82405530,81973921 and 72374068)the Science and Technology Research Project of Hubei Provincial Department of Education(No.B2023098)。
文摘Objective:As an age-related neurodegenerative disease,the prevalence of mild cognitive impairment(MCI)increases with age.Within the framework of traditional Chinese medicine,spleen-kidney deficiency syndrome(SKDS)is recognized as the most frequent MCI subtype.Due to the covert and gradual onset of MCI,in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes.There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS(MCI-SKDS).Methods:This investigation enrolled 312 elderly individuals diagnosed with MCI,who were randomly distributed into training and test datasets at a 3:1 ratio.Five machine learning methods,including logistic regression(LR),decision tree(DT),naive Bayes(NB),support vector machine(SVM),and gradient boosting(GB),were used to build a diagnostic prediction model for MCI-SKDS.Accuracy,sensitivity,specificity,precision,F1 score,and area under the curve were used to evaluate model performance.Furthermore,the clinical applicability of the model was evaluated through decision curve analysis(DCA).Results:The accuracy,precision,specificity and F1 score of the DT model performed best in the training set(test set),with scores of 0.904(0.845),0.875(0.795),0.973(0.875)and 0.973(0.875).The sensitivity of the training set(test set)of the SVM model performed best among the five models with a score of 0.865(0.821).The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset.The DCA of all models showed good clinical application value.The study identified ten indicators that were significant predictors of MCI-SKDS.Conclusion:The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical;the model demonstrates good predictive value and clinical applicability,and the DT model had the best performance.
文摘Objective:To observe the therapeutic effect of Moist Burn Ointment combined with rotating moxibustion on patients with pressure ulcers and deficiency of both Qi and blood.Methods:40 patients with pressure ulcers and deficiency of both Qi and blood were randomly divided into two groups from July 2024 to November 2025.Group A received Moist Burn Ointment combined with rotating moxibustion,while Group B received Moist Burn Ointment only.Results:Group A showed better efficacy,wound healing time,dressing change frequency,satisfaction,PUSH score,and adverse reaction indicators compared to Group B(P<0.05).Conclusion:The combination of Moist Burn Ointment and rotating moxibustion in the treatment of patients with pressure ulcers and deficiency of both Qi and blood can shorten wound healing time,reduce dressing change frequency,and alleviate the degree of pressure ulcers,which is safe and efficient.
文摘Metformin-induced vitamin B12 deficiency is a prevalent condition among pa-tients with type 2 diabetes mellitus.In recent years,a growing body of evidence has demonstrated the association between vitamin B12 deficiency and the onset,progression,and worsening of diabetic neuropathy(DNP)as well as its im-provement with supplementation in cases of deficiency.Major clinical guidelines for diabetes and DNP remain vague in their recommendations for B12 measu-rement and supplementation,and some guidelines do not address it at all.Given that vitamin B12 therapy is an economical,safe,and widely available treatment in most countries and supported by emerging evidence of its potential benefits,greater efforts should be made to promote systematic screening for vitamin B12 deficiency in all patients with DNP before establishing a definitive diagnosis as well as in patients with diabetes with risk factors for deficiency.Vitamin B12 deficiency should be treated in all affected patients,and supplementation should be considered in those with borderline levels when confirmatory diagnostic tests for deficiency are unavailable.Clinical guidelines should place greater emphasis on the recommendations for measuring and supplementing vitamin B12 in these patients.
