OBJECTIVES To evaluate the predictive value of fasting plasma glucose(FPG)for in-hospital mortality in patients with acute myocardial infarction(AMI)with different glucose metabolism status.METHODS We selected 5,308 p...OBJECTIVES To evaluate the predictive value of fasting plasma glucose(FPG)for in-hospital mortality in patients with acute myocardial infarction(AMI)with different glucose metabolism status.METHODS We selected 5,308 participants with AMI from the prospective,nationwide,multicenter CAMI registry,of which 2,081 were diabetic and 3,227 were nondiabetic.Patients were divided into high FPG and low FPG groups according to the optim-al cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts,respectively.The primary endpoint was in-hospital mortality.RESULTS Overall,94 diabetic patients(4.5%)and 131 nondiabetic patients(4.1%)died during hospitalization,and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L,respectively.Compared with individuals who had low FPG,those with high FPG were significantly associated with higher in-hospital mortality in diabet-ic cohort(10.1%vs.2.8%;odds ratio[OR]=3.862,95%confidence interval[CI]:2.542-5.869)and nondiabetic cohort(7.4%vs.1.7%;HR=4.542,95%CI:3.041-6.782).After adjusting the potential confounders,this significant association was not changed.Further-more,FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status.Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts.CONCLUSIONS This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mor-tality in AMI patients with and without diabetes.FPG might be useful to stratify patients with AMI.展开更多
BACKGROUND The annual incidence of gastric cancer in elderly patients is increasing.Despite the continuous progress in treatment methods,the prognosis of elderly patients remains poor,and postoperative complications a...BACKGROUND The annual incidence of gastric cancer in elderly patients is increasing.Despite the continuous progress in treatment methods,the prognosis of elderly patients remains poor,and postoperative complications are frequent.Obesity is believed to be associated with the risk of gastric cancer and postoperative prognosis;however,the effect of visceral fat distribution on postoperative complications of gastric cancer in elderly patients remains unclear.AIM To explore the effect of visceral fat distribution on postoperative complications of gastric cancer in elderly patients.METHODS A total of 163 elderly patients treated at the Affiliated Longyan First Hospital of Fujian Medical University after radical gastrectomy between January 2021 and January 2024 were enrolled.The patients'visceral and subcutaneous fat distributions were measured and divided into a high visceral fat area(VFA-H)group and a low visceral fat area(VFA-L)group,with a critical value of 100 cm^(2).The ttest andχ^(2) test were used to calculate and analyze the relationship between visceral fat area(VFA)and complications.Independent risk factors for postoperative complications were analyzed using binary logistic regression analysis.RESULTS Compared with the VFA-L group,the incidence of postoperative complications was higher in the VFA-H group(27.8%vs 6.4%,P<0.001),and the operation time was longer(268.55±63.41 vs 224.31±51.89,P<0.001).The amount of blood loss was more(163.77±105.27 mL vs 127.93±98.26 mL,P<0.001).Logistic regression analysis showed that VFA[odds ratio(OR):2.597,95%CI:1.479-4.853,P=0.004],total fat area(OR:1.655,95%CI:1.076-4.040,P=0.013),and the visceral subcutaneous fat area ratio(OR:2.046,95%CI:1.196-5.640,P=0.008)were independent risk factors for postoperative complications.CONCLUSION This study showed that postoperative complications are closely related to fat distribution in elderly patients with gastric cancer undergoing gastrectomy.A high VFA is associated by a high incidence of postoperative complications.展开更多
BACKGROUND Female depression is a prevalent and increasingly recognized mental health issue.Due to cultural and social factors,many female patients still face challenges in diagnosis and treatment,and traditional asse...BACKGROUND Female depression is a prevalent and increasingly recognized mental health issue.Due to cultural and social factors,many female patients still face challenges in diagnosis and treatment,and traditional assessment methods often fail to identify high-risk individuals accurately.This highlights the necessity of developing more precise predictive tools.Utilizing machine learning(ML)algorithms to construct predictive models may overcome the limitations of traditional methods,providing more comprehensive support for women’s mental health.AIM To construct an ML-nomogram hybrid model that translates multivariate risk predictors of female depressive symptoms into actionable clinical scoring thresholds,optimizing predictive accuracy and interpretability for healthcare applications.METHODS We analyzed data from 7609 female participants aged 18 to 85 years from the Guangdong Provincial Sleep and Psychosomatic Health Survey.Sixteen variables,including anxiety symptoms,insomnia,chronic diseases,exercise habits,and age,were selected based on prior literature and comprehensively incorporated into ML models to maximize predictive information utilization.Three ML algorithms,extreme gradient boosting,support vector machine,and light gradient boosting machine,were employed to construct predictive models.Model performance was evaluated using accuracy,precision,recall,F1 score,and area under the curve(AUC).Feature importance was interpreted using SHapley Additive exPlanations(SHAP),with ablation studies validating the impact of the top five SHAPderived features on predictive performance,and a nomogram was constructed based on these prioritized predictors.Clinical utility was assessed through decision curve analysis.RESULTS The prevalence of depressive symptoms was 6.8%among the sample.The evaluation of predictive models revealed that light gradient boosting machine achieved a top-performing AUC of 0.867,placing it ahead of extreme gradient boosting(AUC=0.862)and support vector machine(AUC=0.849).SHAP analysis identified insomnia,anxiety symptoms,age,chronic disease,and exercise as the top five predictors.The nomogram based on these features demonstrated excellent discrimination(AUC=0.910)and calibration,with significant net benefits in decision curve analysis compared to baseline strategies.The model effectively stratifies depressive symptoms risk,facilitating personalized and quantitative assessments in clinical settings.We also developed an interactive digital version of the nomogram to facilitate its application in clinical practice.CONCLUSION The ML-based model effectively predicts depressive symptoms in women,identifying insomnia,anxiety symptoms,age,chronic diseases,and exercise as key predictors,offering a practical tool for early detection and intervention.展开更多
Objective:Pathologic complete response(pCR)following neoadjuvant therapy(NAT)for gastric cancer(GC)is rare but associated with a favorable prognosis.This study aims to reassess the optimal response population(ORP)foll...Objective:Pathologic complete response(pCR)following neoadjuvant therapy(NAT)for gastric cancer(GC)is rare but associated with a favorable prognosis.This study aims to reassess the optimal response population(ORP)following NAT by evaluating the prognostic outcomes associated with various T and N stages,utilizing multicenter data from China.Methods:Patients who underwent NAT following radical gastrectomy at 10 tertiary hospitals in China between2008 and 2021 were included.The ORP was introduced to explore the disease-free survival(DFS),overall survival(OS),recurrence patterns,and influencing factors following propensity score matching(PSM).Results:A total of 1,076 patients were enrolled in this study(median follow-up period:60 months).We defined ORP as a pCR or tumor infiltration of the mucosal or submucosal layer without lymph node metastasis(pCR or yp T1N0)after NAT.The ORP group comprised 136 patients(12.6%),while the non-ORP group comprised 940patients(87.4%).After applying a 1:4 PSM,we obtained an ORP group of 136 patients and non-ORP group of 544patients.Survival analysis demonstrated that both the 3-year OS(before PSM:89.0%vs.55.0%,P<0.001;after PSM:89.0%vs.55.4%,P<0.001)and DFS(before PSM:85.8%vs.49.7%,P<0.001;after PSM:85.8%vs.50.6%,P<0.001)were significantly superior in the ORP group compared to that in the non-ORP group.Remarkably,adjuvant chemotherapy did not impact the prognosis of patients in the ORP group(3-year OS:89.0%vs.89.7%,P=0.988;3-year DFS:84.9%vs.89.7%,P=0.700).Conclusions:This study reevaluates patients with ORP following NAT,providing a more comprehensive and accurate depiction of the potential beneficiary group and survival outcomes in patients with locally advanced GC.展开更多
BACKGROUND Intraoperative fluid management is an important aspect of anesthesia mana-gement in gastrointestinal surgery.Intraoperative goal-directed fluid therapy(GDFT)is a method for optimizing a patient's physio...BACKGROUND Intraoperative fluid management is an important aspect of anesthesia mana-gement in gastrointestinal surgery.Intraoperative goal-directed fluid therapy(GDFT)is a method for optimizing a patient's physiological state by monitoring and regulating fluid input in real-time.AIM To evaluate the efficacy of intraoperative GDFT in patients under anesthesia for gastrointestinal surgery.METHODS This study utilized a retrospective comparative study design and included 60 patients who underwent gastrointestinal surgery at a hospital.The experimental group(GDFT group)and the control group,each comprising 30 patients,received intraoperative GDFT and traditional fluid management strategies,respectively.The effect of GDFT was evaluated by comparing postoperative recovery,com-plication rates,hospitalization time,and other indicators between the two patient groups.RESULTS Intraoperative blood loss in the experimental and control groups was 296.64±46.71 mL and 470.05±73.26 mL(P<0.001),and urine volume was 415.13±96.72 mL and 239.15±94.69 mL(P<0.001),respectively.The postoperative recovery time was 5.44±1.1 days for the experimental group compared to 7.59±1.45 days(P<0.001)for the control group.Hospitalization time for the experimental group was 10.87±2.36 days vs 13.65±3 days for the control group(P<0.001).The visual analogue scale scores of the experimental and control groups at 24 h and 48 h INTRODUCTION Gastrointestinal surgery is one of the most common procedures in the field of general surgery[1],involving the stomach,intestines,liver,pancreas,spleen,and other internal abdominal organs[2,3].With advancements in surgical technology and anesthesia methods,the safety and success rates of surgery have significantly improved[4,5].However,intraop-erative fluid management remains a critical challenge[6].Traditional fluid management strategies often rely on experience and basic physiological parameters,which may lead to excessive or insufficient fluid input,thereby affecting postoperative recovery and complication rates.Intraoperative goal-directed fluid therapy(GDFT)is an emerging fluid management strategy that dynamically adjusts fluid input volume by monitoring the patient's hemodynamic parameters in real-time to optimize the patient's physiological state[7,8].GDFT has shown superiority in many surgical fields;however,its application in gastrointestinal surgery requires further research and verification[9,10].The application of intraoperative GDFT in clinical settings has gradually increased in recent years[11,12].Studies have demonstrated that GDFT can optimize tissue perfusion and oxygenation by precisely controlling fluid input and reducing the occurrence of postoperative complications[13,14].For example,in cardiac and major vascular surgeries,GDFT significantly reduced the incidence of postoperative acute kidney injury and cardiovascular events[15,16].Similarly,in abdominal surgery,GDFT effectively reduced postoperative infections and expedited recovery[17].However,studies on the utilization of GDFT in gastrointestinal surgery are relatively limited and they are confounded by contradictory findings[18].Traditional fluid management strategies typically rely on estimating fluid input volume based on the patient's weight,preoperative status,and basic physiological parameters[19].However,this method lacks real-time dynamic adjustment,which may result in either insufficient or excessive fluid input,consequently affecting postoperative recovery.Insufficient fluid input can lead to hypovolemia and inadequate tissue perfusion,whereas excessive fluid input can cause tissue edema and postoperative complications,such as pulmonary edema and heart failure.GDFT involves dynamically adjusting fluid input volume by monitoring the patient's hemodynamic parameters in real-time,such as cardiac output,pulse pressure variability,and central venous pressure.Commonly used monitoring equipment include esophageal Doppler and pulse wave profile analyzers[20].These devices provide real-time hemo-dynamic data to assist anesthesiologists in tailoring fluid therapy to a patient's specific condition.Firstly,the patient's volume responsiveness is assessed by preloading fluid;secondly,fluid input volume is dynamically adjusted based on real-time monitoring data;finally,vasoactive and inotropic drugs are administered in combination to further optimize the patient’s hemodynamic status.Through personalized fluid management,GDFT can more accurately maintain intraop-erative hemodynamic stability and reduce complications[21].Gastrointestinal surgery involves procedures on multiple organs,often requiring prolonged operative times and extensive tissue trauma,which presents challenges for intraop-erative fluid management.Surgical procedures can lead to significant bleeding and fluid loss,requiring prompt and effective fluid replenishment.In addition,the slow recovery of gastrointestinal function after surgery and susceptibility to complications such as intestinal obstruction and delayed gastric emptying elevate the necessity for postoperative fluid management.展开更多
Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia.However,whether there is a synergistic effect between the two remains unclea...Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia.However,whether there is a synergistic effect between the two remains unclear.In this study,we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours.Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes(MSC-exos)via the tail vein and underwent 14 successive days of treadmill exercise.Neurological assessment,histopathology,and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume,evident synaptic formation and axonal regeneration,and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment.These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone.Mechanistically,further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling.These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment,which may be related to activation of the JNK1/c-Jun signaling pathway.This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.展开更多
Objectives: To observe the effectiveness of acupuncture therapy for relieving throat and opening orifice on dysphagia due to different brain infarct sites.Methods: According to the random number table, 128 patients wi...Objectives: To observe the effectiveness of acupuncture therapy for relieving throat and opening orifice on dysphagia due to different brain infarct sites.Methods: According to the random number table, 128 patients with post-stroke dysphagia were divided into group A(63 cases, intervention with deglutition training and acupuncture) and group B(65 cases,intervention with simple deglutition training). The conventional treatment and deglutition rehabilitation training in neurology department were used in the two groups. In group B, according to patient's condition, the rehabilitation trainings, such as respiration and neck movement range were used selectively.In group A, on the base of deglutition training, acupuncture therapy for relieving throat and opening orifice was supplemented. The acupoints included Sìshéncōng(四神聪EX HN 1),Bāihuì(百会GV 20), Tàiyang(太阳EX-HN5) bilateral, Fēngchi(风池GB 20) bilateral and Shésānzhēn(舌三针).Electrostimulator was attached on EX-HN 1, bilateral GB 20 and Shesanzhen(舌三针). Needles were retained for 30 min in each treatment. The treatment was given once a day, 5 treatments a week and the treatment for 3 weeks as 1 course. After 6 weeks of treatment, the deglutition ability scale developed by Fujishima Ichiro was adopted to determine the therapeutic effects and observe the score increase for dysphagia related to brain infarct sites before and after treatment.Results: In assessment after 6-week treatment, the improvements of deglutition ability were different corresponding to different brain infarct sites in group A. Specially, the improvements in the patients with dysphagia related to cerebral hemisphere infarction in group A were better than group B(8.68 ±1.12 vs7.32 ±0.91, P<0.05), followed by the improvements in the patients with dysphagia related to internal capsule/basal ganglia/diencephalon infarction(6.53 ±0.65 vs 6.36 ±0.84, P>0.05). Regarding the therapeutic effects in comparison of the two groups, the total effective rates in dysphagia related to cerebral hemisphere infarction were different between the two groups significantly(96.67% vs 82.75%, P< 0.05), as well as in the patients related to internal capsule/basal ganglia/diencephalon infarction(88.89% vs 66.67%,P<0.05). The therapeutic effects were not different in the patients related to cerebral stem and cerebella infarction between the two groups(P>0.05).Conclusion: The acupuncture therapy for relieving throat and opening orifice combined with deglutition training achieves the satisfactory therapeutic effects on dysphagia induced by cortical infarction in stroke.However, a large sample and multicentral clinical trial with this therapy is needed for a further argument so that this therapy is likely promoted in clinical practice in future.展开更多
Dear Sir,I am Dr.Zhe Xu,from the Eye Center,Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,China.We write to present a case of resolution of siderotic glaucoma after removal of a retained f...Dear Sir,I am Dr.Zhe Xu,from the Eye Center,Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,China.We write to present a case of resolution of siderotic glaucoma after removal of a retained ferrous foreign body.This study has been performed in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of the Second Affiliated Hospital.展开更多
Background Few studies have investigated the safe limits of total intravenous plus oral hydration to prevent contrast-induced nephropathy （CIN）. The present study was conducted to evaluate the effects of different c...Background Few studies have investigated the safe limits of total intravenous plus oral hydration to prevent contrast-induced nephropathy （CIN）. The present study was conducted to evaluate the effects of different composite hydration rate （intravenous plus oral） on CIN prevention in patients undergoing emergent percutaneous coronary intervention （PCI）. Methods This was a retrospective observational study that included 307 eligible patients, who were stratified into quartiles of rate of the composite hydration volumn to body weight and time （HV/ W/T）. CIN was defined as an absolute≥0.5 mg/dL or a relative ≥25% increase in the serum creatinine level within 72 hours after the procedure. Results In terms of risks of CIN, there were no statistical differences among individuals in four groups with different composite HV/W/T （27.6%, 19.0%, 23.0%, and 26.9% respectively in quartiles Q1, Q2, Q3, and Q4, P=0.565）. Additionally, higher composite hydration ratio seemed not to decrease the risk of in-hospital death, worsening heart failure and stroke （all P〉0.05）. After adjusting for other risk factors, multivariate analysis showed no statistical difference between Q2, Q3 or Q4, compared with Q1 （Q2 vs. QI： adjusted odds ratio [OR], 0.67, P=0.383; Q3 vs QI： adjusted OR, 0.77, P=0.550; Q4 vs. QI： adjusted OR, 0.75, P= 0.489）. Conclusion Excessive composite hydration may not provide supplemental benefit of CIN prevention and in-hospital outcomes in patients following emergent PCI, and moderate and prophylactic hydration is warranted.展开更多
Platelets act as a crucial indicator for monitoring hypercoagulability and thrombosis and a key target for pharmacological intervention.Genotype-phenotype association studies have confirmed that platelet traits are qu...Platelets act as a crucial indicator for monitoring hypercoagulability and thrombosis and a key target for pharmacological intervention.Genotype-phenotype association studies have confirmed that platelet traits are quantitatively regulated by multiple genes.However,there is currently a lack of genetic studies on the heterogeneity of platelet traits in β-thalassemia under a hypercoagulable state.Here,we studied the phenotypic heterogeneity of platelet count(PLT)and mean platelet volume(MPV)in a cohort of 1020β-thalassemia patients.We further performed a functionally informed whole-genome sequencing(WGS)association analysis of common variants and rare variants for PLT and MPV in 916 patients through integrative analysis of WGS data and functional annotation data.Extreme phenotypic heterogeneity of platelet traits was observed in β-thalassemia patients.Additionally,the common variant-based gene-level analysis identified RNF144B as a novel gene associated with MPV.The rare variant analysis identified several novel associations in both coding and noncoding regions,including missense rare variants of PPP2R5C associated with PLT and missense rare variants of TSSK1B associated with MPV.In conclusion,this comprehensive and systematic whole-genome scan of platelet traits in the β-thalassemia cohort reveals the specific genetic regulation of platelet traits in the context of β-thalassemia,providing potential targets for intervention.展开更多
Objective：To evaluate the efficacy of Chinese medicine（CM）adjunct to conventional medications for idiopathic Parkinson’s disease（PD）.Methods：Electronic English and Chinese databases including Pub Med,Cochrane L...Objective：To evaluate the efficacy of Chinese medicine（CM）adjunct to conventional medications for idiopathic Parkinson’s disease（PD）.Methods：Electronic English and Chinese databases including Pub Med,Cochrane Library,Web of Science,Chinese Medical Current Contents,China National Knowledge Infrastructure,China Science and Technology Journal Database,Wanfang Med Database,and Traditional Chinese Medical Database System were used for key words searching in a highly sensitive search strategy.The extracted data was analyzed by the Review Manager 5.0.Results：Twelve trials involving 869 participants were included in the meta-analysis.Unified PD Rating Scale（UPDRS）Ⅰ,Ⅱ,Ⅲ,Ⅳscores and UPDRSⅠ–Ⅳtotal scores were used to be the primary outcomes,Parkinson Disease Question-39（PDQ-39）and Scores of Chinese Medical Symptoms were the secondary outcomes.CM adjunct therapy had greater improvement in UPDRSⅠ[2 trials;standardized mean difference（SMD）–0.40,95%confidence interval（CI）–0.71 to–0.09;Z=2.49（P=0.01）],Ⅱ[5 trials;SMD–0.47,95%CI–0.69 to–0.25;Z=4.20（P〈0.01）],Ⅲ[5 trials;SMD-0.35,95%CI–0.57 to–0.13;Z=3.16（P=0.002）],Ⅳscores[3 trials;SMD-0.32,95%CI–0.60 to–0.03;Z=2.17（P=0.03）],UPDRSⅠ–Ⅳtotal scores[7 trials;SMD-0.36,95%CI–0.53 to–0.20;Z=4.24（P〈0.05）].PDQ-39 and Chinese medical symptoms compared to the conventional medication only.Conclusion：CM adjunct therapy has potential therapeutic benefits by decreasing UPDRS scores and reducing adverse effect.展开更多
Background:Sleep disorders are one of the earliest non-motor symptoms of Parkinson's disease(PD).Sleep disorders could,therefore,have value for recognition and diagnosis in PD.However,no unified classification and...Background:Sleep disorders are one of the earliest non-motor symptoms of Parkinson's disease(PD).Sleep disorders could,therefore,have value for recognition and diagnosis in PD.However,no unified classification and diagnostic criteria exist to evaluate sleep disorders by polysomnography(PSG).Utilizing PSG to monitor sleep processes of patients with PD and analyze sleep disorder characteristics and their relationship with demographic parameters could aid in bridging this gap.This preliminary study aimed to evaluate the clinical characteristic of sleep disorders in PD using PSG.Methods:PSG was used to evaluate sleep disorders in 27 patients with PD and 20 healthy volunteers between August 2015 and July 2018 in Fujian Medical University Union Hospital.Total sleep time(TST),sleep efficiency(SE),total wake time,and other parameters were compared between the two groups.Finally,the correlation between sleep disorders and age,disease duration,Unified Parkinson's Disease Rating Scale-Ⅲscores,Hoehn-Yahr stage,and levodopa dose were analyzed.The main statistical methods included Chi-square test,two independent samples t test,Fisher exact test,and Pearson correlation.Results:Sleep fragmentation in the PD group was significantly increased(74.1%)while difficulty falling asleep and early awakening were not,as compared to healthy controls.No significant differences were found in time in bed,sleep latency(SL),non-rapid eye movement(NREM)stage 1(N1),N1%,N2,N2%,N3%,and NREM%between PD and control groups;but TST(327.96±105.26 min vs.414.67±78.31 min,P=0.003),SE(63.26%±14.83%vs.76.8%±11.57%,P=0.001),R N3(20.00[39.00]min vs.61.50[48.87]min,P=0.001),NREM(262.59±91.20 min vs.337.17±63.47 min,P=0.003),rapid-eyemovement(REM)(32.50[33.00]min vs.85.25[32.12]min,P<0.001),REM%(9.56±6.01 vs.15.50±4.81,P=0.001),REM sleep latency(157.89±99.04 min vs.103.47±71.70 min,P=0.034)were significantly reduced in PD group.Conclusion:This preliminary study supported that sleep fragmentation was an important clinical characteristic of sleep disorders in PD.Whether sleep fragmentation is a potential quantifiable marker in PD needs to be further investigated in the future study.展开更多
Background:Intracellular accumulation of the microtubule-associated protein tau and its hyperphosphorylated forms is a key neuropathological feature of Alzheimer’s disease(AD).Melatonin has been shown to prevent tau ...Background:Intracellular accumulation of the microtubule-associated protein tau and its hyperphosphorylated forms is a key neuropathological feature of Alzheimer’s disease(AD).Melatonin has been shown to prevent tau hyperphosphorylation in cellular and animal models.However,the molecular mechanisms by which melatonin attenuates tau hyperphosphorylation and tau-related pathologies are not fully understood.Methods:Immunofluorescence,immunoblotting analysis and thioflavin-S staining were employed to examine the effects of early and late treatment of melatonin on tau-related pathology in hTau mice,in which nonmutated human tau is overexpressed on a mouse tau knockout background.High-throughput microRNA(miRNA)sequencing,quantitative RT-PCR,luciferase reporter assay and immunoblotting analysis were performed to determine the molecular mechanism.Results:We found that both early and late treatment of melatonin efficiently decreased the phosphorylation of soluble and insoluble tau at sites related to AD.Moreover,melatonin significantly reduced the number of neurofibrillary tangles(NFTs)and attenuated neuronal loss in the cortex and hippocampus.Furthermore,using miRNA microarray analysis,we found that miR-504-3p expression was upregulated by melatonin in the hTau mice.The administration of miR-504-3p mimics dramatically decreased tau phosphorylation by targeting p39,an activator of the well-known tau kinase cyclin-dependent kinase 5(CDK5).Compared with miR-504-3p mimics alone,co-treatment with miR-504-3p mimics and p39 failed to reduce tau hyperphosphorylation.Conclusions:Our results suggest for the first time that melatonin alleviates tau-related pathologies through upregulation of miR-504-3p expression by targeting the p39/CDK5 axis and provide novel insights into AD treatment strategies.展开更多
To treat 30 cases of diarrhea of insufficiency of the spleen-yang type by moxibustion with salt at Shenque (CV 8). The total effective rate was 93.3%. Key Words Diarrhea, chronic - Salt-partitioned Moxibustion - Poin...To treat 30 cases of diarrhea of insufficiency of the spleen-yang type by moxibustion with salt at Shenque (CV 8). The total effective rate was 93.3%. Key Words Diarrhea, chronic - Salt-partitioned Moxibustion - Point CV 8 - Acupuncture-moxibustion Translator: WANG Si-you展开更多
Background:Although many causative genes of hereditary spastic paraplegia(HSP)have been uncovered in recent years,there are still approximately 50% of HSP patients without genetically diagnosis,especially in autosomal...Background:Although many causative genes of hereditary spastic paraplegia(HSP)have been uncovered in recent years,there are still approximately 50% of HSP patients without genetically diagnosis,especially in autosomal recessive(AR)HSP patients.Rare studies have been performed to determine the genetic spectrum and clinical profiles of recessive HSP patients in the Chinese population.Methods:In this study,we investigated 24 Chinese index AR/sporadic patients by targeted next-generation sequencing(NGS),Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA).Further functional studies were performed to identify pathogenicity of those uncertain significance variants.Results:We identified 11 mutations in HSP related genes including 7 novel mutations,including two(p.V1979_L1980delinsX,p.F2343 fs)in SPG11,two(p.T55 M,p.S308 T)in AP5Z1,one(p.S242N)in ALDH18A1,one(p.D597fs)in GBA2,and one(p.Q486X)in ATP13A2 in 8 index patients and their family members.Mutations in ALDH18A1,AP5Z1,CAPN1 and ATP13A2 genes were firstly reported in the Chinese population.Furthermore,the clinical phenotypes of the patients carrying mutations were described in detail.The mutation(p.S242 N)in ALDH18A1 decreased enzyme activity of P5CS and mutations(p.T55 M,p.S308 T)in AP5Z1 induced lysosomal dysfunction.Conclusion:Our results expanded the genetic spectrum and clinical profiles of AR-HSP patients and further demonstrated the efficiency and reliability of targeted NGS diagnosing suspected HSP patients.展开更多
Objective:To construct a risk prediction model for in-hospital cardiac arrest(IHCA)in patients with chronic obstructive pulmonary disease(COPD)complicated with respiratory failure.Methods:The clinical data of 550 pati...Objective:To construct a risk prediction model for in-hospital cardiac arrest(IHCA)in patients with chronic obstructive pulmonary disease(COPD)complicated with respiratory failure.Methods:The clinical data of 550 patients with COPD complicated with respiratory failure in our hospital from January 2016 to June 2022 were retrospectively analyzed.According to the occurrence of IHCA,they were divided into the IHCA group and non-IHCA group.The general data and clinical indicators of the two groups were compared,and logistic regression analysis was performed,R software was used to establish the risk prediction model(nomogram model)for predicting the occurrence of IHCA in patients with COPD complicated with respiratory failure.The risk prediction model(line graph model)for patients with IHCA was validated by the Bootstrap method,and the predictive value was analyzed by applying the receiver operating characteristic(ROC)curve.Results:Among 550 COPD patients complicated with respiratory failure,95 cases(17.27%)had IHCA.There were significant differences in age,old myocardial infarction,heart failure,moderate and severe chronic kidney disease,assisted breathing mode,state of consciousness,body temperature,heart rate,respiratory rate,systolic blood pressure,lactic acid,Sa O,Pa CO,serum creatinine,albumin,and prealbumin between the non-IHCA group and IHCA group(P<0.05).Logistic regression analysis showed that age,heart failure,heart rate,respiratory rate,systolic blood pressure,unclear state of consciousness,serum creatinine and prealbumin were independent influencing factors of IHCA in COPD patients complicated with respiratory failure(P<0.05).According to the results of binary logistic regression analysis,a nomogram model for predicting the incidence of IHCA in COPD patients complicated with respiratory failure was constructed.The fitting degree of the model was determined by the H-L test.The calibration curve showed that the incidence of IHCA in COPD patients complicated with respiratory failure predicted by nomogram was in good agreement with the actual incidence of IHCA in patients with COPD complicated with respiratory failure(χ~2=2.017,P=0.334).The ROC curve showed an AUC of 0.627(95%CI:0.593-0.689,P<0.005),and the optimal cut point value for diagnosis was 0.69,at which the sensitivity and specificity were 42.57%and 96.03%,respectively.Conclusion:According to the independent influencing factors of IHCA in COPD patients complicated with respiratory failure,the establishment of a risk prediction nomogram model has high predictive value,which is worthy of clinical promotion.展开更多
基金supported by CAMS Innovation Fund for Medical Sciences (CIFMS: 2021-I2M-1008)Beijing Municipal Health Commission-Capital Health Development Research Project (20201–4032)+1 种基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS: 2020I2M-C&T-B-056)the Twelfth Five-Year Planning Project of the Scientific and Technological Department of China (2011BAI11B02)
文摘OBJECTIVES To evaluate the predictive value of fasting plasma glucose(FPG)for in-hospital mortality in patients with acute myocardial infarction(AMI)with different glucose metabolism status.METHODS We selected 5,308 participants with AMI from the prospective,nationwide,multicenter CAMI registry,of which 2,081 were diabetic and 3,227 were nondiabetic.Patients were divided into high FPG and low FPG groups according to the optim-al cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts,respectively.The primary endpoint was in-hospital mortality.RESULTS Overall,94 diabetic patients(4.5%)and 131 nondiabetic patients(4.1%)died during hospitalization,and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L,respectively.Compared with individuals who had low FPG,those with high FPG were significantly associated with higher in-hospital mortality in diabet-ic cohort(10.1%vs.2.8%;odds ratio[OR]=3.862,95%confidence interval[CI]:2.542-5.869)and nondiabetic cohort(7.4%vs.1.7%;HR=4.542,95%CI:3.041-6.782).After adjusting the potential confounders,this significant association was not changed.Further-more,FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status.Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts.CONCLUSIONS This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mor-tality in AMI patients with and without diabetes.FPG might be useful to stratify patients with AMI.
文摘BACKGROUND The annual incidence of gastric cancer in elderly patients is increasing.Despite the continuous progress in treatment methods,the prognosis of elderly patients remains poor,and postoperative complications are frequent.Obesity is believed to be associated with the risk of gastric cancer and postoperative prognosis;however,the effect of visceral fat distribution on postoperative complications of gastric cancer in elderly patients remains unclear.AIM To explore the effect of visceral fat distribution on postoperative complications of gastric cancer in elderly patients.METHODS A total of 163 elderly patients treated at the Affiliated Longyan First Hospital of Fujian Medical University after radical gastrectomy between January 2021 and January 2024 were enrolled.The patients'visceral and subcutaneous fat distributions were measured and divided into a high visceral fat area(VFA-H)group and a low visceral fat area(VFA-L)group,with a critical value of 100 cm^(2).The ttest andχ^(2) test were used to calculate and analyze the relationship between visceral fat area(VFA)and complications.Independent risk factors for postoperative complications were analyzed using binary logistic regression analysis.RESULTS Compared with the VFA-L group,the incidence of postoperative complications was higher in the VFA-H group(27.8%vs 6.4%,P<0.001),and the operation time was longer(268.55±63.41 vs 224.31±51.89,P<0.001).The amount of blood loss was more(163.77±105.27 mL vs 127.93±98.26 mL,P<0.001).Logistic regression analysis showed that VFA[odds ratio(OR):2.597,95%CI:1.479-4.853,P=0.004],total fat area(OR:1.655,95%CI:1.076-4.040,P=0.013),and the visceral subcutaneous fat area ratio(OR:2.046,95%CI:1.196-5.640,P=0.008)were independent risk factors for postoperative complications.CONCLUSION This study showed that postoperative complications are closely related to fat distribution in elderly patients with gastric cancer undergoing gastrectomy.A high VFA is associated by a high incidence of postoperative complications.
基金Supported by Longyan City Science and Technology Plan Project,No.2024 LYF17067.
文摘BACKGROUND Female depression is a prevalent and increasingly recognized mental health issue.Due to cultural and social factors,many female patients still face challenges in diagnosis and treatment,and traditional assessment methods often fail to identify high-risk individuals accurately.This highlights the necessity of developing more precise predictive tools.Utilizing machine learning(ML)algorithms to construct predictive models may overcome the limitations of traditional methods,providing more comprehensive support for women’s mental health.AIM To construct an ML-nomogram hybrid model that translates multivariate risk predictors of female depressive symptoms into actionable clinical scoring thresholds,optimizing predictive accuracy and interpretability for healthcare applications.METHODS We analyzed data from 7609 female participants aged 18 to 85 years from the Guangdong Provincial Sleep and Psychosomatic Health Survey.Sixteen variables,including anxiety symptoms,insomnia,chronic diseases,exercise habits,and age,were selected based on prior literature and comprehensively incorporated into ML models to maximize predictive information utilization.Three ML algorithms,extreme gradient boosting,support vector machine,and light gradient boosting machine,were employed to construct predictive models.Model performance was evaluated using accuracy,precision,recall,F1 score,and area under the curve(AUC).Feature importance was interpreted using SHapley Additive exPlanations(SHAP),with ablation studies validating the impact of the top five SHAPderived features on predictive performance,and a nomogram was constructed based on these prioritized predictors.Clinical utility was assessed through decision curve analysis.RESULTS The prevalence of depressive symptoms was 6.8%among the sample.The evaluation of predictive models revealed that light gradient boosting machine achieved a top-performing AUC of 0.867,placing it ahead of extreme gradient boosting(AUC=0.862)and support vector machine(AUC=0.849).SHAP analysis identified insomnia,anxiety symptoms,age,chronic disease,and exercise as the top five predictors.The nomogram based on these features demonstrated excellent discrimination(AUC=0.910)and calibration,with significant net benefits in decision curve analysis compared to baseline strategies.The model effectively stratifies depressive symptoms risk,facilitating personalized and quantitative assessments in clinical settings.We also developed an interactive digital version of the nomogram to facilitate its application in clinical practice.CONCLUSION The ML-based model effectively predicts depressive symptoms in women,identifying insomnia,anxiety symptoms,age,chronic diseases,and exercise as key predictors,offering a practical tool for early detection and intervention.
基金supported by the construction funds for“high-level hospitals and clinical specialties”of Fujian Province(No.[2021]76)。
文摘Objective:Pathologic complete response(pCR)following neoadjuvant therapy(NAT)for gastric cancer(GC)is rare but associated with a favorable prognosis.This study aims to reassess the optimal response population(ORP)following NAT by evaluating the prognostic outcomes associated with various T and N stages,utilizing multicenter data from China.Methods:Patients who underwent NAT following radical gastrectomy at 10 tertiary hospitals in China between2008 and 2021 were included.The ORP was introduced to explore the disease-free survival(DFS),overall survival(OS),recurrence patterns,and influencing factors following propensity score matching(PSM).Results:A total of 1,076 patients were enrolled in this study(median follow-up period:60 months).We defined ORP as a pCR or tumor infiltration of the mucosal or submucosal layer without lymph node metastasis(pCR or yp T1N0)after NAT.The ORP group comprised 136 patients(12.6%),while the non-ORP group comprised 940patients(87.4%).After applying a 1:4 PSM,we obtained an ORP group of 136 patients and non-ORP group of 544patients.Survival analysis demonstrated that both the 3-year OS(before PSM:89.0%vs.55.0%,P<0.001;after PSM:89.0%vs.55.4%,P<0.001)and DFS(before PSM:85.8%vs.49.7%,P<0.001;after PSM:85.8%vs.50.6%,P<0.001)were significantly superior in the ORP group compared to that in the non-ORP group.Remarkably,adjuvant chemotherapy did not impact the prognosis of patients in the ORP group(3-year OS:89.0%vs.89.7%,P=0.988;3-year DFS:84.9%vs.89.7%,P=0.700).Conclusions:This study reevaluates patients with ORP following NAT,providing a more comprehensive and accurate depiction of the potential beneficiary group and survival outcomes in patients with locally advanced GC.
文摘BACKGROUND Intraoperative fluid management is an important aspect of anesthesia mana-gement in gastrointestinal surgery.Intraoperative goal-directed fluid therapy(GDFT)is a method for optimizing a patient's physiological state by monitoring and regulating fluid input in real-time.AIM To evaluate the efficacy of intraoperative GDFT in patients under anesthesia for gastrointestinal surgery.METHODS This study utilized a retrospective comparative study design and included 60 patients who underwent gastrointestinal surgery at a hospital.The experimental group(GDFT group)and the control group,each comprising 30 patients,received intraoperative GDFT and traditional fluid management strategies,respectively.The effect of GDFT was evaluated by comparing postoperative recovery,com-plication rates,hospitalization time,and other indicators between the two patient groups.RESULTS Intraoperative blood loss in the experimental and control groups was 296.64±46.71 mL and 470.05±73.26 mL(P<0.001),and urine volume was 415.13±96.72 mL and 239.15±94.69 mL(P<0.001),respectively.The postoperative recovery time was 5.44±1.1 days for the experimental group compared to 7.59±1.45 days(P<0.001)for the control group.Hospitalization time for the experimental group was 10.87±2.36 days vs 13.65±3 days for the control group(P<0.001).The visual analogue scale scores of the experimental and control groups at 24 h and 48 h INTRODUCTION Gastrointestinal surgery is one of the most common procedures in the field of general surgery[1],involving the stomach,intestines,liver,pancreas,spleen,and other internal abdominal organs[2,3].With advancements in surgical technology and anesthesia methods,the safety and success rates of surgery have significantly improved[4,5].However,intraop-erative fluid management remains a critical challenge[6].Traditional fluid management strategies often rely on experience and basic physiological parameters,which may lead to excessive or insufficient fluid input,thereby affecting postoperative recovery and complication rates.Intraoperative goal-directed fluid therapy(GDFT)is an emerging fluid management strategy that dynamically adjusts fluid input volume by monitoring the patient's hemodynamic parameters in real-time to optimize the patient's physiological state[7,8].GDFT has shown superiority in many surgical fields;however,its application in gastrointestinal surgery requires further research and verification[9,10].The application of intraoperative GDFT in clinical settings has gradually increased in recent years[11,12].Studies have demonstrated that GDFT can optimize tissue perfusion and oxygenation by precisely controlling fluid input and reducing the occurrence of postoperative complications[13,14].For example,in cardiac and major vascular surgeries,GDFT significantly reduced the incidence of postoperative acute kidney injury and cardiovascular events[15,16].Similarly,in abdominal surgery,GDFT effectively reduced postoperative infections and expedited recovery[17].However,studies on the utilization of GDFT in gastrointestinal surgery are relatively limited and they are confounded by contradictory findings[18].Traditional fluid management strategies typically rely on estimating fluid input volume based on the patient's weight,preoperative status,and basic physiological parameters[19].However,this method lacks real-time dynamic adjustment,which may result in either insufficient or excessive fluid input,consequently affecting postoperative recovery.Insufficient fluid input can lead to hypovolemia and inadequate tissue perfusion,whereas excessive fluid input can cause tissue edema and postoperative complications,such as pulmonary edema and heart failure.GDFT involves dynamically adjusting fluid input volume by monitoring the patient's hemodynamic parameters in real-time,such as cardiac output,pulse pressure variability,and central venous pressure.Commonly used monitoring equipment include esophageal Doppler and pulse wave profile analyzers[20].These devices provide real-time hemo-dynamic data to assist anesthesiologists in tailoring fluid therapy to a patient's specific condition.Firstly,the patient's volume responsiveness is assessed by preloading fluid;secondly,fluid input volume is dynamically adjusted based on real-time monitoring data;finally,vasoactive and inotropic drugs are administered in combination to further optimize the patient’s hemodynamic status.Through personalized fluid management,GDFT can more accurately maintain intraop-erative hemodynamic stability and reduce complications[21].Gastrointestinal surgery involves procedures on multiple organs,often requiring prolonged operative times and extensive tissue trauma,which presents challenges for intraop-erative fluid management.Surgical procedures can lead to significant bleeding and fluid loss,requiring prompt and effective fluid replenishment.In addition,the slow recovery of gastrointestinal function after surgery and susceptibility to complications such as intestinal obstruction and delayed gastric emptying elevate the necessity for postoperative fluid management.
基金supported by the National Natural Science Foundation of China,No.81772452(to NL)the Fujian Province Joint Funds for the Innovation of Science and Technology,No.2020Y9065(to NL)+1 种基金Fujian Province Special Foundation for Natural Science Innovation Project,No.2016B014(to NL)the Natural Science Foundation of Fujian Province,No.2019J01160(to XHJ).
文摘Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia.However,whether there is a synergistic effect between the two remains unclear.In this study,we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours.Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes(MSC-exos)via the tail vein and underwent 14 successive days of treadmill exercise.Neurological assessment,histopathology,and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume,evident synaptic formation and axonal regeneration,and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment.These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone.Mechanistically,further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling.These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment,which may be related to activation of the JNK1/c-Jun signaling pathway.This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.
基金Supported by Youth Talent Program of Longyan Municipal Science and Technology Bureau:2017LY085
文摘Objectives: To observe the effectiveness of acupuncture therapy for relieving throat and opening orifice on dysphagia due to different brain infarct sites.Methods: According to the random number table, 128 patients with post-stroke dysphagia were divided into group A(63 cases, intervention with deglutition training and acupuncture) and group B(65 cases,intervention with simple deglutition training). The conventional treatment and deglutition rehabilitation training in neurology department were used in the two groups. In group B, according to patient's condition, the rehabilitation trainings, such as respiration and neck movement range were used selectively.In group A, on the base of deglutition training, acupuncture therapy for relieving throat and opening orifice was supplemented. The acupoints included Sìshéncōng(四神聪EX HN 1),Bāihuì(百会GV 20), Tàiyang(太阳EX-HN5) bilateral, Fēngchi(风池GB 20) bilateral and Shésānzhēn(舌三针).Electrostimulator was attached on EX-HN 1, bilateral GB 20 and Shesanzhen(舌三针). Needles were retained for 30 min in each treatment. The treatment was given once a day, 5 treatments a week and the treatment for 3 weeks as 1 course. After 6 weeks of treatment, the deglutition ability scale developed by Fujishima Ichiro was adopted to determine the therapeutic effects and observe the score increase for dysphagia related to brain infarct sites before and after treatment.Results: In assessment after 6-week treatment, the improvements of deglutition ability were different corresponding to different brain infarct sites in group A. Specially, the improvements in the patients with dysphagia related to cerebral hemisphere infarction in group A were better than group B(8.68 ±1.12 vs7.32 ±0.91, P<0.05), followed by the improvements in the patients with dysphagia related to internal capsule/basal ganglia/diencephalon infarction(6.53 ±0.65 vs 6.36 ±0.84, P>0.05). Regarding the therapeutic effects in comparison of the two groups, the total effective rates in dysphagia related to cerebral hemisphere infarction were different between the two groups significantly(96.67% vs 82.75%, P< 0.05), as well as in the patients related to internal capsule/basal ganglia/diencephalon infarction(88.89% vs 66.67%,P<0.05). The therapeutic effects were not different in the patients related to cerebral stem and cerebella infarction between the two groups(P>0.05).Conclusion: The acupuncture therapy for relieving throat and opening orifice combined with deglutition training achieves the satisfactory therapeutic effects on dysphagia induced by cortical infarction in stroke.However, a large sample and multicentral clinical trial with this therapy is needed for a further argument so that this therapy is likely promoted in clinical practice in future.
基金Supported by the National Natural Science Foundation of China(No.81800877)the Natural Science Foundation of Zhejiang Province(No.LY15H120001,No.LQ17H120008)。
文摘Dear Sir,I am Dr.Zhe Xu,from the Eye Center,Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,China.We write to present a case of resolution of siderotic glaucoma after removal of a retained ferrous foreign body.This study has been performed in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of the Second Affiliated Hospital.
基金supported by Science and Technology Planning Project of Longyan city in Fujian province(No.2015LY33)
文摘Background Few studies have investigated the safe limits of total intravenous plus oral hydration to prevent contrast-induced nephropathy （CIN）. The present study was conducted to evaluate the effects of different composite hydration rate （intravenous plus oral） on CIN prevention in patients undergoing emergent percutaneous coronary intervention （PCI）. Methods This was a retrospective observational study that included 307 eligible patients, who were stratified into quartiles of rate of the composite hydration volumn to body weight and time （HV/ W/T）. CIN was defined as an absolute≥0.5 mg/dL or a relative ≥25% increase in the serum creatinine level within 72 hours after the procedure. Results In terms of risks of CIN, there were no statistical differences among individuals in four groups with different composite HV/W/T （27.6%, 19.0%, 23.0%, and 26.9% respectively in quartiles Q1, Q2, Q3, and Q4, P=0.565）. Additionally, higher composite hydration ratio seemed not to decrease the risk of in-hospital death, worsening heart failure and stroke （all P〉0.05）. After adjusting for other risk factors, multivariate analysis showed no statistical difference between Q2, Q3 or Q4, compared with Q1 （Q2 vs. QI： adjusted odds ratio [OR], 0.67, P=0.383; Q3 vs QI： adjusted OR, 0.77, P=0.550; Q4 vs. QI： adjusted OR, 0.75, P= 0.489）. Conclusion Excessive composite hydration may not provide supplemental benefit of CIN prevention and in-hospital outcomes in patients following emergent PCI, and moderate and prophylactic hydration is warranted.
基金supported by research funding from the National Natural Science Foundation of China(Grant No.U20A20353)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515110850)+1 种基金the China Postdoctoral Science Foundation(Grant No.2023M741585)the Medical Scientific Research Foundation of Guangdong Province(Grant No.A2022443),China.
文摘Platelets act as a crucial indicator for monitoring hypercoagulability and thrombosis and a key target for pharmacological intervention.Genotype-phenotype association studies have confirmed that platelet traits are quantitatively regulated by multiple genes.However,there is currently a lack of genetic studies on the heterogeneity of platelet traits in β-thalassemia under a hypercoagulable state.Here,we studied the phenotypic heterogeneity of platelet count(PLT)and mean platelet volume(MPV)in a cohort of 1020β-thalassemia patients.We further performed a functionally informed whole-genome sequencing(WGS)association analysis of common variants and rare variants for PLT and MPV in 916 patients through integrative analysis of WGS data and functional annotation data.Extreme phenotypic heterogeneity of platelet traits was observed in β-thalassemia patients.Additionally,the common variant-based gene-level analysis identified RNF144B as a novel gene associated with MPV.The rare variant analysis identified several novel associations in both coding and noncoding regions,including missense rare variants of PPP2R5C associated with PLT and missense rare variants of TSSK1B associated with MPV.In conclusion,this comprehensive and systematic whole-genome scan of platelet traits in the β-thalassemia cohort reveals the specific genetic regulation of platelet traits in the context of β-thalassemia,providing potential targets for intervention.
基金Supported Chen Keji Integrative Foundation(CKJ2015004)Foundation of Fujian University of Traditional Chinese Medicine(X2014010-xueke)the Scientific Research Fund of the National Health and Family Planning Commission of the People's Republic of China(No.WKJ-FJ-38)
文摘Objective：To evaluate the efficacy of Chinese medicine（CM）adjunct to conventional medications for idiopathic Parkinson’s disease（PD）.Methods：Electronic English and Chinese databases including Pub Med,Cochrane Library,Web of Science,Chinese Medical Current Contents,China National Knowledge Infrastructure,China Science and Technology Journal Database,Wanfang Med Database,and Traditional Chinese Medical Database System were used for key words searching in a highly sensitive search strategy.The extracted data was analyzed by the Review Manager 5.0.Results：Twelve trials involving 869 participants were included in the meta-analysis.Unified PD Rating Scale（UPDRS）Ⅰ,Ⅱ,Ⅲ,Ⅳscores and UPDRSⅠ–Ⅳtotal scores were used to be the primary outcomes,Parkinson Disease Question-39（PDQ-39）and Scores of Chinese Medical Symptoms were the secondary outcomes.CM adjunct therapy had greater improvement in UPDRSⅠ[2 trials;standardized mean difference（SMD）–0.40,95%confidence interval（CI）–0.71 to–0.09;Z=2.49（P=0.01）],Ⅱ[5 trials;SMD–0.47,95%CI–0.69 to–0.25;Z=4.20（P〈0.01）],Ⅲ[5 trials;SMD-0.35,95%CI–0.57 to–0.13;Z=3.16（P=0.002）],Ⅳscores[3 trials;SMD-0.32,95%CI–0.60 to–0.03;Z=2.17（P=0.03）],UPDRSⅠ–Ⅳtotal scores[7 trials;SMD-0.36,95%CI–0.53 to–0.20;Z=4.24（P〈0.05）].PDQ-39 and Chinese medical symptoms compared to the conventional medication only.Conclusion：CM adjunct therapy has potential therapeutic benefits by decreasing UPDRS scores and reducing adverse effect.
基金supported by grants from the National Key Research&Development Program of China(No.2017YFC1310200)the Fujian Provincial Science and Technology Guiding Project(No.2016Y0043 and No.2017Y0041)the Key ClinicalSpecialty Discipline Construction Program of Fujian and Nation,China.
文摘Background:Sleep disorders are one of the earliest non-motor symptoms of Parkinson's disease(PD).Sleep disorders could,therefore,have value for recognition and diagnosis in PD.However,no unified classification and diagnostic criteria exist to evaluate sleep disorders by polysomnography(PSG).Utilizing PSG to monitor sleep processes of patients with PD and analyze sleep disorder characteristics and their relationship with demographic parameters could aid in bridging this gap.This preliminary study aimed to evaluate the clinical characteristic of sleep disorders in PD using PSG.Methods:PSG was used to evaluate sleep disorders in 27 patients with PD and 20 healthy volunteers between August 2015 and July 2018 in Fujian Medical University Union Hospital.Total sleep time(TST),sleep efficiency(SE),total wake time,and other parameters were compared between the two groups.Finally,the correlation between sleep disorders and age,disease duration,Unified Parkinson's Disease Rating Scale-Ⅲscores,Hoehn-Yahr stage,and levodopa dose were analyzed.The main statistical methods included Chi-square test,two independent samples t test,Fisher exact test,and Pearson correlation.Results:Sleep fragmentation in the PD group was significantly increased(74.1%)while difficulty falling asleep and early awakening were not,as compared to healthy controls.No significant differences were found in time in bed,sleep latency(SL),non-rapid eye movement(NREM)stage 1(N1),N1%,N2,N2%,N3%,and NREM%between PD and control groups;but TST(327.96±105.26 min vs.414.67±78.31 min,P=0.003),SE(63.26%±14.83%vs.76.8%±11.57%,P=0.001),R N3(20.00[39.00]min vs.61.50[48.87]min,P=0.001),NREM(262.59±91.20 min vs.337.17±63.47 min,P=0.003),rapid-eyemovement(REM)(32.50[33.00]min vs.85.25[32.12]min,P<0.001),REM%(9.56±6.01 vs.15.50±4.81,P=0.001),REM sleep latency(157.89±99.04 min vs.103.47±71.70 min,P=0.034)were significantly reduced in PD group.Conclusion:This preliminary study supported that sleep fragmentation was an important clinical characteristic of sleep disorders in PD.Whether sleep fragmentation is a potential quantifiable marker in PD needs to be further investigated in the future study.
基金the National Natural Science Foundation of China(81901071 and 81970993)the Natural Science Foundation of Fujian Province(2019J01297 and 2019J05072)the Medical Innovation Grant of Fujian Province(2019-CX-36).
文摘Background:Intracellular accumulation of the microtubule-associated protein tau and its hyperphosphorylated forms is a key neuropathological feature of Alzheimer’s disease(AD).Melatonin has been shown to prevent tau hyperphosphorylation in cellular and animal models.However,the molecular mechanisms by which melatonin attenuates tau hyperphosphorylation and tau-related pathologies are not fully understood.Methods:Immunofluorescence,immunoblotting analysis and thioflavin-S staining were employed to examine the effects of early and late treatment of melatonin on tau-related pathology in hTau mice,in which nonmutated human tau is overexpressed on a mouse tau knockout background.High-throughput microRNA(miRNA)sequencing,quantitative RT-PCR,luciferase reporter assay and immunoblotting analysis were performed to determine the molecular mechanism.Results:We found that both early and late treatment of melatonin efficiently decreased the phosphorylation of soluble and insoluble tau at sites related to AD.Moreover,melatonin significantly reduced the number of neurofibrillary tangles(NFTs)and attenuated neuronal loss in the cortex and hippocampus.Furthermore,using miRNA microarray analysis,we found that miR-504-3p expression was upregulated by melatonin in the hTau mice.The administration of miR-504-3p mimics dramatically decreased tau phosphorylation by targeting p39,an activator of the well-known tau kinase cyclin-dependent kinase 5(CDK5).Compared with miR-504-3p mimics alone,co-treatment with miR-504-3p mimics and p39 failed to reduce tau hyperphosphorylation.Conclusions:Our results suggest for the first time that melatonin alleviates tau-related pathologies through upregulation of miR-504-3p expression by targeting the p39/CDK5 axis and provide novel insights into AD treatment strategies.
文摘To treat 30 cases of diarrhea of insufficiency of the spleen-yang type by moxibustion with salt at Shenque (CV 8). The total effective rate was 93.3%. Key Words Diarrhea, chronic - Salt-partitioned Moxibustion - Point CV 8 - Acupuncture-moxibustion Translator: WANG Si-you
基金This study was supported by a grant from the National Natural Science Foundation of China to Zhi-Ying Wu(81125009)the research foundation for distinguished scholar of Zhejiang University to Zhi-Ying Wu(188020-193810101/089)the Fundamental Research Funds for the Central Universities(2019XZZX001-01-04).
文摘Background:Although many causative genes of hereditary spastic paraplegia(HSP)have been uncovered in recent years,there are still approximately 50% of HSP patients without genetically diagnosis,especially in autosomal recessive(AR)HSP patients.Rare studies have been performed to determine the genetic spectrum and clinical profiles of recessive HSP patients in the Chinese population.Methods:In this study,we investigated 24 Chinese index AR/sporadic patients by targeted next-generation sequencing(NGS),Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA).Further functional studies were performed to identify pathogenicity of those uncertain significance variants.Results:We identified 11 mutations in HSP related genes including 7 novel mutations,including two(p.V1979_L1980delinsX,p.F2343 fs)in SPG11,two(p.T55 M,p.S308 T)in AP5Z1,one(p.S242N)in ALDH18A1,one(p.D597fs)in GBA2,and one(p.Q486X)in ATP13A2 in 8 index patients and their family members.Mutations in ALDH18A1,AP5Z1,CAPN1 and ATP13A2 genes were firstly reported in the Chinese population.Furthermore,the clinical phenotypes of the patients carrying mutations were described in detail.The mutation(p.S242 N)in ALDH18A1 decreased enzyme activity of P5CS and mutations(p.T55 M,p.S308 T)in AP5Z1 induced lysosomal dysfunction.Conclusion:Our results expanded the genetic spectrum and clinical profiles of AR-HSP patients and further demonstrated the efficiency and reliability of targeted NGS diagnosing suspected HSP patients.
文摘Objective:To construct a risk prediction model for in-hospital cardiac arrest(IHCA)in patients with chronic obstructive pulmonary disease(COPD)complicated with respiratory failure.Methods:The clinical data of 550 patients with COPD complicated with respiratory failure in our hospital from January 2016 to June 2022 were retrospectively analyzed.According to the occurrence of IHCA,they were divided into the IHCA group and non-IHCA group.The general data and clinical indicators of the two groups were compared,and logistic regression analysis was performed,R software was used to establish the risk prediction model(nomogram model)for predicting the occurrence of IHCA in patients with COPD complicated with respiratory failure.The risk prediction model(line graph model)for patients with IHCA was validated by the Bootstrap method,and the predictive value was analyzed by applying the receiver operating characteristic(ROC)curve.Results:Among 550 COPD patients complicated with respiratory failure,95 cases(17.27%)had IHCA.There were significant differences in age,old myocardial infarction,heart failure,moderate and severe chronic kidney disease,assisted breathing mode,state of consciousness,body temperature,heart rate,respiratory rate,systolic blood pressure,lactic acid,Sa O,Pa CO,serum creatinine,albumin,and prealbumin between the non-IHCA group and IHCA group(P<0.05).Logistic regression analysis showed that age,heart failure,heart rate,respiratory rate,systolic blood pressure,unclear state of consciousness,serum creatinine and prealbumin were independent influencing factors of IHCA in COPD patients complicated with respiratory failure(P<0.05).According to the results of binary logistic regression analysis,a nomogram model for predicting the incidence of IHCA in COPD patients complicated with respiratory failure was constructed.The fitting degree of the model was determined by the H-L test.The calibration curve showed that the incidence of IHCA in COPD patients complicated with respiratory failure predicted by nomogram was in good agreement with the actual incidence of IHCA in patients with COPD complicated with respiratory failure(χ~2=2.017,P=0.334).The ROC curve showed an AUC of 0.627(95%CI:0.593-0.689,P<0.005),and the optimal cut point value for diagnosis was 0.69,at which the sensitivity and specificity were 42.57%and 96.03%,respectively.Conclusion:According to the independent influencing factors of IHCA in COPD patients complicated with respiratory failure,the establishment of a risk prediction nomogram model has high predictive value,which is worthy of clinical promotion.
