BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling p...BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.展开更多
BACKGROUND Constipation is one of the chronic gastrointestinal functional diseases.It seriously affects the quality of life.Cistanche deserticola(C.deserticola)can treat constipation obviously,but its mechanism has no...BACKGROUND Constipation is one of the chronic gastrointestinal functional diseases.It seriously affects the quality of life.Cistanche deserticola(C.deserticola)can treat constipation obviously,but its mechanism has not been clarified.We supposed that mechanism of it improved the intestinal motility by stimulating interstitial Cajal cells(ICC).Activation of the C-kit receptor on the surface of ICC is closely related to ICC function,and the stem cell factor(SCF)/C-kit signaling pathways plays an important role on it.To investigate the mechanism of how C.deserticola treats constipation,this study aimed to establish a constipation model in rats and explore the role of SCF/C-kit signaling pathway in the treatment.AIM To explore the SCF/C-kit signaling pathways in the role of C.deserticola for treatment of constipation by a constipation rat model.METHODS Forty-eight 8-mo-old Sprague–Dawley rats were divided into 4 groups by random weight method:Normal group(n=12),model group(n=12),C.deserticola group(n=12)and blocker group(n=12).The normal group received normal saline by gavage;the model group received loperamide by gavage;the blocker group received loperamide and C.deserticola by gavage,and STI571 was injected by intraperitoneally.During treatment,the weight,fecal granules and fecal quality were recorded every 10 d.On day 20 after model induction,the colon tissues of each group were removed.Hematoxylin and eosin staining was used to observe pathological changes.Expression levels of SCF,C-kit and Aquaporin genes were detected by immunohistochemistry,western blotting,and real-time-quantitative polymerase chain reaction.The colonic epithelial mitochondria and goblet cells were observed by transmission electron microscopy.RESULTS Compared with the normal group,as treatment progressed,the weight of rats in the model and blocker groups decreased significantly,the stool weight decreased,and the stool quality was dry(P<0.05).C.deserticola reversed the decrease in body weight and stool weight and improved stool quality.Histopathological analysis indicated that the colonic mucosal epithelium in the model group was incomplete,and the arrangement of the glands was irregular or damaged.Treatment with C.deserticola improved the integrity and continuity of the epithelial cells and regular arrangement of the glands.The blocking agents inhibited the effects of C.deserticola Immunohistochemistry and real-timequantitative polymerase chain reaction showed that expression of SCF and C-kit protein or genes in the colonic tissue of the model group was decreased(P<0.05),while treatment with C.deserticola increased protein or gene expression(P<0.05).Western blotting showed that expression of aquaporin APQ3 was increased,while the expression of Cx43 decreased in the model group.Treatment with C.deserticola inhibited expression of APQ3 and promoted expression of Cx43.Transmission electron microscopy showed that the mitochondria of the colonic epithelium in the model group were swollen and arranged disorderly,and microvilli were sparse.The condition was better in the C.deserticola group.Mice treated with STI571 blocker confirmed that blocking the SCF/C-kit pathway inhibited the improvement of constipation by C.deserticola.CONCLUSION C.deserticola improved defecation in rats with constipation,and the SCF/C-kit signaling pathway,which is a key link of ICC function,played an important role of the treatment.展开更多
Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Metho...Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Methods:Chemical composition of HXTJD was analyzed by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry(MS).The change rates of mean contraction tension forces,mean amplitudes,and mean frequencies for the lower esophageal sphincter(LES)were recorded using the isolated tissue bath system,mechanical tension transducer,and PowerLab physiological recorder.After weighing the stomach,the phenol red labeling method was used to measure the gastric emptying rate.The LES ultrastructure was observed through transmission electron microscopy.Immunofluorescence and western blotting were used to detect the number of interstitial cells of Cajal(ICC)and the expression levels of c-kit protein,connexin43(Cx43),and stem cell factor(SCF).Flow cytometric analysis and enzyme-linked immunosorbent assay were conducted to detect the percentages of T helper 17(Th17)cells and regulatory T(Treg)cells and the serum concentrations of interleukin 6(IL-6),interleukin 17(IL-17),and interleukin 10(IL-10)in the rats.Results:We identified 28 chemical constituents in HXTJD.Regarding esophageal motility,we revealed that HXTJD increased the mean contraction tension forces,mean amplitudes,and mean frequency change rate of LES and the gastric emptying rate;decreased stomach weight;and improved the LES ultrastructure.Additionally,HXTJD increased the number of ICC-positive cells,and c-kit,Cx43,and SCF expression levels.Regarding esophageal inflammation,HXTJD significantly decreased the percentage of Th17 cells,and IL-6 and IL-17 concentrations,and increased the percentage of Treg cells and IL-10 concentration.Conclusion:HXTJD was found to be efficacious in the rat RE model.It may promote esophageal motility and alleviate the inflammatory response by activating the SCF/c-kit/ICC pathway and regulating the Th17/Treg cell balance.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is cha...Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.展开更多
BACKGROUND:Acute pain is a sudden experience secondary to injuries and varies in perception among individuals.In trauma patients,it can negatively aff ect respiratory function,immune response,and wound healing,making ...BACKGROUND:Acute pain is a sudden experience secondary to injuries and varies in perception among individuals.In trauma patients,it can negatively aff ect respiratory function,immune response,and wound healing,making it a signifi cant public health concern.This study is to determine the prevalence and factors associated with acute pain among emergency trauma patients.METHODS:A multicenter cross-sectional study was conducted.Data were collected via interviewer-administered questionnaires and patient chart review.The data were analyzed via the statistical package for social science version 25.Bivariable and multivariable logistic regression analyses were used.Variables with a P-value<0.05 were considered statistically signifi cant.RESULTS:A total of 397 patients were included in the study,for a response rate of 96.8%.The prevalence of pain during admission was 91.9%(95%confi dence intervals[95%CIs]:88.8%-94.4%).Blunt trauma(adjusted odds ratio[aOR]=2.82;95%CI:1.23-6.45),analgesia before admission to the emergency department(aOR=2.71;95%CI:1.16-6.36),documentation of pain severity in the chart(aOR=2.71;95%CI:1.16-6.36),analgesia provided within two hours after admission(aOR=7.60;95%CI:2.79-20.68),use of non-pharmacological pain management methods(aOR=3.09;95%CI:1.35-7.08)and availability of analgesia(aOR=3.95;95%CI:1.36-11.43)were associated with acute pain experience.CONCLUSION:The prevalence of acute pain among emergency trauma patients was high in the study area.Analgesia should be administered prior to admission,and non-pharmacological pain management should be implemented.Moreover,training on pain assessment and management should be provided for healthcare providers in the emergency department.展开更多
Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability...Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.展开更多
BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
Understanding water chemistry in karst regions is crucial for improving global water resource management and deepening our knowledge of the biogeochemical cycles shaping these sensitive environments.Despite advance-me...Understanding water chemistry in karst regions is crucial for improving global water resource management and deepening our knowledge of the biogeochemical cycles shaping these sensitive environments.Despite advance-ments in karst hydrology,significant gaps remain in long-term trends,underlying processes,and quantitative effects of environmental changes.This is especially true in areas like the Wujiang River(WJ)in China,where human activities such as reservoir construction and land use/cover changes have accelerated hydrochemical changes.We combined recent and historical monitoring data to provide a detailed analysis of the spatial and temporal characteristics,evolution,and controlling factors of major ions in WJ.These findings are important for local water management and contribute to global efforts to manage similar karst systems facing human-induced pressures.Our research shows clear seasonal differences in solute concentrations,with higher levels during the dry season.WJ’s water is rich in calcium,with Ca-HCO_(3) ion pairs being the most common.Reservoir monitor-ing stations show much higher levels of NO_(3)^(−)and SO_(4)^(2−)compared to river-type stations,likely due to longer hydraulic retention time and increased acid deposition.The study confirms the significant role of pH and water temperature in rock weathering processes.Land use/cover changes were identified as the primary drivers of solute variations(46.37%),followed by lithology(13.92%)and temperature(8.35%).Over the past two decades,in-tense carbonate weathering has been observed,especially during wet seasons.Among karstic provinces,Guizhou Province stands out with the highest ion concentrations,indicative of its extensive karst coverage and heightened weathering processes.展开更多
Landslides pose a formidable natural hazard across the Qinghai-Tibet Plateau(QTP),endangering both ecosystems and human life.Identifying the driving factors behind landslides and accurately assessing susceptibility ar...Landslides pose a formidable natural hazard across the Qinghai-Tibet Plateau(QTP),endangering both ecosystems and human life.Identifying the driving factors behind landslides and accurately assessing susceptibility are key to mitigating disaster risk.This study integrated multi-source historical landslide data with 15 predictive factors and used several machine learning models—Random Forest(RF),Gradient Boosting Regression Trees(GBRT),Extreme Gradient Boosting(XGBoost),and Categorical Boosting(CatBoost)—to generate susceptibility maps.The Shapley additive explanation(SHAP)method was applied to quantify factor importance and explore their nonlinear effects.The results showed that:(1)CatBoost was the best-performing model(CA=0.938,AUC=0.980)in assessing landslide susceptibility,with altitude emerging as the most significant factor,followed by distance to roads and earthquake sites,precipitation,and slope;(2)the SHAP method revealed critical nonlinear thresholds,demonstrating that historical landslides were concentrated at mid-altitudes(1400-4000 m)and decreased markedly above 4000 m,with a parallel reduction in probability beyond 700 m from roads;and(3)landslide-prone areas,comprising 13%of the QTP,were concentrated in the southeastern and northeastern parts of the plateau.By integrating machine learning and SHAP analysis,this study revealed landslide hazard-prone areas and their driving factors,providing insights to support disaster management strategies and sustainable regional planning.展开更多
Objectives This study aimed to explore the lagged and cumulative effects of risk factors on disability in older adults using distributed lag non-linear models(DLNMs).Methods We utilized data from the China Health and ...Objectives This study aimed to explore the lagged and cumulative effects of risk factors on disability in older adults using distributed lag non-linear models(DLNMs).Methods We utilized data from the China Health and Retirement Longitudinal Study(CHARLS).After feature selection via Elastic Net Regularization,we applied DLNMs to evaluate the lagged effects of risk factors.Disability was defined as the presence of any difficulties in basic activities of daily living(BADL).The cumulative relative risk(CRR)was calculated by summing the lag-specific risk estimates,representing the cumulative disability risk over the specified lag period.Effect modifications and sensitivity analyses were also performed.Results This study included a total of 2,318 participants.Early-phase lag factors,such as the difficulty in stooping(CRR=3.58;95%CI:2.31-5.55;P<0.001)and walking(CRR=2.77;95%CI:1.39-5.55;P<0.001),exerted the strongest effects immediately upon occurrence.Mid-phase lag factors,such as arthritis(CRR=1.51;95%CI:1.10-2.06;P=0.001),showed a resurgence in disability risk within 2-3 years.Late-phase lag factors,including depressive symptoms(CRR=2.38;95%CI:1.30-4.35;P<0.001)and elevated systolic blood pressure(CRR=1.64;95%CI:1.06-2.79;P=0.02),exhibited significant long-term cumulative risks.Conversely,grip strength(CRR=0.80;95%CI:0.54-0.95;P=0.02)and social participation(CRR=0.89;95%CI:0.73-0.99;P=0.04)were significant protective factors.Conclusions The findings underscore the importance of tailored interventions that account for various lag characteristics of different factors to effectively mitigate disability risk.Future studies should explore the underlying biological and sociological mechanisms of these lagged effects,identify intervention strategies that target risk factors with different lagged patterns,and evaluate their effectiveness.展开更多
Objective:Based on the theory of“Taiyang governs tendons”,to explore the effect of acupuncture at points of the Bladder Meridian of Foot-Taiyang on the expression of serum inflammatory factors in rabbit models of ce...Objective:Based on the theory of“Taiyang governs tendons”,to explore the effect of acupuncture at points of the Bladder Meridian of Foot-Taiyang on the expression of serum inflammatory factors in rabbit models of cervical spondylosis.Methods:Thirty New Zealand white rabbits were randomly divided into a blank group,a model group,and a treatment group,with 10 rabbits in each group.The models of cervical spondylosis in the model group and treatment group were established by long-term head-down flexion combined with cold-damp stimulation.After modeling,the treatment group received acupuncture at three points(Kunlun,Weizhong,and Feishu)on the Bladder Meridian of Foot-Taiyang,once a day for 20 minutes each time,for 14 consecutive days;the model group and blank group received no therapeutic intervention.After the intervention,cardiac blood was collected from all rabbits to detect the expression levels of serum inflammatory factors IL-6,TNF-α,and IL-1β.Meanwhile,cervical muscle tissue was collected,stained with HE,and the morphological changes of the posterior cervical muscle tissue in each group were observed under an optical microscope.Results:After modeling,the levels of inflammatory factors in the serum of rabbits in the model group and treatment group were significantly increased compared with those before modeling,with a statistically significant difference(p<0.01).After intervention,the serum inflammatory factors in the treatment group decreased significantly compared with those in the model group,and the difference was statistically significant(p<0.01).Conclusion:Acupuncture at points of the Bladder Meridian of Foot-Taiyang in rabbit models of cervical spondylosis can reduce the serum levels of inflammatory factors TNF-α,IL-1β,and IL-6.展开更多
This paper provides a systematic review of the histochemical localization,content characteristics,and influencing factors of saponins in Pseudostellaria heterophylla based on an extensive literature survey.It provides...This paper provides a systematic review of the histochemical localization,content characteristics,and influencing factors of saponins in Pseudostellaria heterophylla based on an extensive literature survey.It provides an in-depth analysis and summary of the effects of biological factors,environmental conditions,agronomic practices,processing methods,and continuous cropping obstacles on the synthesis of P.heterophylla saponins,as well as their underlying mechanisms.Based on identified gaps in the current literature,future research directions and prospects are proposed.The findings of this review offer valuable insights for advancing the understanding of the saponin biosynthesis mechanisms in P.heterophylla and for enhancing its quality.展开更多
Understanding the spatial distributions and corresponding variation mechanisms of key soil nutrients in fragile karst ecosystems can assist in promoting sustainable development.However,due to the implementation of eco...Understanding the spatial distributions and corresponding variation mechanisms of key soil nutrients in fragile karst ecosystems can assist in promoting sustainable development.However,due to the implementation of ecological restoration initiatives such as land-use conversions,novel changes in the spatial characteristics of soil nutrients remain unknown.To address this gap,we explored nutrient variations and the drivers of the variation in the 0–15 cm topsoil layer using a regional-scale sampling method in a typical karst area in northwest Guangxi Zhuang Autonomous Region,Southwest China.Descriptive statistics,geostatistics,and spatial analysis were used to assess the soil nutrient variability.The results indicated that soil organic carbon(SOC),total nitrogen(TN),total phosphorus(TP),and total potassium(TK)concentrations showed moderate variations,with coefficients of variance being 0.60,0.60,0.71,and 0.72,respectively.Moreover,they demonstrated positive spatial autocorrelations,with global Moran's indices being 0.68,0.77,0.64,and 0.68,respectively.However,local Moran's index values were low,indicating large spatial variations in soil nutrients.The best-fitting semi-variogram models for SOC,TN,TP,and TK concentrations were spherical,Gaussian,exponential,and exponential,respectively.According to the classification criteria of the Second National Soil Census in China,SOC and TN concentrations were relatively sufficient,with the proportions of rich and very rich levels being up to 90.9 and 96.0%,respectively.TP concentration was in the mediumdeficient level,with the areas of medium and deficient levels accounting for 33.7 and 30.1%of the total,respectively.TK concentration was deficient,with the cumulative area of extremely deficient,very deficient,and deficient levels accounting for 87.6%of the total area.Consequently,the terrestrial ecosystems in the study area were more vulnerable to soil P and K than soil N deficiencies.Furthermore,variance partitioning analysis of the influencing factors showed that,except for the interactions,the single effect of other soil properties accounted more for soil nutrient variations than spatial and environmental variables.These results will aid in the future management of terrestrial ecosystems.展开更多
BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty(pTHA).However,the literature demonstrates significant variability regarding the relative contributions of different ...BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty(pTHA).However,the literature demonstrates significant variability regarding the relative contributions of different factors.AIM To investigate the key determinants of aseptic loosening,we performed a systematic review and meta-analysis.METHODS A comprehensive search of PubMed,Web of Science,EMBASE,and the Cochrane Library was conducted,encompassing studies from database inception to January 1,2025.Meta-analyses were performed to evaluate factors associated with aseptic loosening following pTHA.Inclusion and exclusion criteria were systematically applied at each stage to ensure methodological transparency and reproducibility.Study quality was assessed using standardized categories.Pooled odds ratio(OR)with corresponding 95%confidence interval were calculated with random-or fixed-effects models to generate reliability estimates,and study heterogeneity was visualized using forest plots.Ten factors,categorized into patient-,surgeon-,and device-related domains,were reviewed and meta-analyzed.Funnel plot analysis demonstrated a relatively symmetrical distribution,suggesting minimal publication bias.RESULTS A meta-analysis of 20 studies(520789 participants)found a pooled prevalence of 1.96%.Significant risk factors for aseptic loosening after pTHA included elevated body mass index(OR=1.116,P<0.001),higher Charlson comorbidity index(OR=1.378,P<0.001),prosthesis-related factors(OR=1.497,P<0.001),and adverse lifestyles(OR=2.198,P=0.037).Protective factors were non-white race(OR=0.445,P<0.001)and favorable genetics(OR=0.723,P<0.001).Male sex increased risk(OR=1.232,P=0.016),while age and anatomy were not significant.Surgical expertise showed a slight protective effect(OR=1.048,P<0.001).A comprehensive understanding of the modifiable and non-modifiable factors contributing to aseptic loosening after pTHA requires consideration of patient-related factors,surgical expertise,and prosthesis characteristics.CONCLUSION The identification of these factors is critical for risk mitigation.High-risk patients should receive targeted counseling regarding individualized profiles.Further studies are warranted to establish clearer causal relationships and identify additional contributing factors.展开更多
To achieve low-carbon regulation of electric vehicle(EV)charging loads under the“dual carbon”goals,this paper proposes a coordinated scheduling strategy that integrates dynamic carbon factor prediction and multiobje...To achieve low-carbon regulation of electric vehicle(EV)charging loads under the“dual carbon”goals,this paper proposes a coordinated scheduling strategy that integrates dynamic carbon factor prediction and multiobjective optimization.First,a dual-convolution enhanced improved Crossformer prediction model is constructed,which employs parallel 1×1 global and 3×3 local convolutionmodules(Integrated Convolution Block,ICB)formultiscale feature extraction,combinedwith anAdaptive Spectral Block(ASB)to enhance time-series fluctuationmodeling.Based on high-precision predictions,a carbon-electricity cost joint optimization model is further designed to balance economic,environmental,and grid-friendly objectives.The model’s superiority was validated through a case study using real-world data from a renewable-heavy grid.Simulation results show that the proposed multi-objective strategy demonstrated a superior balance compared to baseline and benchmark models,achieving a 15.8%reduction in carbon emissions and a 5.2%reduction in economic costs,while still providing a substantial 22.2%reduction in the peak-valley difference.Its balanced performance significantly outperformed both a single-objective strategy and a state-of-the-art Model Predictive Control(MPC)benchmark,highlighting the advantage of a global optimization approach.This study provides theoretical and technical pathways for dynamic carbon factor-driven EV charging optimization.展开更多
AIM:To assess risk factors for epiretinal membranes(ERM)and examine their interactions in a nationally representative U.S.dataset.METHODS:Data from the 2005–2008 National Health and Nutrition Examination Survey(NHANE...AIM:To assess risk factors for epiretinal membranes(ERM)and examine their interactions in a nationally representative U.S.dataset.METHODS:Data from the 2005–2008 National Health and Nutrition Examination Survey(NHANES)were analyzed,a nationally representative U.S.dataset.ERM was identified via retinal imaging based on the presence of cellophane changes.Key predictors included age group,eye surgery history,and refractive error,with additional demographic and health-related covariates.Weighted univariate and multiple logistic regression models were used to assess associations and interaction effects between eye surgery and refractive error.RESULTS:Totally 3925 participants were analyzed.Older age,eye surgery,and refractive errors were significantly associated with ERM.Compared to those under 65y,the odds ratio(OR)for ERM was 3.08 for ages 65–75y(P=0.0014)and 4.76 for ages 75+years(P=0.0069).Eye surgery increased ERM risk(OR=3.48,P=0.0018).Moderate to high hyperopia and myopia were also associated with ERM(OR=2.65 and 1.80,respectively).A significant interaction between refractive error and eye surgery was observed(P<0.0001).Moderate to high myopia was associated with ERM only in those without eye surgery(OR=1.92,P=0.0443).Eye surgery was most strongly associated with ERM in the emmetropic group(OR=3.60,P=0.0027),followed by the moderate to high myopia group(OR=3.01,P=0.0031).CONCLUSION:ERM is significantly associated with aging,eye surgery,and refractive errors.The interaction between eye surgery and refractive error modifies ERM risk and highlights the importance of considering combined effects in clinical risk assessments.These findings may help guide individualized ERM risk assessment that may inform personalized approaches to ERM prevention and management.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such a...BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.展开更多
文摘BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.
基金Natural Science Foundation of Chongqing,No.cstc2017jcyjAX0306。
文摘BACKGROUND Constipation is one of the chronic gastrointestinal functional diseases.It seriously affects the quality of life.Cistanche deserticola(C.deserticola)can treat constipation obviously,but its mechanism has not been clarified.We supposed that mechanism of it improved the intestinal motility by stimulating interstitial Cajal cells(ICC).Activation of the C-kit receptor on the surface of ICC is closely related to ICC function,and the stem cell factor(SCF)/C-kit signaling pathways plays an important role on it.To investigate the mechanism of how C.deserticola treats constipation,this study aimed to establish a constipation model in rats and explore the role of SCF/C-kit signaling pathway in the treatment.AIM To explore the SCF/C-kit signaling pathways in the role of C.deserticola for treatment of constipation by a constipation rat model.METHODS Forty-eight 8-mo-old Sprague–Dawley rats were divided into 4 groups by random weight method:Normal group(n=12),model group(n=12),C.deserticola group(n=12)and blocker group(n=12).The normal group received normal saline by gavage;the model group received loperamide by gavage;the blocker group received loperamide and C.deserticola by gavage,and STI571 was injected by intraperitoneally.During treatment,the weight,fecal granules and fecal quality were recorded every 10 d.On day 20 after model induction,the colon tissues of each group were removed.Hematoxylin and eosin staining was used to observe pathological changes.Expression levels of SCF,C-kit and Aquaporin genes were detected by immunohistochemistry,western blotting,and real-time-quantitative polymerase chain reaction.The colonic epithelial mitochondria and goblet cells were observed by transmission electron microscopy.RESULTS Compared with the normal group,as treatment progressed,the weight of rats in the model and blocker groups decreased significantly,the stool weight decreased,and the stool quality was dry(P<0.05).C.deserticola reversed the decrease in body weight and stool weight and improved stool quality.Histopathological analysis indicated that the colonic mucosal epithelium in the model group was incomplete,and the arrangement of the glands was irregular or damaged.Treatment with C.deserticola improved the integrity and continuity of the epithelial cells and regular arrangement of the glands.The blocking agents inhibited the effects of C.deserticola Immunohistochemistry and real-timequantitative polymerase chain reaction showed that expression of SCF and C-kit protein or genes in the colonic tissue of the model group was decreased(P<0.05),while treatment with C.deserticola increased protein or gene expression(P<0.05).Western blotting showed that expression of aquaporin APQ3 was increased,while the expression of Cx43 decreased in the model group.Treatment with C.deserticola inhibited expression of APQ3 and promoted expression of Cx43.Transmission electron microscopy showed that the mitochondria of the colonic epithelium in the model group were swollen and arranged disorderly,and microvilli were sparse.The condition was better in the C.deserticola group.Mice treated with STI571 blocker confirmed that blocking the SCF/C-kit pathway inhibited the improvement of constipation by C.deserticola.CONCLUSION C.deserticola improved defecation in rats with constipation,and the SCF/C-kit signaling pathway,which is a key link of ICC function,played an important role of the treatment.
基金supported by the National Natural Science Foundation of China(No.81573737 and 82074213)the science foundation of Tianjin Municipal Health Bureau(No.2023169 and 2021045)the Tianjin Municipal Health Commission Science and Technology Project(No.TJWJ2022QN057).
文摘Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Methods:Chemical composition of HXTJD was analyzed by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry(MS).The change rates of mean contraction tension forces,mean amplitudes,and mean frequencies for the lower esophageal sphincter(LES)were recorded using the isolated tissue bath system,mechanical tension transducer,and PowerLab physiological recorder.After weighing the stomach,the phenol red labeling method was used to measure the gastric emptying rate.The LES ultrastructure was observed through transmission electron microscopy.Immunofluorescence and western blotting were used to detect the number of interstitial cells of Cajal(ICC)and the expression levels of c-kit protein,connexin43(Cx43),and stem cell factor(SCF).Flow cytometric analysis and enzyme-linked immunosorbent assay were conducted to detect the percentages of T helper 17(Th17)cells and regulatory T(Treg)cells and the serum concentrations of interleukin 6(IL-6),interleukin 17(IL-17),and interleukin 10(IL-10)in the rats.Results:We identified 28 chemical constituents in HXTJD.Regarding esophageal motility,we revealed that HXTJD increased the mean contraction tension forces,mean amplitudes,and mean frequency change rate of LES and the gastric emptying rate;decreased stomach weight;and improved the LES ultrastructure.Additionally,HXTJD increased the number of ICC-positive cells,and c-kit,Cx43,and SCF expression levels.Regarding esophageal inflammation,HXTJD significantly decreased the percentage of Th17 cells,and IL-6 and IL-17 concentrations,and increased the percentage of Treg cells and IL-10 concentration.Conclusion:HXTJD was found to be efficacious in the rat RE model.It may promote esophageal motility and alleviate the inflammatory response by activating the SCF/c-kit/ICC pathway and regulating the Th17/Treg cell balance.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by grants from the Zhejiang Provincial TCM Science and Technology Plan Project,No.2023ZL156(to YH)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)+1 种基金the Natural Science Foundation of Ningbo,No.2023J019(to YH)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.
文摘BACKGROUND:Acute pain is a sudden experience secondary to injuries and varies in perception among individuals.In trauma patients,it can negatively aff ect respiratory function,immune response,and wound healing,making it a signifi cant public health concern.This study is to determine the prevalence and factors associated with acute pain among emergency trauma patients.METHODS:A multicenter cross-sectional study was conducted.Data were collected via interviewer-administered questionnaires and patient chart review.The data were analyzed via the statistical package for social science version 25.Bivariable and multivariable logistic regression analyses were used.Variables with a P-value<0.05 were considered statistically signifi cant.RESULTS:A total of 397 patients were included in the study,for a response rate of 96.8%.The prevalence of pain during admission was 91.9%(95%confi dence intervals[95%CIs]:88.8%-94.4%).Blunt trauma(adjusted odds ratio[aOR]=2.82;95%CI:1.23-6.45),analgesia before admission to the emergency department(aOR=2.71;95%CI:1.16-6.36),documentation of pain severity in the chart(aOR=2.71;95%CI:1.16-6.36),analgesia provided within two hours after admission(aOR=7.60;95%CI:2.79-20.68),use of non-pharmacological pain management methods(aOR=3.09;95%CI:1.35-7.08)and availability of analgesia(aOR=3.95;95%CI:1.36-11.43)were associated with acute pain experience.CONCLUSION:The prevalence of acute pain among emergency trauma patients was high in the study area.Analgesia should be administered prior to admission,and non-pharmacological pain management should be implemented.Moreover,training on pain assessment and management should be provided for healthcare providers in the emergency department.
文摘Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
基金supported by Guangdong Basic and Applied Basic Research Foundation(Nos.2023A1515110824 and 2025A1515011839)Shenzhen Science and Technology Program(No.RCBS20231211090638066).
文摘Understanding water chemistry in karst regions is crucial for improving global water resource management and deepening our knowledge of the biogeochemical cycles shaping these sensitive environments.Despite advance-ments in karst hydrology,significant gaps remain in long-term trends,underlying processes,and quantitative effects of environmental changes.This is especially true in areas like the Wujiang River(WJ)in China,where human activities such as reservoir construction and land use/cover changes have accelerated hydrochemical changes.We combined recent and historical monitoring data to provide a detailed analysis of the spatial and temporal characteristics,evolution,and controlling factors of major ions in WJ.These findings are important for local water management and contribute to global efforts to manage similar karst systems facing human-induced pressures.Our research shows clear seasonal differences in solute concentrations,with higher levels during the dry season.WJ’s water is rich in calcium,with Ca-HCO_(3) ion pairs being the most common.Reservoir monitor-ing stations show much higher levels of NO_(3)^(−)and SO_(4)^(2−)compared to river-type stations,likely due to longer hydraulic retention time and increased acid deposition.The study confirms the significant role of pH and water temperature in rock weathering processes.Land use/cover changes were identified as the primary drivers of solute variations(46.37%),followed by lithology(13.92%)and temperature(8.35%).Over the past two decades,in-tense carbonate weathering has been observed,especially during wet seasons.Among karstic provinces,Guizhou Province stands out with the highest ion concentrations,indicative of its extensive karst coverage and heightened weathering processes.
基金The National Key Research and Development Program of China,No.2023YFC3206601。
文摘Landslides pose a formidable natural hazard across the Qinghai-Tibet Plateau(QTP),endangering both ecosystems and human life.Identifying the driving factors behind landslides and accurately assessing susceptibility are key to mitigating disaster risk.This study integrated multi-source historical landslide data with 15 predictive factors and used several machine learning models—Random Forest(RF),Gradient Boosting Regression Trees(GBRT),Extreme Gradient Boosting(XGBoost),and Categorical Boosting(CatBoost)—to generate susceptibility maps.The Shapley additive explanation(SHAP)method was applied to quantify factor importance and explore their nonlinear effects.The results showed that:(1)CatBoost was the best-performing model(CA=0.938,AUC=0.980)in assessing landslide susceptibility,with altitude emerging as the most significant factor,followed by distance to roads and earthquake sites,precipitation,and slope;(2)the SHAP method revealed critical nonlinear thresholds,demonstrating that historical landslides were concentrated at mid-altitudes(1400-4000 m)and decreased markedly above 4000 m,with a parallel reduction in probability beyond 700 m from roads;and(3)landslide-prone areas,comprising 13%of the QTP,were concentrated in the southeastern and northeastern parts of the plateau.By integrating machine learning and SHAP analysis,this study revealed landslide hazard-prone areas and their driving factors,providing insights to support disaster management strategies and sustainable regional planning.
基金supported by ScientificResearch Fund of National Health Commission of the People’s Republic of China-Major Science and Technology Program for Medicine and Health in Zhejiang Province(WKJ-ZJ-2406).
文摘Objectives This study aimed to explore the lagged and cumulative effects of risk factors on disability in older adults using distributed lag non-linear models(DLNMs).Methods We utilized data from the China Health and Retirement Longitudinal Study(CHARLS).After feature selection via Elastic Net Regularization,we applied DLNMs to evaluate the lagged effects of risk factors.Disability was defined as the presence of any difficulties in basic activities of daily living(BADL).The cumulative relative risk(CRR)was calculated by summing the lag-specific risk estimates,representing the cumulative disability risk over the specified lag period.Effect modifications and sensitivity analyses were also performed.Results This study included a total of 2,318 participants.Early-phase lag factors,such as the difficulty in stooping(CRR=3.58;95%CI:2.31-5.55;P<0.001)and walking(CRR=2.77;95%CI:1.39-5.55;P<0.001),exerted the strongest effects immediately upon occurrence.Mid-phase lag factors,such as arthritis(CRR=1.51;95%CI:1.10-2.06;P=0.001),showed a resurgence in disability risk within 2-3 years.Late-phase lag factors,including depressive symptoms(CRR=2.38;95%CI:1.30-4.35;P<0.001)and elevated systolic blood pressure(CRR=1.64;95%CI:1.06-2.79;P=0.02),exhibited significant long-term cumulative risks.Conversely,grip strength(CRR=0.80;95%CI:0.54-0.95;P=0.02)and social participation(CRR=0.89;95%CI:0.73-0.99;P=0.04)were significant protective factors.Conclusions The findings underscore the importance of tailored interventions that account for various lag characteristics of different factors to effectively mitigate disability risk.Future studies should explore the underlying biological and sociological mechanisms of these lagged effects,identify intervention strategies that target risk factors with different lagged patterns,and evaluate their effectiveness.
基金Yunnan Provincial High-Level Traditional Chinese Medicine Talent Training ProjectYunnan Provincial Department of Science and Technology Traditional Chinese Medicine Basic Research Joint Special Project(Project No.:202101AZ070001-138)。
文摘Objective:Based on the theory of“Taiyang governs tendons”,to explore the effect of acupuncture at points of the Bladder Meridian of Foot-Taiyang on the expression of serum inflammatory factors in rabbit models of cervical spondylosis.Methods:Thirty New Zealand white rabbits were randomly divided into a blank group,a model group,and a treatment group,with 10 rabbits in each group.The models of cervical spondylosis in the model group and treatment group were established by long-term head-down flexion combined with cold-damp stimulation.After modeling,the treatment group received acupuncture at three points(Kunlun,Weizhong,and Feishu)on the Bladder Meridian of Foot-Taiyang,once a day for 20 minutes each time,for 14 consecutive days;the model group and blank group received no therapeutic intervention.After the intervention,cardiac blood was collected from all rabbits to detect the expression levels of serum inflammatory factors IL-6,TNF-α,and IL-1β.Meanwhile,cervical muscle tissue was collected,stained with HE,and the morphological changes of the posterior cervical muscle tissue in each group were observed under an optical microscope.Results:After modeling,the levels of inflammatory factors in the serum of rabbits in the model group and treatment group were significantly increased compared with those before modeling,with a statistically significant difference(p<0.01).After intervention,the serum inflammatory factors in the treatment group decreased significantly compared with those in the model group,and the difference was statistically significant(p<0.01).Conclusion:Acupuncture at points of the Bladder Meridian of Foot-Taiyang in rabbit models of cervical spondylosis can reduce the serum levels of inflammatory factors TNF-α,IL-1β,and IL-6.
基金Supported by Open Fund Project of the Engineering Technology Research Center of Characteristic Medicinal Plants of Fujian(PP202003).
文摘This paper provides a systematic review of the histochemical localization,content characteristics,and influencing factors of saponins in Pseudostellaria heterophylla based on an extensive literature survey.It provides an in-depth analysis and summary of the effects of biological factors,environmental conditions,agronomic practices,processing methods,and continuous cropping obstacles on the synthesis of P.heterophylla saponins,as well as their underlying mechanisms.Based on identified gaps in the current literature,future research directions and prospects are proposed.The findings of this review offer valuable insights for advancing the understanding of the saponin biosynthesis mechanisms in P.heterophylla and for enhancing its quality.
基金supported by the National Natural Science Foundation of China(U2344201 and 42101316)the Natural Science Foundation of Hunan Province,China(2022JJ40866)the Outstanding Youth Project of Education Bureau of Hunan Province,China(20B613)。
文摘Understanding the spatial distributions and corresponding variation mechanisms of key soil nutrients in fragile karst ecosystems can assist in promoting sustainable development.However,due to the implementation of ecological restoration initiatives such as land-use conversions,novel changes in the spatial characteristics of soil nutrients remain unknown.To address this gap,we explored nutrient variations and the drivers of the variation in the 0–15 cm topsoil layer using a regional-scale sampling method in a typical karst area in northwest Guangxi Zhuang Autonomous Region,Southwest China.Descriptive statistics,geostatistics,and spatial analysis were used to assess the soil nutrient variability.The results indicated that soil organic carbon(SOC),total nitrogen(TN),total phosphorus(TP),and total potassium(TK)concentrations showed moderate variations,with coefficients of variance being 0.60,0.60,0.71,and 0.72,respectively.Moreover,they demonstrated positive spatial autocorrelations,with global Moran's indices being 0.68,0.77,0.64,and 0.68,respectively.However,local Moran's index values were low,indicating large spatial variations in soil nutrients.The best-fitting semi-variogram models for SOC,TN,TP,and TK concentrations were spherical,Gaussian,exponential,and exponential,respectively.According to the classification criteria of the Second National Soil Census in China,SOC and TN concentrations were relatively sufficient,with the proportions of rich and very rich levels being up to 90.9 and 96.0%,respectively.TP concentration was in the mediumdeficient level,with the areas of medium and deficient levels accounting for 33.7 and 30.1%of the total,respectively.TK concentration was deficient,with the cumulative area of extremely deficient,very deficient,and deficient levels accounting for 87.6%of the total area.Consequently,the terrestrial ecosystems in the study area were more vulnerable to soil P and K than soil N deficiencies.Furthermore,variance partitioning analysis of the influencing factors showed that,except for the interactions,the single effect of other soil properties accounted more for soil nutrient variations than spatial and environmental variables.These results will aid in the future management of terrestrial ecosystems.
基金Supported by the National Natural Science Foundation of China,No.82402789Beijing Jishuitan Hospital Youcai Plan,No.KYYC202402+1 种基金Beijing Jishuitan Research Funding,No.HL202402and Beijing Natural Science Foundation,No.L232062,No.L222063.
文摘BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty(pTHA).However,the literature demonstrates significant variability regarding the relative contributions of different factors.AIM To investigate the key determinants of aseptic loosening,we performed a systematic review and meta-analysis.METHODS A comprehensive search of PubMed,Web of Science,EMBASE,and the Cochrane Library was conducted,encompassing studies from database inception to January 1,2025.Meta-analyses were performed to evaluate factors associated with aseptic loosening following pTHA.Inclusion and exclusion criteria were systematically applied at each stage to ensure methodological transparency and reproducibility.Study quality was assessed using standardized categories.Pooled odds ratio(OR)with corresponding 95%confidence interval were calculated with random-or fixed-effects models to generate reliability estimates,and study heterogeneity was visualized using forest plots.Ten factors,categorized into patient-,surgeon-,and device-related domains,were reviewed and meta-analyzed.Funnel plot analysis demonstrated a relatively symmetrical distribution,suggesting minimal publication bias.RESULTS A meta-analysis of 20 studies(520789 participants)found a pooled prevalence of 1.96%.Significant risk factors for aseptic loosening after pTHA included elevated body mass index(OR=1.116,P<0.001),higher Charlson comorbidity index(OR=1.378,P<0.001),prosthesis-related factors(OR=1.497,P<0.001),and adverse lifestyles(OR=2.198,P=0.037).Protective factors were non-white race(OR=0.445,P<0.001)and favorable genetics(OR=0.723,P<0.001).Male sex increased risk(OR=1.232,P=0.016),while age and anatomy were not significant.Surgical expertise showed a slight protective effect(OR=1.048,P<0.001).A comprehensive understanding of the modifiable and non-modifiable factors contributing to aseptic loosening after pTHA requires consideration of patient-related factors,surgical expertise,and prosthesis characteristics.CONCLUSION The identification of these factors is critical for risk mitigation.High-risk patients should receive targeted counseling regarding individualized profiles.Further studies are warranted to establish clearer causal relationships and identify additional contributing factors.
基金Supported by State Grid Corporation of China Science and Technology Project:Research on Key Technologies for Intelligent Carbon Metrology in Vehicle-to-Grid Interaction(Project Number:B3018524000Q).
文摘To achieve low-carbon regulation of electric vehicle(EV)charging loads under the“dual carbon”goals,this paper proposes a coordinated scheduling strategy that integrates dynamic carbon factor prediction and multiobjective optimization.First,a dual-convolution enhanced improved Crossformer prediction model is constructed,which employs parallel 1×1 global and 3×3 local convolutionmodules(Integrated Convolution Block,ICB)formultiscale feature extraction,combinedwith anAdaptive Spectral Block(ASB)to enhance time-series fluctuationmodeling.Based on high-precision predictions,a carbon-electricity cost joint optimization model is further designed to balance economic,environmental,and grid-friendly objectives.The model’s superiority was validated through a case study using real-world data from a renewable-heavy grid.Simulation results show that the proposed multi-objective strategy demonstrated a superior balance compared to baseline and benchmark models,achieving a 15.8%reduction in carbon emissions and a 5.2%reduction in economic costs,while still providing a substantial 22.2%reduction in the peak-valley difference.Its balanced performance significantly outperformed both a single-objective strategy and a state-of-the-art Model Predictive Control(MPC)benchmark,highlighting the advantage of a global optimization approach.This study provides theoretical and technical pathways for dynamic carbon factor-driven EV charging optimization.
基金Supported by Chengdu Municipal Science and Technology Bureau Key R&D Support Program(No.2023-YF09-00041-SN)。
文摘AIM:To assess risk factors for epiretinal membranes(ERM)and examine their interactions in a nationally representative U.S.dataset.METHODS:Data from the 2005–2008 National Health and Nutrition Examination Survey(NHANES)were analyzed,a nationally representative U.S.dataset.ERM was identified via retinal imaging based on the presence of cellophane changes.Key predictors included age group,eye surgery history,and refractive error,with additional demographic and health-related covariates.Weighted univariate and multiple logistic regression models were used to assess associations and interaction effects between eye surgery and refractive error.RESULTS:Totally 3925 participants were analyzed.Older age,eye surgery,and refractive errors were significantly associated with ERM.Compared to those under 65y,the odds ratio(OR)for ERM was 3.08 for ages 65–75y(P=0.0014)and 4.76 for ages 75+years(P=0.0069).Eye surgery increased ERM risk(OR=3.48,P=0.0018).Moderate to high hyperopia and myopia were also associated with ERM(OR=2.65 and 1.80,respectively).A significant interaction between refractive error and eye surgery was observed(P<0.0001).Moderate to high myopia was associated with ERM only in those without eye surgery(OR=1.92,P=0.0443).Eye surgery was most strongly associated with ERM in the emmetropic group(OR=3.60,P=0.0027),followed by the moderate to high myopia group(OR=3.01,P=0.0031).CONCLUSION:ERM is significantly associated with aging,eye surgery,and refractive errors.The interaction between eye surgery and refractive error modifies ERM risk and highlights the importance of considering combined effects in clinical risk assessments.These findings may help guide individualized ERM risk assessment that may inform personalized approaches to ERM prevention and management.
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
文摘BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.
