Background Biomarkers for predicting suicide risk in hospitalised patients with mental disorders have been understudied.Currently,suicide risk assessment tools based on objective indicators are limited in China.Aims T...Background Biomarkers for predicting suicide risk in hospitalised patients with mental disorders have been understudied.Currently,suicide risk assessment tools based on objective indicators are limited in China.Aims To examine the value of various biomarkers in suicide risk prediction and develop a risk assessment model with clinical utility using machine learning.Methods This cohort study analysed patients with major depressive disorder(MDD) who were hospitalised for the first time between January 2016 and March 2023 from four specialised mental health institutions.A total of 139 features,including biomarker measurements,medical orders and psychological scales,were assessed for analysis.Their suicide risk was evaluated by qualified nurses using Nurse s Global Assessment of Suicide Risk within 1 week after admission.Five machine learning models were trained with 10-fold cross-validation across three hospitals and were externally validated in an independent cohort.The primary performance was assessed using the area under the receiver operating characteristic curve(AUROC).The model was interpreted using the SHapley Additive exPlanations(SHAP) analysis.Biomarker importance was evaluated by comparing model performance with and without these biomarkers.Results Of 3143 patients with MDD included in this study,the incidence of high suicide risk within 1 week after first admission was 660(21.0%).Among all models,the Extreme Gradient Boosting can more effectively predict future risks,with an AUROC higher than 0.8(p<0.001).The SHAP values identified the 10 most important features,including five biomarkers.After clustering analysis,electroconvulsive therapy,physical restraint,β2-microglobulin and triiodothyronine were found to have heterogeneous effects on suicide risk.Combining biomarkers with other data from electronic health records significantly improved the performance and clinical utility of machine learning models based on demographics,diagnosis,laboratory tests,medical orders and psychological scales.Conclusions This study demonstrates the potential for a biomarker-based suicide risk assessment for patients with MDD,emphasising the interaction between biomarkers and therapeutic interventions.展开更多
Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant...Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.展开更多
BACKGROUND The global incidence of metabolic dysfunction-associated steatotic liver disease(MASLD)has increased in recent years.It has already been demonstrated that exercise and weight change are associated with the ...BACKGROUND The global incidence of metabolic dysfunction-associated steatotic liver disease(MASLD)has increased in recent years.It has already been demonstrated that exercise and weight change are associated with the occurrence of MASLD;however,the association between weight fluctuation caused by different exercise intensities and the risk of MASLD remains to be studied.AIM To investigate the impact of weight fluctuation and physical activity intensity on the risk of MASLD prevalence.METHODS Data from the National Health and Nutrition Examination Survey database including five cycles from 2009 to 2018 were analyzed.The model included variables such as age,sex,and poverty income ratio.Weighted multivariate logistic regression was used to examine the influence of different weight fluctuation patterns within the two time intervals on the prevalence of MASLD.Nonparametric restricted cubic spline curves were used to analyze the non-linear relationship between net weight change and MASLD prevalence.RESULTS Among 3183 MASLD cases,the risk of MASLD increased with age for individuals transitioning from non-obese to obese or maintaining obesity,with odds ratio(OR)changing from 8.91(95%CI:7.40-10.88)and 11.87(95%CI:9.65-14.60)at 10 years before baseline to 9.58(95%CI:8.08-11.37)and 12.51(95%CI:9.33-16.78)at 25 years.Stable obesity correlated with age-dependent MASLD prevalence escalation,whereas increased physical activity attenuated MASLD risk in this group,with an OR changing from 13.64(95%CI:10.59-17.57)to 6.42(95%CI:4.24-9.72).Further analysis of the net weight changes revealed a paradoxical risk elevation with intensified physical activity during different time periods.CONCLUSION The risk of MASLD increases in individuals transitioning from non-obese to obese or maintaining obesity.Highintensity physical activity is beneficial for MASLD among individuals with stable obesity.展开更多
Traditional Chinese medicine(TCM)establishes that the kidney serves vital systemic functions and its deficiency represents a fundamental factor influencing various diseases,including asthma.The kidney-tonifying method...Traditional Chinese medicine(TCM)establishes that the kidney serves vital systemic functions and its deficiency represents a fundamental factor influencing various diseases,including asthma.The kidney-tonifying method represents a widely implemented clinical approach in TCM to address kidney deficiency.This study hypothesized that bone marrow mesenchymal stem cells(BMSCs)function as key contributors to the kidney-tonifying method.An ovalbumin(OVA)-induced asthma mouse model received treatment with the traditional kidney-tonifying formula,Qi-Xian decoction(QXD).QXD demonstrated significant therapeutic efficacy,enhanced BMSC proliferation in mouse bone marrow,and facilitated their migration to lung tissues.Inhibition of the CXCL12/CXCR4 axis diminished the QXD-induced migration of endogenous BMSCs and reduced QXD's efficacy in asthma treatment.QXD-containing serum enhanced BMSC proliferation and promoted CXCL12-induced BMSC migration in vitro.These findings indicate that endogenous BMSCs may serve as a crucial mediator in the therapeutic effects of the kidney-tonifying method.Furthermore,the mild and sustained stimulation of production and enhanced homing of endogenous BMSCs presents a potential novel approach for effective asthma treatment.展开更多
Cholangiocarcinoma(CCA)is a particularly aggressive and challenging type of cancer,known for its poor prognosis,which is worsened by the complex interplay of various biological and environmental factors that contribut...Cholangiocarcinoma(CCA)is a particularly aggressive and challenging type of cancer,known for its poor prognosis,which is worsened by the complex interplay of various biological and environmental factors that contribute to its development.Recently,researchers have increasingly focused on the significant role of the biliary-enteric communication of liver-gut axis in the pathogenesis of CCA,highlighting a complex relationship that has not been thoroughly explored before.This review aims to summarize the key concepts related to the biliary-enteric communication of liver-gut axis and investigate its potential mechanisms that may lead to the onset and progression of CCA,a disease that presents substantial treatment challenges.Important areas of focus will include the microbiome's profound influence,which interacts with host physiology in ways that may worsen cancer development;changes in bile acid metabolism that can create toxic environments favorable for tumor growth;the regulation of inflammatory processes that may either promote or inhibit tumor progression;the immune system's involvement,which is crucial in the body's response to cancer;and the complex interactions within metabolic pathways that can affect cellular behavior and tumor dynamics.By integrating recent research findings from various studies,we aim to explore the multifaceted roles of the biliary-enteric communication of liver-gut axis in CCA,providing new insights and perspectives for future research while identifying promising therapeutic targets that could lead to innovative treatment strategies aimed at improving patient outcomes in this challenging disease.展开更多
OBJECTIVE:To confirm the therapeutic effect and mechanism of Jingui Shenqi pill(金匮肾气丸,JGSQP)on cardiorenal syndrome.METHODS:Doxorubicin was used to build heart-kidney coinjury rat model.After the modeling was com...OBJECTIVE:To confirm the therapeutic effect and mechanism of Jingui Shenqi pill(金匮肾气丸,JGSQP)on cardiorenal syndrome.METHODS:Doxorubicin was used to build heart-kidney coinjury rat model.After the modeling was completed,JGSQP gavage intervention was performed.The cardiac function of rats in each group was evaluated by ultrasound detection.Serum of rats was collected and examined for markers of heart and kidney damage.Enzyme linked immunosorbent assay detected serum inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)expression.Quantitative real-time polymerase chain reaction(PCR)and Western blot detected the changes of related genes and proteins.RESULTS:JGSQP significantly increased left ventricular ejection fraction(EF)and left ventricular shortening fraction(FS)values,decreased the heart and kidney damage markers and fibrosis levels(P<0.05).Furthermore,it can reduce IL-1β,IL-6,and TNF-αinflammatory expression(P<0.05).Mechanistically,JGSQP significantly inhibited the expression of key genes and proteins of mitogen-activated protein kinase(MAPK)signaling pathway(P<0.05).CONCLUSIONS:Jingui Shenqi pill can exert therapeutic effects on cardiorenal syndrome by inhibiting the activation of the MAPK signaling pathway and inflammatory responses.展开更多
Background Chronic heart failure(CHF)and osteoporosis(OP)are major health issues affecting the middle-aged and elderly population.With the intensification of population aging,the incidences of both conditions are in-c...Background Chronic heart failure(CHF)and osteoporosis(OP)are major health issues affecting the middle-aged and elderly population.With the intensification of population aging,the incidences of both conditions are in-creasing,severely affecting the quality of life of patients and the development of social medical care.In recent years,many studies have found a close relationship between the two conditions,with mutual influences,especially the impact of CHF on the risk and prognosis of OP,which has attracted increasing attention.Comprehensively un-derstanding the risk of OP in heart failure patients and providing targeted interventions to prevent fractures is of great significance.However,the pathophysiological mechanisms of osteoporosis in patients with heart failure are not yet fully understood.A large number of recent studies have proven that,in addition to common risk factors(such as age,gender,blood lipids,smoking,etc.),there are still independent mutual connections between the two condi-tions.Domestic and international research has found that changes in cytokine or hormone levels in bone metabo-lism can affect the pathophysiological processes of CHF.Therefore,this article reviewed the correlation between bone metabolism and chronic heart failure and elderly osteoporosis,hoping to provide a reference for clinical treat-ment and prevention.展开更多
BACKGROUND Sepsis-associated encephalopathy(SAE)is a common complication of sepsis,characterized by cognitive impairment,altered consciousness,and psychiatric symptoms,including anxiety and depression.These psychiatri...BACKGROUND Sepsis-associated encephalopathy(SAE)is a common complication of sepsis,characterized by cognitive impairment,altered consciousness,and psychiatric symptoms,including anxiety and depression.These psychiatric symptoms often exacerbate the overall prognosis and quality of life of affected patients.However,the underlying metabolic and proteomic features associated with SAE-induced psychiatric symptoms remain poorly understood.AIM To investigate the clinical manifestations of anxiety and depression in patients with sepsis and SAE and to explore their associated metabolic and proteomic characteristics.METHODS A total of 88 patients were enrolled,comprising 30 healthy controls,29 patients with sepsis,and 29 with SAE.Anxiety and depression symptoms were evaluated using the Hamilton anxiety rating scale(HAM-A)and Hamilton depression rating scale(HAM-D)in sepsis and SAE.Cognitive function was assessed using the Montreal Cognitive Assessment(MoCA),and quality of life was measured using the 36-Item Short Form Health Survey.Plasma samples were analyzed for metabolomic and proteomic profiling.Metabolic alterations were identified through liquid chromatography-mass spectrometry,while protein expression was assessed using Olink targeted proteomics.RESULTS Compared to the sepsis group,patients with SAE exhibited significantly higher levels of anxiety(HAM-A:15.2±4.0 vs 10.4±3.0,P=0.012)and depression(HAM-D:16.0±3.5 vs 9.1±2.3,P=0.003).Cognitive function,as measured by MoCA,was notably impaired in the SAE group(MoCA:18.5±4.0 vs 24.5±3.2,P=0.007).Quality of life scores,particularly in physical functioning,emotional well-being,and mental health,were significantly lower in patients with SAE.Metabolomic and proteomic analyses revealed substantial alterations in oxidative stress and nicotinamide adenine dinucleotide(NAD+)metabolism pathways,with cluster of differentiation(CD)38 emerging as a potential biomarker associated with psychiatric symptoms in SAE.Further validation in an independent cohort confirmed the diagnostic relevance of CD38.CONCLUSION This study highlights the significant psychological burden of SAE,manifested as anxiety and depression.Multiomics analysis identified distinct metabolic alterations,particularly in NAD+metabolism,that may contribute to psychiatric symptom development and progression.Furthermore,CD38 was identified as a promising biomarker for the early detection of SAE,providing potential avenues for early intervention and therapeutic targeting.展开更多
Black rice,as a dietary supplement,has received increasing attention because of its beneficial health properties.Although black rice and its major ingredients have been considered a potential therapy for ulcerative co...Black rice,as a dietary supplement,has received increasing attention because of its beneficial health properties.Although black rice and its major ingredients have been considered a potential therapy for ulcerative colitis(UC),its effect and underlying mechanism of action remain obscure.In this study,black rice was demonstrated to improve dextran sulfate sodium salt(DSS)-induced UC and restore intestinal barrier dysfunction.Cyanidin 3-O-glucoside(C3G)is the most abundant ingredient in black rice.Similarly,in vivo and in vitro studies have demonstrated that C3G alleviates colitis and intestinal barrier dysfunction.Proteomic analysis showed that C3G significantly reduced abnormallyelevated swiprosin-1 levels in mice with colitis.Furthermore,the effect of C3G on mitigating colitis was inhibited after swiprosin-1 was overexpressed in intestinal tissue in vivo and Caco-2 cells in vitro.Acyl-CoA synthetase long-chain family member 1(ACSL1)was identified as a potential protein that interacts with swiprosin-1 byco-immunoprecipitation and liquid chromatography-tandem mass spectrometry.By integratingmetabolomics experiments and bioinformatics analysis of single-cell sequencing,ACSL1 was found to selectively bind to swiprosin-1 and regulate downstream linoleic acid metabolism in colitis.Moreover,C3G was observed to prevent the localization of ACSL1 within mitochondria via swiprosin-1,thereby inhibiting the oxidation of linoleic acid.This study demonstrated that C3G targeted swiprosin-1 to ameliorate UC via ASCLl-mediated linoleic acid metabolism,thereby providing a novel potential insight into the mechanism of C3G protection against colitis and establishing the groundwork for its clinical application.展开更多
AIM: To investigate the prevalence and risk factors of polypoid lesions of gallbladder (PLG) among the health examinees in the Shanghai region, China. METHODS: A total of 11 816 subjects who underwent health examinati...AIM: To investigate the prevalence and risk factors of polypoid lesions of gallbladder (PLG) among the health examinees in the Shanghai region, China. METHODS: A total of 11 816 subjects who underwent health examinations in our hospital between August 2010 and February 2011 were analyzed retrospectively. Among them, there were 7174 men and 4642 women. PLG was diagnosed by the real-time ultrasonography. Those with the body mass index (BMI) ≥ 28 were considered to be obese. Blood biochemical indices were detected with the fully automatic biochemical analyzer and hepatitis B surface antigen (HBsAg) was tested by the automated enzyme immunoassay. The correlations between the prevalence of PLG and age, sex, BMI, serum cholesterol (T-Cho), triglycerides (TG),blood sugar, HBsAg, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), gallstone and fatty liver were investigated. After univariate analysis of 11 variables, stepwise logistic regression analysis was performed to explore the risk factors of PLG. RESULTS: There was a significant difference in sex, T-Cho, HBsAg, HDL-C, LDL-C and fatty liver between the PLG-positive group and the PLG-negative group (332/163 vs 6842/4479, P = 0.003; 22/473 vs 295/11 026, P =0.013; 92/403 vs 993/10 328, P = 0.001; 47/448 vs 332/10 989, P = 0.001; 32/463 vs 381/10 940, P = 0.001; 83/412 vs 3260/8061, P = 0.001). No significant difference was found in the age, BMI, TG, blood sugar and gallstone between the two groups (47.3 ± 26 vs 45.1 ± 33, P = 0.173; 59/436 vs 1097/10 224, P = 0.102; 52/443 vs 982/10 339, P = 0.158; 17/478 vs 295/11 026, P = 0.26; 24/471 vs 395/10 926, P = 0.109). Logistic regression analysis showed that the sex, HBsAg and HDL-C were independent risk factors for the development of PLG in a descending order of HDL-C > HBsAg > sex. CONCLUSION: In healthy people, the male gender, positive HBsAg, and low HDL-C confer higher risks of PLG development.展开更多
OBJECTIVE:To compare the effects of electrical stimulation of different acupoint combinations among postoperative bedridden elderly patients on hemorheology and deep venous blood flow velocity and investigate the role...OBJECTIVE:To compare the effects of electrical stimulation of different acupoint combinations among postoperative bedridden elderly patients on hemorheology and deep venous blood flow velocity and investigate the role of electrical stimulation against deep vein thrombosis(DVT).METHODS:From November 2010 to October 2011,a total of 160 elderly bedridden patients after major surgery were divided into the conventional care group,invigorating and promoting Qi group,blood-activating and damp-eliminating group,and acupoint-combination stimulation group.Whole blood viscosity,plasma viscosity,D-dimer levels,lower limb skin temperature,lower limb circumference,and flow velocities of the external iliac vein,femoral vein,popliteal vein,and deep calf veins in all patients were documented and compared among the four groups.RESULTS:Whole blood viscosity,plasma viscosity,D-dimer levels,and lower limb circumference were significantly reduced in the blood-activating and damp-eliminating group compared with the conventional care group(P<0.05) and were almost equal to those in the acupoint-combination stimulation group(P>0.05).Lower limb venous flow velocities were accelerated in the invigorating and promoting Qi group compared with the other groups,excluding the acupoint-combination stimulation group(P<0.05).CONCLUSION:Hemorheological indices in postoperative bedridden elderly patients were improved after combined electrical stimulation at Yinlingquan(SP 9) and Sanyinjiao(SP 6).Combined electrical stimulation at Zusanli(ST 36) and Taichong(LR 3),on the other hand,accelerated lower limb venous flow.展开更多
AIM: To investigate the effect of glycyrrhizic acid (GA) on carbon tetrachloride (CCl4)-induced hepatocyte apo-ptosis in rats via a p53-dependent mitochondrial path-way. METHODS: Forty-five male Sprague-Dawley rats we...AIM: To investigate the effect of glycyrrhizic acid (GA) on carbon tetrachloride (CCl4)-induced hepatocyte apo-ptosis in rats via a p53-dependent mitochondrial path-way. METHODS: Forty-five male Sprague-Dawley rats were randomly and equally divided into three groups, the control group, the CCl4 group, and the GA treatment group. To induce liver fibrosis in this model, rats were given a subcutaneous injection of a 40% solution of CCl4 in olive oil at a dose of 0.3 mL/100 g body weight biweekly for 8 wk, while controls received the same isovolumetric dose of olive oil by hypodermic injection, with an initial double-dose injection. In the GA group,rats were also treated with a 40% solution of CCl4 plus 0.2% GA solution in double distilled water by the intraperitoneal injection of 3 mL per rat three times a week from the first week following previously published methods, with modifications. Controls were given the same isovolumetric dose of double distilled water. Liver function parameters, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were de-termined. Pathologic changes in the liver were detected by hematoxylin and eosin staining. Collagen fibers were evaluated by Sirius red staining. Hepatocyte apoptosis was investigated using the terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) assay and the cleaved caspase-3 immunohistochemistry assay. The expression levels of p53 and apoptosis-related proteins were evaluated by immunohistochemistry or Western blotting analysis. RESULTS: After 8 wk of treatment, GA significantly re-duced serum activity of ALT (from 526.7 ± 57.2 to 342 ± 44.8, P<0.05) and AST (from 640 ± 33.7 to 462.8 ± 30.6, P<0.05), attenuated the changes in liver his-topathology and reduced the staging score (from 3.53 ± 0.74 to 3.00 ± 0.76, P<0.05) in CCl4 -treated rats. GA markedly reduced the positive area of Sirius red and the ratio of the hepatic fibrotic region (from 7.87% ± 0.66% to 3.68% ± 0.32%, P<0.05) compared with the CCl4 group. GA also decreased the expression level of cleaved caspase-3 compared to the CCl4 group. TU-NEL assay indicated that GA significantly diminished the number of TUNEL-positive cells compared with the CCl4 group (P<0.05). GA treatment clearly decreased the level of p53 (P<0.05) detected by immunohis-tochemistry and Western blotting analysis. Compared with the CCl4 group, we also found that GA reduced the Bax/Bcl-2 ratio (P<0.05), the expression of cleaved caspase-3 (P<0.05), cleaved caspase-9 (P<0.05), and inhibited cytochrome C and second mitochondria-derived activator of caspases (Smac) release from mito-chondria to cytoplasm, i.e. , GA reduced the expressionlevel of Smac, which inhibited c-IAP1 activity (P<0.05), ultimately inhibiting the activity of caspase-3, according to Western blotting analysis. As a result, GA suppressed activation of the caspase cascades and prevented he-patocyte apoptosis.展开更多
OBJECTIVE:To evaluate the effects of electric acupoint stimulation on gastrointestinal hormones and motility among geriatric postoperative patients with gastrointestinal tumors,and to explore an efficient and noninvas...OBJECTIVE:To evaluate the effects of electric acupoint stimulation on gastrointestinal hormones and motility among geriatric postoperative patients with gastrointestinal tumors,and to explore an efficient and noninvasive method for postoperative recovery of bowel functions.METHODS:Forty patients were randomly and evenly assigned into a regular nursing care group(RNC) and an acupoint electric stimulation group(AES).Patients in the RNC group received regular nursing care and patients in the AES group received regular nursing care plus electric stimulation of acupoints.The serum levels of gastrin(GAS),motilin(MOT),and cholecystokinin(CCK),and an electrogastrogram(EGG) of all the patients were evaluated on the first,third,and fifth day after surgery.The time to first flatus after surgery and the number of patients with side effects such as abdominal pain,abdominal distention,and diarrhea were recorded.RESULTS:There were significant differences between the two groups in GAS,MOT,EGG,time to first flatus,abdominal pain,abdominal distention,and diarrhea(P < 0.05).CONCLUSION:Electric stimulation on acupoints could increase levels of GAS and MOT,promote the recovery of gastrointestinal functions,and decrease complications among postoperative senile patients with gastrointestinal tumors.展开更多
Diabetic nephropathy(DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protecti...Diabetic nephropathy(DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin(30 mg·kg^(-1) body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L^(-1) were selected for experiments. The DN rats were treated with Taxus chinensis orally(0.32, 0.64, and 1.28 g·kg^(-1)) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-β1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-β1/Smad signaling pathway.展开更多
Echinacoside （ECH） is protective in a mouse model of Parkinson＇ s disease （PD） induced by 1-methyl-4- phenylpyridinium ion （MPP＋）. To investigate the mechanisms involved, SH-SYSY neuroblastoma ceils were treat...Echinacoside （ECH） is protective in a mouse model of Parkinson＇ s disease （PD） induced by 1-methyl-4- phenylpyridinium ion （MPP＋）. To investigate the mechanisms involved, SH-SYSY neuroblastoma ceils were treated with MPP＋ or a combination of MPP＋ and ECH, and the expression of ATF3 （activating transcription factor 3）, CHOP （C/EBP-homologous protein）, SCNA （synuclein alpha）, and GDNF （glial cell line-derived neurotrophic factor） was assessed. The results showed that ECH significantly improved cell survival by inhibiting the generation of MPP＋-induced reactive oxygen species （ROS）. In addition, ECH suppressed the ROS and MPP＋- induced expression of apoptotic genes （ATF3, CHOP, and SCNA）. ECH markedly decreased the MPP＋-induced cas- pase-3 activity in a dose-dependent manner. ATF3- knockdown also decreased the CHOP and cleaved caspase- 3 levels and inhibited the apoptosis induced by MPP＋. Interestingly, ECH partially restored the GDNF expression that was down-regulated by MPP＋. ECH also improved dopaminergic neuron survival during MPP＋ treatment and protected these neurons against the apoptosis induced by MPTP. Taken together, these data suggest that the ROS/ ATF3/CHOP pathway plays a critical role in mechanisms by which ECH protects against MPP＋-induced apoptosis in PD.展开更多
Resistance to cisplatin(DDP)-based chemotherapy is a major cause of treatment failure in human gastric cancer(GC). It is necessary to identify the drugs to re-sensitize GC cells to DDP. In our previous research, Zuo J...Resistance to cisplatin(DDP)-based chemotherapy is a major cause of treatment failure in human gastric cancer(GC). It is necessary to identify the drugs to re-sensitize GC cells to DDP. In our previous research, Zuo Jin Wan Formula(ZJW) has been proved could increase the mitochondrial apoptosis via cofilin-1 in a immortalized cell line, SGC-7901/DDP. Due to the immortalized cells may still difficult highly recapitulate the important molecular events in vivo, primary GC cells model derived from clinical patient was constructed in the present study to further evaluate the effect of ZJW and the underlying molecular mechanism. Immunofluorescent staining was used to indentify primary cultured human GC cells. Western blotting was carried out to detect the protein expression. Cell Counting Kit-8(CCK-8) was used to evaluate cell proliferation. Flow cytometry analysis was performed to assess cell apoptosis. ZJW inhibited proliferation and induced apoptosis in primary DDP-resistant GC cells. Notably, the apoptosis in GC cells was mediated by inducing cofilin-1 mitochondrial translocation, down-regulating Bcl-2 and up-regulating Bax expression. Surprisingly, the level of p-AKT protein was higher in DDP-resistant GC cells than that of the DDP-sensitive GC cells, and the activation of AKT could attenuate ZJW-induced sensitivity to DDP. These data revealed that ZJW can increase the chemosensitivity in DDP-resistant primary GC cells by inducing mitochondrial apoptosis and AKT inactivation. The combining chemotherapy with ZJW may be an effective therapeutic strategy for GC chemoresistance patients.展开更多
AIM：To investigate the expression of matrix metalloproteinases 1 and 3（MMP-1 and MMP-3） and their tissue inhibitors of metalloproteinases 1 and 3（ TIMP-1 and TIMP-3） in the conjunctiva of eyes with conjunctivocha...AIM：To investigate the expression of matrix metalloproteinases 1 and 3（MMP-1 and MMP-3） and their tissue inhibitors of metalloproteinases 1 and 3（ TIMP-1 and TIMP-3） in the conjunctiva of eyes with conjunctivochalasis（CCh）.METHODS：The conjunctival tissue was obtained from the CCh patients and controls,the MMPs/TIMPs expression concentration was determined by enzyme-linked immunosorbent assay（ELISA） and immunofluorescence staining.The expression levels of MMPs/TIMPs in the CCh fibroblasts were determined by analyzing its concentration in the cellular supernatant that was abstracted from the in vitro cultured CCh fibroblasts.RESULTS：MMP-1 and MMP-3 levels determined by ELISA were both significantly higher in the CCh group than that in the control group（P= 0.042,0.022,respectively）,so was the levels of TIMP-1（P= 0.010）.No significant difference in the expression of TIMP-3 in conjunctiva was found between the two groups（P= 0.298）.The expression of MMP-1 and MMP-3 were both up-regulated significantly in the CCh group（P= 0.040,0.001,respectively） on immunofluorescence staining.MMP-1 and MMP-3 expression in the fibroblasts were both significantly higher in the CCh group than that in the control group（P= 0.027,0.001,respectively）,while neither the TIMP-1 nor TIMP-3 expression was significantly different between the two groups（P= 0.421,0.237,respectively）.CONCLUSION：The overexpression of MMP-1 and MMP-3 in conjunctival tissue and fibroblasts may play an important role in the pathogenesis and development of CCh.展开更多
OBJECTIVE:To evaluated the effect of calycosin on left ventricular ejection fraction and angiogenesis.METHODS:Adult male Sprague-Dawley rats were randomly assigned into calycosin-treated groups(0.5,1,2,and 4 mg/kg qd)...OBJECTIVE:To evaluated the effect of calycosin on left ventricular ejection fraction and angiogenesis.METHODS:Adult male Sprague-Dawley rats were randomly assigned into calycosin-treated groups(0.5,1,2,and 4 mg/kg qd),a dimethyl sulfoxide(DMSO),or a sham-operated control group.The myocardial ischaemia(Ml)model was intraperitoneally administered calycosin for 28 days.The survival rates and left ventricular ejection fractions(LVEF)were compared between groups.The expression levels of vascular endothelial growth factor(VEGF)and cluster of differentiation 31(CD31)in ischaemic myocardium were also measured and compared.RESULTS:The construction of MI model resulted in a LVEF reduction of 50%compared with the sham-control.After 28 days,the LVEF value was 10%higher when calycosin(4 mg/kg)was administered compared with the DMSO group.The expression of VEGF and CD31 showed a dose-dependent manner when calycosin was administrated.The calycosin-treated(4 mg/kg)group displayed a twofold increase in VEGF expression at both the mRNA and protein levels compared with the DMSO group.In addition,CD31 expression in the microvascular increased 1.5-fold in the 4 mg/kg calycosin-treated group.CONCLUSION:Calycosin improved left ventricular ejection fraction in the MI rat models,induced VEGF expression in the ischaemic myocardium,increased CD31 expression and promoted angiogenesis.展开更多
The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment(TIME).This study aimed to mechanistically assess whether Chang Wei Qing(CWQ)Decoction can enh...The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment(TIME).This study aimed to mechanistically assess whether Chang Wei Qing(CWQ)Decoction can enhance the anti-tumor effect of PD-1 inhibitor therapy.PD-1 inhibitor therapy showed the significant anti-tumor effect in patients with mismatch repairdeficient/microsatellite instability-high(dMMR/MSI-H)colorectal cancer(CRC),rather than those with mismatch repairproficient/microsatellite stable(pMMR/MSS)CRC.Hence,immunofluorescence double-label staining was utilized to explore the difference in the TIME between dMMR/MSI-H and pMMR/MSS CRC patients.Flow cytometry was used to analyze T-lymphocytes in tumors from mice.Western blot was used to measure the expression of PD-L1 protein in mouse tumors.The intestinal mucosal barrier of mice was evaluated by hematoxylin-eosin staining and immunohistochemistry.16S rRNA-gene sequencing was used to examine the structure of the gut microbiota in mice.Subsequently,Spearman’s correlation analysis was used to analyze the relationship between the gut microbiota and tumor-infiltrating T-lymphocytes.The results showed that dMMR/MSI-H CRC patients had more CD8+T cells and higher expression of PD-1 and PD-L1 proteins.In vivo,CWQ enhanced the anti-tumor effect of anti-PD-1 antibody and increased the infiltration of CD8+and PD-1+CD8+T cells in tumors.Additionally,the combination of CWQ with anti-PD-1 antibody resulted in lower inflammation in the intestinal mucosa than that induced by anti-PD-1 antibody alone.CWQ and anti-PD-1 antibody co-treatment upregulated PD-L1 protein and reduced the abundance of Bacteroides in the gut microbiota but increased the abundance of Akkermansia,Firmicutes,and Actinobacteria.Additionally,the proportion of infiltrated CD8+PD-1+,CD8+,and CD3+T cells were found to be positively correlated with the abundance of Akkermansia.Accordingly,CWQ may modulate the TIME by modifying the gut microbiota and consequently enhance the anti-tumor effect of PD-1 inhibitor therapy.展开更多
基金supported by projects from Shanghai Putuo District Municipal Health Committee(ptkwws202413)Shanghai Municipal Health Commission(202340018)+2 种基金Shanghai Hospital Development Center(Data Sharing and Emulation of Clinical Trials,CCS-DASET:SHDC2024CRI008)Shanghai Changning District Municipal Commission of Health(CNWJXY026)School of Innovation and Entrepreneurship,Tongji University(S202310247388,X2024085 and X2024048).
文摘Background Biomarkers for predicting suicide risk in hospitalised patients with mental disorders have been understudied.Currently,suicide risk assessment tools based on objective indicators are limited in China.Aims To examine the value of various biomarkers in suicide risk prediction and develop a risk assessment model with clinical utility using machine learning.Methods This cohort study analysed patients with major depressive disorder(MDD) who were hospitalised for the first time between January 2016 and March 2023 from four specialised mental health institutions.A total of 139 features,including biomarker measurements,medical orders and psychological scales,were assessed for analysis.Their suicide risk was evaluated by qualified nurses using Nurse s Global Assessment of Suicide Risk within 1 week after admission.Five machine learning models were trained with 10-fold cross-validation across three hospitals and were externally validated in an independent cohort.The primary performance was assessed using the area under the receiver operating characteristic curve(AUROC).The model was interpreted using the SHapley Additive exPlanations(SHAP) analysis.Biomarker importance was evaluated by comparing model performance with and without these biomarkers.Results Of 3143 patients with MDD included in this study,the incidence of high suicide risk within 1 week after first admission was 660(21.0%).Among all models,the Extreme Gradient Boosting can more effectively predict future risks,with an AUROC higher than 0.8(p<0.001).The SHAP values identified the 10 most important features,including five biomarkers.After clustering analysis,electroconvulsive therapy,physical restraint,β2-microglobulin and triiodothyronine were found to have heterogeneous effects on suicide risk.Combining biomarkers with other data from electronic health records significantly improved the performance and clinical utility of machine learning models based on demographics,diagnosis,laboratory tests,medical orders and psychological scales.Conclusions This study demonstrates the potential for a biomarker-based suicide risk assessment for patients with MDD,emphasising the interaction between biomarkers and therapeutic interventions.
基金supported by the National Natural Science Foundation of China(Nos.82171552 and 82170479)the Natural Science Foundation of Shanghai Ctiy(No.21ZR1457500)the Science and Technology Bureau of Shanghai Putuo District(No.ptkwws202102).
文摘Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.
基金Supported by National Natural Science Foundation of China,No.82474378Shanghai Natural Science Foundation,No.22ZR1455900+4 种基金Shanghai Municipal Health Planning Commission Clinical Research Specialized Face Project,No.201940449Key Project of Science and Technology Innovation Program of Shanghai Putuo District Health and Health System,No.ptkwws202201Reserve Excellent Chinese Medicine Talent Program of Shanghai University of Traditional Chinese Medicine,No.20D-RC-02Apricot Grove,Shanghai Putuo District Excellent Young Talent Training Program,No.ptxlyq2201Shanghai Putuo District Health and Health System Characteristic Specialty Disease Construction Project,No.2023tszb01.
文摘BACKGROUND The global incidence of metabolic dysfunction-associated steatotic liver disease(MASLD)has increased in recent years.It has already been demonstrated that exercise and weight change are associated with the occurrence of MASLD;however,the association between weight fluctuation caused by different exercise intensities and the risk of MASLD remains to be studied.AIM To investigate the impact of weight fluctuation and physical activity intensity on the risk of MASLD prevalence.METHODS Data from the National Health and Nutrition Examination Survey database including five cycles from 2009 to 2018 were analyzed.The model included variables such as age,sex,and poverty income ratio.Weighted multivariate logistic regression was used to examine the influence of different weight fluctuation patterns within the two time intervals on the prevalence of MASLD.Nonparametric restricted cubic spline curves were used to analyze the non-linear relationship between net weight change and MASLD prevalence.RESULTS Among 3183 MASLD cases,the risk of MASLD increased with age for individuals transitioning from non-obese to obese or maintaining obesity,with odds ratio(OR)changing from 8.91(95%CI:7.40-10.88)and 11.87(95%CI:9.65-14.60)at 10 years before baseline to 9.58(95%CI:8.08-11.37)and 12.51(95%CI:9.33-16.78)at 25 years.Stable obesity correlated with age-dependent MASLD prevalence escalation,whereas increased physical activity attenuated MASLD risk in this group,with an OR changing from 13.64(95%CI:10.59-17.57)to 6.42(95%CI:4.24-9.72).Further analysis of the net weight changes revealed a paradoxical risk elevation with intensified physical activity during different time periods.CONCLUSION The risk of MASLD increases in individuals transitioning from non-obese to obese or maintaining obesity.Highintensity physical activity is beneficial for MASLD among individuals with stable obesity.
基金suppout by Putuo District(No.ptkwws202508)the Science and Technology Development Project Funding of Shanghai University of Traditional Chinese Medicine(Nos.23KFL082 and 24KFL057)+1 种基金the Plan of Clinical Specialty Construction in Shanghai Putuo District Health System(No.2020tszk02)the National Natural Science Foundation of China(Youth)Program(No.82405349)。
文摘Traditional Chinese medicine(TCM)establishes that the kidney serves vital systemic functions and its deficiency represents a fundamental factor influencing various diseases,including asthma.The kidney-tonifying method represents a widely implemented clinical approach in TCM to address kidney deficiency.This study hypothesized that bone marrow mesenchymal stem cells(BMSCs)function as key contributors to the kidney-tonifying method.An ovalbumin(OVA)-induced asthma mouse model received treatment with the traditional kidney-tonifying formula,Qi-Xian decoction(QXD).QXD demonstrated significant therapeutic efficacy,enhanced BMSC proliferation in mouse bone marrow,and facilitated their migration to lung tissues.Inhibition of the CXCL12/CXCR4 axis diminished the QXD-induced migration of endogenous BMSCs and reduced QXD's efficacy in asthma treatment.QXD-containing serum enhanced BMSC proliferation and promoted CXCL12-induced BMSC migration in vitro.These findings indicate that endogenous BMSCs may serve as a crucial mediator in the therapeutic effects of the kidney-tonifying method.Furthermore,the mild and sustained stimulation of production and enhanced homing of endogenous BMSCs presents a potential novel approach for effective asthma treatment.
文摘Cholangiocarcinoma(CCA)is a particularly aggressive and challenging type of cancer,known for its poor prognosis,which is worsened by the complex interplay of various biological and environmental factors that contribute to its development.Recently,researchers have increasingly focused on the significant role of the biliary-enteric communication of liver-gut axis in the pathogenesis of CCA,highlighting a complex relationship that has not been thoroughly explored before.This review aims to summarize the key concepts related to the biliary-enteric communication of liver-gut axis and investigate its potential mechanisms that may lead to the onset and progression of CCA,a disease that presents substantial treatment challenges.Important areas of focus will include the microbiome's profound influence,which interacts with host physiology in ways that may worsen cancer development;changes in bile acid metabolism that can create toxic environments favorable for tumor growth;the regulation of inflammatory processes that may either promote or inhibit tumor progression;the immune system's involvement,which is crucial in the body's response to cancer;and the complex interactions within metabolic pathways that can affect cellular behavior and tumor dynamics.By integrating recent research findings from various studies,we aim to explore the multifaceted roles of the biliary-enteric communication of liver-gut axis in CCA,providing new insights and perspectives for future research while identifying promising therapeutic targets that could lead to innovative treatment strategies aimed at improving patient outcomes in this challenging disease.
基金Supported by Shanghai Putuo District Health System Science and Technology Innovation Project:Study on the Effect and Mechanism of Jinkui Shenqi Pills on Renal Water Metabolism via provirus integration site for moloney murine leukemia virus 3/aquaporin 2 Regulation (No. PTKWS202104)Chengdu University of Traditional Chinese Medicine "Xinglin Scholar" Discipline Talent Research Enhancement Plan:Based on provirus integration site for moloney murine leukemia virus 3 to Explore the Molecular Mechanism of Jingui Shenqi pill in Regulating Water Metabolism in Renal Tubular Cells (No. YYZX2022165)the Clinical Advantage Discipline of Health System of Putuo District in Shanghai (2019ysxk01)
文摘OBJECTIVE:To confirm the therapeutic effect and mechanism of Jingui Shenqi pill(金匮肾气丸,JGSQP)on cardiorenal syndrome.METHODS:Doxorubicin was used to build heart-kidney coinjury rat model.After the modeling was completed,JGSQP gavage intervention was performed.The cardiac function of rats in each group was evaluated by ultrasound detection.Serum of rats was collected and examined for markers of heart and kidney damage.Enzyme linked immunosorbent assay detected serum inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)expression.Quantitative real-time polymerase chain reaction(PCR)and Western blot detected the changes of related genes and proteins.RESULTS:JGSQP significantly increased left ventricular ejection fraction(EF)and left ventricular shortening fraction(FS)values,decreased the heart and kidney damage markers and fibrosis levels(P<0.05).Furthermore,it can reduce IL-1β,IL-6,and TNF-αinflammatory expression(P<0.05).Mechanistically,JGSQP significantly inhibited the expression of key genes and proteins of mitogen-activated protein kinase(MAPK)signaling pathway(P<0.05).CONCLUSIONS:Jingui Shenqi pill can exert therapeutic effects on cardiorenal syndrome by inhibiting the activation of the MAPK signaling pathway and inflammatory responses.
基金supported by the Shanghai Putuo District Health System Science and Technology Innovation Project (No. ptkwws202221)。
文摘Background Chronic heart failure(CHF)and osteoporosis(OP)are major health issues affecting the middle-aged and elderly population.With the intensification of population aging,the incidences of both conditions are in-creasing,severely affecting the quality of life of patients and the development of social medical care.In recent years,many studies have found a close relationship between the two conditions,with mutual influences,especially the impact of CHF on the risk and prognosis of OP,which has attracted increasing attention.Comprehensively un-derstanding the risk of OP in heart failure patients and providing targeted interventions to prevent fractures is of great significance.However,the pathophysiological mechanisms of osteoporosis in patients with heart failure are not yet fully understood.A large number of recent studies have proven that,in addition to common risk factors(such as age,gender,blood lipids,smoking,etc.),there are still independent mutual connections between the two condi-tions.Domestic and international research has found that changes in cytokine or hormone levels in bone metabo-lism can affect the pathophysiological processes of CHF.Therefore,this article reviewed the correlation between bone metabolism and chronic heart failure and elderly osteoporosis,hoping to provide a reference for clinical treat-ment and prevention.
基金the Shanghai Municipal Health Commission Medical New Technology Research and Translation Seed Program,No.2024ZZ2052Scientific Research Project funded by Shanghai Fifth People’s Hospital,Fudan University,No.2023WYRH03 and No.2025GZRFY05+2 种基金Shanghai Putuo District Health System Clinical Medicine Discipline Construction Project,No.2024tszk01Shanghai Health System Key Discipline,No.2024ZDXK0005Shanghai Minhang District Health and Family Planning Commission,No.2024MWDXK01.
文摘BACKGROUND Sepsis-associated encephalopathy(SAE)is a common complication of sepsis,characterized by cognitive impairment,altered consciousness,and psychiatric symptoms,including anxiety and depression.These psychiatric symptoms often exacerbate the overall prognosis and quality of life of affected patients.However,the underlying metabolic and proteomic features associated with SAE-induced psychiatric symptoms remain poorly understood.AIM To investigate the clinical manifestations of anxiety and depression in patients with sepsis and SAE and to explore their associated metabolic and proteomic characteristics.METHODS A total of 88 patients were enrolled,comprising 30 healthy controls,29 patients with sepsis,and 29 with SAE.Anxiety and depression symptoms were evaluated using the Hamilton anxiety rating scale(HAM-A)and Hamilton depression rating scale(HAM-D)in sepsis and SAE.Cognitive function was assessed using the Montreal Cognitive Assessment(MoCA),and quality of life was measured using the 36-Item Short Form Health Survey.Plasma samples were analyzed for metabolomic and proteomic profiling.Metabolic alterations were identified through liquid chromatography-mass spectrometry,while protein expression was assessed using Olink targeted proteomics.RESULTS Compared to the sepsis group,patients with SAE exhibited significantly higher levels of anxiety(HAM-A:15.2±4.0 vs 10.4±3.0,P=0.012)and depression(HAM-D:16.0±3.5 vs 9.1±2.3,P=0.003).Cognitive function,as measured by MoCA,was notably impaired in the SAE group(MoCA:18.5±4.0 vs 24.5±3.2,P=0.007).Quality of life scores,particularly in physical functioning,emotional well-being,and mental health,were significantly lower in patients with SAE.Metabolomic and proteomic analyses revealed substantial alterations in oxidative stress and nicotinamide adenine dinucleotide(NAD+)metabolism pathways,with cluster of differentiation(CD)38 emerging as a potential biomarker associated with psychiatric symptoms in SAE.Further validation in an independent cohort confirmed the diagnostic relevance of CD38.CONCLUSION This study highlights the significant psychological burden of SAE,manifested as anxiety and depression.Multiomics analysis identified distinct metabolic alterations,particularly in NAD+metabolism,that may contribute to psychiatric symptom development and progression.Furthermore,CD38 was identified as a promising biomarker for the early detection of SAE,providing potential avenues for early intervention and therapeutic targeting.
基金supported by grants from the National Natural Science Foundation of China(81973551,82204737,82204686)the Science and Technology Commission of Shanghai Municipality(19ZR1451800,21ZR1460400,and 21140905300)+4 种基金Guoyiqiangyou foundation of Shanghai Hongkou(HGY-KY-2018-03 and HGYMGB-2018-01-05)the Health Commission of Shanghai Municipality(ZY(2021-2023)-0203-04)Shanghai Natural Science Foundation(22ZR1455900)Future Plan for Traditional Chinese Medicine Inheritance and Development of Shanghai Municipal Hospital of TraditionalChineseMedicine(WLJH2021ZY-ZYY007,WL-HBBD-2021001K)Shanghai Putuo District Health System Special Disease Construction Project(2023tszb01).
文摘Black rice,as a dietary supplement,has received increasing attention because of its beneficial health properties.Although black rice and its major ingredients have been considered a potential therapy for ulcerative colitis(UC),its effect and underlying mechanism of action remain obscure.In this study,black rice was demonstrated to improve dextran sulfate sodium salt(DSS)-induced UC and restore intestinal barrier dysfunction.Cyanidin 3-O-glucoside(C3G)is the most abundant ingredient in black rice.Similarly,in vivo and in vitro studies have demonstrated that C3G alleviates colitis and intestinal barrier dysfunction.Proteomic analysis showed that C3G significantly reduced abnormallyelevated swiprosin-1 levels in mice with colitis.Furthermore,the effect of C3G on mitigating colitis was inhibited after swiprosin-1 was overexpressed in intestinal tissue in vivo and Caco-2 cells in vitro.Acyl-CoA synthetase long-chain family member 1(ACSL1)was identified as a potential protein that interacts with swiprosin-1 byco-immunoprecipitation and liquid chromatography-tandem mass spectrometry.By integratingmetabolomics experiments and bioinformatics analysis of single-cell sequencing,ACSL1 was found to selectively bind to swiprosin-1 and regulate downstream linoleic acid metabolism in colitis.Moreover,C3G was observed to prevent the localization of ACSL1 within mitochondria via swiprosin-1,thereby inhibiting the oxidation of linoleic acid.This study demonstrated that C3G targeted swiprosin-1 to ameliorate UC via ASCLl-mediated linoleic acid metabolism,thereby providing a novel potential insight into the mechanism of C3G protection against colitis and establishing the groundwork for its clinical application.
文摘AIM: To investigate the prevalence and risk factors of polypoid lesions of gallbladder (PLG) among the health examinees in the Shanghai region, China. METHODS: A total of 11 816 subjects who underwent health examinations in our hospital between August 2010 and February 2011 were analyzed retrospectively. Among them, there were 7174 men and 4642 women. PLG was diagnosed by the real-time ultrasonography. Those with the body mass index (BMI) ≥ 28 were considered to be obese. Blood biochemical indices were detected with the fully automatic biochemical analyzer and hepatitis B surface antigen (HBsAg) was tested by the automated enzyme immunoassay. The correlations between the prevalence of PLG and age, sex, BMI, serum cholesterol (T-Cho), triglycerides (TG),blood sugar, HBsAg, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), gallstone and fatty liver were investigated. After univariate analysis of 11 variables, stepwise logistic regression analysis was performed to explore the risk factors of PLG. RESULTS: There was a significant difference in sex, T-Cho, HBsAg, HDL-C, LDL-C and fatty liver between the PLG-positive group and the PLG-negative group (332/163 vs 6842/4479, P = 0.003; 22/473 vs 295/11 026, P =0.013; 92/403 vs 993/10 328, P = 0.001; 47/448 vs 332/10 989, P = 0.001; 32/463 vs 381/10 940, P = 0.001; 83/412 vs 3260/8061, P = 0.001). No significant difference was found in the age, BMI, TG, blood sugar and gallstone between the two groups (47.3 ± 26 vs 45.1 ± 33, P = 0.173; 59/436 vs 1097/10 224, P = 0.102; 52/443 vs 982/10 339, P = 0.158; 17/478 vs 295/11 026, P = 0.26; 24/471 vs 395/10 926, P = 0.109). Logistic regression analysis showed that the sex, HBsAg and HDL-C were independent risk factors for the development of PLG in a descending order of HDL-C > HBsAg > sex. CONCLUSION: In healthy people, the male gender, positive HBsAg, and low HDL-C confer higher risks of PLG development.
基金Supported by the Construct Program of the Key Discipline of State Administration of Traditional Chinese Medicine of the People's Republic of China and by the Science and Technology Development Fund of the Shanghai Municipal Public Health Bureau (No. 2011Y200,2008Y127,and 2005L019A)
文摘OBJECTIVE:To compare the effects of electrical stimulation of different acupoint combinations among postoperative bedridden elderly patients on hemorheology and deep venous blood flow velocity and investigate the role of electrical stimulation against deep vein thrombosis(DVT).METHODS:From November 2010 to October 2011,a total of 160 elderly bedridden patients after major surgery were divided into the conventional care group,invigorating and promoting Qi group,blood-activating and damp-eliminating group,and acupoint-combination stimulation group.Whole blood viscosity,plasma viscosity,D-dimer levels,lower limb skin temperature,lower limb circumference,and flow velocities of the external iliac vein,femoral vein,popliteal vein,and deep calf veins in all patients were documented and compared among the four groups.RESULTS:Whole blood viscosity,plasma viscosity,D-dimer levels,and lower limb circumference were significantly reduced in the blood-activating and damp-eliminating group compared with the conventional care group(P<0.05) and were almost equal to those in the acupoint-combination stimulation group(P>0.05).Lower limb venous flow velocities were accelerated in the invigorating and promoting Qi group compared with the other groups,excluding the acupoint-combination stimulation group(P<0.05).CONCLUSION:Hemorheological indices in postoperative bedridden elderly patients were improved after combined electrical stimulation at Yinlingquan(SP 9) and Sanyinjiao(SP 6).Combined electrical stimulation at Zusanli(ST 36) and Taichong(LR 3),on the other hand,accelerated lower limb venous flow.
基金Supported by Leading Academic Discipline Project of State Administration of Traditional Chinese Medicine of China
文摘AIM: To investigate the effect of glycyrrhizic acid (GA) on carbon tetrachloride (CCl4)-induced hepatocyte apo-ptosis in rats via a p53-dependent mitochondrial path-way. METHODS: Forty-five male Sprague-Dawley rats were randomly and equally divided into three groups, the control group, the CCl4 group, and the GA treatment group. To induce liver fibrosis in this model, rats were given a subcutaneous injection of a 40% solution of CCl4 in olive oil at a dose of 0.3 mL/100 g body weight biweekly for 8 wk, while controls received the same isovolumetric dose of olive oil by hypodermic injection, with an initial double-dose injection. In the GA group,rats were also treated with a 40% solution of CCl4 plus 0.2% GA solution in double distilled water by the intraperitoneal injection of 3 mL per rat three times a week from the first week following previously published methods, with modifications. Controls were given the same isovolumetric dose of double distilled water. Liver function parameters, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were de-termined. Pathologic changes in the liver were detected by hematoxylin and eosin staining. Collagen fibers were evaluated by Sirius red staining. Hepatocyte apoptosis was investigated using the terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) assay and the cleaved caspase-3 immunohistochemistry assay. The expression levels of p53 and apoptosis-related proteins were evaluated by immunohistochemistry or Western blotting analysis. RESULTS: After 8 wk of treatment, GA significantly re-duced serum activity of ALT (from 526.7 ± 57.2 to 342 ± 44.8, P<0.05) and AST (from 640 ± 33.7 to 462.8 ± 30.6, P<0.05), attenuated the changes in liver his-topathology and reduced the staging score (from 3.53 ± 0.74 to 3.00 ± 0.76, P<0.05) in CCl4 -treated rats. GA markedly reduced the positive area of Sirius red and the ratio of the hepatic fibrotic region (from 7.87% ± 0.66% to 3.68% ± 0.32%, P<0.05) compared with the CCl4 group. GA also decreased the expression level of cleaved caspase-3 compared to the CCl4 group. TU-NEL assay indicated that GA significantly diminished the number of TUNEL-positive cells compared with the CCl4 group (P<0.05). GA treatment clearly decreased the level of p53 (P<0.05) detected by immunohis-tochemistry and Western blotting analysis. Compared with the CCl4 group, we also found that GA reduced the Bax/Bcl-2 ratio (P<0.05), the expression of cleaved caspase-3 (P<0.05), cleaved caspase-9 (P<0.05), and inhibited cytochrome C and second mitochondria-derived activator of caspases (Smac) release from mito-chondria to cytoplasm, i.e. , GA reduced the expressionlevel of Smac, which inhibited c-IAP1 activity (P<0.05), ultimately inhibiting the activity of caspase-3, according to Western blotting analysis. As a result, GA suppressed activation of the caspase cascades and prevented he-patocyte apoptosis.
基金Supported by the National Natural Science Foundation Project of China(Transcutaneous Electrical Acupoint Stimulation Prevents the Deep Vein Thrombosis:the Role of Endothelium Modulation,No.81202750)
文摘OBJECTIVE:To evaluate the effects of electric acupoint stimulation on gastrointestinal hormones and motility among geriatric postoperative patients with gastrointestinal tumors,and to explore an efficient and noninvasive method for postoperative recovery of bowel functions.METHODS:Forty patients were randomly and evenly assigned into a regular nursing care group(RNC) and an acupoint electric stimulation group(AES).Patients in the RNC group received regular nursing care and patients in the AES group received regular nursing care plus electric stimulation of acupoints.The serum levels of gastrin(GAS),motilin(MOT),and cholecystokinin(CCK),and an electrogastrogram(EGG) of all the patients were evaluated on the first,third,and fifth day after surgery.The time to first flatus after surgery and the number of patients with side effects such as abdominal pain,abdominal distention,and diarrhea were recorded.RESULTS:There were significant differences between the two groups in GAS,MOT,EGG,time to first flatus,abdominal pain,abdominal distention,and diarrhea(P < 0.05).CONCLUSION:Electric stimulation on acupoints could increase levels of GAS and MOT,promote the recovery of gastrointestinal functions,and decrease complications among postoperative senile patients with gastrointestinal tumors.
基金supported by Shanghai Health Bureau Project(Nos.20124007 and 20134120)
文摘Diabetic nephropathy(DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin(30 mg·kg^(-1) body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L^(-1) were selected for experiments. The DN rats were treated with Taxus chinensis orally(0.32, 0.64, and 1.28 g·kg^(-1)) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-β1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-β1/Smad signaling pathway.
基金supported by the National Natural Science Foundation of China(81202814)the Shanghai Municipal Commission of Health and Family Planning(20124y116)the Young Teachers Training Funding Scheme of Shanghai Colleges and Universities,China(zzszy12026)
文摘Echinacoside （ECH） is protective in a mouse model of Parkinson＇ s disease （PD） induced by 1-methyl-4- phenylpyridinium ion （MPP＋）. To investigate the mechanisms involved, SH-SYSY neuroblastoma ceils were treated with MPP＋ or a combination of MPP＋ and ECH, and the expression of ATF3 （activating transcription factor 3）, CHOP （C/EBP-homologous protein）, SCNA （synuclein alpha）, and GDNF （glial cell line-derived neurotrophic factor） was assessed. The results showed that ECH significantly improved cell survival by inhibiting the generation of MPP＋-induced reactive oxygen species （ROS）. In addition, ECH suppressed the ROS and MPP＋- induced expression of apoptotic genes （ATF3, CHOP, and SCNA）. ECH markedly decreased the MPP＋-induced cas- pase-3 activity in a dose-dependent manner. ATF3- knockdown also decreased the CHOP and cleaved caspase- 3 levels and inhibited the apoptosis induced by MPP＋. Interestingly, ECH partially restored the GDNF expression that was down-regulated by MPP＋. ECH also improved dopaminergic neuron survival during MPP＋ treatment and protected these neurons against the apoptosis induced by MPTP. Taken together, these data suggest that the ROS/ ATF3/CHOP pathway plays a critical role in mechanisms by which ECH protects against MPP＋-induced apoptosis in PD.
基金supported by the National Natural Science Foundation of China(No.81473481)Health System independent Innovation Science Foundation of Shanghai Putuo District(ptkwws201704)Shanghai Municipal Commission of Health and Family Planning(No.201840002)
文摘Resistance to cisplatin(DDP)-based chemotherapy is a major cause of treatment failure in human gastric cancer(GC). It is necessary to identify the drugs to re-sensitize GC cells to DDP. In our previous research, Zuo Jin Wan Formula(ZJW) has been proved could increase the mitochondrial apoptosis via cofilin-1 in a immortalized cell line, SGC-7901/DDP. Due to the immortalized cells may still difficult highly recapitulate the important molecular events in vivo, primary GC cells model derived from clinical patient was constructed in the present study to further evaluate the effect of ZJW and the underlying molecular mechanism. Immunofluorescent staining was used to indentify primary cultured human GC cells. Western blotting was carried out to detect the protein expression. Cell Counting Kit-8(CCK-8) was used to evaluate cell proliferation. Flow cytometry analysis was performed to assess cell apoptosis. ZJW inhibited proliferation and induced apoptosis in primary DDP-resistant GC cells. Notably, the apoptosis in GC cells was mediated by inducing cofilin-1 mitochondrial translocation, down-regulating Bcl-2 and up-regulating Bax expression. Surprisingly, the level of p-AKT protein was higher in DDP-resistant GC cells than that of the DDP-sensitive GC cells, and the activation of AKT could attenuate ZJW-induced sensitivity to DDP. These data revealed that ZJW can increase the chemosensitivity in DDP-resistant primary GC cells by inducing mitochondrial apoptosis and AKT inactivation. The combining chemotherapy with ZJW may be an effective therapeutic strategy for GC chemoresistance patients.
基金Supported by Shanghai Municipal Health and Family Planning Commission Project(No.20124108)Putuo District of Shanghai Independent Innovation Research Foundation(No.2013PTKW009)
文摘AIM：To investigate the expression of matrix metalloproteinases 1 and 3（MMP-1 and MMP-3） and their tissue inhibitors of metalloproteinases 1 and 3（ TIMP-1 and TIMP-3） in the conjunctiva of eyes with conjunctivochalasis（CCh）.METHODS：The conjunctival tissue was obtained from the CCh patients and controls,the MMPs/TIMPs expression concentration was determined by enzyme-linked immunosorbent assay（ELISA） and immunofluorescence staining.The expression levels of MMPs/TIMPs in the CCh fibroblasts were determined by analyzing its concentration in the cellular supernatant that was abstracted from the in vitro cultured CCh fibroblasts.RESULTS：MMP-1 and MMP-3 levels determined by ELISA were both significantly higher in the CCh group than that in the control group（P= 0.042,0.022,respectively）,so was the levels of TIMP-1（P= 0.010）.No significant difference in the expression of TIMP-3 in conjunctiva was found between the two groups（P= 0.298）.The expression of MMP-1 and MMP-3 were both up-regulated significantly in the CCh group（P= 0.040,0.001,respectively） on immunofluorescence staining.MMP-1 and MMP-3 expression in the fibroblasts were both significantly higher in the CCh group than that in the control group（P= 0.027,0.001,respectively）,while neither the TIMP-1 nor TIMP-3 expression was significantly different between the two groups（P= 0.421,0.237,respectively）.CONCLUSION：The overexpression of MMP-1 and MMP-3 in conjunctival tissue and fibroblasts may play an important role in the pathogenesis and development of CCh.
基金Supported by the State Administration of Traditional Chinese Medicine Key Specialty ItemsShanghai Science and Technology Committee Project:Clinical Study of Intravascular Ultrasound and Fractional Flow Reserve of Coronary Artery Critical Evaluation Guidance of Interventional Treatment(No.124119b1601)the Project of National Natural Science Foundation:the Effect of Ginkgolide B Drug Eluting Stents on Endothelialization and On P38mapk Signal(No.81303145)
文摘OBJECTIVE:To evaluated the effect of calycosin on left ventricular ejection fraction and angiogenesis.METHODS:Adult male Sprague-Dawley rats were randomly assigned into calycosin-treated groups(0.5,1,2,and 4 mg/kg qd),a dimethyl sulfoxide(DMSO),or a sham-operated control group.The myocardial ischaemia(Ml)model was intraperitoneally administered calycosin for 28 days.The survival rates and left ventricular ejection fractions(LVEF)were compared between groups.The expression levels of vascular endothelial growth factor(VEGF)and cluster of differentiation 31(CD31)in ischaemic myocardium were also measured and compared.RESULTS:The construction of MI model resulted in a LVEF reduction of 50%compared with the sham-control.After 28 days,the LVEF value was 10%higher when calycosin(4 mg/kg)was administered compared with the DMSO group.The expression of VEGF and CD31 showed a dose-dependent manner when calycosin was administrated.The calycosin-treated(4 mg/kg)group displayed a twofold increase in VEGF expression at both the mRNA and protein levels compared with the DMSO group.In addition,CD31 expression in the microvascular increased 1.5-fold in the 4 mg/kg calycosin-treated group.CONCLUSION:Calycosin improved left ventricular ejection fraction in the MI rat models,induced VEGF expression in the ischaemic myocardium,increased CD31 expression and promoted angiogenesis.
基金the Health System Innovation Project of Shanghai Putuo Science and Technology Commission(No.ptkwws202002)the Traditional Chinese Medicine Clinical Key Specialty Construction Project of Shanghai Putuo District(No.ptzyzk2101)the Clinical Specialized Discipline of Health System of Putuo District in Shanghai(No.2021tszk01).
文摘The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment(TIME).This study aimed to mechanistically assess whether Chang Wei Qing(CWQ)Decoction can enhance the anti-tumor effect of PD-1 inhibitor therapy.PD-1 inhibitor therapy showed the significant anti-tumor effect in patients with mismatch repairdeficient/microsatellite instability-high(dMMR/MSI-H)colorectal cancer(CRC),rather than those with mismatch repairproficient/microsatellite stable(pMMR/MSS)CRC.Hence,immunofluorescence double-label staining was utilized to explore the difference in the TIME between dMMR/MSI-H and pMMR/MSS CRC patients.Flow cytometry was used to analyze T-lymphocytes in tumors from mice.Western blot was used to measure the expression of PD-L1 protein in mouse tumors.The intestinal mucosal barrier of mice was evaluated by hematoxylin-eosin staining and immunohistochemistry.16S rRNA-gene sequencing was used to examine the structure of the gut microbiota in mice.Subsequently,Spearman’s correlation analysis was used to analyze the relationship between the gut microbiota and tumor-infiltrating T-lymphocytes.The results showed that dMMR/MSI-H CRC patients had more CD8+T cells and higher expression of PD-1 and PD-L1 proteins.In vivo,CWQ enhanced the anti-tumor effect of anti-PD-1 antibody and increased the infiltration of CD8+and PD-1+CD8+T cells in tumors.Additionally,the combination of CWQ with anti-PD-1 antibody resulted in lower inflammation in the intestinal mucosa than that induced by anti-PD-1 antibody alone.CWQ and anti-PD-1 antibody co-treatment upregulated PD-L1 protein and reduced the abundance of Bacteroides in the gut microbiota but increased the abundance of Akkermansia,Firmicutes,and Actinobacteria.Additionally,the proportion of infiltrated CD8+PD-1+,CD8+,and CD3+T cells were found to be positively correlated with the abundance of Akkermansia.Accordingly,CWQ may modulate the TIME by modifying the gut microbiota and consequently enhance the anti-tumor effect of PD-1 inhibitor therapy.
