OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MR-Egger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81～0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01～1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03～1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02～0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

This study analyzed the genetic evolutionary characteristics of sandflies and their effects on the spread of kala-azar in various environments in endemic provinces in China,to provide a scientific basis for kala-azar disease prevention and control.Sand-flies were collected in kala-azar endemic areas such as southern Xinjiang,the large hilly areas of southern Gansu,the northern Sich-uan and Taihang Mountains,and surrounding small hills.The cytochrome c oxidase subunit I and cytochrome b gene fragments of mito-chondrial DNA were amplified to identify sandfly species.The COI and Cytb gene sequences of sandflies from southern Xinjiang and Si-chuan recorded in NCBI were also collected.The intraspecific and interspecific genetic differences of sandflies were calculated in MEGA11.0,and a phylogenetic tree was constructed through the neighbor-joining method,for analysis of the genetic and evolutionary characteristics of sandfly populations and their effects on disease transmission.A total of 155 sandflies were collected from nine sam-pling sites in seven provinces of China;the species included Phlebotomus chinensis,Phlebotomus wui,and Sergentomyia squamirostris.Five sandfly species belonging to two genera were collected:P.chinensis,P.wui,and Phlebotomus alexandri in the genus Phleboto-mus,and S.squamirostris in the genus Sergentomyia.Genetic evolution analysis based on COI and Cytb gene sequences indicated intra-specific genetic distances of 0-0.062 and 0-0.056,respectively,and interspecific genetic distances of 0.126-0.176 and 0.110-0.171,respectively.The phylogenetic tree indicated that P.wui,P.alexandri,Phlebotomus longiductus,and S.squamirostris clus-tered into one branch.The sequences of P.chinensis in the large and small hilly areas clustered into two geographical clades.In the small hilly areas,the sequences of P.chinensis aggregates showed small genetic differences,the pathogen infection was consistent,and the cases showed an epidemic spread trend.Large genetic differences at the molecular level were observed among sandflies in dif-ferent ecological regions,thus indicating key effects on leishmaniasis transmission.On the basis of these findings,prevention and con-trol strategies should be adapted to local conditions,and precise and effective prevention and control measures should be formulated according to the genetic evolution characteristics of sandflies in different regions,to better control the transmission of Kala-azar.

Objective:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MR-Egger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81～0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01～1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03～1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02～0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

This study analyzed the genetic evolutionary characteristics of sandflies and their effects on the spread of kala-azar in various environments in endemic provinces in China,to provide a scientific basis for kala-azar disease prevention and control.Sand-flies were collected in kala-azar endemic areas such as southern Xinjiang,the large hilly areas of southern Gansu,the northern Sich-uan and Taihang Mountains,and surrounding small hills.The cytochrome c oxidase subunit I and cytochrome b gene fragments of mito-chondrial DNA were amplified to identify sandfly species.The COI and Cytb gene sequences of sandflies from southern Xinjiang and Si-chuan recorded in NCBI were also collected.The intraspecific and interspecific genetic differences of sandflies were calculated in MEGA11.0,and a phylogenetic tree was constructed through the neighbor-joining method,for analysis of the genetic and evolutionary characteristics of sandfly populations and their effects on disease transmission.A total of 155 sandflies were collected from nine sam-pling sites in seven provinces of China;the species included Phlebotomus chinensis,Phlebotomus wui,and Sergentomyia squamirostris.Five sandfly species belonging to two genera were collected:P.chinensis,P.wui,and Phlebotomus alexandri in the genus Phleboto-mus,and S.squamirostris in the genus Sergentomyia.Genetic evolution analysis based on COI and Cytb gene sequences indicated intra-specific genetic distances of 0-0.062 and 0-0.056,respectively,and interspecific genetic distances of 0.126-0.176 and 0.110-0.171,respectively.The phylogenetic tree indicated that P.wui,P.alexandri,Phlebotomus longiductus,and S.squamirostris clus-tered into one branch.The sequences of P.chinensis in the large and small hilly areas clustered into two geographical clades.In the small hilly areas,the sequences of P.chinensis aggregates showed small genetic differences,the pathogen infection was consistent,and the cases showed an epidemic spread trend.Large genetic differences at the molecular level were observed among sandflies in dif-ferent ecological regions,thus indicating key effects on leishmaniasis transmission.On the basis of these findings,prevention and con-trol strategies should be adapted to local conditions,and precise and effective prevention and control measures should be formulated according to the genetic evolution characteristics of sandflies in different regions,to better control the transmission of Kala-azar.

Objective To explore the current status of traditional Chinese medicine(TCM)research on alopecia areata(AA)and arogenetic alopecia(AGA),analyzing the clinical syndrome and treatment characteristics,and providing reference for TCM clinical diagnosis and treatment.Methods Search for research literature on traditional Chinese medicine treatment of hair loss in CNKI,Wanfang,and VIP separately.Removing duplicates through Notexpress and using CiteSpace and VOSviewer software for bibliometric analysis.Furthermore,focusing on the RCT research of traditional Chinese medicine internal treatment for AA and AGA,the data mining methods were used to analyze the pathogenesis,treatment methods,and prescriptions of traditional Chinese medicine.Results There are a total of 2954 literature on the treatment of hair loss by traditional Chinese medicine,with clinical research being the main research type.Among them,the main pathogenesis of AA is liver and kidney deficiency,qi and blood deficiency,etc.Commonly used herbs includes Polygonum multiflorum,Rehmannia glutinosa,Chuanxiong,Poria cocos,and Ligustrum lucidum,while the pathogenesis of AGA is mainly dampness heat accumulation,yin deficiency dampness heat,etc.,with commonly used herbs such as Platycladus orientalis,Alisma orientalis,Poria cocos,hawthorn,and Coix seed.Meanwhile,AA and AGA both pay more attention to the use of tonifying drugs in their treatment.Conclusion There is a growing trend in literature on the treatment of hair loss with TCM,and there are differences in the pathogenesis and treatment methods between AA and AGA in traditional Chinese medicine.It is worth further reference in the prescription and medication of clinical treatment of hair loss.

Objective:To understand the serotype distribution, drug resistance and molecular characterization of invasive non-typhoid Salmonella (iNTS) in Guangdong Province from 2018 to 2022 and provide scientific evidence for the prevention and treatment of blood flow infection caused by Salmonella. Methods:Serological identification, antimicrobial susceptibility testing, multilocus sequence typing (MLST), and whole genome sequencing were performed on Salmonella isolated from blood and stool samples in Guangdong from 2018 to 2022. Simultaneously, annotated the sequencing results for drug resistance genes and virulence factors by a microbial gene annotation system. Results:The 136 iNTS strains were divided into 25 serotypes, and Salmonella enteritidis accounted for 38.24% (52/136). The OR of other iNTS serotypes were calculated with Salmonella typhimurium as the control. The OR values of Oreninburg, Rysson, and Pomona serotypes were the highest, which were 423.50, 352.92, and 211.75, respectively. The drug resistance rate of iNTS was 0.74%-66.91%, which was lower than that of non-iNTS (3.90%-77.21%). The main iNTS of drug resistance were ampicillin and tetracycline, with resistance rates of 66.91% (91/136) and 50.00% (68/136), respectively, while the resistance rates to ciprofloxacin (5.88%,8/136), ceftazidime (5.88%,8/136), gentamicin (5.13%,7/136) and cefoxitin (0.74%, 1/136) were relatively low. iNTS carried a variety of drug-resistance genes and virulence factors, but no standard virulence factor distribution has been found. MLST cluster analysis showed that iNTS was divided into 26 sequence types, and ST11 accounted for 38.24% (52/136). Conclusions:The iNTS strains in Guangdong were dominated by Salmonella enteritidis, of which three serotypes, Oreninburg, Rison, and Pomona, may be associated with a higher risk of invasive infection during 2018 to 2022 . iNTS was sensitive to clinical first-line therapeutic drugs (cephalosporins and fluoroquinolones), with highly diverse sequences and clear phylogenetic branches. ST11 was the local dominant clone group.