BACKGROUND:Resveratrol is a natural antioxidant extracted from plants.Its mechanism of improving exercise-induced fatigue mainly focuses on the protective effect against oxidative stress and inflammation.In this study,the protective mechanism of resveratrol on exercise-induced fatigue was mainly discussed from the perspective of gluconeogenesis. OBJECTIVE:To investigate the effect of resveratrol on gluconeogenesis in exercise-induced fatigue rats. METHODS:After 1 week of adaptive training,male Sprague-Dawley rats were randomly divided into 4 groups with 12 rats in each group:blank control group,resveratrol group,exercise group,resveratrol + exercise group.Weight-bearing swimming training was used to simulate long-term medium-high intensity exercise.After swimming with a weight of 5%for 1 hour every day,50 mg/kg resveratrol solution or the same volume of dimethyl sulfoxide solvent were given orally,6 days a week,for a total of 6 weeks.Samples were collected 24 hours after the last exercise,and the levels of urea nitrogen,creatine kinase,blood glucose,liver glycogen and lactic acid and pyruvate in liver tissue were detected by the kit.The activity of phosphoenolpyruvate carboxykinase was detected by microassay,and the activity of glucose-6-phosphatase was detected by enzyme-linked immunosorbent assay.Real-time fluorescence quantitative PCR was used to detect the gene expression of silent information regulator 1,cAMP-response element binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α. RESULTS AND CONCLUSION:In the exercise group,plasma urea nitrogen and creatine kinase levels of rats were significantly increased(both P<0.05),liver lactate and pyruvate levels and lactate/pyruvate ratio were significantly increased(all P<0.01),and blood glucose and liver glycogen contents were significantly decreased(both P<0.01).Resveratrol supplementation could effectively improve the above conditions.Exercise significantly decreased the activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase(P<0.01,P<0.05),and resveratrol supplementation significantly increased the activity of phosphoenolpyruvate carboxykinase in liver tissue(P<0.01).The mRNA expression levels of silent information regulator 1,cAMP-response element binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α in liver tissue of the exercise group were significantly decreased(all P<0.01),while resveratrol supplementation could significantly increase the gene expression levels of this pathway.To conclude,resveratrol can relieve exercise-induced fatigue caused by long-term medium-high intensity exercise,and its mechanism may be related to up-regulating the gluconeogenesis regulatory pathway,improving rate-limiting enzyme activity,promoting liver gluconeogenesis,and increasing blood glucose and liver glycogen levels.

Objective To evaluate the effects of puerarin on bone density in rats and mice through a meta-analysis. Methods The databases, including CNKI, SinoMed, Wanfang data, VIP, PubMed, EMBase, Web of Science, the Cochrane Library, and Scopus from their inception to November 6, 2023, were searched for literature on the effects of puerarin treatment on bone density in rats and mice. Inclusion criteria for the literature were randomized controlled trials with a placebo or blank control group; the subject animals were rats or mice; the intervention was puerarin; and the results included bone density measurements. Exclusion criteria included combination therapy with puerarin; lack of original research data; unpublished studies; and using mandible as the measurement site for bone density. Risks of bias were assessed using SYRCLE's RoB tool. Data analysis was conducted with Stata 16.0 and Rev Man 5.3 software. Results After applying the inclusion and exclusion criteria, a total of 429 records were identified and 42 articles covering 41 studies were ultimately included. 925 animals were involved and the data analysis results indicated that puerarin improved bone density in rats and mice compared to the control group: femur [37 studies, n=824, standardized mean difference （SMD)=2.12, 95% confidence interval (CI)=1.69-2.54, P < 0.000 1], lumbar spine (13 studies, n=271, SMD=2.25, 95% CI=1.49-3.01, P < 0.000 1), tibia (4 studies, n=95, SMD=0.94, 95% CI=0.05-1.83, P=0.04), and the whole body (4 studies, n=94, SMD=1.89, 95% CI=0.50-3.29, P=0.008), with all inter-group differences in bone density being statistically significant. Conclusion Puerarin can improve bone density in rats and mice. This study provides a valuable reference for clinical studies on the prevention and treatment of osteoporosis with puerarin.

The aim of this study was to investigate the virulence determinants and genetic diversity of foodborne Yersinia enterocolitica from Wenzhou.A total of 71 strains of Yersinia enterocolitica were isolated from food and foodborne diarrhea ca-ses in Wenzhou,and their biotypes,serotypes,and drug resistance were analyzed.On the basis of whole genome sequencing,we assessed virulence gene profiles,and performed multilocus sequence typing(MLST)and core gene multilocus sequence typ-ing(cgMLST).A total of 94.4％(67/71)of isolates belonged to biotype 1A,and the highest proportion had serotype lA/O∶5(29.6％,21/71).The sensitivity rates of the isolates to 14 antibiotics exceeded 95.8％.A total of 16 categories and 126 viru-lence genes were identified,with two strains carrying the pYV plasmid and chromosome-related virulence genes.ST3(31.6％,12/38)was the most widespread MLST type,and cgMLST analysis revealed no dense clusters of genotypes except for strains sharing the same ST.In conclusion,pathogenic strains were identified from foodborne Yersinia enterocolitica in Wenzhou and were found to exhibit high genetic polymorphism.Enhanced regulatory supervision is essential to prevent the outbreak of food-borne diseases caused by Yersinia enterocolitica.

Objective To study the bioequivalence and safety of two olmesartan medoxomil and hydrochlorothiazide tablets in Chinese healthy subjects.Methods A total of 24 healthy subjects underwent fasting and postprandial tests in a single-center,randomized,open-label,single-dose,two-formulation,two-sequence,two-period,self-cross-over controlled design.The subjects were administered a single oral dose of the test formulation and reference formulation(each containingolmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg)in a random cross-over fashion.The plasma concentrations of olmesartan and hydrochlorothiazide were determined by LC-MS/MS.The non-compartmental model analysis of olmesartan and hydrochlorothiazide was conducted using WinNonlin 7.0 software to calculate pharmacokinetic parameters and assess bioequivalence.Results In the fasting test,the pharmacokinetic parameters of olmesartan of test and reference were as follows:Cmax were(798.35±206.78)and(664.52±168.25)ng·mL-1,AUC0-t were(4 430.71±1 294.87)and(3 976.67±1 083.54)h·ng·mL-1,AUC0-∞ were(4 551.67±1 303.06)and(4 090.37±1 103.97)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(92.39±35.96)and(96.15±38.76)ng·mL-1,AUC0_t were(548.69±217.11)and(564.41±208.68)h·ng·mL-1,AUC0-∞ were(603.04±228.59)and(619.26±223.27)h·ng·mL-1.In the fed test,the pharmacokinetic parameters of olmesartan of T and R were as follows:Cmax were(583.15±149.48)and(550.57±104.76)ng·mL-1,AUC0-t were(3 585.18±952.72)and(3 292.19±904.58)h·ng·mL-1,AUC0-∞ were(3 696.05±996.55)and(3 396.30±923.41)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(70.30±17.88)and(74.70±21.65)ng·mL-1,AUC0-t were(476.60±119.39)and(492.91±144.81)h·ng·mL-1,AUC0-∞ were(523.37±132.67)and(535.81±151.92)h·ng·mL-1.In fasting and fed condition,the 90％confidence interval(90％CI)of Cmax,AUC0-t and AUC0-∞ of olmesartan and hydrochlorothiazide were in 80.00％-125.00％.Conclusion The two olmesartan medoxomil and hydrochlorothiazide tablets were bioequivalent under fasting and fed conditions,and good security.

Objective:To assess the accuracy of two-dimensional (2D) photographs in measuring esthetic parameters of the maxillary anterior teeth by comparing them with measurements obtained from three-dimensional (3D) dental models.Methods:A total of one hundred volunteers (49 males, 51 females, aged 18-23 years) were recruited from School and Hospital of Stomatology, Wuhan University from January to February 2024. 3D digital models of their dentitions were obtained using an intraoral scanner, and standardized frontal 2D intraoral photographs were captured with a digital camera. The lengths, widths and width/length ratio of the bilateral incisors, lateral incisors and canines were measured on both the 3D digital models and the 2D intraoral photographs. The width ratios of adjacent maxillary anterior were also calculated on the 2D intraoral photographs and the frontal view of 3D digital models.Results:The widths of lateral incisors [(5.85±0.60) mm] and canines [(4.73±0.71) mm] and the lengths of canines [(8.72±0.96) mm] in the 2D intraoral photographs were significantly lower than those in 3D digital models [(6.65±0.59), (7.76±0.60), (8.90±0.86) mm] ( t=-18.24, P<0.001; t=-54.43, P<0.001; t=-4.40, P<0.001), while there were no significant differences in the lengths and widths of the other teeth ( P>0.05). The width/length ratios measured from the 2D intraoral photographs for the lateral incisors and canines (0.74±0.08, 0.55±0.08) were significantly lower than those measured in the 3D digital models (0.84±0.09, 0.88±0.09) ( t=-19.68, P<0.001; t=-50.21, P<0.001), and the width/length ratio of the central incisors showed no significant difference between the two groups ( P>0.05). The width ratios of canines/lateral incisors and lateral incisors/central incisors measured on the 2D intraoral photographs (0.72±0.06, 0.85±0.11) were significantly smaller than those measured in the frontal view of 3D digital models (0.75±0.06, 0.89±0.11) ( t=-9.31, P<0.001; t=-6.58, P<0.001). Conclusions:There is a difference between 2D and 3D measurement results of teeth in the esthetic area and the magnitude of the difference varies with their position in the dental arch. When analyzing the measurement of the anterior teeth, it is necessary to choose the appropriate method according to the target tooth position.

Objective:To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities.Methods:This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results:A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged ( M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95% CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95% CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion:The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.

AIM To study the chemical constituents from the branches and leaves of Toona ciliata Roem.var.pubescens(Franch.)Hand-Mazz.and their antitumor activities.METHODS The compounds were isolated and purified by silica gel,RP-18 reverse phase silica gel and semi-preparative HPLC,the structures of compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT method.RESULTS Fifteen compounds were isolated and identified as toonaolide D(1),toonaciliatin E(2),bourjotinolone A(3),(21R,23R)-epoxy-21α-ethoxy-24S,25-dihydroxyapotirucalla-7-en-3-one(4),(Z)-toonasterone C(5),(E)-toonasterone(6),3-epi-dyscusin C(7),(Z)-aglawone(8),(E)-volkendousin(9),8(14),15-isopimaradiene-2α,3α,19-triol(10),(-)-loliolide(11),cyclohexenone(12),pubinernoid A(13),quercetin-3-O-(4″-methoxy)-α-L-rahmnopyranosyl(14),5-hydroxymethyl-2-furancarboxaldehyde(15).The IC50 values of compounds 3 and 4 on K562 cells were 54.2 and 47.3 μmol/L,respectively,and the IC50 values on HEL cells were 47.3 and 61.1 μmol/L,respectively.CONCLUTION Compounds 4,7,10 and 11 are isolated from Toona genus for the first time,and compounds 2,15 are first isolated from this plant.Compounds 3 and 4 show weak antitumor activities.

Objective To construct a prognostic model for liver hepatocellular carcinoma(LIHC)based on immune-related genes.Methods LIHC and normal tissue samples were downloaded from the UCSC Xena database and The Cancer Genome Atlas(TCGA)database.Differential analysis was performed on the gene data of LIHC samples and adjacent/normal samples.Enrichment analysis was conducted on differentially expressed genes.Kaplan-Meier survival analysis was performed on liver cancer samples from the TCGA cohort to obtain survival-and immune-related differentially expressed genes.LASSO Cox and multivariate Cox regression analysis were used to identify hub genes and construct a gene risk prognostic model.Data from a high-throughput gene expression(GEO)database was obtained for external validation.The sensitivity of hub genes to common anticancer drugs was investigated using the CellMiner database.Results Enrichment analysis result indicated that differentially expressed genes were mainly associated with metabolic pathways.Through differential analysis and Kaplan-Meier survival analysis,25 survival-and immune-related differentially expressed genes were obtained.Based on the result of LASSO Cox and multivariate Cox regression analysis,five hub genes(FYN,CSF3R,HLA-G,FOS,BIRC5)were identified and a nomogram was constructed.The concordance index(C-index)value for the training cohort and validation cohort were 0.739 and 0.625,respectively.Based on the sensitivity of hub genes to anticancer drugs,12 types of anticancer drugs were selected for subsequent experiments.Conclusion This model can effectively predict the prognosis of LIHC patients and provide a new insights for immune therapy in LIHC.

Objective To evaluate the application value of the Global Leadership Initiative on Malnutri-tion(GLIM)criteria in the patients with gastric cancer radical surgery,and to explore the relationship be-tween the malnutrition defined by GLIM criteria and the prognosis of the patients with gastric cancer radical surgery.Methods A total of 150 gastric cancer patients receiving radical surgical resection in Zhejiang Provin-cial Tongde Hospital from January 2014 to December 2017 were selected as the study subjects.All the study subjects were diagnosed as malnutrition and graded by the severity of malnutrition.The effect of malnutrition defined by GLIM criteria on the prognosis of the patients with gastric cancer radical surgery was evaluated by the Kaplan Meier survival curve and Cox regression analysis.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of GLIM criteria on the postoperative survival rate of the pa-tients with gastric cancer radical surgery,and the corresponding area under the curve(AUC)was calculated,and the predictive value of inflammatory indicator C-reactive protein(CRP)addition on GLIM criteria in pre-dicting the prognosis of the patients with gastric cancer radical surgery was evaluated.Results Malnutrition diagnosed by GLIM criteria was an independent risk factor affecting the postoperative survival rate of the pa-tients with gastric cancer radical surgery.The results of survival trend analysis of various indicators in GLIM criteria showed that involuntary weight reduction(moderate malnutrition HR=14.13,95％CI:1.70-117.39,severe malnutrition HR=12.50,95％CI:1.40-111.89)and CRP＞10 mg/L(HR=9.70,95％CI:2.31-40.67)were the most important factors affecting the survival rate of the patients with gastric cancer radical surgery.In addition,the addition of inflammatory marker CRP could increase the sensitivity and speci-ficity of the GLIM model in predicting the postoperative survival rate of the patients with gastric cancer radical sur-gery.Conclusion The GLIM criteria can not only reflect the nutritional status of the patients with gastric cancer radi-cal surgery,but also serve as an effective predictive tool for predicting the survival rate after radical surgery.The addition of inflammatory marker CRP increases the sensitivity and specificity of GLIM criteria in predicting postoperative survival rate.

Objective:To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities.Methods:This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results:A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged ( M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95% CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95% CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion:The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.