Objective:To investigate the association between the triglyceride-glucose(TyG)index and the incidence and mortality of cardiovascular disease(CVD)in a large population-based cohort.Methods:Participants aged 40-79 years without a history of CVD at baseline were drawn from the CHi-nese Electronic health Records Research in Yinzhou(CHERRY)study between January 1,2010,and May 31,2020.The TyG index was calculated using baseline triglyceride and fasting blood glucose.Cox proportional hazards models were used to assess the association between the TyG index and the composite outcome of CVD(incidence and mortality),adjusting for age,gender,education,region,smoking sta-tus,body mass index,systolic blood pressure,and total cholesterol.Hazard ratios(HR)and 95％confi-dence intervals(CI)were calculated.Nonlinear associations between the TyG index and CVD were fur-ther evaluated using restricted cubic splines,and subgroup analyses by gender and age were conducted to explore potential differences.Results:A total of 226 406 individuals were included,with a mean age of(55.0±9.7)years at baseline,46.8％of whom were men,and a median TyG index of 8.68.Over a median follow-up of 7.99 years,9 815(4.34％)participants experienced CVD incidence or mortality.After adjusting for age,gender,education,region,smoking status,body mass index,systolic blood pressure and total cholesterol,the risk of CVD increased with higher TyG index levels(P＜0.001).The risk in the highest TyG quartile(TyG＞9.10)was 42％higher than in the lowest quartile(TyG ≤8.32)(HR=1.42,95％CI:1.34-1.51).Individuals under 60 years had a higher HR for CVD compared with those aged 60 years and above(HR:1.71 vs.1.27,P＜0.05).Restricted cubic spline analysis revealed a reverse L-shaped association between the TyG index and CVD risk in the overall population(P＜0.001 for nonlinear trend),with risk increasing after the TyG index exceeded 8.67.However,the threshold varied by gender,with a lower threshold in women(8.51)than in men(8.67).Conclusion:A significant nonlinear relationship was revealed between the TyG index and CVD risk,with a threshold effect.The risk of CVD increased once the TyG index surpassed a certain threshold,with a lower threshold in women than in men.These findings suggest that cardiovascular risk prediction and interven-tions based on the TyG index should be gender-stratified,and early intervention for individuals under 60 years old might have important public health implications.

Objective:To investigate the association between the triglyceride-glucose(TyG)index and the incidence and mortality of cardiovascular disease(CVD)in a large population-based cohort.Methods:Participants aged 40-79 years without a history of CVD at baseline were drawn from the CHi-nese Electronic health Records Research in Yinzhou(CHERRY)study between January 1,2010,and May 31,2020.The TyG index was calculated using baseline triglyceride and fasting blood glucose.Cox proportional hazards models were used to assess the association between the TyG index and the composite outcome of CVD(incidence and mortality),adjusting for age,gender,education,region,smoking sta-tus,body mass index,systolic blood pressure,and total cholesterol.Hazard ratios(HR)and 95％confi-dence intervals(CI)were calculated.Nonlinear associations between the TyG index and CVD were fur-ther evaluated using restricted cubic splines,and subgroup analyses by gender and age were conducted to explore potential differences.Results:A total of 226 406 individuals were included,with a mean age of(55.0±9.7)years at baseline,46.8％of whom were men,and a median TyG index of 8.68.Over a median follow-up of 7.99 years,9 815(4.34％)participants experienced CVD incidence or mortality.After adjusting for age,gender,education,region,smoking status,body mass index,systolic blood pressure and total cholesterol,the risk of CVD increased with higher TyG index levels(P＜0.001).The risk in the highest TyG quartile(TyG＞9.10)was 42％higher than in the lowest quartile(TyG ≤8.32)(HR=1.42,95％CI:1.34-1.51).Individuals under 60 years had a higher HR for CVD compared with those aged 60 years and above(HR:1.71 vs.1.27,P＜0.05).Restricted cubic spline analysis revealed a reverse L-shaped association between the TyG index and CVD risk in the overall population(P＜0.001 for nonlinear trend),with risk increasing after the TyG index exceeded 8.67.However,the threshold varied by gender,with a lower threshold in women(8.51)than in men(8.67).Conclusion:A significant nonlinear relationship was revealed between the TyG index and CVD risk,with a threshold effect.The risk of CVD increased once the TyG index surpassed a certain threshold,with a lower threshold in women than in men.These findings suggest that cardiovascular risk prediction and interven-tions based on the TyG index should be gender-stratified,and early intervention for individuals under 60 years old might have important public health implications.

Objective:To evaluate the health benefits and intervention efficiency of different strategies of initiating antihypertensive therapy for the primary prevention of cardiovascular diseases in a community-based Chinese population from the Chinese electronic health records research in Yinzhou(CHERRY)study.Methods:A decision-analytic Markov model was used to simulate and compare different antihy-pertensive initiation strategies,including:Strategy 1,initiation of antihypertensive therapy for Chinese adults with systolic blood pressure(SBP)≥140 mmHg(2020 Chinese guideline on the primary preven-tion of cardiovascular diseases);Strategy 2,initiation of antihypertensive therapy for Chinese adults with SBP≥130 mmHg;Strategy 3,initiation of antihypertensive therapy for Chinese adults with SBP ≥140 mmHg,or with SBP between 130 and 140 mmHg and at high risk of cardiovascular diseases(2017 American College of Cardiology/American Heart Association guideline for the prevention,detection,evaluation,and management of high blood pressure in adults);Strategy 4,initiation of antihypertensive therapy for Chinese adults with SBP≥ 160 mmHg,or with SBP between 140 and 160 mmHg and at high risk of car-diovascular diseases(2019 United Kingdom National Institute for Health and Care Excellence guideline for the hypertension in adults:Diagnosis and management).The high 10-year cardiovascular risk was de-fined as the predicted risk over 10％based on the 2019 World Health Organization cardiovascular disease risk charts.Different strategies were simulated by the Markov model for ten years(cycles),with parame-ters mainly from the CHERRY study or published literature.After ten cycles of simulation,the numbers of quality-adjusted life years(QALY),cardiovascular events and all-cause deaths were calculated to evaluate the health benefits of each strategy,and the numbers needed to treat(NNT)for each cardiovas-cular event or all-cause death could be prevented were calculated to assess the intervention efficiency.One-way sensitivity analysis on the uncertainty of incidence rates of cardiovascular disease and probabilis-tic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.Results:A to-tal of 213 987 Chinese adults aged 35-79 years without cardiovascular diseases were included.Com-pared with strategy 1,the number of cardiovascular events that could be prevented in strategy 2 increased by 666(95％UI:334-975),while the NNT per cardiovascular event prevented increased by 10(95％UI:7-20).In contrast to strategy 1,the number of cardiovascular events that could be prevented in strategy 3 increased by 388(95％UI:194-569),and the NNT per cardiovascular event prevented decreased by 6(95％UI:4-12),suggesting that strategy 3 had better health benefits and intervention efficiency.Compared to strategy 1,although the number of cardiovascular events that could be prevented decreased by 193(95％UI:98-281)in strategy 4,the NNT per cardiovascular event prevented decreased by 18(95％UI:13-37)with better efficiency.The results were consistent in the sensitivity analyses.Conclusion:When initiating antihypertensive therapy in an economically developed area of China,the strategy combined with cardiovascular risk assessment is more efficient than those purely based on the SBP threshold.The cardiovascular risk assessment strategy with different SBP thresholds is suggested to balance health benefits and intervention efficiency in diverse populations.

Objective This study aimed to investigate the effects of silencing Ras homolog family member C(RhoC)on the proliferation,apoptosis,invasion,migration,and epithelial-mesenchymal transition(EMT)of salivary adenoid cystic carcinoma(SACC)and its molecular mechanisms.Methods A total of 27 SACC lesions and normal salivary gland tissues that were surgically resected at Qingdao Municipal Hospital from January 1,2019 to March 1,2024 were selected,and the expression levels of RhoC were detected by Western blot and immunohistochemistry.Three small interfering RNA(siRNAs)were designed to target the RhoC gene sequence,transfected into SACC-LM and SACC-83 cell lines,and evaluated for transfection efficiency.The protein expression levels of RhoC,Rho-asso-ciated protein kinase-1(ROCK1),p38 mitogen-activated protein kinase(p38MAPK),phosphorylated-p38MAPK(p-p38MAPK),twist family bHLH transcription factor 1(TWIST1),E-cadherin,N-cadherin,and Vimentin were com-pared using Western blot.CCK-8 assay,flow cytometry,transwell invasion assay,and wound healing assay were conducted to assess the differences in cell proliferation,apoptosis,invasion,and migration abilities among the groups.Bioinformatics methods were also used to predict possible upstream micro RNAs(miRNAs)of RhoC and their expression levels in SACC.Moreover,dual-luciferase reporter gene experiments were performed to verify the binding sites of miR-138-5p and RhoC.Results RhoC was highly expressed in SACC(P＜0.05).After silencing RhoC,the test group showed a significant decrease in the expression level of ROCK1,p-p38MAPK,TWIST1,N-cadherin,and Vimentin,as well as a significant increase in the expression level of E-cadherin(P＜0.05).No signifi-cant difference in the expression level of p38MAPK was observed(P＞0.05).The cell proliferation,invasion,and mi-gration ability decreased in the test group,whereas the apoptosis rates significantly increased(P＜0.05).miR-138-5p was lowly expressed in SACC,and miR-138-5p mimic can significantly downregulated the luciferase activity of 293T cells after transfection with a RhoC wild-type plasmid(P＜0.05).Conclusion RhoC is highly expressed in SACC,and RhoC silencing may target the downstream ROCK1/p38MAPK/TWISTl signaling pathway,thereby in-hibiting the proliferation,invasion,migration,and EMT of SACC while promoting its apoptosis.On the contrary,miR-138-5p is lowly expressed in SACC and is a potential upstream gene of RhoC,and there may be binding sites between the two genes.

Objective:To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants.Methods:This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1 st, 2015 to December 31 st, 2021 of the Seventh Medical Center of the People′s Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children′s Hospital from January 1 st, 2020 to December 31 st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks′ corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model′s discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results:A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95% CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions:A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)is one of the most common clinical critical illnesses in ICU.The basic pathological features of this disease are uncontrolled inflammation, destruction of the alveolar-capillary barrier and diffuse alveolar and interstitial edema.In severe cases, patients may develop significant pulmonary fibrosis.Based on the pathological changes, repairing damaged alveolar-capillary membrane and reducing fibrosis seem to be the key to the treatments of ALI/ARDS.Vascular endothelial growth factor(VEGF) is known to be the main regulator of endothelial cell proliferation and differentiation.Previous studies have suggested that VEGF plays an important role in the inflammatory reactions and pathological manifestations of ALI/ARDS, but the results are complex.This review mainly focused on the expression changes of VEGF in ALI/ ARDS and the effects and mechanisms of regulating VEGF signaling.

Peritoneal dialysis is the most common form of renal replacement therapy in neonates.Due to its technical simplicity and compliance with neonatal physiological characteristics, peritoneal dialysis, especially acute peritoneal dialysis(APD), has been paid increasing attention in clinical practice in recent years.APD in neonates can be effective in treating critical diseases such as renal failure and metabolic disturbances.Despite the increasingly extensive application of APD, existing clinical practice shows a relatively high rate of complications and mortality in APD neonates.In this article, the application, prognosis and related factors of APD in neonates were reviewed.

Objective:To evaluate the cryopreservation effect of the home-made Strawtop micro-carrier method and Straw method for cryopreservation of human low volume sperm.Methods:A prospective study was performed to analyze the post-thaw results of cryopreserved human sperm using the home-made Strawtop method and Straw method. Compare the survival rate, sperm DNA fragmentation index (DFI), ultrastructure, fertilization ability and embryo developmental competence of donated semen samples from the patients who underwent intracytoplasmic sperm injection (ICSI) treatment in Center for Reproductive Medicine, Shanghai East Hospital, Tongji University School of Medicine during the period from May 1, 2018 to June 30, 2018.Results:The survival rate of Strawtop group (46.8%±17.1%) was significantly higher than that of Straw group (23.1%±13.7%, P=0.001). Compared with fresh sperm (18.9%±11.6%), Straw method (33.5%±15.0%) significantly increased the sperm DFI ( P=0.019), while Strawtop method didn't (23.4%±11.7%, P=0.375). The sperm ultrastructure of Strawtop group was superior to that of Straw group. There was no difference among Strawtop, Straw and fresh group in normal fertilization rates, cleavage rates and day 2 high-quality embryo rates. Conclusion:For human low volume sperm cryopreservation, the Strawtop method was simple and convenient. The survival rate of Strawtop method was higher than that of straw method and the sperm could be used for ICSI directly after thawing. The strawtop method is worth to be widely used in clinical practice.

Objective:To evaluate the cryopreservation effect of the home-made Strawtop micro-carrier method and Straw method for cryopreservation of human low volume sperm.Methods:A prospective study was performed to analyze the post-thaw results of cryopreserved human sperm using the home-made Strawtop method and Straw method. Compare the survival rate, sperm DNA fragmentation index (DFI), ultrastructure, fertilization ability and embryo developmental competence of donated semen samples from the patients who underwent intracytoplasmic sperm injection (ICSI) treatment in Center for Reproductive Medicine, Shanghai East Hospital, Tongji University School of Medicine during the period from May 1, 2018 to June 30, 2018.Results:The survival rate of Strawtop group (46.8%±17.1%) was significantly higher than that of Straw group (23.1%±13.7%, P=0.001). Compared with fresh sperm (18.9%±11.6%), Straw method (33.5%±15.0%) significantly increased the sperm DFI ( P=0.019), while Strawtop method didn't (23.4%±11.7%, P=0.375). The sperm ultrastructure of Strawtop group was superior to that of Straw group. There was no difference among Strawtop, Straw and fresh group in normal fertilization rates, cleavage rates and day 2 high-quality embryo rates. Conclusion:For human low volume sperm cryopreservation, the Strawtop method was simple and convenient. The survival rate of Strawtop method was higher than that of straw method and the sperm could be used for ICSI directly after thawing. The strawtop method is worth to be widely used in clinical practice.