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.

Condyle is a critical growth region of the mandible where mandible by endochondral ossification occurs. Condylar cartilage belongs to the secondary cartilage, which is not only affected by genetic factors but also by stress, drug intake, and other local factors. To promote the growth of the mandible, various exogenous and local factors were used to alter the biological environment of the condylar cartilage to stimulate endochondral ossification. This article reviews studies on the influence of exogenous factors on condylar growth and reconstruction. This literature review will provide a reference point for the treatment of patients with mandibular retraction.

Objective To investigate the connection between sex hormones and gender differences and cognitive func-tion in patients with schizophrenia. Methods A total of 80 eligible patients including 60 female and 20 male with schizophrenia conducted general information collection and Digit Span Task(DST) and Trial Making Test (TMT) mea-surement. The data o f the schizophrenic patients were collected and analyzed with sex hormones. Results There were significant differences between male and female schizophrenic patients in the age of first onset, course of disease,degree of education and antipsychotic treatment effects(P<0.05). The digit span-forward Task(DSF) score of female patients was higher than that of male patients, TMTA and TMTB were lower than those of male patients (P<0.05). In both male and female schizophrenic patients, E2 level was positively related to the age of first onset, and degree of education, oth-erwise,it was negatively related to the course of disease and antipsychotic treatment effects. In male patients,there was no connection between T level and the age of first onset, course of disease,degree of education and antipsychotic treat-ment effects. The estrogen level of male and female patients was positively correlated with the DSF and was negatively related to the TMTA and TMTB. The testosterone level of male patients was negatively correlated with the TMTand TMTB. Conclusion Estrogen may be related to gender differences in schizophrenia. Estrogen and testosterone have a certain correlation with cognitive function.

Objective To investigate the clinical application of laparoscopic adhesiolysis and efficacy of adhesive ileus. Methods In our hospital adhesive ileus patients from January 2011 to December 2013 were treated 100 cases, all pa-tients had abdominal surgery, all patients were divided according to the different ways laparoscopic surgery group and open surgery group, operative time, blood loss, postoperative recovery time to flatus, ambulation and hospital days were compared between two groups. Results The two groups were not significantly different except for operative time(P>0.05) outside the laparoscopic surgery group blood loss, the amount of postoperative analgesics, postoperative dis-charge time, ambulation and hospital stay were significantly less than open surgery group (P<0.05);and laparoscopic surgery and postoperative complication rate was significantly less than the obstruction again open surgery group (P<0.05). Conclusion Laparoscopic treatment of intestinal obstruction in patients with safe, effective, feasible and low recur-rence rate,worthy of promotion.

[Objective]To evaluate the role of mature cumulus cells from oocyte-cumulus complex(OCC)in in-vitro maturation(IVM)and establish a new culture technique which is convenient to carry out.[Methods]The cumulus cells of OCC were cut off and dispersed by 1 mL syringe.The cumulus cells were co-cultured with the immature oocytes retrieved from the COH cycles after they adherent to the bottom of the dish.The immature oocytes were experienced IVM procedures in different culture media.They were divided into 3 groups(the oocytes at germinal vesicle stage from one woman were allotted to the same group randomly).Group 1(solution A):basic culture medium+human follicular fluid(hFF);Group 2(solution B):solution A+ cumulus cells(OCC);Group 3(solution C):solution A+ OCC+ follicle stimulating hormone(FSH)+ epidermal growth factor (EGF).Then,the maturation rate,fertilization rate and formation rate of available embryo were observed.[Results]In 113 treatment cycles,298 immature oocytes were performed IVM with solution A,B,and C.The difference for 24 hour maturation rates among 3 groups wag statistically significant(A:45.2%,B:61.7%,C:78.2%,P＜0.05).There was no statistical difference for 25～48 hour maturation rates and normal fertilization rates of mature oocytes.The differences of cleavage rates and rescued embryo rates between group 1 and 2,group 1 and 3 were statistically significant(P＜0.05).The formation rates of available embryo showed an increasing trend from group 1,2,to 3.[Conclusion]After being dispersed by simply beat upon with syringe and adherent culture,the mature cumulus eells from mature OCCs in COH cycles,together with growth factors in the follicular fluid or extraneously supplemented,could promote the IVM of immature oocyte.