ObjectiveThis study aims to investigate the effects of Linggui Zhugantang （LGZGT） on ventricular remodeling （VR） in mice with myocardial infarction （MI） and its impact on the Ras homologgene A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway. MethodsThe MI model of mice was established by ligating the left anterior descending coronary artery （LAD）. They were divided into the sham-operated group， the model group， the low-dose， medium-dose， and high-dose groups of LGZGT （2.34， 4.68， 9.36 g·kg^-1）， and the captopril group （3.25 mg·kg^-1）， with 10 mice in each group. After four weeks of continuous drug administration by gavage， the level of cardiac function in each group of mice was examined using small animal Doppler ultrasound. Hematoxylin-eosin （HE） staining and Masson staining was used to assess the morphological changes of myocardial tissue and calculate the rate of collagen fiber deposition in mouse myocardial tissue. Wheat germ agglutinin （WGA） staining was employed to compare the cross-sectional area of cardiomyocytes in each group of mice. The expression levels of α-smooth muscle actin （α-SMA）， matrix metalloproteinase-2 （MMP-2）， type Ⅰcollagen （Col Ⅰ）， Col Ⅲ， tissue inhibitor of metalloproteinase 1（TIMP1）， B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， Bcl-2， Caspase-3， and cleaved Caspase-3 were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to evaluate the mRNA levels of the pathway-related genes RhoA， ROCK1， and ROCK2. The protein expression levels of RhoA， ROCK1， and ROCK2 were tested by Western blot. ResultsThe level of cardiac function was markedly declined in the model group compared to the sham-operated group（P<0.01）. Myocardial tissue morphology changed significantly. The cross-sectional area of cardiomyocytes was significantly enlarged. The expression of α-SMA， MMP-2， Col Ⅰ， and Col Ⅲ was significantly upregulated（P<0.01）， and TIMP1 protein expression was significantly reduced（P<0.01）. The expressions of apoptosis-related proteins Bax were significantly up-regulated（P<0.01）， while the expression of Bcl-2 protein was significantly decreased（P<0.01）. The mRNA expression of RhoA， ROCK1， and ROCK2 were significantly upregulated （P<0.01）. Compared to the model group， the low-dose， medium-dose， and high-dose groups of LGZGT and the captopril group significantly reversed the experimental results of the model group in a dose-dependent manner （P<0.05， P<0.01）. ConclusionLGZGT significantly attenuated myocardial fibrosis， myocardial hypertrophy， and cardiomyocyte apoptosis after MI in mice and effectively reversed VR， the mechanism of which may be related to the modulation of the RhoA/ROCK signaling pathway.

ObjectiveThis study aims to investigate the effects of Linggui Zhugantang （LGZGT） on ventricular remodeling （VR） in mice with myocardial infarction （MI） and its impact on the Ras homologgene A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway. MethodsThe MI model of mice was established by ligating the left anterior descending coronary artery （LAD）. They were divided into the sham-operated group， the model group， the low-dose， medium-dose， and high-dose groups of LGZGT （2.34， 4.68， 9.36 g·kg^-1）， and the captopril group （3.25 mg·kg^-1）， with 10 mice in each group. After four weeks of continuous drug administration by gavage， the level of cardiac function in each group of mice was examined using small animal Doppler ultrasound. Hematoxylin-eosin （HE） staining and Masson staining was used to assess the morphological changes of myocardial tissue and calculate the rate of collagen fiber deposition in mouse myocardial tissue. Wheat germ agglutinin （WGA） staining was employed to compare the cross-sectional area of cardiomyocytes in each group of mice. The expression levels of α-smooth muscle actin （α-SMA）， matrix metalloproteinase-2 （MMP-2）， type Ⅰcollagen （Col Ⅰ）， Col Ⅲ， tissue inhibitor of metalloproteinase 1（TIMP1）， B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， Bcl-2， Caspase-3， and cleaved Caspase-3 were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to evaluate the mRNA levels of the pathway-related genes RhoA， ROCK1， and ROCK2. The protein expression levels of RhoA， ROCK1， and ROCK2 were tested by Western blot. ResultsThe level of cardiac function was markedly declined in the model group compared to the sham-operated group（P<0.01）. Myocardial tissue morphology changed significantly. The cross-sectional area of cardiomyocytes was significantly enlarged. The expression of α-SMA， MMP-2， Col Ⅰ， and Col Ⅲ was significantly upregulated（P<0.01）， and TIMP1 protein expression was significantly reduced（P<0.01）. The expressions of apoptosis-related proteins Bax were significantly up-regulated（P<0.01）， while the expression of Bcl-2 protein was significantly decreased（P<0.01）. The mRNA expression of RhoA， ROCK1， and ROCK2 were significantly upregulated （P<0.01）. Compared to the model group， the low-dose， medium-dose， and high-dose groups of LGZGT and the captopril group significantly reversed the experimental results of the model group in a dose-dependent manner （P<0.05， P<0.01）. ConclusionLGZGT significantly attenuated myocardial fibrosis， myocardial hypertrophy， and cardiomyocyte apoptosis after MI in mice and effectively reversed VR， the mechanism of which may be related to the modulation of the RhoA/ROCK signaling pathway.

ObjectiveTo evaluate the clinical effectiveness and safety of Lianling Formula （连苓方） in the treatment of adolescent atopic dermatitis （AD） exacerbation stage with heart fire and spleen deficiency syndrome. MethodsNinety-two patients were randomly divided into a treatment group and a control group， with 46 cases in each group. Patients in the control group took oral ebastine tablets， and patients in the treatment group took Lianling Formula orally， and both groups used 0.03% topical tacrolimus for 4 weeks. Before and after treatment， the improvement of scoring atopic dermatitis index by 50% （SCORAD50） and 75% （SCORAD75）， scoring atopic dermatitis index （SCORAD）， visual analog scale （VAS）， traditional Chinese medicine （TCM） symptom score， the children's dermatology life quality index （CDLQI）， Athens insomnia scale （AIS） score of both groups were evaluated， and the adverse reactions in both groups were recorded. ResultsFour cases in the treatment group and five cases in the control group were dropped， and intention-to-treat analysis was used. Finally 46 cases in each group were included in the statistics. The SCORAD scores after treatment were lower than those before treatment， and the scores in treatment group were lower than those of the control group （P＜0.01）； the attainment rates of SCORAD50 and SCORAD75 after treatment in the treatment group were 80.43% and 47.83%， which were significantly higher than those in the control group of 63.04% and 26.09%， respectively （P＜0.05）. VAS scores， TCM symptom scores， CDLQI scores， and AIS scores were lower than those before treatment （P＜0.01）， and VAS scores， TCM symptom scores， and CDLQI scores of the treatment group were lower than those of the control group after treatment （P＜0.05 or P＜0.01）， while AIS scores were higher than those of the control group （P＜0.05）. The erythema， papule/edema， oozing/crusting， epidermal peeling， and dryness in the SCORAD scores of the treatment group after treatment were lower than those before treatment （P＜0.05 or P＜0.01）， and the erythema， papule/edema， oozing/crusting， and dryness of children in the control group were lower than those before treatment （P＜0.05 or P＜0.01）. The scores of erythema， oozing/crusting， and epidermal peeling in the treatment group after treatment were all lower than those in the control group （P＜0.05）. The scores of vexation， itching， dry mouth， poor appetite and irregular bowel movements in terms of TCM symptoms in the treatment group after treatment were lower than those before treatment （P＜0.01）， and the scores of itching， vexation， dark urine in the control group were lower than those before treatment （P＜0.05 or P＜0.01）. The scores of itching， dry mouth， poor appetite， irregular bowel movements， and dark urine in the treatment group after treatment were all lower than that in the control group （P＜0.05 or P＜0.01）. No adverse reactions occurred in both groups of children during treatment. ConclusionLianling Formula combined with topical tacrolimus can effectively improve the clinical symptoms of adolescent AD exacerbation with heart fire and spleen deficiency syndrome， and the formula is effective and safe in improving the children's skin lesions， reducing itching， relieving the accompanied TCM symptoms， and improving the quality of life.

Objective To elucidate the influence of two procedures aortic root remodeling using a straight tubular artificial vessel while preserving the aortic valve and the Florida sleeve procedure on the biomechanics of the aortic root.Methods Five finite element models of the aortic root were reconstructed using computed tomography angiography images,including two cases of aortic root remodeling(A1 and A2),two cases of the Florida sleeve procedure(B1 and B2),and one control group without aortic root pathology(C).Numerical simulations were performed to obtain the blood flow and pressure distribution result to assess the differences in the hemodynamics of the aortic root.Results There were no significant differences in the peak systolic velocity between the two procedures and the control.However,the flow velocity after aortic root remodeling was smoother,similar to the model of the control group,with a more stable average aortic pressure and wall shear stress.In the Florida sleeve procedure,high-speed blood flow affected the vessel wall,leading to various degrees of wall shear stress and pressure concentrations along the aortic wall.Conclusions After aortic root replacement with valve preservation,blood flow patterns in the reconstructed aortic root depended on postoperative changes in sinus geometry.Both surgical procedures showed favorable blood flow patterns;however,the flow pattern after aortic root remodeling was more stable than that after the Florida sleeve procedure.

Objective:To examine the prevention effecacy and safety of preprotein convertase subtilisin-kexin 9 (PCSK9) inhibitors in stroke in patients with atherosclerotic cardiovascular disease (ASCVD) at primary and secondary prevention.Methods:PubMed, Embase, Web of Science, Cochrane Library, and Wanfang and CNKI databases were searched for randomized controlled trials comparing evolocumab, alirocumab, tafolecimab or inclisiran (experimental group) with placebo or conventional therapy (control group) in hyperlipidemia and ASCVD from inception to March 2024. Valid data were extracted after screening and applying Cochrane Literature quality assessment tool to assess the literature quality. Efficacy outcome (incidences of stroke and ischemic stroke) and safety outcome (cardiovascular mortality, and incidences of aminotransferase increased by more than 3 times, creatine kinase increased by more than 3 times, allergic reaction and hemorrhagic stroke) were recorded. Meta analysis of the extracted data was conducted using Stata software to calculate the risk difference ( RD). Results:Twenty articles (21 randomized controlled trials) were included with 62 799 patients. For primary prevention, no significant difference was found between PCSK9 inhibitors and control groups in stroke incidence ( RD=0.000, 95% CI: -0.002-0.003, P=0.905) or ischemic stroke incidence ( RD=0.001, 95% CI: -0.005-0.006, P=0.824); incidence of creatine kinase increased by more than 3 times in the PCSK9 inhibitors group was significantly decreased compared with that in the control group ( RD=-0.005, 95% CI: -0.010-0.000, P=0.039). For secondary prevention, PCSK9 inhibitors group had significantly reduced stroke incidence ( RD=-0.004, 95% CI: -0.006--0.002, P<0.001) and ischemic stroke incidence ( RD=-0.003, 95% CI: -0.005--0.002, P<0.001) compared with control group; no significant differences in cardiovascular mortality, or incidences of aminotransferase increased by more than 3 times, creatine kinase increased by more than 3 times, allergic reaction and hemorrhagic stroke were noted between the PCSK9 inhibitors group and control group ( P>0.05). Conclusion:PCSK9 inhibitors in primary prevention have no significant effect on stroke or ischemic stroke incidences, but can decrease the incidence of creatine kinase increased by more than 3 times; PCSK9 inhibitors in secondary prevention can reduce stroke and ischemic stroke incidences without increasing complications and thus enjoying certain safety.

Objective To construct and appraise a new model for predicting the prognosis of rectal cancer patients using the Lasso-Cox strategy.Methods The clinical pathological data of 599 rectal cancer patients who underwent radical resection were analyzed.Comparison between groups,Lasso and Cox regression were used to select varia-bles and construct a model,and its discrimination,consistency,and clinical benefits were appraised by the receiv-er operating characteristic(ROC),calibration curve,and decision curve analysis.Results Comparison between groups showed that age,body mass index(BMI),preoperational nutrition status,carbohydrate antigen199(CA199),preoperative chemotherapy,intraoperative blood transfusion,vascular or nerve invasion,cancer nod-ules,pathologic T,N,and TNM stages,tumor recurrence or metastasis,radiotherapy and postoperative survival time were associated with grouping of death or survival in rectal cancer patients.Among them,8 variables were se-lected by lasso and contained into the Cox regression model.Age(HR=1.04,P＜0.05),BMI(HR=0.89,P＜0.05),blood transfusion(HR=2.29,P＜0.05),postoperative chemotherapy(HR=0.16,P＜0.01),recur-rence(HR=43.67,P＜0.01),and metastasis(HR=2.75,P＜0.05)were identified as independent prognostic factors,which were used to construct a nomogram model.The area under the curve(AUC)and the 95％confi-dence interval of the receiver operating characteristic(ROC)curve of the predictive model was 0.95(0.91-0.99),P＜0.01.The predicted probability of 1-year and 3-year survival was close to the actual probability.The DCA curve of the model was far away from a decision line parallel to the X-axis and another line with a negative slope.Conclusion The newly established nomogram has good discrimination,consistency and clinical benefits,which help predict the prognosis of rectal cancer after surgery.

Objective:To evaluate the post-marketing safety and immunogenicity of a 23-valent pneumococcal polysaccharide vaccine (PPV23).Methods:From September 2020 to June 2021, a clinical trial of single-dose PPV23 was conducted in people ≥3 years old in Centers for Disease Control and Prevention of Guizhou, Hunan and Fujian provinces. Blood samples were collects from the subjects before and 30 d after vaccination. ELISA was used to quantitatively detect IgG antibodies against capsular polysaccharides of 23 Streptococcus pneumoniae serotypes in serum samples. The adverse events (AEs) were monitored within 7 d after vaccination. Results:A total of 409 subjects were enrolled and included in safety analysis. Except for one with antibody level inversion, the other 408 participants were included in immunogenicity analysis. The levels of antibodies against the 23 Streptococcus pneumoniae serotypes were all increased after vaccination by an average of 4.24 folds. The two-fold growth rates of the antibodies ranged from 51.72% to 96.81% with a total two-fold growth rate of 78.59%. The overall rate of AEs was 27.14% (111/409). Local AEs were mainly pain, induration, redness and swollen. No serious adverse events related to vaccination occurred. Conclusions:This study preliminarily demonstrated the good immunogenicity and safety of PPV23 vaccine.

Objective: To explore the influential factors on tumor diameters in rectal cancer. Methods : Cross sectional study data were collected from patients undergoing radical resection of rectal cancer.Patients were grouped by median value of tumor diameter, and the clinical pathological characteristics were compared between the two groups.The associations between tumor diameter and continuous variables were analyzed using locally weighted scatterplot smoothing(LOWESS) method.The associating factors of tumor diameter were further analyzed using generalized additive model(GAM). Results : Patients with rectal cancer were divided into two groups with tumor diameter either<4 centimeters or ≥4 centimeters.Proportions of T,TNM stages differed significantly between different groups.Median carcinoembryonic antigen(CEA) in≥4 centimeters group were 4.90 ng/ml(inter-quartile range [IQR] 2.39,9.53 ng/ml),much higher than that in<4 centimeters group(2.93 ng/ml [IQR:1.78,4.90 ng/ml]),P<0.01.LOWESS analysis showed that there were non-linear relationships between tumor diameter and the following variables: age, the distance between tumor and anal verge, CEA,neutrophils, lymphocytes, platelets, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio.GAM showed that increased blood platelets(P<0.05) and later T stage(P<0.01) were significantly associated with increased tumor diameters, and increased CEA levels were also associated with larger tumors(P<0.01),but there were saturation effects. Conclusion Platelets, T stage and CEA are associated with tumor diameter in rectal cancer, indicating that the above factors should be considered when studying associated factors of tumor diameter in rectal cancer.

Objective To understand the awareness level of iodine deficiency (ID) impairments and the attitude on edible iodized salt,and its consumption among doctors and nurses in cities,in order to provide scientific evidence for health education on iodine deficient disorders (IDD) in the future.Methods The questionnaire was self-designed,and spread through the web page of Wenjuanxing,an online server company,from May 6 to June 6,2017.At the end of the survey,a total of 481 valid questionnaires were reclaimed,in which ratio of gender was female 63.8％ (307/481),male 36.2％ (174/481).The data were analyzed by SPSS 22.0,including logistic regression analysis with backward according to the statistical significant level of P ＜ 0.05.Results Among doctors and nurses,90.4％ (435/481) knew ID impairments;72.8％ (350/481) answered intelligent disability as the most serious problem of ID;55.5％ (267/481)misunderstood that the areas in which they lived were not ID areas,although all cities surveyed were ID areas;41.0％ (197/481) of doctors and nurses misunderstood that coastal residents did not need to consume iodized salt.About the evaluation of iodine nutrition status of current population,15.6％ (75/481) of respondents judged as iodine excess.About consuming edible salt,76.3％ (367/481) selected iodized,9.6％ (46/481)non-iodized,and 14.1％ (68/481) both iodized and non-iodized.The results of logistic regression analysis showed the factors that prevents health care workers from choosing iodized salt were:"living in coastal areas","think him or her as iodine adequate","know that iodine deficiency can affect the development of children but still adhere to the consumption of non-iodized salt";the factors that promoted the choice of iodized salt for medical staff were "insist on buying iodized salt,and do not choose non-iodized salt",and 75.8％ (238/314)of them knew that intelligent disability as the most serious problem of ID.Conclusions Most doctors and nurses have high level of knowledge on ID and its control.But lack of information,as well as misunderstanding of "coastal areas iodine adequate" and worry about "excess iodine causes thyroid diseases and cancer",which would hinder the active consumption of iodized salt.Health education for them should be conducted through professional ways,stressing on the threaten of ID environment,sharing the information about national and local progress on control of IDD and iodized salt safety,and clarifying the relationship between iodine salt or iodine and thyroid cancer and nodules.

Objective To examine the distribution,volume and glucose-uptake activity of brown adipose tissue (BAT) in adults and investigate their correlations with metabolic indicators.Methods 18F-flurodeoxyglucose (FDG) PET/CT was used to analyze the distribution,volume and glucose-uptake activity of BAT.The clinical and metabolic differences between BAT positive group (n =121) and BAT negative group (n=257) were compared.The influences of metabolic indicators (fast blood glucose (FBG),triglyceride (TG),total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),uric acid (UA)) on the distribution,volume and activity of BAT were investigated.Logistic regression analysis,two-sample t test,x2 test and multiple linear regression were used to analyze the data.Results The distribution,volume and glucose-uptake activity of BAT were found to be significantly higher in subjects being tested in colder seasons than those who were tested in warmer seasons:2.91％ (87/2 991) vs 1.68％(34/2018),(433±402) vs (329±298) ml,(212±183) vs (169±145) g (x2=7.66,t values:3.36 and 2.98,all P＜0.05).The female proportion was significantly higher in BAT positive group than that in BAT negative group:68.60％ (83/121) vs 31.91％ (82/257) (x2 =16.10,P＜0.01).The average levels of age,body mass index (BMI),FBG,TG,TC,LDL-C and UA in BAT positive group were significantly low-er than those in BAT negative group:(41.30±10.90) vs (48.70±9.60) years,(21.30±2.40) vs (24.50± 3.10) kg/m2,(4.56±0.74) vs (5.34±1.33) mmol/L,(0.94±0.36) vs (2.06±1.64) mmol/L,(4.42± 0.79) vs (4.88±0.87) mmol/L,(1.99±0.58) vs (3.10±0.77) mmol/L,(285.11±70.00) vs (347.70± 101.10) μmol/L (t values:from-6.25 to-2.94,all P＜0.01).Logistic regression analysis revealed that season,gender,age,BMI,FBG,TG and LDL-C levels were all independent influencing factors of BAT distribution in adults (odds ratios:5.36,2.06,0.95,0.79,0.49,0.23,0.02;P＜0.01 or P＜0.05).Among BAT positive adults,gender and FBG levels were found to be strongly affected by the volume and glucose-uptake activity of BAT (β values:0.28,-0.21,both P＜0.05).Conclusions The distribution,volume and glucose-uptake activity of BAT in adults are associated with multiple metabolic indicators including BMI,levels of glucose,lipid and UA.The distribution of BAT is affected by gender,age,season,BMI,blood glucose,and blood lipids.