OBJECTIVES: To evaluate the protective effect of Schistosoma japonicum cystatin (rSj-Cystatin) in a mouse mode of "two-hit" sepsis. METHODS: Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP. At 12 h after rSj-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival. RESULTS: The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of "two-hit" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by rSj-Cystatin treatment. Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by rSj-Cystatin treatment. CONCLUSIONS rSj-Cystatin has a protective effect against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
Animals ; Mice ; Sepsis/drug therapy* ; Male ; Schistosoma japonicum/chemistry* ; Mice, Inbred C57BL ; Cystatins/therapeutic use* ; Interleukin-10/metabolism* ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Disease Models, Animal ; Transforming Growth Factor beta/metabolism*

Objective To evaluate the protective effect of Schistosoma japonicum cystatin(rSj-Cystatin)in a mouse mode of"two-hit"sepsis.Methods Sixty male C57BL/6 mice randomized equally into sham-operated group,protein group,"two-hit"modeling group,and protein intervention group.In the former two groups,the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later;In the latter two groups,100 μL PBS containing LPS(5 mg/kg)was injected intraperitoneally 24 h before cecal ligation and puncture(CLP),and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP.At 12 h after rSj-Cystatin treatment,6 mice from each group were sacrificed for detection of TNF-α,IL-6,IL-10,TGF-β,iNOS and Arg-1 in the serum,spleen,liver,lung and kidney tissues using ELISA,for examinations of liver,lung and kidney pathologies with HE staining,and for analysis of CD3+CD4+CD25+Foxp3+T cell percentage in the spleen using flow cytometry.The remaining mice were observed for general condition and 72-h survival.Results The 72-h survival rates in the 4 groups were 100％,100％,0％and 20％,respectively,showing significant differences between the latter two groups.The mouse models of"two-hit"sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate,which were significantly ameliorated by rSj-Cystatin treatment.Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3+CD4+CD25+Foxp3+T cell percentage.The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney,and these changes were obviously improved by rSj-Cystatin treatment.Conclusion rSj-Cystatin has a protective effect against"two-hit"sepsis in mice by regulating the inflammatory microenvironment.

Objective:To analyze the characteristics of non-seroconverted cases after rabies vaccination and observe the effect of booster vaccination.Methods:A retrospective collection of data was conducted from March 2022 to March 2023 across 409 rabies vaccination clinics in 27 provinces in China, focusing on cases with rabies virus neutralizing antibody (RVNA) levels less than 0.5 IU/ml after vaccination.Results:A total of 77 cases were identified in whom seroconversion was not observed within 30 days post-vaccination with the rabies vaccine. The gender distribution was 51.9% male and 48.1% female, with ages ranging from 2 to 83 years old. Delayed vaccination was observed in 11 cases (14.3%), and 63 cases (81.8%) received human rabies immunoglobulin (HRIG) injections. None of the cases had a confirmed immunosuppressive disease or taking immunosuppressive drugs, and the body mass index (BMI) distribution ranged from 14.37 to 34.74 kg/m 2. Seventy-six cases seroconverted after 1 to 3 doses of rabies vaccines as a booster vaccination. One case that did not seroconvert after the initial booster vaccination seroconverted after receiving additional 2 doses of vaccine. All patients were followed up for one year, with no cases of rabies reported. Conclusions:The characteristics of cases that failed to seroconvert after the full course of rabies vaccination lacked specificity, and booster vaccination could lead to seroconversion.

Objective:To analyze the characteristics of non-seroconverted cases after rabies vaccination and observe the effect of booster vaccination.Methods:A retrospective collection of data was conducted from March 2022 to March 2023 across 409 rabies vaccination clinics in 27 provinces in China, focusing on cases with rabies virus neutralizing antibody (RVNA) levels less than 0.5 IU/ml after vaccination.Results:A total of 77 cases were identified in whom seroconversion was not observed within 30 days post-vaccination with the rabies vaccine. The gender distribution was 51.9% male and 48.1% female, with ages ranging from 2 to 83 years old. Delayed vaccination was observed in 11 cases (14.3%), and 63 cases (81.8%) received human rabies immunoglobulin (HRIG) injections. None of the cases had a confirmed immunosuppressive disease or taking immunosuppressive drugs, and the body mass index (BMI) distribution ranged from 14.37 to 34.74 kg/m 2. Seventy-six cases seroconverted after 1 to 3 doses of rabies vaccines as a booster vaccination. One case that did not seroconvert after the initial booster vaccination seroconverted after receiving additional 2 doses of vaccine. All patients were followed up for one year, with no cases of rabies reported. Conclusions:The characteristics of cases that failed to seroconvert after the full course of rabies vaccination lacked specificity, and booster vaccination could lead to seroconversion.

This article presented the maternal and infant outcomes of glycogen storage disease type Ⅲa (GSDⅢa) in a woman with full-term pregnancy. The woman exhibited symptoms of hypoglycemia when she was three months old, which were alleviated with intravenous glucose infusion. At the age of 19, during surgical treatment for scoliosis, she was found with liver cirrhosis, splenomegaly, and thrombocytopenia. Glycogen debranching enzyme deficiency was detected through liver biopsies, leading to the clinical diagnosis of GSDⅢ (unspecified genotype). The patient was admitted after conceiption due to "irregular lower abdominal pain for 1 day" at 34 weeks and 3 days. Through multidisciplinary management in the late pregnancy, which included medication adjustments, dietary instruction, and platelet transfusions both at half an hour before and during the operation, the patient underwent a cesarean section at 37 +1 weeks of gestation and delivered a healthy boy with normal Apgar scores at 1, 5, and 10 min. The mother followed a high-protein diet postpartum and the newborn experienced hypoglycemia after birth. Intravenous glucose was supplied to the infant, restabilizing his blood glucose. Maternal and neonatal blood glucose both remained stable. Postpartum whole-exome sequencing identified compound heterozygous variants in the mother, which were in the AGL gene at chr1:100379102-100379103 with gene variant information of NM_000642.2:c.3971_3972delAT(p.Tyr1324*) and at chr1:100345603 with gene variant information of NM_000642.2:c.1735+1G>T, confirming the diagnosis of GSDⅢa. The newborn carried a heterozygous variant in the AGL gene at chr1:100379102-100379103 with gene variant information of NM_000642.2:c.3971_3972delAT(p.Tyr1324*). Postpartum follow-ups showed stable blood glucose levels for the mother and normal growth and development for the newborn.

Objective To investigate the risk factors for heart failure in patients with coronary atherosclerotic heart disease and to analyze the influence of different blood pressure levels on the risk of heart failure.Methods A total of 826 coronary atherosclerotic heart disease patients admitted to the Department of Cardiovascular Medicine of First Hospital of Qinhuangdao from October 2018 to October 2020 were selected as the research subjects.The patients were divided into the heart failure group(n=27)and the non-heart failure group(n=799)based on whether heart failure occurred.The clinical data of patients in the two groups were collected,and the risk factors for heart failure in patients with coronary atherosclerotic heart disease were analyzed by using the univariate and multivariate logistic regression.According to the history of hypertension,the patients were divided into the hypertension history group(n=522)and the normal blood pressure group(n=304),and according to the blood pressure levels,the patients were further divided into the normal blood pressure group(n=304),grade 1 hypertension group(n=102),grade 2 hypertension group(n=254)and grade 3 hypertension group(n=166).The cumulative incidence of heart failure of patients was compared among all groups,and the impact of hypertension history and blood pressure levels on the occurrence of heart failure in patients with coronary atherosclerotic heart disease was analyzed by using the multivariate Cox proportional hazards regression model.Results Univariate analysis showed that there were statistically significant differences in the proportion of advanced age,history of hypertension,history of smoking,coronary artery disease,hemoglobin level,proportion of left atrial enlargement,and proportion of left ventricular hypertrophy between the heart failure group and the non-heart failure group(P＜0.05);and there was no significant difference in gender,history of hyperlipidemia,body mass index,history of diabetes,albumin level,and serum creatinine level between the two groups(P＞0.05).Multivariate logistic regression analysis showed that the history of hypertension,advanced age,multivessel coronary artery disease(≥2 vessels),and left ventricular hypertrophy were risk factors for heart failure in patients with coronary atherosclerotic heart disease(P＜0.05).The cumulative incidence of heart failure in the hypertension history group and the normal blood pressure group was 3.63％(19/522)and 2.63％(8/304),respectively;and the cumulative incidence of heart failure in the hypertension history group was significantly higher than that in the normal blood pressure group(x2=6.792,P＜0.05).The cumulative incidence of heart failure in the normal blood pressure group,grade 1 hypertension group,grade 2 hypertension group,and grade 3 hypertension group was 2.63％(8/304),2.94％(3/102),3.54％(9/254),and 4.22％(7/166),respectively,showing an increasing trend,and there was a significant difference between each group(P＜0.05).In the Cox proportional hazards model,model 1(unadjusted for confounding factors),model 2(adjusted for age factors),and model 3(adjusted for confounding factors such as the history of hypertension,history of smoking,coronary artery distase,hemoglobin level,left atrial enlargement,and left ventricular hypertrophy on the basis of model 2)all showed that the history of hypertension was the risk factor for heart failure in patients with coronary atherosclerotic heart disease,and the higher the blood pressure level,the higher the risk of developing heart failure(P＜0.05).Conclusion The history of hypertension,advanced age,multi vessel coronary artery disease(≥2 vessels),and left ventricular hypertrophy are risk factors for heart failure in patients with coronary atherosclerotic heart disease,among which the history of hypertension has the greatest influence,and the probability of developing heart failure increases as the blood pressure grade increases.

Abstract Gut flora undergoes a dynamic colonization and development process at different stages of human life. Sex specific gut flora development begins during puberty, which is influenced by sex hormone levels. The potential relationship between sex hormone levels, which suggests that there may be a two way interaction between intestinal flora and sex hormones. In addition, evidence is emerging for bidirectional effects of the microbiome in human health. Therefore, the review presents the dimorphism of intestinal flora, the characteristics of intestinal flora during puberty and the latest research progress, explores the close relationship between intestinal flora and precocious puberty and reproductive system diseases, and further explains the influence mechanism and treatment measures of considering gender factors in intestinal microflora, precocious puberty and reproductive system related diseases.

OBJECTIVE To explore the role and underlying mechanism of tournefolic acid B （TAB） on the improvement of glucose metabolism and renal function in diabetic nephropathy （DN） model mice. METHODS DN model mice were established by high-fat diet combined with streptozotocin， and then randomly divided into model group， positive control group （vitamin E， 20 mg/kg）， TAB low-dose， medium-dose and high-dose groups （1， 2， 4 mg/kg）， with 12 mice in each group； normal control group was given regular diet. Each group was given relevant medicine or normal saline intragastrically， once a day， for 4 consecutive weeks. The glucose metabolic function was estimated by fasting blood glucose， glucose tolerance test， insulin tolerance test and serum insulin concentration. The renal coefficients and biochemical indicators related to renal function [serum uric acid， blood urea nitrogen， creatinine levels， and ratio of urine microalbumin to creatinine] were detected in mice； the contents of biochemical indicators related to oxidative stress [superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， 8-hydroxydeoxyguanosine （8-OHdG）] were determined in renal tissue of mice； the pathological morphology of renal tissue was observed； the expressions of extracellular matrix （ECM） deposition related factors [transforming growth factor β1 （TGF- β1）， fibronectin （Fn）， type Ⅳ collagen （Col Ⅳ）] and protein kinase B （Akt）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway related proteins were determined in renal tissue of mice. RESULTS Compared with normal control group， fasting blood glucose， area under glucose tolerance curve， area under insulin tolerance curve， serum insulin content， the levels of uric acid， urea nitrogen and creatinine @qq.com and ratio of urinary microalbumin to creatinine in serum， the contents of MDA and 8-OHdG and the protein expressions of TGF-β1， Fn and Col Ⅳ were increased significantly in model group （P＜0.05）， while the contents of SOD， GSH-Px and the protein expressions of p-Akt， Nrf2， HO-1 in renal tissue were decreased significantly （P＜0.05）； the significant thickening of the basement membrane， accumulation of mesangial matrix， glomerulosclerosis and interstitial fibrosis of the renal tubules were all found. Compared with model group， above indexes of mice were all reversed significantly in TAB groups （P＜0.05）， and pathological changes were alleviated in a dose-dependent manner. CONCLUSIONS TAB can improve blood glucose metabolism and kidney function and alleviate renal tubulointerstitial fibrosis in DN model mice， the mechanism of which may be associated with activating the Akt/Nrf2/HO-1 signaling pathway and suppressing ECM deposition.

3-iodothyronamine（T1AM）is an endog enous derivative of thyroid hormone. It can also be used as exogenous drug. It can play pharmacological effects such as reducing cardiac output and coronary flow ，slowing heart rate ，promoting lipolysis ， reducing basic metabolism and improving learning and memory ability. Its regulatory effect on metabolism is similar to that of thyroxine，but regulatory effect on heart and thermogenic function is opposite to that of thyroxine. As a new chemical messenger ， T1AM can exert different pharmacological effects through a variety of receptors and signal pathways. This review summarizes the research progress of various pharmacological effects and mechanisms of exogenous T 1AM，in order to provide new therapeutic drugs of cardiovascular ，metabolic diseases and nervous system diseases.

Objective : To explore the material basis and mechanism of Yindan Xinnaotong soft capsule( YD) in treating myocardial ischemia⁃reperfusion injury (MIRI) based on network pharmacology , so as to provide theoreti⁃ cal reference for the treatment of MIRI. Methods : The main active components and action targets of YD were searched by TCMSP , SwissTargetPrediction and China knowledge Network . The disease targets of MIRI were screened by GeneCards database. The“ drug⁃component⁃disease⁃target ”network relationship was constructed by fication was carried out between the top three main active components and the top six targets in PPI network. Human myocardial AC⁃16 cells were constructed hypoxia/reoxygenation (H/R) model to initially verify the core target. Using CCK⁃8 assay was usedto detect cell viability and explore the optimal drugconcentration. The influence of YD on cell morphology was observed by using optical microscope. LDH content was detected to assess the integrity of cell membrane ; Western blot was used to detect the expression of STAT3 , p ⁃STAT3 , PI3K , AKT1 and p ⁃AKT1 . Results : A total of 105 active components , 382 drug targets , 1223 MIRI disease targets and 160 drug⁃disease common targets of YD were obtained. The key targets involved AKT1 , STAT3 , VEGFA , TNF , MAPK8 , PIK3CA and so on. GO analysis mainly involved apoptosis , lipolysis , muscle cell proliferation , cytokine⁃mediated inflammation , oxidative stress and so on. The results of molecular docking showed that VEGFA , APP and PIK3CA could bind to quercetin , luteolin and kaempferol. Our results showed that 200 mg/L YD could significantly promote the proliferation of AC⁃16 cells and reduce LDH leakage. Western blot results showed that YD could activate STAT3 and PI3K⁃AKT1 signaling pathways and protect myocardium. Conclusion YD can protect MIRI through multi⁃components , multi⁃targets and multi⁃pathways.