Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitor (empagliflozin, EMPA) on myocardial remodeling in a mouse uremic cardiomyopathy (UCM) model induced by 5/6 nephrectomy, through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB/AKT)/p65 signaling pathway. Methods The animals were divided into three groups: Sham group (n=6), UCM group (n=8), and UCM＋EMPA group (n=8). A UCM model was established in C57BL/6N mice using the 5/6 nephrectomy. Starting from 5 weeks post-surgery, EMPA or a placebo was administered. After 16 weeks, blood pressure, serum creatinine, blood urea nitrogen, 24-hour urine glucose and urine sodium were measured. Cardiac structure and function were assessed by echocardiography. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe pathological changes in the heart and kidneys. Wheat germ agglutinin (WGA) staining was used to evaluate myocardial hypertrophy. The real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of myocardial hypertrophy- and fibrosis-related mRNAs. Western blotting was used to detect the expression levels of PI3K, AKT and p65 in myocardial tissues. Results After 16 weeks, UCM group exhibited significantly higher blood pressure, serum creatinine, blood urea nitrogen than sham group (P＜0.01); UCM＋EMPA group exhibited lower blood pressure, serum creatinine, blood urea nitrogen, and higher 24 h urine sodium and glucose than UCM group (P＜0.05). Echocardiographic results showed ventricular remodeling in the UCM group, evidenced by left ventricular wall thickening, left ventricular enlargement, increased left ventricular mass, and decreased systolic function (P＜0.05); ventricular remodeling was alleviated (P＜0.05), though there was no significant improvement in systolic function in UCM＋EMPA group. HE and Masson stainings revealed myocardial degeneration, necrosis, and interstitial fibrosis in UCM group (P＜0.01); the myocardial pathology improved with reduced collagen deposition in UCM＋EMPA group (P＜0.01). WGA staining confirmed myocardial hypertrophy in UCM group (P＜0.01), while myocardial hypertrophy was alleviated in UCM＋EMPA group (P＜0.01). RT-qPCR results showed myocardial hypertrophy- and fibrosis-related genes (NPPA, NPPB, MYH7, COL1A1, COL3A1, TGF-β1) were upregulated in UCM group (P＜0.05), but downregulated in UCM＋EMPA group. Western blotting showed PI3K, p-AKT/AKT ratio, and p-p65/p65 ratio were increased in UCM group, but decreased in UCM＋EMPA group (P＜0.05). Conclusion EMPA can improve myocardial hypertrophy and fibrosis in the UCM mouse model, and it may play the role through inhibiting the PI3K/AKT/p65 signaling pathway.

The genus jujube(Ziziphus jujuba Mill.)within the Rhamnaceae family encompasses numerous varieties,such as Ziziphus jujuba Mill.var.jujuba,Ziziphus jujuba var.inermis,and var.spinosa,etc.Among these,the jujube fructus has the most abundant cultivated variants across the country,including Ziziphus jujuba cv.Hamidazao and Ziziphus jujuba cv.Huanghetanzao.Jujube plants are rich in variety and are used for both medicinal and food purposes.Polysaccharides,one of the main active ingredients of jujube,are important medicinal components that contribute to its efficacy.Jujube polysaccharides have been found to promote hematopoiesis,exhibit antioxidant and anti-tumor activities,repair liver damage,regulate the immune system,and provide anti-inflammatory effects.By comprehensively summarizing and analyzing the literature on jujube polysaccharides from different varieties and origins,this paper reviews the potential mechanisms of action of jujube polysaccharides in exerting biological activities.It also summarizes the primary structural features,such as relative molecular mass,monosaccharide composition,glycosidic linkage,and the substituent modifications of jujube polysaccharides by sulfation,phosphorylation,carboxymethylation,selenization,and acetylation.This review aims to provide a reference for the research and development of jujube in the fields of innovative polysaccharide drugs and functional foods.

Objective To explore the effect of urine mixing degree on 24-hour urinary total protein(24 h UTP)in patients with chronic kidney disease(CKD).Methods From October 1,2023 to December 31,2023,30 hospitalized patients who needed to complete 24 h UTP testing in Zhongshan Hospital,Fudan University were selected.A 5 L unified container was used to collect urine for 24 hours.After collection and one hour's standing,the urine sample was divided into upper,middle,and lower equal parts according to volume,which was defined as direct-sampling group.Then,the urine samples were fully mixed with a magnetic stirrer and sampled again according to the above-mentioned three-equal sampling method,which was defined as mixed-sampling group.The generalized estimating equation was used to compare the urinary protein concentration before and after mixing and at different sampling location.Results The results of generalized estimating equation showed that after controlling the variable"sampling position",there was no significant difference in urinary protein concentration between the direct-sampling group and the mixed-sampling group.After controlling the variable"mixing method",there was still no significant difference in urinary protein concentration at different sampling positions.After adjusting the covariates such as age,gender,and estimated glomerular filtration rate(eGFR),the results were consistent.Conclusions With standard protocol,the entire 24-hour urine sample is a relatively even-distributed solution.After the total urine collection is completed,the temporary sample can be directly extracted from any level of the original urine within 1 hour,and the urine protein concentration of the sample multiplied by the urine volume can reflect the 24 h UTR.

Objective:To analyze the disease burden of chronic kidney disease (CKD) in the Belt and Road countries and its change trend.Methods:It was a cross-sectional epidemiological study based on surveillance data. Data on age-standardized prevalence rate (ASPR) and age-standardized mortality rate (ASMR) of CKD were derived from the 2019 Global Burden of Disease Study. The annual percentage change (APC) was calculated to evaluate the ASPR trend of CKD from 1990 to 2019.Results:In 2019, the number of CKD cases and deaths in the Belt and Road countries was 426 million and 798 000, respectively, accounting for 61.1% and 55.9% of CKD cases and deaths worldwide. The ASPR and ASMR of CKD in China were 8.1% and 11.2 per 100 000 population, slightly lower than the global average. Countries in North America and Oceania had a higher burden of CKD, and European countries had a lower burden. In the etiology, hypertension and diabetes-related CKD morbidity and mortality accounted for 23.7% and 68.8% of total CKD morbidity and mortality, respectively. From 1990 to 2019, the ASPR of CKD increased in 150 countries (98.0%) and the fastest increase was observed in Morocco ( APC=1.52%). The hotspots with high ASPR of CKD were located in Belt and Road countries from Asia, South/North America and Oceania, and the hotspots with high ASMR were distributed in countries from Africa, South/North America and Oceania. The sociodemographic index and life expectancy were positively correlated with the ASPR of CKD ( r=0.409, P<0.001; r=0.361, P<0.001) , and negatively correlated with the ASMR of CKD ( r=-0.317, P<0.001; r=-0.391, P<0.001). Conclusions:Belt and Road countries have substantial disease burdens of CKD, and the prevalence rate of CKD is rising fast. Health cooperation among member states should be strengthened to jointly address the challenges posed by chronic diseases such as CKD.

Objective: To analyze the factors affecting the complication of pulmonary atelectasis among children with tracheobronchial tuberculosis (TBTB), so as to provide the reference for the prevention and treatment of pulmonary atelectasis complicated by TBTB. Methods: Children with TBTB admitted to Department of Paediatrics, Linping Division of the Second Affiliated Hospital of Zhejiang University School of Medicine were selected as the study subjects from October 2018 to March 2023. Subjects's basic information, etiological examination results and laboratory testing results were collected using a self-designed questionnaire, and factors affecting the complication of pulmonary atelectasis among children with TBTB were identified using a multivariable logistic regression model. Results: A total of 120 children with TBTB were included, with the age of 6 months to 12 years. There were 33 children at ages of less than one year (27.50%), 71 girls (59.17%) and 25 children with TBTB and pulmonary atelectasis (20.83%). Multivariable logistic regression analysis identified less than one year of age (OR=1.720, 95%CI: 1.126-3.358), type Ⅵ of TBTB (OR=1.669, 95%CI: 1.101-2.236), high level of C-reactive protein (OR=1.887, 95%CI: 1.088-2.686) and high level of procalcitonin (OR=1.844, 95%CI: 1.034-2.654) as risk factors for the complication of pulmonary atelectasis in children with TBTB. Conclusion Less than one year of age, type Ⅵ of TBTB, high level of C-reactive protein and high level of procalcitonin may increase the risk of pulmonary atelectasis in children with TBTB.

Cardiovascular diseases, including heart failure, coronary artery disease, atherosclerosis, aneurysm, thrombosis, and hypertension, are a great economic burden and threat to human health and are the major cause of death worldwide. Recently, researchers have begun to appreciate the role of microbial ecosystems within the human body in contributing to metabolic and cardiovascular disorders. Accumulating evidence has demonstrated that the gut microbiota is closely associated with the occurrence and development of cardiovascular diseases. The gut microbiota functions as an endocrine organ that secretes bioactive metabolites that participate in the maintenance of cardiovascular homeostasis, and their dysfunction can directly influence the progression of cardiovascular disease. This review summarizes the current literature demonstrating the role of the gut microbiota in the development of cardiovascular diseases. We also highlight the mechanism by which well-documented gut microbiota-derived metabolites, especially trimethylamine N-oxide, short-chain fatty acids, and phenylacetylglutamine, promote or inhibit the pathogenesis of cardiovascular diseases. We also discuss the therapeutic potential of altering the gut microbiota and microbiota-derived metabolites to improve or prevent cardiovascular diseases.

Objective:To evaluate the influence of cytomegalovirus (CMV) infection on T cell senescence and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients.Methods:It was a single center cross sectional study. Patients aged over 18 years old and received hemodialysis for at least 6 months at the Blood Purification Centre of the Department of Nephrology of Zhongshan Hospital Affiliated to Fudan University from January 2021 to April 2021 were enrolled. Demographic, hematological, nutritional and inflammatory markers were obtained. Anti-CMV-IgM and IgG antibodies were detected using the Roche Elecsys assay. CD28 - T cell was evaluated by flow cytometry. Mann-Whitney U test or Kruskal-Wallis H test was used for anti-CMV-IgG comparison among groups. Spearman correlation and linear regression were used to assess the relationship between anti-CMV-IgG and CD28 - T cell compartment. Logistic regression was used to assess the relationship between anti-CMV-IgG and CVD. Results:A total of 438 MHD patients (270 men and 168 women) were enrolled in the study. The median age was 62 (51, 70) years. The median time on hemodialysis was 57 (21, 100) months. The primary diseases included chronic glomerulonephritis [213 cases (48.6%)], diabetic nephropathy [82 cases (18.7%)], polycystic kidney disease [34 cases (7.8%)], hypertensive renal disease [34 cases (7.8%)], etc. Of these patients, 430 (98.2%) were seropositive for anti-CMV-IgG, 206 (47.0%) had anti-CMV-IgG titers exceeding the upper limit of 500 U/ml. Patients aged over 70 years old were 100% seropositive for anti-CMV-IgG. Patients on HD for more than 5 years had a higher seropositive rate of 99.1% than those with shorter HD duration, although these results were not statistically significant. Spearman correlation analysis showed that the anti-CMV-IgG titers in MHD patients were positively correlated with the proportion of CD4 + CD28 - T cells and CD8 + CD28 - T cells ( r=0.316, P<0.001; r=0.272, P<0.001). Multiple linear regression analysis showed that after adjusting for age and gender, lg[CD4 + CD28 - T cells(%)] and lg[CD8 + CD28 - T cells(%)] were positively correlated with lg[anti-CMV-IgG titers (U/ml)], respectively ( β=0.455, t=8.315, P<0.001; β=0.412, t=7.282, P<0.001). In analyzing the relationship between anti-CMV-IgG titers and CVD, patients were divided into six groups according to age and anti-CMV-IgG level. Group 1 included young patients with a lower anti-CMV-IgG titers (age ≤55 years old, anti-CMV-IgG <400 U/ml); Group 2 included young patients with a higher anti-CMV-IgG titers (age≤55 years old, anti-CMV-IgG ≥400 U/ml); Group 3 included middle-aged patients with a lower anti-CMV-IgG titers (5565 years old, anti-CMV-IgG<400 U/ml); Group 6 included old aged patients with a higher anti-CMV-IgG titers (age>65 years old, anti-CMV-IgG≥400 U/ml). The incidence of CVD was significantly different among the six groups ( χ2=18.780, P=0.002) and patients aged over 55 years old with higher anti-CMV-IgG level had a higher CVD incidence compared with group 1 ( P<0.05). Multivariate logistic regression analysis showed that increased age ( OR=1.020, 95% CI 1.002-1.038, P=0.033), male ( OR=1.855, 95% CI 1.161-2.965, P=0.010), history of diabetes ( OR=1.867, 95% CI 1.145-3.046, P=0.012), increased lg[NT-proBNP(μg/L)] ( OR=2.848, 95% CI 1.816-4.467, P<0.001) and lg[anti-CMV-IgG (U/ml)] ( OR=3.183, 95% CI 1.582- 6.405, P=0.001) were independent factors associated with CVD in MHD patients. Conclusions:CMV infection is extremely common in MHD patients. Increased anti-CMV-IgG is related to T cell senescence and CVD complications in MHD patients.

Objective:To explore the mechanism of Tanshinone ⅡA(TⅡA)in improving ischemia/reperfusion(I/R)injury of H9c2 cardiomyocytes by activating Sirtuin 1(SIRT1)-adenosine 5'-monophosphateactivated protein kinase(AMPK)pathway through miR-155-5p.Methods:H9c2 cells were cultured in vitro and I/R damage model was established.After modeling,H9c2 cells were randomly divided into model group,TⅡA group,TⅡA+miR-NC group,TⅡA+miR-155-5p mimics group,10 μmol/L TⅡA was added for intervention after transfection,and the H9c2 cells supplemented with DMSO were used as control group.qRT-PCR was used to detect expression level of miR-155-5p;MTT method was used to analyze cell proliferation ability;flow cytometry was used to evaluate cell apoptosis;ELISA was used to determine the levels of TNF-α,IL-4,IL-10,IL-17,lactate dehydrogenase(LDH),malo-ndialdehyde(MDA)and superoxide dismutase(SOD);Western blot was used to detect relative expressions of SIRT1,AMPK and p-AMPK proteins.Results:Compared with control group,expression of miR-155-5p in model group was increased,cell viability was decreased,apoptosis rate and expressions of TNF-α,IL-17,LDH and MDA were increased,while expressions of IL-4,IL-10,SOD,SIRT1 and p-AMPK were decreased(P<0.05);compared with model group,expression of miR-155-5p in TⅡA group was reduced,cell viability was increased,apoptosis rate and expressions of TNF-α,IL-17,LDH and MDA were decreased,while expressions of IL-4,IL-10,SOD,SIRT1 and p-AMPK were increased(P<0.05);compared with TⅡA group and TⅡA+miR-NC group,expression of miR-155-5p in TⅡA+miR-155-5p mimics group was increased,cell viability was decreased,apoptosis rate and expressions of TNF-α,IL-17,LDH and MDA were increased,while expressions of IL-4,IL-10,SOD,SIRT1 and p-AMPK were decreased(P<0.05).Conclusion:TⅡA can improve I/R injury of H9c2 cardiomyocytes by down-regulating miR-155-5p,and its mechanism may be related to the activation of SIRT1-AMPK pathway.

Objective:To retrospectively analyze the pregnancy outcomes of patients with adenomyosis requiring fertility in a single center under real world condition.Methods:From June 2015 to May 2020, 231 cases of pregnancy complicated with adenomyosis diagnosed by ultrasound with fertility requirements were treated in the Women′s and Children′s Hospital Affiliated to Qingdao University with complete clinical data. And they were divided into three groups according to the treatment of adenomyosis before pregnancy: expectation group, drug group and operation group. The relevant data before pregnancy of the three groups were analyzed, and the pregnancy outcomes of the patients were summarized. According to whether the early pregnancy was treated with medication, the patients who were naturally conceived without symptoms of threatened abortion were divided into observation group and fetus protection group, and the pregnancy outcomes of the two groups were compared.Results:(1) Compared with the expectation group, the ages of patients in the drug group and the operation group were larger [(31.5±1.8) vs (34.1±3.7) vs (36.9±3.6) years old], and the difference was statistically significant ( P<0.05). Only 9 patients (11.5%, 9/78) had clinical symptoms in the expectation group, while the patients in the drug group and the operation group had a higher proportion of dysmenorrhea and increased menstrual volume. The uterine volume of the drug group and the operation group were larger than that of the expectation group [(151±46) vs (166±27) vs (97±18) cm 3], the difference was statistically significant ( P<0.05). 78.6% (33/42) of the operation group were focal adenomyosis. The proportion of natural pregnancy in the expectation group was 97.4% (76/78), and in vitro fertilization and embryo transfer was mainly used in the drug group and the operation group. (2) The abortion rates of the three groups were 48.7% (26/111), 4/17, 67.5% (27/78) respectively. Compared with the drug group and the operation group, the preterm birth rate was lower [55.9% (33/111) vs 11/17 vs 12.5% (5/78)] and the natural delivery rate was higher [44.1% (26/111) vs 4/17 vs 67.5% (27/78)] in the expectation group. (3) There were 89 cases of spontaneous pregnancy without threatened abortion symptoms, including 31 cases in the observation group and 58 cases in the fetus protection group. Compared with the observation group, the abortion rate of patients in the fetus protection group was lower [41.9% (13/31) vs 34.5% (20/58)], and the difference was statistically significant ( P<0.05). Conclusions:Patients with adenomyosis who have fertility requirements should be comprehensively evaluated and individualized treatment plans should be given. Pregnancy patients with adenomyosis have a high rate of miscarriage, and they should be included in the management of high-risk pregnant women. Active fetal protection treatment during early pregnancy might improve pregnancy outcomes.

Atherosclerosis (AS) is a chronic and progressive arterial disease. It is an important cause of the occurrence and development of cardiovascular and cerebrovascular diseases. With the development of Traditional Chinese Medicine (TCM), TCM has many advantages in the therapy of AS, with less adverse reactions. Studies have shown that TCM can resist AS, and the mechanism mainly belongs to regulating lipid metabolism, anti-lipid peroxidation, anti-inflammation, anticoagulation, and protecting the structure and function of vascular endothelial cells. The mechanism of TCM for AS is warranted to be studied systematically, and the chemical components need to be further clarified.