Objective To explore the number of peripheral blood regulatory T cells (Treg) in patients with chronic kidney disease (CKD) and its correlation with vascular calcification. Methods This was a single-center, cross-sectional, and observational study. Non-dialysis patients with CKD treated at Zhongshan Hospital, Fudan University from March 2021 to March 2022 were enrolled. Abdominal aortic calcification (AAC) was assessed using lateral abdominal X-ray. Number of Treg and cytokine levels were measured by flow cytometry. Logistic regression analysis was performed to evaluate the related factors for AAC in CKD patients. Results A total of 83 patients were included, aged 17–86 years, with 57 males (68.7%). The distribution of CKD stages was as follows: stage G1 in 7 patients (8.4%), stage G2 in 17 patients (20.5%), stage G3 in 21 patients (25.3%), stage G4 in 19 patients (22.9%), and stage G5 in 19 patients (22.9%). No AAC was observed in patients with stages G1 and G2, while the prevalence of AAC in patients with stages G3, G4, and G5 was 23.8%, 21.1%, and 26.3%, respectively. Compared with stage G1 patients, those with stages G3–5 showed decreased number of peripheral blood Treg and elevated levels of interleukin (IL)-6 and IL-17F (P＜0.05). The area under the receiver operating characteristic curve for number of peripheral blood Treg in predicting AAC in CKD patients was 0.766 (95%CI 0.652–0.879, P＝0.002). Logistic regression analysis showed that decreased number of Treg was related factor for AAC in CKD patients (OR＝0.957, 95%CI 0.922–0.992, P＝0.018). Conclusion As CKD progresses, number of peripheral blood Treg significantly decreases, which is correlated with AAC in CKD patients.

OBJECTIVE To investigate the levels of high-mobility group box 1(HMGB1)protein,soluble fms-like tyrosine kinase 1(sFLT-1)and lactate-to-albumin ratio(LAR)in patients with severe pulmonary infection-associ-ated sepsis undergoing continuous renal replacement therapy(CRRT),and their correlation with 28-day clinical outcomes.METHODS A total of 102 patients with severe pulmonary infection-associated sepsis undergoing CRRT admitted to the People's Hospital of Nanchuan Chongqing from Jul.2021 to Jul.2024 were enrolled.Based on 28-day clinical outcomes,they were divided into a favorable prognosis group(71 cases)and a poor prognosis group(31 cases).The levels of HMGB1,sFLT-1,lactate,albumin and LAR were compared between the two groups.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of HMGB1,sFLT-1 and LAR for 28-day clinical outcomes in patients with severe pulmonary infection-associated sepsis undergoing CRRT.RESULTS Gram-negative bacteria were the predominant pathogens in patients with se-vere pulmonary infection-associated sepsis undergoing CRRT.The poor prognosis group had higher lactate levels(4.01±1.07 mmol/L)and lower albumin levels(27.46±4.15 g/L)than the favorable prognosis group(P＜0.05).The levels of HMGB1(62.66±15.66 ng/ml),sFLT-1(0.71±0.17 ng/ml)and LAR(14.59±3.64％)in the poor prognosis group were significantly higher than those in the favorable prognosis group(P＜0.05).The combined detection of HMGB1,sFLT-1 and LAR yielded an area under the curve(AUC)of 0.949 for predicting poor 28-day mortality in patients with severe pulmonary infection-associated sepsis undergoing CRRT,superior to the single detection of the indexes(P＜0.05),with a sensitivity of 93.55％and specificity of 87.32％.CONCLUSIONS In patients with severe pulmonary infection-associated sepsis undergoing CRRT,gram-negative bacteria are the predominant pathogens.Patients with poor prognosis exhibit abnormally elevated levels of HMGB1,sFLT-1 and LAR,and the combined detection of these three markers demonstrates high predictive value for 28-day mortality.

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.

OBJECTIVE To investigate the levels of high-mobility group box 1(HMGB1)protein,soluble fms-like tyrosine kinase 1(sFLT-1)and lactate-to-albumin ratio(LAR)in patients with severe pulmonary infection-associ-ated sepsis undergoing continuous renal replacement therapy(CRRT),and their correlation with 28-day clinical outcomes.METHODS A total of 102 patients with severe pulmonary infection-associated sepsis undergoing CRRT admitted to the People's Hospital of Nanchuan Chongqing from Jul.2021 to Jul.2024 were enrolled.Based on 28-day clinical outcomes,they were divided into a favorable prognosis group(71 cases)and a poor prognosis group(31 cases).The levels of HMGB1,sFLT-1,lactate,albumin and LAR were compared between the two groups.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of HMGB1,sFLT-1 and LAR for 28-day clinical outcomes in patients with severe pulmonary infection-associated sepsis undergoing CRRT.RESULTS Gram-negative bacteria were the predominant pathogens in patients with se-vere pulmonary infection-associated sepsis undergoing CRRT.The poor prognosis group had higher lactate levels(4.01±1.07 mmol/L)and lower albumin levels(27.46±4.15 g/L)than the favorable prognosis group(P＜0.05).The levels of HMGB1(62.66±15.66 ng/ml),sFLT-1(0.71±0.17 ng/ml)and LAR(14.59±3.64％)in the poor prognosis group were significantly higher than those in the favorable prognosis group(P＜0.05).The combined detection of HMGB1,sFLT-1 and LAR yielded an area under the curve(AUC)of 0.949 for predicting poor 28-day mortality in patients with severe pulmonary infection-associated sepsis undergoing CRRT,superior to the single detection of the indexes(P＜0.05),with a sensitivity of 93.55％and specificity of 87.32％.CONCLUSIONS In patients with severe pulmonary infection-associated sepsis undergoing CRRT,gram-negative bacteria are the predominant pathogens.Patients with poor prognosis exhibit abnormally elevated levels of HMGB1,sFLT-1 and LAR,and the combined detection of these three markers demonstrates high predictive value for 28-day mortality.

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 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.

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 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.