Objective This study aimed to explore the effect of the combined Danzhi Jiangtang Capsule with dapagliflozin on the blood lipid profile and related inflammatory markers in patients with type 2 diabetes mellitus with peripheral vascular disease. Methods 72 patients with type 2 diabetes mellitus with peripheral vascular disease who met the inclusion criteria were admitted to the Department of Endocrinology,The First Affiliated Hospital of Anhui University of Chinese Medicine,from April 2021 to April 2023. The patients were assigned to the experimental group and the control group using the random number table method (36 cases in each group). The control group was treated with dapagliflozin in addition to standard treatment,while the experimental group received the Danzhi Jiangtang Capsule for 12 weeks. Clinical efficacy,glucose and lipid metabolism indicators,hypersensitive C-reactive protein (hs-CRP),body mass index (BMI) levels,and traditional Chinese medicine (TCM) syndrome scores were observed pre-and post-treatment.Results In post-treatment,the clinical efficacy was higher in the experimental group than in the control group. Significant reductions in fasting blood glucose (FPG),2 h postprandial glucose (2 hPG),triglycerides (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),hs-CRP,BMI,and increased high-density lipoprotein cholesterol (HDL-C) were observed. Scores for TCM syndrome and individual items also decreased (P<0.05). Comparisons within the groups for pre-and post-treatment showed reductions in FPG,2 hPG,TG,TC,LDL-C,hs-CRP,and an increase in HDL-C,along with a decrease in total scores of TCM syndrome (P<0.05). Conclusion The Danzhi Jiangtang Capsule combined with dapagliflozin in the treatment of type 2 diabetes mellitus with peripheral vascular disease can regulate the blood lipid profile,reduce inflammatory factors,and improve patient's symptoms. Integrated traditional Chinese and Western medicine treatment are more conducive to controlling the disease,and TCM can be used in clinical practice as a combination treatment.

Objective:To investigate the value of soluble interleukin-6 (IL-6) receptor (sIL-6R) level in predicting ultrafiltration insufficiency in peritoneal dialysis (PD) patients.Methods:It was a prospective cohort study. The patients who received continuous ambulatory PD and regular follow-up between November 2016 and July 2018 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled. Enzyme-linked immunosorbent assay was used to determine dialysate sIL-6R and its appearance rate (AR) was calculated. Patients were divided into high sIL-6R AR group and low sIL-6R AR group according to median value of sIL-6R AR and prospectively followed up until death, PD cessation, or the end of the study (December 31, 2022). Multiple linear regression was used to analyze the related factors of sIL-6R AR. Kaplan-Meier method and log-rank test were used to compare the survival rate difference of ultrafiltration insufficiency between high sIL-6R AR group and low sIL-6R AR group. Multivariate Cox regression and multivariate competing risk models were used to assess the risk factors associated with occurrence of ultrafiltration insufficiency.Results:A total of 198 PD patients were enrolled, including 115 (58.1%) males, with age of (54.9±13.7) years old and PD duration of 22.5 (6.6, 65.0) months. The sIL-6R AR of the cohort was 2 094.7 (1 672.4, 2 920.9) pg/min. Compared with low sIL-6R AR（<2 094.7 pg/min）group, high sIL-6R AR（>2 094.7 pg/min）group had older age ( t=-3.269, P=0.001), higher body mass index ( t=-3.248, P=0.001), proportion of combined diabetes mellitus ( χ2=8.890, P=0.003), 24 h glucose exposure ( Z=-2.257, P=0.024), 24 h ultrafiltration capacity ( Z=-2.515, P=0.012), 4 h dialysate creatinine to serum creatinine ratio ( t=-2.609, P=0.010), mass transfer area coefficient of creatinine ( Z=-2.308, P=0.021), IL-6 AR ( Z=-3.533, P<0.001) and solute glycoprotein 130 AR ( Z=-8.670, P<0.001), and lower serum albumin ( t=2.595, P=0.010) and residual renal function ( t=2.133, P=0.033). Multiple linear regression analysis showed that body mass index ( β=0.194, P=0.005), serum albumin ( β=-0.215, P=0.002) and dialysate lg[IL-6 AR] ( β=0.197, P=0.011) were independently correlated with sIL-6R AR. By the end of the study, 57 (28.8%) patients developed ultrafiltration insufficiency. Kaplan-Meier analysis showed that high sIL-6R AR group had a significantly inferior ultrafiltration insufficiency-free survival rate than that in low sIL-6R AR group (log-rank χ 2=5.375, P=0.020). Multivariate Cox regression analysis and multivariate competing risk models showed that high dialysate sIL-6R AR (>2 094.7 pg/min) was an independent influencing factor of ultrafiltration insufficiency ( HR=2.286 , 95% CI 1.254-4.165 , P=0.007 ; SHR=2.074, 95% CI 1.124-3.828, P=0.020) in PD patients. Conclusions:Dialysate sIL-6R level was associated with body mass index, serum albumin and dialysate IL-6 level. Dialysate sIL-6R may be a predictive factor of ultrafiltration insufficiency in PD patients.

Objective:To screen the differentially expressed genes(DEGs)under high phosphate-induced calcification in the vascular smooth muscle cells(VSMCs)by mRNA high-throughput sequencing technology,and to analyze the key genes and signaling pathways involved in the VSMCs calcification.Methods:The human VSMCs were divided into control group and model group.The cells in model group was exposed to the high-phosphate medium,while the cells in control group were cultured in DMEM supplemented with 10%fetal bovine serum under the same conditions.The VSMCs in two groups,stably transfected,were cultured for 12 d.The morphology of the cells in two groups were observed and photographed under inverted microscope.The DEGs were selected by Hisat2 software,and Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by Stringtie software from three aspects,such as biological processes(BP),molecular functions(MF),and cellular components(CC).The calcification of the cells in two groups was observed by Von Kossa staining method.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to analyze the expression levels of alkaline phosphatase(ALP),bone morphogenetic protein 2(BMP2),alpha-smooth muscle actin(α-SMA),tumor protein 53(Tp53),glutathione peroxidase 4(GPX4),ferritin light chain 1(Ftl1),and glycosylphosphatidylinositol-specific phospholipase D1(GPLD1)mRNA in the cells in two groups.Results:Compared with control group,there were 2 524 DEGs in the cells in model group,and there were 1 368 upregulated DEGs and 1 156 downregulated DEGs.Clustering of DEGs between the cells in two groups was distinct.The GO functional and KEGG pathway enrichment analysis results showed that the upregulated DEGs were primarily involved in regulating the microtubule cytoskeleton,cell polarity,protein localization,and cell cycle regulation among BPs;in constructing cell membrane,microtubule organization,chromosomes,and kinetochore among CCs;and functioning in phosphatidylinositol phosphate,Rho GTPase protein binding,transmembrane transport,and protein kinase regulatory activity among MFs.Downregulated DEGs were mainly involved in cytoplasmic translation,protein membrane localization,mRNA metabolism,and protein endoplasmic reticulum localization among BPs;in forming ribosome subunits,cell membrane,and autophagy among CCs;and functioning in single-stranded DNA,ribonucleoprotein complex,growth factor binding,regulating protein kinase activity,and catalytic activity among MFs.Seven signaling pathways were significantly enriched in upregulated genes,most notably in the biosynthesis of glycosylphosphatidylinositol(GPI)anchors;whereas 18 signaling pathways were significantly enriched in the downregulated genes,most notably in ferroptosis.The RT-qPCR results showed that compared with control group,the expression levels of GPX4,Ftl1,and Tp53 mRNA in the cells in model group were significantly decreased(P<0.01),while the expression level of GPLD1 mRNA was significantly increased(P<0.01);compared with control group,the expression level of α-SMA mRNA in the cells in model group was significantly decreased(P<0.01),and the expression levels of ALP and BMP2 mRNA were significantly increased(P<0.01).Conclusion:The VSMCs underwent calcification and normal cells exhibit the DEGs.The key signaling pathways in the calcification induced by high phosphate in the VSMCs include ferroptosis and GPI anchor biosynthesis,mediated primarily through GPX4,Ftl1,Tp53,and GPLD1.

Objective:To evaluate the influencing factors of carotid-femoral pulse wave velocity (CF-PWV) and its value to predict outcomes in peritoneal dialysis (PD) patients.Methods:Eligible patients undergoing PD in Renji Hospital of Shanghai Jiao Tong University between August 2016 and July 2018 were recruited and prospectively followed up until death, PD cessation, or to the end of the study. CF-PWV was measured by an arterial pulse wave velocity meter to assess arterial stiffness (July 31, 2020). Overhydration was measured by bioimpedance spectroscopy. The patients were divided into CF-PWV≤10 m/s group and CF-PWV>10 m/s group according to the measured value of CF-PWV. The influencing factors of elevated CF-PWV were analyzed by multivariate logistic regression. Survival curves were generated using the Kaplan-Meier method and multivariate Cox proportional hazards models were used to analyze the difference for all-cause mortality and cardiovascular disease (CVD) mortality between the two groups.Results:A total of 224 PD patients were enrolled, including 133 males (59.4%). The age was (55.2±13.4) years old, and median PD vintage was 22.3(6.5, 59.3) months. Among them, 47(21.0%) patients were comorbid with diabetes, and 37(16.5%) patients had CVD history. The median CF-PWV was 9.6(8.4, 11.4) m/s for the cohort, and 105(46.9%) participants had CF-PWV over 10 m/s. Compared with CF-PWV≤10 m/s group, CF-PWV>10 m/s group patients had older age, increased percentage of diabetes and CVD (all P<0.05). Multivariate logistic analysis showed that increased age ( OR=1.070, 95% CI 1.043-1.099, P<0.001), diabetes ( OR=3.693, 95% CI 1.646-8.287, P=0.002) and higher overhydration ( OR=1.238, 95% CI 1.034-1.483, P=0.020) were independent influencing factors for elevated CF-PWV in PD patients. After followed up for 37.4(25.6, 41.7) months, 24 patients died, including 19 cases of CVD-related deaths. Kaplan-Meier survival analysis showed that all-cause mortality and CVD mortality were significantly higher in the CF-PWV>10 m/s group than those in CF-PWV≤10 m/s group (Log-rank χ2=6.423, P=0.011; Log-rank χ2=6.243, P=0.012, respectively). Multivariate Cox proportional hazards models showed that increased age was an independent influencing factor for both all-cause mortality and CVD mortality ( HR=1.057, 95% CI 1.010-1.107, P=0.018; HR=1.062, 95% CI 1.009-1.118, P=0.022). Conclusions:Increased arterial stiffness is relatively common in PD patients. Higher CF-PWV in PD patients is associated with increased age, diabetes and higher overhydration, and it is probably a valuable predictor of outcome in PD patients.

Objective:To investigate the curative efficacy of radical prostatectomy (RP) for T 4 stage prostate cancer invading bladder neck. Methods:The clinical data of 22 patients with T 4 stage prostate cancer invading bladder neck treated with RP from April 2013 to March 2021 were analyzed retrospectively. The mean age of the patients was (64.09±6.33) years, and the preoperative blood PSA was 57.70(39.40, 68.56) ng/ml. Preoperative MRI or PSMA-PET examination revealed bladder neck invasion, including 16 cases (72.73%) of urinary retention. Clinical stage of T 4N 0M 0 accounted for 40.91% (9/22), T 4N 1M 0 accounted for 45.45% (10/22), and T 4N 1M 1 accounted for 13.64% (3/22). Preoperative patients were not treated with neoadjuvant endocrine or chemotherapy. Laparoscopic or robotic assisted laparoscopic radical prostatectomy and pelvic lymph node dissection were performed. Results:The 22 operations were successfully completed without conversion. The operation time was(184.27±34.82) min, the amount of intraoperative bleeding was (210.91±83.03) ml, the retention time of drainage tube was (4.73 ± 1.03) days, the recovery of gastrointestinal function took 3 (2, 3) days, and the postoperative hospital stay was (6.68 ± 1.39) days. Postoperative pathology showed that the Gleason score of 7 points accounted for 4.54% (1/22), 8 points accounted for 13.64% (3/22), and 9 points accounted for 81.82% (18/22). The positive rate of margin was 81.82% (18/22). Pathological stage of T 4N 0M 0 accounted for 22.73% (5/22), T 4N 1M 0 accounted for 63.64% (14/22), and T 4N 1M 1 accounted for 13.64% (3/22), of which extracapsular or seminal vesicle invasion accounted for 90.91% (20/22). The incidence of postoperative complications above grade 3 was 9.09% (2/22), and the rate of urinary control recovery after 3 months of surgery was 90.91% (20/22). 16 patients with preoperative urinary retention were able to urinate normally after operation. All patients were treated with adjuvant androgen deprivation therapy (ADT) with or without antiandrogens, and 13 cases (59.09%) were treated with adjuvant radiotherapy. The postoperative PSA value before adjuvant treatment was 2.53 (0.51, 5.44) ng/ml. The median survival time was not reached. Two patients died of prostate cancer at 71 and 84 months and one patient died of heart disease at 28 months. Conclusions:RP surgery could effectively relieve the condition of urinary retention with low incidence of operative complications. Although the positive rate of surgical margin is high, RP could be used as one of the treatment options for T 4 stage prostate cancer invading bladder neck, while the long-term effect is still needed to be further analyzed.

Objective:To investigate the predictive value of peritoneal protein clearance (Pcl) for cardiovascular events and cardiovascular mortality in peritoneal dialysis (PD) patients.Methods:Eligible PD patients were prospectively enrolled from January 2014 to April 2015 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University. All patients were followed up until death, withdrawing from PD, transferring to other centers, or the end of study period (October 1, 2018). The patients were divided into high Pcl group and low Pcl group by the median Pcl, and the differences of related indicators between the two groups were compared. A multiple linear regression model was used to analyze the influencing factors of Pcl. The Kaplan-Meier method and Log-rank test were used to compare the cumulative survival rates of patients between the two groups. A multivariate Cox regression model was used to estimate the risk of cardiovascular events and cardiovascular mortality in relation to Pcl in PD patients.Results:A total of 271 patients were enrolled, with 135 males (49.8%), age of (56.92±0.84) years old and a median PD duration of 38.77(19.00, 63.10) months. There were 70 patients (25.8%) comorbiding with diabetes and 81 patients (29.9%) with cardiovascular diseases (CVD). The median Pcl of this cohort was 67.93(52.31, 88.36) ml/d. Compared with the low Pcl group (Pcl<67.93 ml/d), the high Pcl group (Pcl≥67.93 ml/d) had older age, and greater proportion of CVD, body mass index (BMI), pulse pressure, brain natriuretic peptide, mass transfer area coefficient of creatinine (MTACcr), and lower serum albumin (all P<0.05). There was no significant difference in gender, dialysis duration, proportion of diabetes, proportion of angiotensin converting enzyme inhibitor and angiotensin receptor blocker, proportion of continuous ambulatory PD, high sensitivity C reactive protein, fluid removal including 24 h urine volume and 24 h ultrafiltration, and residual renal function between the two groups (all P>0.05). Multiple linear regression analysis showed that serum albumin ( β=-0.388, P<0.001), BMI ( β=0.189, P<0.001), and MTACcr ( β=0.247, P<0.001) were independently related to lg(Pcl). During the study period, 55 patients experienced one or more cardiovascular events and 39 patients had cardiovascular mortality. According to Kaplan-Meier analysis, cardiovascular mortality in the high Pcl group was higher than that of low Pcl group (Log-rank χ2=6.902, P=0.009). Multivariate Cox regression analysis showed that, high lg(Pcl) was an independent influencing factor of cardiovascular events in PD patients ( HR=7.654, 95% CI 1.676-34.945, P=0.009). Conclusions:Serum albumin, BMI and MTACcr are independently associated with Pcl, and Pcl is an independent predictor of cardiovascular events in PD patients.

Objective:To explore the association of abdominal aortic calcification score (AACS) with cardiovascular disease (CVD) outcomes in peritoneal dialysis (PD) patients.Methods:The patients who underwent regular PD at Renji Hospital between July 2011 and July 2014 were recruited and prospectively followed up until the end of the study (August 31, 2018), death, or dropout PD. Abdomen lateral X-ray was used to determine AACS for each patient at enrollment. Patients were divided into three groups based on the tertiles of AACS: non-calcified group, AACS group (AACS=0), mild-moderate calcification group AACS group (0

Objective To investigate the prevalence and risk factors of sarcopenia in peritoneal dialysis (PD) patients.Methods The patients who underwent regular peritoneal dialysis at Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine between November 2016 and March 2018 were enrolled.Handgrip strength (HGS) was measured to assess muscle strength.Bioelectrical impedance spectroscopy (BIS) was applied to measure the lean tissue index (LTI).Reduced LTI plus decreased HGS was defined as sarcopenia.The prevalence of sarcopenia in PD patients was evaluated.According to the presence or absence of sarcopenia,they were divided into the sarcopenia group and the non-sarcopenia group,and the differences in clinical indicators between the two groups were compared.Multivariate logistic regression was used to explore the risk factors of sarcopenia in PD patients.Results A total of 207 patients were enrolled in the study with age of (55.3±13.7) years and a median PD duration of 22.9(7.3,60.9) months.Of them,122 patients (58.9％) were male,45 patients (21.7％) had diabetics and 32 patients (15.5％) suffered from cardiovascular diseases.There were 27 patients (13.0％) diagnosed with sarcopenia.These patients presented with longer PD duration,more prevalent diabetics,lower residual renal function (RRF) and serum pre-albumin,greater ratio of extracellular water to intracellular water (ECW/ICW) and high sensitive C-reactive protein in contrast with those in the non-sarcopenia group (all P ＜ 0.05).Multivariate logistic analysis showed that male (OR=3.94,95％ CI 1.35-11.50,P=0.O12),longer PD duration (OR=1.01,95％CI 1.00-1.02,P=0.029) and higher ECW/ICW (OR=1.09,95％CI 1.05-1.14,P ＜ 0.001) were independent risk factors of sarcopenia in PD patients.Conclusions Sarcopenia is common in PD patients.Male,longer PD duration and higher ECW/ICW were independent risk factors of sarcopenia in PD patients.

Objective To investigate the effect of pyrin domain 3 (NLRP3) inflammasome in the process of contrast induced human kidney cell apoptosis.Methods Human kidney 2 (HK-2) cells were cultured in DMEM-F12 medium with 5％ FBS.Cells were divided into control group,Contrast group (O group),NLRP3-siRNA+Iohexol group (si-NLRP3+O group),ASC-siRNA+Iohexol group (si-ASC+O group),and mannitol group (M group).Different concentrations of hypotonic contrast agent were added to HK-2 cell culture plates for 24,48 and 72 h.Flow cytometry was used to detect apoptosis.NLRP3 and ASC mRNA expressions were detected by RT-PCR.The expressions of NLRP3,ASC,caspase-8/cleaved caspase-8,Bcl-2/Bax,caspase-1/cleaved caspase-1,and caspase-3/cleaved caspase-3 protein were detected by Western blot.The levels of interleukin (IL) 1β and IL-18 in supernatant were detected by ELISA.Results Compared with the control group,the rate of apoptotic cells,as well as the expressions of NLRP3,ASC and cleaved caspase-1 proteins were increased in HK-2 cells of contrast group.The expressions of NLRP3 and ASC mRNA in the contrast group also increased,so did IL-1β and IL-18 levels (all P＜0.05),suggesting that NLRP3 inflammasome in HK-2 cells was activated by contrast.Compared with the control group,the expressions of cleaved caspase-8,Bax and cleaved caspase-3 protein were increased,and the expression of anti-apoptotic protein Bcl-2 was decreased (all P ＜ 0.05).Compared with the contrast group,the rate of apoptotic cells in the si-NLRP3 + contrast group and si-ASC + contrast group was significantly decreased;the expression of cleaved caspase-1 was decreased;the expressions of Bax and cleaved caspase-3 were decreased,and Bcl-2 level was increased.The expressions of IL-1β and IL-18 in the supernatant of cells were decreased (all P ＜ 0.05).Conclusion Contrast agent can activate the NLRP3 pathway in HK-2 cells and induce apoptosis,which could be reduced by blocking the NLRP3 pathway.