Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ² test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ²=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ²=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.
Male ; Female ; Humans ; Retrospective Studies ; Pancreatitis, Acute Necrotizing/complications* ; Acute Disease ; Intraabdominal Infections/complications* ; Necrosis/complications* ; Treatment Outcome

OBJECTIVE: To observe the occurrence time of neuralgia and the expression of purinergic ligand-gated ion channel 7 receptor (P2X7R) in the dorsal horn of the spinal cord after intraperitoneal injection of streptozotocin (STZ) in diabetic rats, and to explore the effect of electroacupuncture (EA) and pretreatment of EA on the heat pain threshold and expression of P2X7R in the spinal dorsal horn in rats with diabetic neuropathic pain (DNP), and to explore the possible mechanism of EA for DNP. METHODS: PartⅠ: Thirty male SD rats were randomly selected from 64 male SD rats as the control group; the remaining rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model, and 30 rats were successfully modeled as the model group. The control group and the model group were divided into three subgroups respectively at 7, 14 and 21 days, with 10 rats in each subgroup. Body mass, fasting blood glucose (FBG) and thermal pain threshold were recorded at 7, 14 and 21 days after injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot. PartⅡ: Eight SD rats were randomly selected from 35 male SD rats as the blank group, and the remaining 27 rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model. The 24 rats with successful diabetes model were randomly divided into a DNP group, an EA group and a pre-EA group, 8 rats in each group. Fifteen to 21 days after STZ injection, the EA group received EA at "Zusanli" (ST 36) and "Kunlun" (BL 60), continuous wave, frequency of 2 Hz, 30 min each time, once a day; the intervention method in the pre-EA group was the same as that in the EA group. The intervention time was 8 to 14 days after STZ injection. The body mass, FBG and thermal pain threshold were recorded before STZ injection and 7, 14 and 21 days after STZ injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot 21 days after injection. RESULTS: PartⅠ: Compared with the control group, in the model group, the body mass was decreased and FBG was increased 7, 14 and 21 days after STZ injection (P<0.01), and the thermal pain threshold was decreased 14 and 21 days after STZ injection (P<0.05), and the expression of P2X7R in spinal dorsal horn was increased 7, 14 and 21 days after STZ injection (P<0.05, P<0.01). PartⅡ: Compared with the blank group, in the DNP group, the body mass was decreased and fasting blood glucose were increased 7, 14 and 21 days after STZ injection (P<0.01). Compared with the DNP group, in the pre-EA group, the heat pain threshold was increased 14 and 21 days after STZ injection (P<0.05), while in the EA group, the heat pain threshold was increased 21 days after STZ injection (P<0.01), and the expression of P2X7R in the dorsal horn in the EA group and the pre-EA group was decreased (P<0.01). CONCLUSION The diabetic neuropathic pain is observed 14 days after STZ injection. EA could not only treat but also prevent the occurrence of DNP, and its mechanism may be related to down-regulation of P2X7R expression in the dorsal horn of the spinal cord.
Animals ; Diabetes Mellitus, Experimental/therapy* ; Electroacupuncture ; Male ; Neuralgia/therapy* ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; Spinal Cord Dorsal Horn

OBJECTIVE: To identify the effect of preoperative anemia on the prognosis of patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy. METHODS: Clinicopathological and prognosis data on 686 patients with UTUC who underwent RNU at Peking University First Hospital between January 2000 and December 2013 were retrospectively analyzed. Preoperative anemia was defined as hemoglobin <130 g/L in men and <120 g/L in women based on the World Health Organization classification. The Kaplan-Meier method with log-rank test was applied to estimate the effect of anemia on survival. The associations of clinicopathologic features with overall survival and cancer-specific survival were evaluated using univariate and multivariate Cox regression models. RESULTS: There were 303(44.2%, 303/686) male and 383(55.8%, 383/686) female patients, and the median age was 68 years (interquartile range: 60-74 years). In all, 320 (46.6%, 320/686) patients were anemic before surgery. The median follow-up duration was 47 months. In all, 160 (23.3%) patients died, 141 (20.6%) died of cancer and 19 (2.7%) died of other disease or accidents. Preoperative anemia was associated with gender (P=0.002), age (P<0.001), lymph node positive (P=0.026), increased tumor grade (P=0.018), concomitant carcinoma in situ (P=0.038), tumor necrosis (P=0.007) and poor renal function (P<0.001). In univariate analysis, overall mortality was correlated with pre-operative anemia (P<0.001), gender (P=0.009), hydronephrosis (P=0.024), tumor stage (P<0.001), lymph node positive (P<0.001), tumor grade (P<0.001), tumor architecture(P<0.001), sarcomatoid differentiation (P=0.013), history of ureteroscope (P=0.033) and tumor hemorrhage (P<0.001); cancer-specific mortality was correlated with preoperative anemia (P=0.001), gender (P=0.001), hydronephrosis (P=0.043), tumor stage (P<0.001), lymph node positive (P<0.001), tumor grade (P<0.001), tumor architecture (P<0.001), sarcomatoid differentiation (P=0.016), history of ureteroscope (P=0.028) and tumor hemorrhage (P=0.003). A multivariate Cox proportional hazards model indicated that preoperative anemia was an independent prognositic predictor for overall mortality (P<0.001, HR=1.861) and cancer-specific mortality (P=0.003, HR=1.688). CONCLUSION The preoperative anemia is an independent risk factor for cancer-specific survival and overall survival. Hemoglobin levels should be considered during patient counseling and in decision-making for further therapy.
Aged ; Anemia ; Carcinoma, Transitional Cell/surgery* ; Female ; Humans ; Male ; Middle Aged ; Nephrectomy ; Nephroureterectomy ; Prognosis ; Retrospective Studies ; Urologic Neoplasms/surgery*

Objective To compare the efficacy and safety of tacrolimus with those of cyclosporine in treating idiopathic membranous nephropathy (IMN) via network meta-analysis. Methods Databases including PubMed,Embase,CENTRAL (Cochrane),Wanfang Database,CNKI,and VIP citation database were searched for relevant studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Package Meta 4.5.0 and Gemtc 0.8.1 in R 3.3.1 were used to analyze the included studies. Results In this network meta-analysis,the complete remission rate (RR=0.98,95% CI:0.70-1.40)and the total remission rate (RR=1.00,95% CI:0.90-1.20)of idiopathic membranous nephropathy did not differ significantly between IMN patients treated with cyclosporine A or tacrolimusand,nor did the incidences of hepatic dysfunction(RR=1.40,95% CI:0.52-4.00),infection(RR=0.75,95% CI:0.18-3.10),or gastrointestinal syndrome(RR=2.1,95% CI:0.36-28.00). Conclusion Cyclosporine A seems to have similar effectiveness and safety to tacrolimus in treating IMN.

Objective To identify the epidemic characteristics and risk factors of an emerging infectious disease-severe fever with thrombocytopenia syndrome (SFTS) in Hubei province.Methods Active surveillance program on SFTS was set up in monitoring sites-hospitals,at the township level or above,in Suizhou,Huanggang and Wuhan from January to December,2010.Specific surveillance program on SFTS was launched across the province in hospitals above the county level.Cases that matched the definition of surveillance case were identified and reported to Centers for Disease Control and Prevention (CDCs).Cases were interviewed and their blood samples collected and detected using PCR and virus isolation.We also conducted serum antibody surveys among healthy population and livestock and surveillance on vector ticks in those high-epidemic areas.Results 188 cases that matched the definition of surveillance case and 21 deaths were reported in 11 cities,32 countries and 100 towns in 2010,with an incidence rate of 0.33/106.The fatality rate was 11.2％.Data showed that the patients were from hilly areas at the altitude elevated between 28-940 meters.The epidemic period was between April and December with the peak from May to September.The youngest case was an 11-year old,while the eldest was 81 with median age as 56-year old.95.3 ％ of the patients were farmers.All Patients did not have the history of traveling,two weeks before the onset of SFTS.93.6％ of the patients engaged in different kind of work which was associated with agriculture.52.8％ of the patients had been exposed to ticks.22.0％ of the patients had been bitten by ticks.Skin injury was found in 64.2％ of the patients.Samples from 129 cases (68.6％) were collected and detected,with 67.4％ of them (87 cases) showed positive by Real time-PCR for SFTS virus.An elevation in antibody titer by a factor of four or evidence of sero-conversion was observed in 11 patients; SFTS virus was isolated from 2 patients.The total antibody positive rates were 3.8％,55.0％ (6/11 ),36.7％ (2/3) and 80.0％ (4/5) respectively in healthy population,dogs,sheep and cows.Ticks from grass,cattle and sheep were detected positive by Real time-PCR.Conclusion Most cases of SFTS in Hubei were infected by SFTS virus,and cases of livestock were infected by SFTS virus.Ticks might serve as an important vector.Skin injury,exposure to tick bites seemed to be the risk factors.

Animals ; Glutathione ; therapeutic use ; Liver ; metabolism ; physiopathology ; Male ; NF-kappa B ; biosynthesis ; Pancreatitis, Acute Necrotizing ; drug therapy ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley