Recent advances of clinical researches on antibody-mediated rejection by targeting interleukin-6 and its receptor / 中华器官移植杂志

Chronic kidney disease has been a global public health problem with a heavy disease burden.As a kidney replacement therapy, kidney transplantation(KT)has a higher long-term survival rate and quality-of-life as compared with dialysis.Antibody-mediated rejection(AMR)is a major complication after KT.Currently its core treatments are steroid hormones, plasma exchange and immunoglobulin.However, the effectiveness of new therapeutic agents such as anti-CD20 antibody and bortezomib has remained controversial.Despite these combination treatments, AMR is still a predominant cause of graft loss and it is imperative to seek novel effective treatments.Interleukin-6(IL-6)is a vital cytokine involved in the regulation of inflammation and the development, maturation and activation of T/B cells.Specifically targeting IL-6, ptolizumab and crazizumab are currently widely applied for managing AMR and blunting highly sensitized KT recipients.This review summarized the clinical applications of IL-6 for AMR.

The mechanism by which tamoxifen attenuates high glucose-induced epithelial-to-mesenchymal transition of rat peritoneal mesothelial cells / 中国基层医药

Objective:To investigate the effects of tamoxifen on high glucose-induced epithelial-to-mesenchymal transition of rat peritoneal mesothelial cells and the underlying mechanism.Methods:The peritoneal mesothelial cells of normal male SD rats were selected between January 2015 and June 2016 and then cultured and divided into blank control, high-glucose stimulation and drug intervention groups. High-glucose stimulation group: primary cultured rat peritoneal mesothelial cells (RPMCs) were treated with 60 mmol/L high-concentration glucose to induce epithelial-to-mesenchymal transition. Drug intervention group: (1) RPMCs were treated with 60 mmol/L high-concentration glucose and different concentrations (0.5 μmol/L, 2 μmol/L) of tamoxifen. After 72 hours of stimulation, protein was extracted. (2) RPMCs were treated with 60 mmol/L high-concentration glucose and 2 μmol/L tamoxifen with or without 2 μmol/L ER-α antagonist for 1 hour to extract protein and for 6 hours to extract RNA. (3) RPMCs were treated with high-concentration glucose and 2 μmol/L tamoxifen with or without 1 μmol/L 1 μM proteasome inhibitor for 1 hour to extract protein. Western blot analysis was performed to analyze change in E-cadherin, α-SMA, Smad2, p-Smad2, Smad3, p-Smad3 and Smad4 protein. Real-time fluorescence quantitative PCR was performed to detect the change in mRNA expression of Smad2, Smad3, connective tissue growth factor and plasminogen activator inhibitor 1.Results:Tamoxifen attenuated epithelial-to-mesenchymal transition on RPMCs induced by high-level glucose, showing increased expression of epithelial cell marker E-cadherin and decreased expression of α-SMA in a concentration-dependent manner ( tE-cadherin = 2.31, tα-SMA =-2.53, both P < 0.05).TGF-β1/R-Smad signal pathway was activated by high-concentration glucose. Phosphorylation of Smad2/3 and mRNA expression of CTGF and PAI-1 were increased. Tamoxifen remarkably reduced protein and mRNA level of above mentioned protein and related target genes ( tp-Smad2 = -3.38, tCTGF = -3.81, P < 0.05), which could be blocked by ER-α antagonist. Finally, proteasome inhibitor could weaken the inhibitory effects of tamoxifen on p-Smad2/3 and increase p-Smad2/3 protein level ( tp-Smad2 = 3.94, P < 0.05). Conclusion:Tamoxifen activates ER-α on RPMCs, weakens the activation of TGF-β1/R-Smad signal pathway through decreasing p-Smad2 protein level, and effectively inhibits the progression of high-concentration glucose-induced epithelial-to-mesenchymal transition possibly through degrading p-Smad2 protein through proteasome. The role of tamoxifen in epithelial-to-mesenchymal transition may provide a possible guide for research, prevention and treatment of peritoneal fibrosis.

Management practice of COVID-19 prevention in transplant patients based on crisis leadership model / 中华医院管理杂志

In the COVID-19 epidemic prevention and control work, not only the safety management of in-hospital organ transplantation is facing severe challenges, but also a large number of patients at home after transplantation are in immunosuppressive state, and professional protection management is urgently needed. Since the outbreak of the epidemic, Shulan(Hangzhou)hospital fully identified the risks of transplant patients, established a special team, and formulated and implemented the control management plan for organ transplant patients based on the crisis leadership model. The control management plan has achieved staged results.From January 15 to March 2, 2020, 29 liver transplants and 31 kidney transplants were performed in our hospital. The remote health education of 1 002 patients after liver and kidney transplantation was completed. The goal of " zero infection" was achieved, and the protection management quality indicators were ideal.

Effects of Niaoduqing granule on urine metabolic profile in chronic renal failure rats / 浙江大学学报·医学版

OBJECTIVE@#To investigate the effects of Niaoduqing granule on the urine metabolic profile in chronic renal failure (CRF) rats.@*METHODS@#Thirty six male SD rats were divided into the normal control group, the model group, and the Niaoduqing group with 12 rats in each group. The CRF was induced by gavage of 250 mg·kg·d adenine for 21 d. UPLC-Q-TOF-MS/MS technique was used in combination with principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) to analyze the urine metabolic profiles in three groups. The endogenous substances with the variable importance projection (VIP)>1 and <0.05 were screened as the potential biomarkers for CRF, and enrichment analysis of metabolic pathways was carried out.@*RESULTS@#Compared with the normal control group, the model group had lower body weight, higher kidney coefficient, higher serum creatinine and urea nitrogen levels (all <0.01), while the above indexes in the Niaoduqing group were ameliorated compared with the model group (all <0.01). Fifteen potential biomarkers were found in the urine of the model group, which were involved in 9 metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, glyoxylate and dicarboxylate metabolism, valine, leucine and isoleucine biosynthesis, arachidonic acid metabolism, cysteine and methionine metabolism, tricarboxylic acid cycle, glycerophosphatide metabolism, tryptophan metabolism and tyrosine metabolism.@*CONCLUSIONS@#Niaoduqing granules has therapeutic effect on rats with CRF, which may be related to the regulation of amino acid metabolism, lipid metabolism and energy metabolism.

Hookworm Anemia in a Peritoneal Dialysis Patient in China

Hookworm infections as well as other intestinal nematodiases are endemic in China. In this case, a 70-year-old male showed symptoms of chest tightness, shortness of breath, and both lower extremities edema. The diagnostic result was chronic renal insufficiency, chronic kidney disease (5th stage), and renal anemia at first. Then, he received treatment with traditional drugs. However, this treatment did not help to alleviate the symptoms of the patient significantly. The results of gastroendoscopy showed hookworms in the duodenum, also confirmed by pathology examination. Anemia was markedly ameliorated after eliminating the parasites. The results mentioned above suggested that ancylostomiasis was the leading causes of anemia in this patient, and the etiology of anemia in uremic patients should be systematically considered. Especially when anemia could not be cured by regular treatments, rare diseases should be investigated.

Effects of interim hemodialysis on survival and clinical outcomes in patients with maintenance peritoneal dialysis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of interim hemodialysis (HD) on survival and clinical outcomes in patients with maintenance peritoneal dialysis (PD).</p><p><b>METHODS</b>The clinical data of 908 patients undergoing maintenance PD from January 2010 to December 2014 registered in Zhejiang Dialysis Regisration System were retrospectively analyzed. Among all PD patients, 176 cases received interim HD for less than 3 months, and then transferred to PD (transfer group) and 732 cases had initial PD (non-transfer group). The demographic parameters, biochemical data, comorbidity, details of peritonitis and transplantation were documented. Survival curves were made by the Kaplan-Meier method; univariate and multivariate analyses were performed with Cox proportional hazard regression model to identify risk factors of mortality.</p><p><b>RESULTS</b>Compared with patients in transfer group, patients in non-transfer group had significantly higher serum albumin and total Kt/V levels. The survival rate was significantly higher in non-transfer group, but there was no significant difference in technique survival between two groups. After multivariable adjustment, initial dialysis modality (HR=1.60, 95% CI: 1.01~2.56), age (HR=1.07, 95% CI:1.05~1.09) and serum albumin (HR=0.96, 95% CI: 0.93~0.99) and Charslon comorbidity index (HR=2.54, 95% CI:1.63~3.94) were independent factors for long-term survival.</p><p><b>CONCLUSION</b>Patients who transfer to PD after interim HD have lower survival rate than patients who start with and are maintained on PD. HD is an independent risk factor for PD patients, therefore, patients with PD should be well informed and educated with dialysis protocols.</p>

Effect of lipoic acid on oxidative stress, inflammation and nutritional status in peritoneal dialysis patients / 中国免疫学杂志

Objective:To explore the effect of lipoic acid on oxidative stress,inflammation and nutritional status in peritoneal dialysis patients.Methods:94 peritoneal dialysis patients were randomly divided into the observe group(n=47) the control group(n=47).They all accepted the conventional treatment,but the patients in the observed group were given the treatment of lipoic acid capsules(0.2 g tid) for 12 weeks.Superoxide dismutase(SOD),malondialdehyde(MDA),serum advanced oxidation protein products ( AOPPs ) were used to reflect the level of oxidative stress, high sensitive CRP, IL-6 and TNF-αwere used to reflect the micro inflammatory state, modified quantitative subjective global assessment ( MQSGA ) , mid-arm circumference, mid-arm muscle circumference,triceps skinfold thickness ( TSF ) , body mass index ( BMI ) , and serum albumin were used to reflect the nutritional status.The difference of oxidative stress, micro inflammatory state and nutritional status were compared between the two groups.Results:①In the observation group,the concentrations of AOPPs and MDA after treatment were significantly lower than that before treatment,and the concentration of SOD after treatment was significantly higher than that before treatment ( P<0.05 );after treatment,the concentrations of AOPPs and MDA in the observe group were significantly lower than that in the control group(P<0.05), and the concentration of SOD in the observe group was significantly higher than that in the control group ( P<0.05 ) .②In the observation group,the concentrations of high sensitive CRP,IL-6 and TNF-αafter treatment were significantly lower than that before treatment(P<0.05);after treatment,the concentrations of high sensitive CRP,IL-6 and TNF-αin the observe group were significantly lower than that in the control group ( P<0.05 ) .③In the observation group, the TSF, mid-arm circumference, mid-arm muscle circumference,BMI and albumin after treatment were significantly higher than that before treatment(P<0.05),and the MQSGA after treatment was significantly lower than that before treatment ( P<0.05 );after treatment, the MQSGA in the observe group was significantly lower than that in the control group(P<0.05),and serum albumin in the observe group was significantly higher than that in the control group(P<0.05).Conclusion:Lipoic acid could improve oxidative stress in peritoneal dialysis patients,so as to improve the micro inflammatory state and nutritional status.

In vitro study of inhibitory effects of pregnancy-induced regulatory T cells on na?ve T cells prolifera-tion / 中华微生物学和免疫学杂志

Objective To investigate the in vitro inhibitory effects of regulatory T cells ( Treg ) from unpregnant mice and pregnancy-induced regulatory T cells ( piTreg) on the proliferation of na?ve T cells and their differences .Methods The numbers of piTreg cells from allogeneic pregnant mice ( C57/B6 fe-male×BALB/c male) on day 12.5 (E12.5d) of gestation and Treg cells from unpregnant C57/B6 mice were detected respectively by flow cytometry .The percentages of piTreg cells and Treg cells in CD 4+T cells of age-matched female mice and their intracellular expression of Foxp 3 were analyzed .The in vitro inhibitory effects of piTreg cells and Treg cells on the CFSE-labeled na?ve T cells ( effector cells ) were compared in a one-way mixed lymphocyte culture system using mitomycin C-inactivated CD4-T cells as stimulator cells . Results The level of piTreg cells in splenic mononuclear cells was significantly higher than that of Treg cells (P<0.001) from normal mice.Foxp3 was highly expressed in both piTreg cells and Treg cells , howev-er slightly increased in piTreg cells .Moreover , piTreg cells had a significant stronger in vitro inhibitory effect on na?ve T cells proliferation than that of Tregs cells (P<0.006), which was in a cell-dependent manner. Conclusion The present study suggests that the piTreg cells have a stronger inhibitory effect on na ?ve T cell proliferation as compared with Terg cells from unpregnant mice , The differential activity of CD 4+CD25+Treg might be mediated by the paternal antigens during pregnancy .

Clinical analysis of 2520 renal transplantations in one center / 中华器官移植杂志

Objective To evaluate the effects of different strategies on short-and long-term clinical outcomes of renal transplantation in Chinese subjects.Methods 2520 renal transplantations were retrospectively evaluated,including 2490 first renal transplantations and 30 second renal transplantations.Triple-immunosuppressant including cyclosporine A,azathioprine or myeophenolate mofetil(MMF)and prednisone(Pred)was adopted.Patients receiving kidney transplantation were given low dose immunosuppressants since 2000.Immunosuppressants including tacrolimus,MMF and Pred were adopted in some patients since 2000.Risk factors leading to graft loss and patients'death were analyzed.Results Until the cut date of June 30,2009,135 patients lost follow-up,and the follow-up rate was 94.6%.Incidence of acute(within 6 months post-transplantation) rejection was 18% among 2520 patients.Incidence of acute rejection (within 6 months post-transplantation) was 25.7% in panel reactive antibody (PRA) positive patients,significantly higher than 17.0% in PRA negative patients(P<0.05).Incidence of acute rejection within 6 months post-transplantation was 16.9% in HLA mismatches<4 patients,significantly lower than 23.7% in HLA≥4 patients (P<0.01).Total patient/death censored graft 1-,3-,5- and 1O-year survivals were 94.5%/96.0%,91.6%/93.1%,88.5%/90.1% and 81.7%/80.6%,respectively.Acute rejection and immunosuppressant regimen were independent risks for allograft loss.1mmunosuppressant regiment,pulmonary infection,cardio-brain-vessel accident, hepatic failure and tumor were independent risks for patients' death.Conclusion Renal allograft and patient survival appeared to be improved by optimal immunosuppressant regimen,strict HLA match and efficient post-transplant complication prophylaxis.

SHARP-2 gene silence by lentiviral-based short hairpin RNA interference prolongs survival time of rat kidney transplant recipients / 中华肾脏病杂志

Objective To investigate if rat enhancer of split- and hairy-related protein-2 (SHARP-2) short hairpin RNA interference (shRNAi) prolongs the survival time of rat kidney transplant recipients. Methods Gene recombinant procedures, transfection and co-transfection were carried out to introduce short hairpin RNA interference sequences target for SHARP-2 into 3rd generation self-inactivated lentiviral-ViraPower packaging mix. Limiting dilution method was used for viral titration. Real-time PCR was employed for quantification of gene expression. Rat kidney transplantation was utilized to investigate the effect of SHARP-2 gene silence on the recipient survival. Results A lentiviral-based shRNAi construct LV-SHARP-2iC showed 84% SHARP-2 gene silence efficiency in normal rat kidney cells. At multiplicity of infection 20, 57% T cells could be transfected by lentivirus with spinoculation method. In activated T cells, SHARP-2 g ene silence resulted in 61.3% and 68.7% reduction of intedeukin 2 (IL-2) and interferon γ (IFN-γ) gene expression. When donor kidney was perfused with 5×107 TU LV-SHARP-2iC, the median survival time prolonged for 4-5 days as compared to blank and scramble control groups. Conclusions A recombinant lentivirus LV-SHARP-2iC that effectively silence SHARP-2 gene expression is constructed successfully, leading to the inhibition of IL-2 and IFN-γ. LV-SHARP-2iC treatment can prolong the survival time of rat kidney transplant recipients.

Prophylaxis of pulmonary infection by compound sulfamethoxazole combined with ganciclovir in kidney transplant recipients / 中华肾脏病杂志

Objective To evaluate the prophylactic efficacy of compound sulfamethoxazole (SMZco)combined with ganciclovir on severe pulmonary infection in the early stage of renal transplantation. Methods Between January 2005 and January 2006,two hundred and forty renal allograft patients in our hospital were enrolled in this study.All the patients were divided into two groups.Group A(n=84)received oral SMZco combined with intravenous ganciclovir.Group B(n=156)received intravenous ganciclovir only as control.According to the time of SMZco administration,group A was divided into two subgroups:group A1(within 2weeks after transplantation,n=43)and group A2(more than 2 weeks after transplantation,n=41).All the patients were followed up for 9 months.Incidence of pulmonary infection and effects on graft function by SMZco at different time point were investigated. Results The incidence of severe pulmonary infection and mortality of infection were significantly lower in group A than those in group B (2/84 vs 16/156,P=0.027;0/2 vs 2/16,P＜0.01).There were no significant differences between two groups in terms of age,gender,warm or cold ischemia,complement dependent cytotoxieity test results,incidence of urinary infection and Scr.The incidence of elevatedScr was significantly lower in group A2 than that in group A1(15/43 vs 2/41,P＜0.01),however,all the elevated Scr returned to basal level within 1 week after SMZco was discontinued.Conclusions Oral SMZco combined with ganciclovir administration after renal transplantation is effective on preventing severe pulmonary infection and thus improves graft and recipient survival.The administration of oral SMZco initiated more than 2 weeks after transplantation is better for graft function.

Impact of acute rejection episodes on long-term renal allograft survival / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To assess the impact of the number, and time of acute rejection (AR) and outcome of anti-rejection therapy on the long-term survival of renal allografts and the relative risk factors.</p><p><b>METHODS</b>The Kaplan-Meier analysis and log-rank test were used to calculate the survival rates of patients and grafts in no acute rejection group (NAR, 895 patients), 1 rejection episode group (1AR, 183), 2 and more than 2 rejection episodes group (2AR, 17), acute rejection group [AR (1AR + 2AR), 200], early acute rejection group (within 90 days after transplantation, EAR, 125), late acute rejection group (91 days later, LAR, 58), completely AR reversed group (CAR, 105), and incompletely AR reversed group (IAR, 68). The relative risk factors were analyzed by the Cox proportional hazards regression.</p><p><b>RESULTS</b>The 5- and 10-year survival rates of renal allografts were 75.4% and 17.1% in AR and 93.2% and 86.5% in the NAR group (P < 0.0001). The long-term graft survival was much lower in the 2AR group than in the NAR or 1AR groups (P < 0.0001 and P = 0.002, respectively). It was similar in either the NAR or CAR groups (P = 0.31), but it was significantly lower (P < 0.0001) in the IAR group. Multivariate Cox regression analysis revealed that the outcome of anti-rejection therapy is an important risk factor affecting the long-term survival of allografts.</p><p><b>CONCLUSIONS</b>AR is significantly associated with poor long-term survival of renal allografts. But the long-term graft survival of patients with one acute rejection but completely reversed is not significantly different from that of patients without acute rejection.</p>