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Objective:To explore the significance of coagulation and platelet function analysis (Sonoclot) in monitoring coagulation function, severity evaluation and blood transfusion indication of perioperative liver transplant (LT) recipients.Methods:A total of 95 perioperative LT recipients received Sonoclot, thromboelastography (TEG), routine coagulation panel, liver function panel, blood routine, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scoring and model for end-stage liver disease (MELD) scoring between January 2021 and October 2022.The correlation analysis of the above parameters was performed.According to the scores of APACHE Ⅱ and MELD, they were assigned into three groups of low-risk, medium-risk and high-risk.The levels of Sonoclot parameters in each group were compared.They were divided into two groups of transfusion (n=31) and non-transfusion (n=64) according to the necessity or non-necessity of transfusion..The risk factors for blood transfusion were examined by Logistic regression and receiver operating characteristic (ROC) curve.Results:Pearson's correlation analysis indicated that activated clotting time (ACT) value was correlated positively with the levels of prothrombin time (PT), prothrombin time ratio (PTR), international standard ratio (INR), R/K value, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactic dehydrogenase (LDH)( r=0.279 1, P=0.006 2; r=0.280 2, P=0.006 5; r=0.3, P=0.003 5; r=0.642 8, P<0.000 1; r=0.452 8, P<0.000 1; r=0.377 6, P=0.002; r=0.349 6, P=0.000 6; r=0.271 4, P=0.018 3) and yet negatively with the levels of platelet (PLT), MA, CI and α ( r=-0.339 1, P=0.000 8; r=-0.573 3, P<0.000 1; r=-0.656 3, P<0.000 1; r=-0.632 6, P<0.000 1); CR value was correlated positively with the levels of maximal amplitude (MA), coagulation index (CI), α and ALT ( r=0.466 8, P=0.000 6; r=0.482 7, P=0.000 4; r=0.514 8, P=0.000 1; r=0.229 2, P=0.027 1) and yet negatively with the level of R/K value ( r=-0.366 9, P=0.010 3; r=-0.356 9, P=0.011 0); platelet function (PF) value was correlated positively with the levels of PLT, MA, CI, α and alkaline phosphatase (ALP)( r=0.481 9, P<0.000 1; r=0.630 7, P<0.000 1; r=0.623 5, P<0.000 1; r=0.593 0, P<0.000 1; r=0.223 1, P=0.032 5) and yet negatively with the level of R/K value ( r=-0.421 5, P=0.002 8; r=-0.530 7, P<0.000 1). CR value was correlated negatively with APACHE Ⅱ score ( r=-0.212 3, P=0.038 9) while ACT value was correlated positively with MELD score ( r=0.244, P=0.04). ACT values spiked in low, middle and high-risk groups of APACHE Ⅱ and MELD scores while PF value declined gradually by grouping these recipients based upon scoring systems.CR values decreased merely in MELD score.Logistic regression analysis indicated that ACT was a risk factor for necessity of blood transfusion in perioperative LT recipients ( OR=1.010, 95% CI 1.000-1.019, P<0.05). The maximal area under the curve of ROC curve analysis plus ACT, hemoglobin (Hb) and hematocrit (Hct) was 0.896. Conclusions:Sonoclot parameters of perioperative LT recipients have some certain correlation with thromboelastographic and conventional coagulation parameters.Both may serve as a supplementary means.Associated with liver function parameters and liver scores, Sonoclot parameters are significant for early clinical evaluations.Sonoclot parameters plus Hb/Hct detection have some guiding significance for perioperative LT recipients with necessity for blood transfusion and blood products.
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Autophagy is a conservative biological process of maintaining internal balances through degrading damaged proteins, organelles and intracellular pathogens.It may promote cell survival and accelerate cell death.Ferroptosis is a newly discovered regulated form of cell death characterized by lipid peroxidation and membrane damage in 2012.In recent years, more and more studies have demonstrated complex interactions between autophagy and ferroptosis.Various forms of cell death are regulated during the progression of kidney diseases.And autophagy and ferroptosis play important roles.However, potential connections between autophagy and ferroptosis in renal injury disease has not been fully elucidated.This review focused upon on the regulatory role of autophagy in ferroptosis and its possible link to renal injury, providing new theoretical rationales for researches on acute or chronic kidney injury.
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In order to solve the difficulties and challenges in the implementation of the original blood distribution and collection regulations caused by the expansion of hospital area, the extension of blood transfer time, the changeability of blood transfer environment, and the strain of personnel due to the increase of workload, as well as to ensure the accuracy of the information throughout blood remote verification and distribution and the safety of clinical blood transfusion, , Shanghai experts related to clinical transfusion and blood management had made a systematic study on the applicable scope and management rules of remote verification of blood distribution and collection, and formulated this Expert Consensus combined with the development status of digital, intelligent and remote communication technologies, so as to provide corresponding guidance for clinical medical institutions in line with the changes in reality.
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Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.
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Objective:To explore the in vitro antiviral activity of Mizoribine (Miz) against BK polyomavirus (BKV) and analyze preliminarily the replication stage during inhibition.Methods:The solvent of Miz, was employed as a negative control, while Sirolimus (Sir) with in vitro anti-BKV activity was applied as a positive control. Firstly, the half maximal inhibitory concentrations (IC50) of Miz and Sir were analyzed in different cell lines. Then, prior to BKV infection, cells were treated with a gradient of drug concentrations according to the IC50 results. At different timepoints post-infection, BKV replication curves were measured by quantitative detection of its DNA in supernatant while the cells were subjected to immunofluorescence for detecting the infection rate. Finally 293FT cells treated with drugs was infected by BKV single-round pseudovirus for determining the effects of Miz on the early stage of BKV infection.Results:As compared with control group, immunofluorescence showed a lowered infection rate of BKV in a Miz dose-dependent manner, viral replication curve was significantly inhibited according to the quantitative detection of viral DNA in cell supernatant. The inhibitory effect of Sir on the level of BKV infection and replication was similar to that of Miz. However, neither Miz nor Sir exhibited a significant effect on the early stage of BKV infection.Conclusions:Miz has anti-BKV activity at cellular level and the inhibitory effect does not appear in the early stage of viral infection.
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Objective To explore the efficacy of renal transplantation plus hematopoietic stem cell transplantation on inducing immune tolerance and summarize its long-term follow-up outcomes . Methods From 2009 to 2018 ,a total of 11 cases of living related donor kidney transplantation plus hematopoietic stem cell transplantation were performed .Two of them were HLA-matched and the remainder were mismatched for one HLA haplotype . The donor hematopoietic stem cells were mobilized using granulocyte colony-stimulating factor at 5 days pre-transplantation and collected at 1 day pre-operation .The recipients received total lymphoid irradiation for 3 days pre-transplantation and received anti-thymocyte globulin induction during transplantation .The donor hematopoietic stem cells were infused at 2 ,4 and 6 postoperative day .Postoperative regulatory T cells ,chimerism ,B cell activating factor and mixed lymphocyte culture and other parameters were detected and long-term follow-up outcomes tracked .Results The immune tolerance-inducible recipients had a significant increase in activated Treg .One HLA-matched recipient achieved 30％-50％ of chimerism and lost after 6 months .However ,other recipients did not achieve mixed chimerism .The BAFF of recipient spiked sharply after transplantation .Mixed lymphocyte culture indicated that a donor-specific low response was induced .The recipients were followed up for 717 to 3612 days .The first recipient lost renal function and another ten recipients had stable renal function . None of the recipients had myelosuppression or graft-versus-host disease .Allograft biopsy confirmed only one case of mild acute rejection . The dose of immunosuppressive agents was lowered in 5 patients .Conclusions Hematopoietic stem cell transplantation for inducing tolerance is safe during renal transplantation . And chimerism is essential for inducing immune tolerance .
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Objective To explore the protective effect of ETaR siRNA on renal ischemia reperfusion injury (IRI) by changing the immuno-microenvironment in rats .Methods A total of 40 male Sprague-Dawley (SD) rats were randomized into four groups of sham ,IR ,negative siRNA and ETaR siRNA .A renal IRI model was generated by clamping left renal artery .ETaR siRNA was delivered into kidney through renal vein by a retrograde 'hydrodynamic' injection .Blood samples were collected for detecting renal function and kidney tissue harvested for Hematoxylin & Eosin (HE) staining , TdT-mediated dUTP Nick-End Labeling (TUNEL) staining ,polymerase chain reaction (PCR) and Western blot at 48 h post-reperfusion .Results Serum creatinine ,blood urea nitrogen and renal apoptotic cells increased and renal tissue was injured after IR . The changes were inhibited by ETaR siRNA . PCR showed that ETaR siRNA treatment significantly down-regulated the expressions of inflammatory factors TNF-α , IFN-γ and IL-6 and transcription factor NF-κB induced by IR .Conclusions ETaR siRNA can effectively improve the immunomicroenvironment and thereby alleviate renal ischemia reperfusion injury .
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Objective To evaluate the efficacy and safety of tranexamic acid in blood protection in liver transplantation.Methods We searched the Cochrane library,MEDLINE,CNKI,VIP,CBM (from inception to May 2017),to collect all the randomized controlled trials of tranexamic acid for liver transplantation.the quality of the included studies was evaluated,and meta-analyses were performed with Cochrane Collaboration's RevMan 5.3 software.Results 1) A total of 8 studies involving 1107 patients were included.the results of meta-analyses showed:Compared with placebo,tranexamic acid was effective in reducing postoperative blood loss [SMD =-1.95,95％ CI (-3.21,-0.69)],P＜0.05],there were statistical heterogeneity between the studies (I2=94％,P＜0.05),2)Tranexamic acid was effective in reducing postoperative transfusion rates of RBC during the operation [SMD=-0.43,95％ CI (-0.74,-0.11)],P＜0.05];however,less effective than the placebo in terms of reducing postoperative FFP and PLT transfusion.Compared with placebo and other antifibrinolitic drugs the bleeding,renal insufficiency,thrombosis,infection,death and the incidence of other adverse events were not increased in tranexamic acid group after surgery.Conclusion Tranexamic acid was a safe and effective antifibrinolitic drug in liver transplantation,for it can reduce the amount of bleeding and red blood cell transfusion,However,due to the limited quality of the included studies,further verification with more high quality trials was needed.
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Objective To evaluate the effect of conversion from mycophenolic acid (MPA) to mizoribine (MZR) in renal transplant recipients with gastrointestinal tract (GI) symptoms.Methods A total of 355 renal transplant recipients with GI symptoms caused by MPA administration were enrolled from April 2015 to March 2017 in 25 different renal transplant centers in China.The symptomatic improvement of GI before (baseline) and after conversion to MZR (1,2,4 weeks) was assessed by each item of GI symptoms indication.In addition,the efficacy and safety of the conversion therapy during 12 months were determined.Results Patients showed improvement in GI symptoms including diarrhea,abdominal pain,abdominal distention and stomachache after conversion to MZR 1,2,4 weeks (P＜0.05).In patients with different severity of diarrhea,conversion to MZR therapy significantly improved diarrhea (P＜0.05).During 12 months,no patient experienced clinical immune rejection.We did not observe any infections,leucopenia and other serious side effects.Conclusion MZR could markedly improve GI symptoms caused by MPA administration in renal transplant recipients.
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Objective To investigate the diagnosis and treatment of pulmonary tuberculosis in renal transplantation recipients.Method The clinical data of 8 renal transplantation recipients suffering from pulmonary tuberculosis infection were retrospectively analyzed.Result Fever,cough and expectoration were the most common symptoms,however,lacking typicality.Images of chest Xray and CT scan were various and couldn't verify TB infection from pneumonia.Seven of 8 cases were diagnosed through invasive methods,either bronchofibroscope or fiberthoracoscopy.Immunosuppressants were decreased in all cases.Three-drug regimens,including isoniazide,rifampicin and ethambutol or pyrazinarnide,were administrated as anti-tuberculosis chemotherapy.All the cases were cured,without episodes like acute rejection and liver function impairment.Conclusion Routine examinations are not sufficient to diagnose pulmonary tuberculosis in kidney transplantation recipients.While,invasive methods like bronchofibroscope and fiberthoracoscope are helpful.When diagnosed,patients should receive normative anti-tuberculosis treatment and immunosuppressive agents adjustment,which can benefit the prognosis of pulmonary tuberculosis in renal transplantation recipients.
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Objective To evaluate the hematological adverse events of sunitinib in treatment of advanced renal cell carcinoma.Methods Forty-four male patients and 18 female patients were included in this study.They were all with metastatic renal cell carcinoma and received sunitinib treatment at the dose of 50 mg daily in repeated 6 weeks cycle (4 weeks on and 2 weeks off).Toxicity was assessed every cycle with tumor assessments every 2 cycles via CT or PET-CT.Results Fifty patients (80.6％) had experienced treatment-related hematotoxicity,including leucocytopenia,anemia and thrombocytopenia.Severe hematological adverse events ( grade 3 -4 ) occured in 18 patients ( 29.0％ ) and slight events ( grade 1 - 2 ) in others (51.6％).Most of the hematological adverse events were manageable and reversible and treatment-changes (dose reduction,interruption) were necessary in severe cases.Almost half of the dose reduction (9/21,42.9％ ) were owing to hematotoxicity.Conclusions Sunitinib of 50 mg dose on schedule 4/2 is effective and well-tolerated in advanced renal carcinoma patients.Hematological adverse events are frequent in Chinese patients and can be controlled well.
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Objective To investigate the change and implication of plasma osteopontin (OPN) levels in renal allograft rejection.Methods The clinical data and biological samples of 46 renal transplant recipients were analyzed rerrospecnvely,including 16 patiens with stable allograft function and no evidence of biopsy-proved rejection (Non-R),22 patients with biopsy-proved acute cellular rejection (ACR),and 8 paients with biopsy-proved chronic allograft nephropathy (CAN).Six living related donors served as healthy controls (HC).Plasma OPN level was determined by using the human OPN ELISA kit.Type and grade of ACR were diagnosed based on Banff 03 classification criteria of renal allograft pathology.The plasma OPN levels were compared among different groups.The assistant diagnostic value of plasma OPN levels in differentiating rejection patients were also evaloated.Results The plasma OPN level in HC,Non-R,CAN and ACR groups was ( 12.23 ±5.95),(19.38±8.23),(27.77± 12.27) and (41.84± 18.51) μg/L,respectively.There was no significant difference in plasma OPN levels among HC,Non-R and CAN groups (P＞0.05),but the OPN levels in ACR group were decreased significantly as compared with Non-R and CAN groups (P＜0.05 ).OPN levels were positively correlated with Banff grading of ACR (P＜0.05).OPN levels were significantly different between grade Ia and grade IIb (P＜0.05).Conclusion The change in plasma OPN level has a relationship with acute rejection.Besides,the plasma OPN levels were also positively correlated with the severity of ACR.Monitoring plasma OPN levels should be useful in predicting and evaluating the severity of ACR in renal transplant recipients.
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Objective To observe the protection and distribution of bone marrow mesenchymal stem cells (MSCs) by distinct intravenous infusion time on renal ischemia reperfusion injury (IRI) in rats.Methods We used unilateral nephrectomy and contralateral vascular occlusion method to establish renal IRI model in rats.The experimental groups which received 2 × 106 MSCs infusion through the tail vein,were subsequently divided into 3 subgroups:2 h pre-reperfusion (PreOp,n =16),immediately after reperfusion (Op,n =16),6 h post-reperfusion (PostOp,n - 16).The control groups included sham operation group (n =16) and ischemia group (n =16).Chemotaxis of DAPI-labeled MSCs was detected 6 h after administration in the IR kidney.Renal function was detected at 6,24,and 48 h respectively after operation. Forty eight h after operation,the renal tissues were harvested to observe the pathological changes by HE staining and the tubular epithelial cell apoptosis via TUNEL assay.Results MSCs were found in the experimental groups after IR in the kidney,most in PostOp group.Twenty-four and 48 h after reperfusion,there was no significant difference in Cr and BUN between the experimental groups and sham operation group (P＞0.05),but the levels of Cr and BUN in the experimental groups were significantly lower than in the IR group (P＜ 0.05). As compared with IR group,the renal pathological injury was alleviated,the number of apoptotic cells was decreased in the experimental group,most significantly in PostOp group (P＜0.05).Conclusion MSCs can reduce the inflammatory response and inhibit renal tubular cell apoptosis in rat renal IRI.Post-reperfusion administration of MSCs leads to the best chemotaxis efficiency and protection.
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Objective To analyze the relationship between the genetic polymorphisms of organic anion transporting polypeptide (SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA)pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations (SLCO1B3T334G, SLCO1B1 A338G) were detected in 68 recipients by PCR-LDR. The plasma samples were collected and blood concentration of MPA was measured on the 28 th day after transplantation. The area under the curve (AUC)0-12 of MPA in different genotype recipients was compared to analyze the correlation between single nucleotide polymorphisms (SNPs) and MPA pharmacokinetics. Results MPA AUC0-12 was higher in SLCO1B3 T334G GG carriers group than in TT carriers [(54. 54 ±14.40)vs(37.30±12.88)mg·h·L-1,(P=0.052)].However,there was no difference in MPA AUC0-12 among each genotype of SLCO1B1 A338G (P>0. 05). Conclusion Genetic polymorphisms of SLCO1B3 affect interindividual variety in plasma MPA concentration in Chinese kidney transplantation recipients.
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Objective To analyze the impact of allograft category on the result of living related donor kidney transplantation (LRKT)and to evaluate the predominant donors. Methods A retrospective analysis of 104 recipients receiving LRKT from Apr. 2004 to Mar. 2008 was performed. Based on donor resource, all the recipient-donor pairs were divided into four groups: spousal donation group,parental donation group, sibling donation group and cousinly donation group. The observational parameters were selected for analysis, such as average post-transplant hospitalization dates, time for serum creatinine (Scr) back to normal level, Scr levels of every observational time point, incidence of major complications (infection, rejection, DGF) and recipient/graft survival rate. Results Recipient/graft survival rate of sibling donation group seemed higher. Recipients of sibling donation group seemed to have fewer post-transplant hospitalization dates, but higher rates of infection, while those of parental donation group seemed to have higher rates of rejection. Rates of rejection and infection of spousal donation group were lower than supposed. There was no statistically significant difference in time for Scr back to normal level and Set levels of every observational time point among these four groups. Conclusions The result of sibling donor renal transplantation is better, while short-term outcome of spouse donor renal transplantation is ideal, which is similar with parent or cousin donor renal transplantation. Except for human leukocyte antigen, aspects such as quality of donor kidney, predominance during operation and self-administration post-transplant are also the guarantee for the success.