Influence of continuous veno-venous hemofiltration on the course of acute pancreatitis

AIM： To investigate whether continuous veno-venous hemofiltration （CVVH） in different filtration rate to eliminate cytokines would result in different efficiency in acute pancreatitis, whether the saturation time of filter membrane was related to different filtration rate, and whether the onset time of CWH could influence the survival of acute pancreatitis. METHODS： Thirty-seven patients were classified into four groups randomly. Group 1 underwent low-volume CVVH within 48 h of the onset of abdominal pain （early CVVH, n = 9）. Group 2 received low-volume CVVH after 96 h of the onset of abdominal pain （late CVVH, n= 10）. Group 3 underwent high-volume CVVH within 48 h of the onset of abdominal pain （early CVVH, n = 9）. Group 4 received high-volume CVVH after 96 h of theonset of abdominal pain （late CVVH, n = 9）. CVVH was sustained for at least 72 h. Blood was taken before hemofiltration, and ultrafiltrate was collected at the start of CVVH and every 12 h during CVVH period for the purpose of measuring the concentrations of TNF-α, IL-1β and IL-6. The concentrations of TNF-α, IL-1β and IL-6 were measured by swine-specific ELISA. The Solartron 1 255 B frequency response analyzer （British） was used to observe the resistance of filter membrane. RESULTS： The survival rate had a significant difference （94.44% vs68.42%, P〈0.01） high-volume and low-volume CVVH patients. The survival rate had also a significant difference （88.89% vs 73.68%, P〈0.05） between early and late CVVH patients. The hemodynamic deterioration （MAP, HR, CVP） was less severe in groups 4 and 1 bhan that in group 2, and in group 3 than in group 4. The adsorptive saturation time of filters membranes was 120-180 min if the filtration rate was 1 000-4 000 mL/h. After the first, second and third new hemofilters were changed, serum TNF-α concentrations had a negative correlationwith resistance （r： -0.91, -0.89, and -0.86, respectively in group 1; -0.89, -0.85, and -0.76, respectively in group 2; -0.88, -0.92, and -0.82, respectively in group 3; -0.84, -0.87, and -0.79, respectively in group 4）. The decreasing extent of TNF-α, IL-1β and IL-6 was significantly different between group 3 and group I （TNF-α P〈0.05, IL-1β P〈0.05, IL-6 P〈0.01）, between group 4 and group 2 （TNF-α P〈0.05, IL-1β P〈0.05, IL-6 P〈0.01）, between group 1 and group 2 （TNF-α P〈0.05, IL-1β P〈0.05, IL-6 P〈0.05）, and between group 3 and group 4 （TNF-α P〈0.01, IL-1β P〈0.01, IL-6 P〈0.05）, respectively during CVVH period. The decreasing extent of TNF-α and IL-1β was also significantly different between survival patients and dead patients （TNF-α P〈0.05, IL-1β P〈0.05）. In survival patients, serum concentration of TNF-α and IL-1β decreased more significantly than that in dead patients. CONCLUSION： High-volume and early CWH improve hemodynamic deterioration and survival in acute pancreatitis patients. High-volume CVVH can eliminate cytokines more effidently than low-volume CVVH. The survival rate is related to the decrease extent of TNF-α and IL-1β. The adsorptive saturation time of filter membranes are different under different filtration rate condition. The filter should be changed timely once filter membrane adsorption is saturated.

Open Surgical Insertion of Tenkchoff Straight Catheter Without Guide Wire

Objective To compare the clinical outcomes of open surgical peritoneal dialysis catheter （PDC） insertion with guide wire and the outcomes of PDC insertion without guide wire. Methods Data of the patients receiving open surgical Tenkchoff straight catheter insertion in our department from January 2005 to January 2011 were retrospectively analyzed. The 117 patients in whom PDC insertion was conducted with the guidance of guide wire were enrolled into group A, and the 121 cases receiving PDC insertion without guide wire were enrolled into group B. The incidences of post-operative complications （catheter obstruction, catheter displacement, bloody dialysate, and dialysate leakage）, catheter survival, and patient survival rates were compared between the 2 groups. Results The baseline characteristics （gender, age, body mass index, prothrombin time, activated partial thromboplastin time, platelet count, serum creatinine, follow-up time, primary diseases, and outcomes） of the 2 groups were comparable （all P〉0.05）. In post-operative complications, only the incidence of early bloody dialysate showed significant difference, being 16.2% in group A and 7.4% in group B （P=0.04）. Catheter and patient survival rates were not significantly different between the two groups. Overweight patients showed a higher incidence of catheter obstruction compared with normal weight patients [16.0% （4/25） vs. 3.3% （7/213）, P=0.02], but no differences in post-operative between the 2 groups. complications were found among overweight patients Conclusions Open surgical Tenkchoff straight catheter insertion without guide wire does not lead to higher risk of post-operative complications and catheter removal. It may be an alternative option when guide wire is not available.

Effect and mechanism of high glucose on apoptosis and cell cycle arrest of islet β cells via p27 pathway

Objective:To study the effect of mechanism of high glucose on apoptosis and cell cycle arrest of isletβcells via p27 pathway.Methods:Islet INS-1 cells were cultured and divided into groups.The control group was treated with ordinary medium,the high glucose group was treated with high glucose medium containing 25mmol/L glucose,the high glucose+si-NC group was treated with high glucose medium and transfected with NC siRNA,and the high glucose+si-P27 group was treated with high glucose medium and transfected with p27 siRNA.After 24 hours treatment,MTS assay was used to detect the cell viability A490,TUNEL assay was used to detect apoptosis rate,flow cytometry was used to detect the cell cycle distribution and western blot was used to detect the expression levels of P27,caspase-8 and cyclinD1.Results:Compared with those in the control group,the A490,the ratio of S phase and G2/M phase as well as the expression level of CyclinD1 decreased,while the apoptosis rate,the ratio of G0/G1 phase as well as the expression levels of P27 and caspase-8 increased in the high glucose group(P<0.05);compared with those in the high glucose group,the A490,cell cycle as well as the expression levels of P27,caspase-8 and cyclinD1 were not different from those in the high glucose+si-NC group(P>0.05);compared with those in the high glucose group and high glucose+si-NC group,the A490,the ratio of S phase and G2/M phase as well as the expression levels of cyclinD1 increased,while the apoptosis rate,the ratio of G0/G1 phase as well as the expression levels of p27 and caspase-8 decreased in the high glucose+si-P27 group(P<0.05).Conclusion:The apoptosis and cell cycle arrest induced by high glucose are related to P27 pathway activation.

Beneficial Effect of Moderately Increasing Hypothermic Machine Perfusion Pressure on Donor after Cardiac Death Renal Transplantation

Background:Vascular resistance and flow rate during hypotherrnic machine perfusion (HMP)of kidneys is correlated with graft function. We aimed to determine the effects of increasing HMP pressure versus maintaining the initial pressure on kidney transplantation outcomes. Methods:We retrospectively reviewed the data of 76 primary transplantation patients who received HMP-preserved kidneys from 48 donors after cardiac death between September 1,2013,and August 31,2015.HMP pressure was increased from 30 to 40mmHg (1mmHg =0.133kPa)in kidneys with poor flow and/or vascular resistance (increased pressure [IP]group;36 patients);otherwise,the initial pressure was maintained (constant pressure group;40 patients).Finally,the clinical characteristics and transplantation outcomes in both groups were assessed. Results:Delayed graft function (DGF)incidence,1-year allograft,patient survival,kidney function recovery time,and serum creatinine level on day 30 were similar in both groups,with improved flow and resistance in the IP group.Among patients with DGF,kidney function recovery time and DGF duration were ameliorated in the IP group.Multivariate logistic regression analysis revealed that donor hypertension (odds ratio [OR]:1.43,95%confidence interval [CI]:1.02-2.06,P =0.035),donor terminal serum creatinine (OR:1.27,95%C7:1.06-1.62,P =0.023),warm ischemic time (OR:3.45,95%CI:1.97-6.37,P =0.002),and terminal resistance (OR:3.12,95%CI:1.76-6.09,P =0.012)were independent predictors of DGF.Cox proportional hazards analysis showed that terminal resistance (hazard ratio:2.06,95%C1:1.32-5.16,P =0.032)significantly affected graft survival. Conclusion:Increased HMP pressure improves graft perfusion but does not affect DGF incidence or 1-year graft survival.

Predictive Score Model for Delayed Graft Function Based on Hypothermic Machine Perfusion Variables in Kidney Transplantation

Background: Hypothermic machine perfusion(HMP) is being used more often in cardiac death kidney transplantation; however, the significance of assessing organ quality and predicting delayed graft function(DGF) by HMP parameters is still controversial. Therefore,we used a readily available HMP variable to design a scoring model that can identify the highest risk of DGF and provide the guidance and advice for organ allocation and DCD kidney assessment.Methods: From September 1, 2012 to August 31, 2016, 366 qualified kidneys were randomly assigned to the development and validation cohorts in a 2:1 distribution. The HMP variables of the development cohort served as candidate univariate predictors for DGF. The independent predictors of DGF were identified by multivariate logistic regression analysis with a P < 0.05. According to the odds ratios(ORs) value, each HMP variable was assigned a weighted integer, and the sum of the integers indicated the total risk score for each kidney. The validation cohort was used to verify the accuracy and reliability of the scoring model.Results: HMP duration(OR = 1.165, 95% confidence interval [CI ]: 1.008–1.360, P = 0.043), resistance(OR = 2.190, 95%CI: 1.032–10.20, P < 0.001), and flow rate(OR = 0.931, 95% CI: 0.894–0.967, P = 0.011) were the independent predictors of identified DGF. The HMP predictive score ranged from 0 to 14, and there was a clear increase in the incidence of DGF, from the low predictive score group to the very high predictive score group. We formed four increasingly serious risk categories(scores 0–3, 4–7, 8–11, and 12–14)according to the frequency associated with the different risk scores of DGF. The HMP predictive score indicates good discriminative power with a c?statistic of 0.706 in the validation cohort, and it had significantly better prediction value for DGF compared to both terminal flow(P = 0.012) and resistance(P = 0.006).Conclusion: The HMP predictive score is a good noninvasive tool for assessing the quality of DCD kidneys, and it is potentially useful for physicians in making optimal decisions about the organs donated.

Advances in China＇s Organ Transplantation Achieved with the Guidance of Law

＂Transplantation＂ （Volume 97, Number 8, April 27, 2014） published an open letter from Professor Delmonico along with other seven professors to Mr. Xi Jinping, President of the People＇s Republic of China： China＇s Fight Against Corruption in Organ Transplantation. The article sharply posed this concern, thus evoking great attention at home and abroad within the transplant community. To this end, we hereby state our views and declare our position with regard to the concerns mentioned in the open letter about China＇s organ transplant undertaking.

Comparison of nighttime and daytime operation on outcomes of kidney transplant with deceased donors: a retrospective analysis

Background: Kidney transplant is always emergent operations and frequently need to be performed at nighttime to reduce cold ischemia time (CIT). Previous studies have revealed that fatigue and sleep deprivation can result in adverse consequences of medical procedures. This study aimed to evaluate whether nighttime operation has adverse impact on kidney transplant. Methods: A retrospective analysis of recipients accepted kidney transplant from deceased donors in one center from 2014 to 2016 was performed. Daytime transplant was defined as operation started after 8 AM or ended before 8 PM and nighttime operation was defined as operation ended after 8 PM or started before 8 AM. The incidences of complications such as delayed graft function, acute rejection, surgical complications and nosocomial infections were compared between 2 groups. Student’s t-test was used to analyze continuous variables such as serum creatinine (Scr) at 1-year of post-transplant. The Chi-square test was used to analyze categorical variables. Differences in recipients and graft survival were analyzed using Kaplan–Meier methodology and log-rank tests. Results: Among the 443 recipients, 233 (52.6%) were classified into the daytime group and the others 210 (47.4%) were in the nighttime group. The 1-year survival rate of recipients was similar for the recipients in the daytime and nighttime groups (95.3% vs. 95.2%, P= 0.981). Although the 1-year graft survival rate in the nighttime group was slightly superior to that in the daytime group, the difference was not significant (92.4% vs. 88.4%, P= 0.164). Furthermore, Scr and incidence of complications were also not significantly different between the 2 groups. Conclusions: Our results suggested that operation time of kidney transplant with short CIT has no significant impact on the outcome of kidney transplant. Nighttime operation of kidney transplant with short CIT could be postponed to the following day to alleviate the burden on medical staffs and avoid the potential risk.

Predictive Score Model for Delayed Graft Function Based on Easily Available Variables before Kidney Donation after Cardiac Death

Background： How to evaluate the quality of donation after cardiac transplantation in China. Hence, the aim of this study was to develop kidneys before DCD. death （DCD） kidneys has become a critical problem in kidney a simple donor risk score model to evaluate the quality of DCD Methods： A total of 543 qualified kidneys were randomized in a 2：1 manner to create the development and validation cohorts. The donor variables in the development cohort were considered as candidate univariate predictors of delayed graft function （DGF）. Multivariate logistic regression was then used to identify independent predictors of DGF with P 〈 0.05. Date from validation cohort were used to validate the donor scoring model. Results： Based on the odds ratios, eight identified variables were assigned a weighted integer; the sum of the integer was the total risk score for each kidney. The donor risk score, ranging from 0 to 28, demonstrated good discriminative power with a C-statistic of 0.790. Similar results were obtained from validation cohort with C-statistic of 0.783. Based on the obtained frequencies of DGF in relation to different risk scores, we formed tour risk categories of increasing severity （scores 04, 5 9, 10-14, and 15 28）. Conclusions： The scoring model might be a good noninvasive tool for assessing the quality of DCD kidneys before donation and potentially useful for physicians to make optimal decisions about donor organ offers.

Comparison of the characteristics of macrophages derived from murine spleen, peritoneal cavity, and bone marrow

Macrophages have a diverse set of functions based upon their activation states. The activation states, including resting（M0） and polarizing（M1 and M2） states, of macrophages derived from the mouse bone marrow, spleen, and peritoneal cavity（BMs, SPMs, and PCMs, respectively） were compared. We evaluated the macrophage yield per mouse and compared the surface markers major histocompatibility complex（MHC） Ⅱ and CD86 by flow cytometry. The relative mRNA levels of tumor necrosis factor-α（TNF-α）, interleukin（IL）-1β, mannose receptor（MR）, and Ym1 in the M0, M1, and M2 states were also compared using real-time polymerase chain reaction（PCR） analysis. Bone marrow yielded the most macrophages with the best homogeneity, but they were polarized toward the M2 phenotype. All three types of macrophages had the capacity to polarize into the M1 and M2 states, but SPMs had a stronger capacity to polarize into M1. The three types of macrophages showed no differences in their capacity to polarize into the M2 state. Therefore, the three types of macrophages have distinct characteristics regardless of their resting or polarizing states. Although bone marrow can get large amounts of homogeneous macrophages, the macrophages cannot replace tissue-derived macrophages.

Polyglycolic Acid Fibrous Scaffold Improving Endothelial Cell Coating and Vascularization of Islet

Background：Improving islet graft revascularization has become a crucial task for prolonging islet graft survival.Endothelial cells （ECs） are the basis of new microvessels in an isolated islet,and EC coating has been demonstrated to improve the vascularization and survival of an islet.However,the traditional method of EC coating of islets has low efficiency in vitro.This study was conducted to evaluate the effect of a polyglycolic acid （PGA） scaffold on the efficiency of islet coating by ECs and the angiogenesis in the coated islet graft.Methods：A PGA fibrous scaffold was used for EC coating of islet culture and was evaluated for its efficiency of EC coating on islets and islet graft angiogenesis.Results：In in vitro experiments,we found that apoptosis index of ECs-coating islet in PGA group （27% ± 8%） was significantly lower than that in control group （83% ± 20%,P 〈 0.05） after 7 days culture.Stimulation index was significantly greater in the PGA group than in the control group at day 7 after ECs-coating （2.07 ± 0.31 vs.1.80 ± 0.23,P 〈 0.05）.vascular endothelial growth factor （VEGF） level in the PGA group was significantly higher than the coating in the control group after 7 days culture （52.10 ± 13.50 ng/ml vs.16.30 ± 8.10 ng/ml,P 〈 0.05）.Because of a tight,circumvallated,adhesive and three-dimensional growth microenvironment,islet cultured in a PGA scaffold had higher coating efficiency showing stronger staining intensity of enzyme than those in the control group after 14 days of culture following ECs-coating.For in vivo study,PGA scaffold significantly prolonged the average survival time of EC-coated islet graft after transplantation compared with control group （15.30 ± 5.60 days vs.8.30 ± 2.45 days,P 〈 0.05）.The angiogenesis and area of survived grafts were more in the PGA group compared with the control group by measuring the mean microvessel density （8.60 ± 1.21/mm2 vs.5.20 ± 0.87/mm2,P 〈 0.05）.In addition,expression of VEGF and tyrosin-protein kinase receptor （Tie-2） gene increased in PGA scaffold group than that in control group by real-time reverse transcription-polymerase chain reaction analysis.Conclusions：These results demonstrate that the efficiency of EC coating of islets was successfully increased by culturing ECs on a PGA scaffold.This method enhances the function,survival,and vascularization of isolated islets in vitro and in vivo.

Early Immunosuppressive Exposure of Enteric-Coated-Mycophenolate Sodium Plus Tacrolimus Associated with Acute Rejection in Expanded Criteria Donor Kidney Transplantation

Background： lmmunosuppressive agents are still inefficient in preventing biopsy-proven acute rejection （BPAR） alter expanded criteria donor （ECD） kidney transplantation. The aim of this study was to investigate the relationships between early imrnunosuppressive exposure and the development of BPAR. Methods： We performed a retrospective study of 58 recipients of ECD kidney transplantation treated with enteric-coated-mycophenolate sodium, tacrolirnus （Tac）, and prednisone. The levels of mycophenolic acid-area under the curve （MPA-AUC）0-12h and Tac C0 were measured at the 1st week and the 1st month posttransplant, respectively. The correlation was assessed by multivariate logistic regression. Results： The occurrence rates of BPAR and antibody-mediated rejection were 24.1% and 10.3%, respectively. A low level of MPA-AUC0-12h at the 1st week posttransplant was found in BPAR recipients （38.42 ± 8.37 vs. 50.64 ± 13.22, P 〈 0.01）. In addition, the incidence of BPAR was significantly high （P 〈 0.05） when the MPA-AUC0-12h level was 〈30 mg·h-1·L-1 at the 1st week （ 15.0% vs. 44.4%） or the Tac C0 was 〈4 ng/ml at the 1 st month posttransplant （33.3% vs. 21.6%）. Multivariable logistic regression analysis showed that the MPA-AUC 0-12 h at the 1st week （OR： 0.842, 95% CI： 0.784-0.903） and the Tac C0 at the 1st month （OR： 0.904, 95% C7： 0.822-0.986） had significant inverse correlation with BPA R （ P 〈 0.05 ）. Conclusions： Low-level exposure of MPA and Tac C0 in the early weeks posttransplant reflects an increased acute rejection risk, which suggested that MPA-AUC0-12h 〈30 mg·h-1·L -1 and Tac C0 〈4 ng/ml should be avoided in the first few weeks alter transplantation.

Allograft rejection-related gene expression in the endothelial cells of renal transplantation recipients after cytomegalovirus infection

Objective： To explore the effects of cytomegalovirus （CMV） infection on rejection-related gene expression in the endothelial cells of renal transplantation recipients. Methods： Endothelial cells （ECs） were cultured and stimulated by a variety of factors： A, normal control group; B, inactivated human cytomegalovirus （HCMV） infection group; C, HCMV infection group; D, HCMV supematant infection group; and E, ganciclovir HCMV group. Expression of intercellular adhesion molecule-1 （ICAM-1） and major histocompability complex （MHC） class I and class II antigens was detected by flow cytometry （FCM） and immuno- histochemistry. Results： We found characteristic CMV-infected ECs in this study. There were no significant differences among groups A, B and D （P〉0.05）. Although the expression levels of ICAM-1 were not significantly different between groups C and E （P〉0.05）, the ICAM-1 expression in these two groups was significantly higher than that in group A （P〈0.05）. ICAM-1 expression was detected in groups C and E, while there was no expression in groups A, B and D. Furthermore, there was no significant difference of ICAM-1 mRNA expression between groups C and E （P〉0.05）. Human leucocyte antigen （HLA）-ABC expression was detected in all the groups, while HLA-DR expression was only detected in groups C and E. There were no significant dif- ferences of HLA-ABC and HLA-DR expression among groups A, B and D （P〉0.05）. However, the HLA-ABC and HLA-DR expression levels in groups C and D were higher than those of the remaining groups previously reported （P〈0.05）. Meanwhile, the HLA-ABC and HLA-DR expression levels in group E were lower than those of group C （P〈0.05）. Conclusion： CMV could up-regulate the expression levels of ICAM-1 and MHC antigens, which was closely related to allograft rejection.

Donor-specific antibodies,glomerulitis,and human leukocyte antigen B eplet mismatch are risk factors for peritubular capillary C4d deposition in renal allografts

Background:The complement system plays an important role in the immune response to transplantation,and the diagnostic significance of peritubular capillary(PTC)C4d deposition(C4d+)in grafts is controversial.The study aimed to fully investigate the risk factors for PTC C4d+and analyze its significance in biopsy pathology of kidney transplantation.Methods:This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody(DSA)testing from January 2017 to December 2019 in a single center.The effects of recipient pathological indicators,eplet mismatch(MM),and DSAs on PTC C4d+were examined using univariate and multivariate logistic regression analyses.Results:In total,35/124(28%)were PTC C4d+,including 21 with antibody-mediated rejection(AMR),eight with renal tubular injury,three with T cell-mediated rejection,one with glomerular disease,and two others.Univariate analysis revealed that DSAs(P<0.001),glomerulitis(P<0.001),peritubular capillaritis(P<0.001),and human leukocyte antigen(HLA)B eplet MM(P=0.010)were the influencing factors of PTC C4d+.According to multivariate analysis,DSAs(odds ratio[OR]:9.608,95%confidence interval[CI]:2.742–33.668,P<0.001),glomerulitis(OR:3.581,95%CI:1.246–10.289,P=0.018),and HLA B eplet MM(OR:1.166,95%CI:1.005–1.353,P=0.042)were the independent risk factors for PTC C4d+.In receiver operating characteristic curve analysis,the area under the curve was increased to 0.831 for predicting PTC C4d+when considering glomerulitis,DSAs,and HLA B eplet MM.The proportions of HLA I DSAs and PTC C4d+in active antibody-mediated rejection were 12/17 and 15/17,respectively;the proportions of HLA class II DSAs and PTC C4d+in chronic AMR were 8/12 and 7/12,respectively.Furthermore,the higher the PTC C4d+score was,the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy.Conclusions:PTC C4d+was mainly observed in AMR cases.DSAs,glomerulitis,and HLA B eplet MM are the independent risk factors for PTC C4d+.