Objective To summarize experience and prognosis of repeat renal transplantation after graft loss due to BK virus nephropathy (BKVN).Methods The clinical data of 4 adult patients undergoing repeat transplantation after previous allograft loss due to BKVN were collected and analyzed retrospectively.Results Three of four patients had documented allograft loss caused by BKVN and underwent retransplantation 5 months,9 months and 9 months respectively after hemodialysis with confirmed clearance of viremia.Allograft nephrectomy was performed on 1 of 3 patients 4 months before retransplantation.Maintenance immunosuppression was CsA + MMF + Pred,Tac + MMF + Pred and CsA + Pred in these 3 patients respectively.During the follow-up period of 9 months,5 months and 26 months,viremia kept negative and allografts function stabled normally without recurrence of BKVN.The cause of allograft loss was not illustrated in the other patient before retransplantation,which was performed without dialysis or allograft nephrectomy.BK virus was not monitored routinely after the operation.Four months later,his serum creatinine rose up to 400μmol/L and BKVN recurrence was proved by pathological analysis of the biopsy samples of the first and the second transplantation.Tac was switched to CsA and his serum creatinine declined to 260 μnol/L at 20th month.Conclusion Retransplantation can be performed on the patients with previous allograft loss due to BKVN.Allograft nephrectomy,clearance of viremia,monitoring BK virus and timely adjustment of immunosuppression were the keys to guarantee successful retransplantation.

ObjectiveTo observe the effects of parenteral nutrition (PN) containing ω-3 polyunsaturated fatty acids (ω-3PUFAs) on postoperative systemic inflammatory response syndrome (SIRS) in patients with obstructive jaundice. MethodsTotally 40 patients with obstructive jaundice who underwent hepatobiliary surgery in the Affiliated Hospital of Binzhou Medical College from June 2008 to October 2009 were enrolled in this study and randomly divided into the conventional PN group and PUFAs group with 20 cases in each group. The conventional PN group was provided with medium-chain/long-chain triglycerides lipid emulsion, while the PUFAs group was provided with medium-chain/long-chain triglycerides lipid emulsion supplemented with ω-3PUFAs. The two groups received PN support with equal nitrogen content and calories for 9 days. The non-protein caloric value given was 117.15 kJ/(kg · d) with 0.2 g/(kg · d) of nitrogen. Interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-c) in serum were measured on the day before operation and on the postoperative day 1,3, 5, 7, and 9. Meanwhile, the incidences of SIRS and multiple organ dysfunction syndrome (MODS) were analyzed. ResultsThe levels of IL-6, CRP, and TNF-α on the postoperative day 3, 5, 7, and 9 were significantly lower in the PUFAs group than those in the conventional PN group ( all P ＜ 0.05). The duration of SIRS in the PUFAs group [(3.85 ±2.36) days] was significantly shorter than that in the conventional PN group [(5.31 ±1.47 ) days, P =0.0230]. The incidence of MODS was significantly lower in the PUFAs group ( 10％ ) than that in the conventional PN group (25％, P =0.0076). Conclusionsω-3PUFAs-supplemented PN improves the functions of liver and pancreas and alleviates acute inflammatory response in patients with obstructive jaundice.

Objective To investigate the effect of reinfusion of drained bile and pancreatic juice on the outcome of pancreaticoduodenectomy (PD).Methods The clinical data of 51 patients who received PD at the Affiliated Hospital of Binzhou Medical College from June 2005 to March 2009 were retrospectively analyzed.Nineteen patients received external drainage of bile and pancreatic juice ( ED group) and the other 32 patients received external drainage and intraintestinal administration of autologous bile and pancreatic juice (ID group).The daily volume of output of bile and pancreatic juice,intraoperative condition,tolerance of enteral nutrition,liver function and nutritional parameters of the 2 groups were detected.All data were analyzed by using chi-square test,Fisher exact test,independent t test,Mann-Whitney U test and one-way analysis of variance.Results The pulmonary infection rate of ID group was 3％ (1/32) after operation,which was significantly lower than 26％ (5/19) of the ED group (P ＜ 0.05).The output of pancreatic juice in the ID group was significantly lower than that in the ED group since postoperative day 4 ( t =7.143,9.244,8.808,7.915,6.461,14.097,15.038,P ＜ 0.05 ).There was no significant difference in the daily output of bile between the 2 groups.The incidence of diarrhea in the ID group was 9％ (3/32) after nutritional support,which was significantly lower than 37％ (7/19) of ED group (P＜0.05).The duration of achieving targeted enteral feeding in the ID was 3 days,which was significantly shorter than 4 days of the ED group ( U =145.000,P ＜ 0.05 ).The levels of total bilirubin ( TBil),direct bilirubin (DBil) and indirect bilirubin (IBil) were (261 ± 108 ),( 132 + 55 ) and ( 129 + 55 ) μmol/L in the ID group,and (239 ±92),( 12A ±46) and ( 116 ±46) μmol/L in the ED group before operation.The levels of TBil,DBil and IBil were (39 ± 19),(20 ± 10) and ( 19 +9) μmol/L in the ID group,and (55 ±22),(29 ± 12) and (26 ±11 ) μmol/L in the ED group at 12 days after nutritional support.There were significant differences in the decrease of TBil,DBil and IBil between the 2 groups ( t =7.324,8.437,5.827,P ＜ 0.05 ).The levels of serum prealbumin,retinol binding protein and transferrin were (0.261 ± 0.021 ) g/L,(34.3 ± 2.8 ) mg/L,(3.08 + 0.26 ) g/L in the ID group,and (0.263 ±0.021)g/L,(33.8 +3.5)mg/L and (3.10 +0.27)g/L in the ED group before operation.The levels of serum prealbumin,retinol binding protein and transferrin decreased significantly after operation,and then got increased 3 days after nutritional support.The levels of serum albumin,retinol binding protein and transferrin were (0.238 ±0.025)g/L,(30.7 ±2.0)mg/L,(2.78 ±0.19)g/L in the ID group,and (0.222 +0.025)g/L,(29.3 ±2.1)mg/L and (2.63 +0.21)g/L in the ED group at 12 days after nutritional support.The levels of serum albumin,retinol binding protein and transferrin in the ID group were significantly higher than those in the ED group (t=4.615,6.097,4.913,P＜0.05).Conclusion Reinfusion of external drained bile and pancreatic juice after PD could enhance the tolerance of patients in early enteral nutrition,reduce incidence of pneumonia,promote decrease of serum bilirubin and improve the nutritional status.

Objective To explore the possible role and mechanism of the Kupffer cells (KCs) in liver allo-geneic transplantation at the early stage. Methods In vitro cell contact coculture system was established. Culture supernatants were collected respectively on the 1st, 2nd, 4th, 6th d after cocul-ture and the KCs and PBMCs were harvested on the 6th day after culture. The expression of HLA-G on the membrane of the KCs and PBMCs was detected with immunochemistry. Nitrate reduction test was used to determine the concentration of nitric oxide. IFN-γ, IL-10, TGF-β1 cytokine levels in the supernatants were also measured with ELISA. The proliferation of lymphocytes was evaluated with MTT. Results six days later, no HLA-G molecules were detected on the membrane of the KCs and PBMCs. In the experimental group containing KCs, the levels of NO, IL-10 and TGF-β1 was signifi-cantly increased(P<0. 05), while the levels of IFN-γ was relatively lower(P<0. 05) as compared to the experimental group without KCs. No IL-10 and IFN-γ were detected in the control group, and on-ly few NO and TGF-β1 was found in the control group with KCs. MTT test showed that the value of optical density was lower in the experimental group with KCs than that in any other group(P<0. 05).Conclusion No HLA-G is expressed on the membrane of KCs and PBMCs after contact coculture.KCs may participate in regulating production of NO and Th2/Th3-like cytokines and suppressing the proliferation of lymphocytes, through which KCs probably take part in inducing immunotolerance of liver transplantation in early stage.

BACKGROUND:Transfusion of bone marrow mesenchymal stem cells may become a novel and effective biological therapy for inflammatory bowel disease in clinical practice. Nevertheless, the oncological safety of the treatment is worrisome, and is a key to determine whether mesenchymal stem cells can be widely used in treatment of inflammatory bowel disease, and deserves further investigation. OBJECTIVE:To evaluate the therapeutic effect of bone marrow mesenchymal stem celltransfusion against inflammatory bowel disease in mouse models, and to clarify the effects of mesenchymal stem cells on tumorigenesis of inflammatory bowel disease. METHODS:Mouse model of colitis was established using Balb/c (H-2d) mice exposed to dextran sulfate sodium. Syngeneic bone marrow mesenchymal stem cells were transfused into mouse model through caudal vein. The therapeutic effect of mesenchymal stem cells was compared and observed, and pathological remission of colitis was evaluated. Mouse model of colitis-driven colon carcinogenesis was established using Balb/c (H-2d) mice exposed to dextran sulfate sodium and azoxymethane. Tumor formation within the murine colon was compared and observed after transfusion of mesenchymal stem cells. RESULTS AND CONCLUSION:In models of dextran sulfate sodium-induced colitis, weight loss and fecal occult blood were lessened in the bone marrow mesenchymal stem cellgroup compared with the phosphate buffered saline group. Histological damage score of colitis was less in the bone marrow mesenchymal stem cellgroup:mucosal structure of distal colon was almost intact under microscope, and there was smal area of epithelial defects and cryptal defects. Inflammatory cellinfiltration, proliferation of capil ary and smal vessels could be observed in mucosa and submucosa. Homing and colonization of mesenchymal stem cells in submucosa of inflamed colon could also be observed by in vivo tracing. In the dextran sulfate sodium/azoxymethane model of colitis-driven colon carcinogenesis, the number of intestinal tumors and tumor load were obviously less in the bone marrow mesenchymal stem cellgroup than in the control group. Results indicated that transfusion of bone marrow mesenchymal stem cells can apparently improve colitis lesions of mice with inflammatory bowel disease and inhibit carcinogenesis of colitis, which may provide theoretical support for the biological safety of mesenchymal stem cells transplantation for inflammatory bowel disease.

OBJECTIVETo detect the somatic mutations in peritoneal mesothelioma with whole genome sequencing technique.

METHODSSurgically resected cancer and pericancerous tissue samples from one patient with peritoneal mesothelioma were obtained. The whole genome sequences of tumor tissue and pericancerous tissue were examined by the second generation sequencing technique and compared with reference sequences from human genome database.

RESULTSThere were 639 717 single nucleotide variations (Single Nucleotide Variation SNV) found in both tumor and pericancerous tissue cells; while 20 302 SNVs were unique for tumor cells and 2 185 SNVs unique for pericancerous tissue, but still 223 SNVs found in cancer and pericancerous tissue were differed from those in human genome database.

CONCLUSIONThe preliminary results indicate that merely comparing the gene sequences of cancer and pericancerous tissue samples in an individual with the human genome reference sequence can not accurately locate all somatic mutations in pathological cells. For those individualized diseases caused by random somatic mutations, it is suggested to sequence the whole genome at birth or at least to reserve a DNA sample at early age for both research and clinical needs.

Aged ; DNA Mutational Analysis ; Female ; Humans ; Mesothelioma ; genetics ; Mutation ; Peritoneal Neoplasms ; genetics ; Polymorphism, Single Nucleotide

Objective To summarize the pathological characteristics of polyomavirus-associated nephropathy combined with acute rejection after renal transplantation.Methods The pathological data of 172 patients diagnosed as having polyomavirus nephropathy in our hospital from 2007 to 2018 were reviewed.Results One hundred and seventy-two patients were diagnosed as having polyomavirus nephropathy without acute rejection for the first time.In 75 (43.6％,75/172) patients who received repeat biopsy,10 (5.8％,10/172) patients developed acute rejection with an average interval of 4.8 ± 3.3 months.Common pathological features included:renal tubular epithelial cells virus inclusions reduced or even disappeared or only hyperchromatic nuclei revealed,SV40-T antigen (70％,7/10) staining negative or decreased significantly (30％,3/10),and varying degrees of interstitial inflammation,tubulitis,interstitial fibrosis and tubular atrophy.Four patients developed acute T cell-mediated rejection (Banff ⅡA),revealing aggravating tubulitis and interstitial inflammation in the area of negative SV40-T antigen (70％,7/10) staining,as well as mild endarteritis.Three patients developed acute antibody-mediated rejection,revealing glomerulitis and peritubular capillaritis and positive panel reactive antibody.Only 1 patient revealed C4d deposition of peritubular capillaries.Two patients developed mixed rejection,revealing tubulitis,interstitial inflammation,glomerulitis,peritubular capillaritis,mild endarteritis and C4d deposition of peritubular capillaries.One patient developed suspicious T cell-mediated rejection (Banff IB),revealing aggravating tubulitis and interstitial inflammation in the non-fibrotic areas but without intimal arteritis.Besides,the positive SV40-T antigen (70％,7/10) staining area was reduced significantly.Conclusion The pathological characteristics of polyomavirus nephropathy combined with acute rejection include endarteritis,glomerulitis,peritubular capillaritis and C4d deposition of peritubular capillaries.It is difficult to distinguish polyomavirus nephropathy from Banff I T cell-mediated rejection.Clinical information and repeat biopsy results are helpful for differential diagnosis.

Objective:To construct a double-closed-loop management model for medical equipment and explore its application value in hemodialysis machine maintenance and fault management.Methods:Based on the closed-loop management of clinical operation of medical equipment and the closed-loop management of technical support,a dual closed-loop management model of equipment was constructed.65 hemodialysis machines in clinical use in Huashan Hospital Fudan University from January 2021 to January 2023 were selected and divided into a conventional mode and double-closed-loop mode according to different management modes.The conventional mode adopted conventional equipment management methods,and the double-closed-loop mode adopted a double-closed-loop management model.The cost-effectiveness,social benefit,failure occurrence,effective management quality matters,disinfection status,average patient waiting time and satisfaction were compared between the two groups.Results:The hemodialysis machine operating profit growth rate,diagnosis and treatment cost growth rate,service life index,scientific research service growth rate,diagnosis and treatment service growth rate,startup rate and operation rate of the double-closed-loop mode were(3.95±1.04)%,(3.80±0.58)%,(1.58±0.31)%,(4.30±0.95)%,(7.91±1.58)%,(96.58±2.76)%and(89.90±5.58)%,which were higher than those of the Conventional mode,the difference was statistically significant(t=5.418,10.070,7.490,17.570,11.820,8.849,6.840,P<0.05).The technical support expenses growth rate,bacterial colony count,bacterial endotoxin content and average patient waiting time of patients in the Double-closed-loop mode were(2.60±0.33)%,(0.370±0.008)cfu/ml,(0.0063±0.0011)EU/ml and(0.76±0.13)h,which were less than those of the conventional mode,the difference was statistically significant(t=23.040,82.985,14.482,19.530,P<0.05).The incidence rate of hemodialysis machine failure in the double-closed-loop mode was 9.23%(6/65),which was lower than that in the conventional mode,the difference was statistically significant(x2=6.392,P<0.05);among the 120 items of management data collected,quality control testing,maintenance and repair,clinical operation,information data,and scrap processing effectiveness rates were 95.83%(115/120),89.17%(107/120),96.67%(116/120),95.00%(114/120),and 97.50%(117/120),respectively,which were higher than those of the conventional mode,the difference was statistically significant(x2=15.238,16.596,9.808,15.585,16.119,P<0.05).Conclusion:The application of closed-loop management model to hemodialysis machine maintenance and fault management can effectively improve equipment cost-effectiveness,social benefits,management quality and patient satisfaction,and reduce the incidence of faults.

Objective: To explore the clinical and prognostic features of lipoprotein glomerulopathy (LPG) in renal allografts. Methods: Retrospective analysis was performed for two case of LPG in renal allografts. The onset time was 6 and 9 years after living transplantation respectively. Initial symptoms included proteinuria and hypoproteinemia. Color Doppler ultrasound showed an enlarged graft size and greater parenchymal echogenicity. One patient had hyperlipemia and elevated apolipoprotein E (ApoE). Methylprednisolone pulse was offered with an early control of hyperlipidaemia and proteinuria by fenofibrate and angiotensin-converting enzyme inhibitors (ACEIs). Yet it had no effect on graft function. The definite diagnosis was made by graft biopsy. Pathological examination indicated non-homogeneous lipid deposition in glomerular capillary, glomerular sclerosis, mesangial hypercellularity and tubular atrophy. Results: During a follow-up period of 8 and 10 years post-transplantation, two cases eventually lost their grafts within 2 and 1 year after biopsy respectively. With long-term dietary control and drug therapy, regular dialysis continued and both awaited a second transplantation. Conclusions LPG is generally steroid-resistant and refractory in renal allografts. And routine biopsy is recommended for patients with a high risk of occurrence. Early controls of hyperlipemia and hypoproteinemia and other risk factors should be also properly managed.

Objective:To explore the clinical value of peripheral blood lymphocyte subsets in the differential diagnosis of BK virus nephropathy (BKVN) in renal transplantation recipients.Methods:From 2014 to 2018, a total of 172 renal transplant recipients were recruited. Their peripheral blood lymphocyte subsets were detected. According to the pathological puncture results of transplanted kidney, they were divided into acute rejection group (AR, n=68), BKVN group ( n=73) and stable graft function group (STA, n=31). The proportion and absolute number of peripheral blood lymphocyte subsets in each group were measured by flow cytometry and the proportion and absolute count of peripheral blood lymphocyte subsets in each group compared. Results:The proportion and absolute number of CD19 + B cells were markedly lower in BKVN group than those in AR group ( P=0.005, 0.003; 8.5% vs 13.2%, 0.094×10 9/L vs 0.202×10 9/L) and STA group ( P=0.005, 0.003; 8.5% vs 14.8%, 0.094×10 9/L vs 0.198×10 9/L); the proportion of CD3 + CD8 + T cells was significantly higher in BKVN group than that in AR group ( P=0.013; 36.9% vs 31.2%). In addition, no obvious difference existed in the proportion and absolute number of lymphocytes, CD3 + T, CD3 + CD4 + T and CD16 + CD56 + natural killer (NK) among three groups ( P>0.05). No obvious difference existed in the proportion of CD3 + CD4 + / CD3 + CD8 + T cells among three groups ( P>0.05). Conclusions:No difference exists in T cell-related lymphocyte subsets between BKVN and acute rejection recipients. However, the number and proportion of CD19 + B cells decrease markedly in BKVN.