Objective To study the protective effects of hydrocortisone on glycocalyx in the vascular endothelium after trauma-hemorrhagic shock (T/HS) because the role of glycocalyx in maintaining the permeability of vascular endothelium intact,and in turn to identify the hydrocortisone protecting intestinal microcirculation.Methods Studies were carried out,in vivo,on a model of rats with induced T/HS.Intestinal perfusion and changes in endothelial glycocalyx and the associated molecular mechanism were assessed by using laser-Doppler velocimetry and electron microscopy,and the measurements of heparan sulfate,syndacan-1,and TNF-α in the superior mesenteric vein (SMV) with ELISA and Western-blot,and the expression of NF-κB in the vascular endothelium.Protective effects of hydrocortisone on the intestinal microcirculation after T/HS were evaluated.Results Degradation of the glycocalyx in intestinal vascular endothelium occurred 1-3 hours after T/HS in rats (P ＜0.05).By 3 hours later,significant reduction in intestinal perfusion was observed (P ＜ 0.05).The level of TNF-α in the SMV and the expression of NF-κB in the vascular endothelium increased.With the use of hydrocortisone,intestinal perfusion was improved,and the degradation of glycocalyx was attenuated.Conclusions The degradation of glycocalyx is associated with the malfunction of intestinal microcirculation after T/HS.The NF-κB/TNF-α system in vascular endothelium participates in this process of glycocalyx degradation.Hydrocortisone may be a good agent to interrupt the course of glycocalx degradation.

Objective To analyze and identify the differentially expressed proteins in human renal tubular epithelial cells (HK-2) after injury caused by oxalic acid and calcium oxalate monohydrate (COM) crystal, and to explore the potential role of renal tubular cell injury in kidney stone formation.Methods Normal HK-2 cells were cultured in vitro and the culture medium was changed with serum-free medium after cell growth to confluence. Oxalic acid and COM crystals (final concentration at 2 mmol/L and 200 mg/L, respectively) were added in the experimental group. Cells in both groups were then incubated at 37 ℃ for 12 h. The extracted proteins from both groups were separated by two dimensional electrophoresis followed by analysis, and the differentially expressed proteins were identified by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Two identified proteins were then verified by western blot. Results Reproducible two dimensional gel images of the proteins from both groups were successfully obtained. By using LC-ESI-MS/MS, 12 proteins: FK506-binding protein 4, isoform alpha-enolase of alpha-enolase, isoform M1 of pyruvate kinase isozymes M1/M2, ATP synthase subunit alpha, isoform 1 of 3′(2′), 5′-bisphosphate nucleotidase 1, isoform 2 of nucleophosmin, L-lactate dehydrogenase B chain, Budding uninhibited by benzimidazoles 3, Cofilin-1, Fascin, pyIsoform 1 of cytosol aminopeptidase, were identified. The deferentially expressed proteins were related to cellular processes including energy metabolism, cell multiplication, apoptosis, Ca2+ channel activity regulation, cell movement and signal transduction. Western blot verified that higher ENO1 but lower Cofilin-1 expressed in HK-2 cells after the injury. Conclusions High level oxalic acid and COM crystals can cause protein expression profile changes in normal human HK-2 cells. The changes of protein expression may not only protect HK-2 cells from being injured, but also be related to kidney stone formation.

Objective To explore the management strategy for liver trauma combined with juxla-hepatic venous injury and discuss relating factors leading to postoperative deaths. Methods The clini-cal data of 11 patients with juxtahepatic venous injury were retrospectively analyzed in aspects of prefer-ence of irregular hepatectomy and vein repair.There were 8 males and 3 females,at age range of 22-65 years(mean 33.7 years).Injury causes included traffic injury in 7 patients,fall-from-height injury in 3 and crush injury in 1.Of all,9 patients were combined with other abdominal organ injury and 7 with over one part fractures.All patients showed symptom of shock on admission. Results No patient died dur-ing operation but 3 died after operation.The complications included bleeding in 6 patients,severe infec-tion in 2.liver function failure in 3, acute renaI function failure in 2.bile-1eakage in 4,abdominal ab-scess in 4 and incision infection in 6. Conclusion Low blood pressure in the operation is the main cause for death.It is safe and effective to treat liver trauma combined with juxtahepatic venous injury with irregular hepatectomy and vein repair.

Objective To explore the clinical effects of S-1 single agent chemotherapy for the patients undergoing radical resection of cholangiocarcinoma.Methods The clinical data of 51 patients receiving radical resection of cholangiocarcinoma who were admitted to the Second Affiliated Hospital of Zhejiang University from November 2011 to December 2013 were retrospectively analyzed.After radical resection of cholangiocarcinoma,25 patients receiving non-special treatment and 26 patients receiving S-1 single agent chemotherapy were divided into the operation group and chemotherapy group,respectively.S-1 was taken orally twice per day.Forty mg/once of S-1 was applied to patients with the body surface area ＜ 1.25 m2,50 mg/once of S-1 was applied to patients with the body surface area ≥ 1.25 m2 and ＜ 1.50 m2,and 60 mg/once of S-1 was applied to patients with the body surface area ≥ 1.50 m2.The 14 days usage and 7 days withdrawal of S-1 were used as one course of treatment.The standard usage of S-1 was 6-8 courses of treatment.All the patients were followed up by outpatient examination and telephone interview till December 1,2014.Count data were analyzed using the chi-square test.Measurement data with normal distribution were presented as (x) ± s and analyzed using the t test.Survival curve was drawn by the Kaplan-Meier method,and survival analysis was done using the Log-rank test.Results Twenty-six patients in the chemotherapy group finished the courses of chemotherapy without chemotherapy-related death,and 14 patients had chemotherapy adverse reactions with remission after discontinuation of S-1.All the 51 patients were followed up for 5-37 months with a median time of 19 months.The median overall survival time,1-,3-year overall survival rates,tumor-free median survival time and 1-,3-year tumor-free survival rates were 22 months (range,18-27 months),72.3％,42.9％,21 months (range,16-26 months),60.0％,55.0％ in the operation group and 32 months (range,29-35 months),84.6％,44.4％,26 months (range,21-31 months),76.9％,61.9％ in the chemotherapy group,respectively.There was a significant difference in the overall survival between the 2 groups (x2=6.032,P ＜ 0.05).There was no significant difference in the tumor-free survival between the 2 groups (x2=0.498,P ＞ 0.05).Conclusion S-1 single agent chemotherapy after radical resection of cholangiocarcinoma could improve the survival of patients,while no obvious advantages of inhibiting tumor recurrence is observed.

Objective To investigate the application value of percutaneous sinus-tract cholangioscopy in the diagnosis and treatment of residual intra-and extra-hepatic bile duct stones.Methods The retrospective cross-sectional study was conducted.The clinical data of 1 045 patients with intra-and extra-hepatic bile duct stones who underwent percutaneous sinus-tract cholangioscopy or stone extraction in the Second Affiliated Hospital of Zhejiang University from January 2003 to June 2016 were collected.Patients received percutaneous sinus-tract cholangioscopy or stone extraction at 6-8 weeks after T tube drainage.Observation indicators:(1) diagnosis and stone extraction situstions:cases with residual stones,stone extraction frequency and clearance rate;the critics of clearance rate are no residual stone dnring operation combined with B ultrasound or T-tube cholangiography;(2) postoperative complications:incidence and management of postoperative complications,prognosis and ClavienDindo classification for postoperative complication;(3) follow-up situation.T-tube was removed when there was no residual stone.Patients were followed up by outpatient examination up to April 2017.B ultrasound reexamination was performed to detect the recurrence of stone once every 3-6 months.Results (1) Diagnosis and stone extraction situstions:among 1 045 patients,results of cholangioscopy showed 147 wihout bile duct stones and 898with bile duct stones.Of 898 patients,2 618 times cholangioscopic explorations for stone extraction were performed,with a maximum frequency of 16 times,and 851 had stones clearance,with a overall clearance rate of 94.77％(851/898).The clearance rates of extra-and intra-hepatic bile duct stones were 100.00％(221/221) and 93.06％(630/677).Of 47 patients with residual stones,16 didn't receive cholangioscopy due to branches stricture or occlusion of intrahepatic duct,13 failed to take out stone due to T-tube dislodgement (9 cases) and improper placement (4 cases) induced closed T-tube sinus tract,7 had T-tube sinus tract duodenal fistula,6 gave up stone extraction,3 was due to longer sinus tract induced bending and 2 was due to T-tube sinus tract fracture.(2)Postoperative complications:among 1 045 patients,297 had level Ⅰ-Ⅱ mild complications and 13 had level Ⅲand above severe complications.The common complications included fever,vomiting,diarrhea and so on;the special complications included T-tube sinus tract duodenal fistula of 13 patients,T-tube sinus tract fracture of 4 patients,rupture of broken stones pole of 3 patients,massive hemobilia of 2 patients,acute pancreatitis of 2patients and cardiac arrest of 1 patient.The above complications were improved by symptomatic and supportive treatments.(3) Follow-up situation:among 1 045 patients,558 received long-term follow-up,with follow-up time of 10-171 months and a median time of 79 months.Eight-four patients had stone recurrence.Of 13 patients with recurrence of extrahepatic bile duct stones,7 took out stones by endoscopic retrograde cholangio pancreatography (ERCP) and 6 underwent reoperations.Of 71 patients with recurrence of intrahepatic bile duct stones,43underwent reoperations and 28 received conservative treatment.Conclusions Percutaneous sinus-tract cholangioscopy for residual intra-and extra-hepatic bile duct stones is safe and effective,with good diagnosis and treatment values and a high clerance rate.The integrity of T-tube sinus-tract is a key of complete stones removal.

Objective To analyze the clinical application of donor specific antibodies (DSAs) detected by a single antigen Luminex virtual crossmatch,and to discuss the treatment of DSA and the impact of DSA on renal function.Methods Serum from living-relative renal recipients before and after transplantation was investigated using a Luminex single antigen assay.The relation between DSA and renal acute rejection as well as renal function was analyzed.Results A total of 30 patients and 173 serum samples were tested,including 47 serum samples before transplantation,and 126 after transplantation.DSA was positive in one patient before transplantation,and 8 patients after transplantation.Three of the patients positive for DSA were treated by Bortezomib,3 by addition of MMF,2 by addition of CNI,1 by addition of Sirolimus.The MFI of DSA in one of the patients treated by Bortezomib was decreased to below 1000,while that in the other two decreased by more than 50 ％.The renal eGFR at the time with and without DSA was (1.50 ± 0.59) and (1.23 ± 0.38)ml/s respectively (P＜0.05).Conclusion Dynamic monitoring of single bead antigen antibody DSA conduces to direct the adjustment of immunosuppressant.The appearance of DSA contributes to the declination of renal function.Application of Bortezomib decreased the MFI of DSA.

ObjectiveTo investigate the efficacy of rapamycin combined with CsA/Tacrolimus (Tac) in chronic allograft nephropathy (CAN).MethodsFifty-three cases of CAN accepted the quadruple immunosuppressive drug program,which contained rapamycin combined with CsA/Tac and MMF and prednisone,and CsA/Tac and MMF were reduced to the original amount of 25％ to 50％.After treatment for 12 months,more relevant indicators,including serum creatinine,glomerular filtration rate,serum cholesterol,triglycerides,urinary protein,GPT and bilirubin and other changes were observed.ResultsIn the patients receiving quadruple regimen of rapamycin during 12 months,the blood Ccr was decreased from (161.51 ± 106.48)μmol/L before treatment to (126.51 ± 56.2)μmol/L after treatment for 6 months (P＜0.05) and to (123.43 ± 54.18)μmol/L after for 12 months (P＜0.01).The GFR was increased from (0.754 ± 0.302) ml/s before treatment to (0.952 ± 0.347)ml/s after treatment for 6 months (P＜0.05) and to (1.007 ± 0.394) ml/s after treatment for 12 months (P＜0.01).Cholesterol and triglycerides in patients had no significant change before and after treatment.The positive rate of proteinuria after treatment showed an increasing trend from 9.4％ before treatment to 26.4％ after treatment for 12 months.ConclusionThe quadruple program of rapamycin combined with CsA/FK506 and MMF can significantly improve Ccr and GFR in patients with CAN,but it can increase the incidence of proteinuria in patients:

Extragonadal yolk sac tumor (YST) is a relatively rare entity. We describe here the case of an extragonadal YST that occurred in the pancreas with hepatic metastasis in an adult woman. The contrast enhanced CT images of the abdomen revealed a heterogeneous, solitary mass occupying the pancreatic neck and body with slightly inhomogeneous contrast enhancement. Two low-density lesions in the liver were also displayed on the CT images. The patient underwent surgery and the diagnosis of YST was pathologically verified.
Contrast Media ; Endodermal Sinus Tumor/pathology/*radiography/surgery ; Female ; Humans ; Liver Neoplasms/*radiography/secondary/surgery ; Middle Aged ; Pancreatic Neoplasms/pathology/*radiography ; Tomography, X-Ray Computed/*methods

OBJECTIVETo explore efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) regimen by dose attenuation in locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer(MPC).

METHODSBetween April 2014 and October 2015, 35 patients with LAPC (n=18) or MPC (n=17) were treated with mFOLFIRINOX regimen (irinotecan 135 mg/m(2), oxaliplatin 68 mg/m(2), 5-FU 2 400 mg/m(2), no bolus of 5-FU, leucovorin 400 mg/m(2)) in the Second Affiliated Hospital of Zhejiang University School of Medicine. The primary end point was progression free survival. The second end points were overall survival, objective response rate, adverse effects, surgical resection rate for LAPC.

RESULTSAmong 35 patients, 6 patients (17.1%) who dropped out and received less than 2 cycles were excluded for response analysis. Among the other 29 patients, 9 patients had grade 3 or 4 adverse effects. No patients ceased treatment due to adverse effects. The 29 patients received 5 (2-13) cycles were evaluated by efficacy and found partial remission in 16 cases, stable disease in 10 cases, progression disease in 3 cases. Response rate was 55.2%. Nine patients with LAPC accomplished surgery after neoadjuvant treatment without perioperative complication and death, and 6 patients accepted R0 resection.

CONCLUSIONSThe mFOLFIRINOX regimen used in the study is well-tolerated in Chinese population with high treatment efficacy on patients with LAPC and MPC. Further investigation of efficacy and adverse effects on more advanced pancreatic cancer patients is necessary.

Antineoplastic Combined Chemotherapy Protocols ; Camptothecin ; administration & dosage ; analogs & derivatives ; Disease Progression ; Disease-Free Survival ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Neoadjuvant Therapy ; Organoplatinum Compounds ; administration & dosage ; Pancreatic Neoplasms ; drug therapy ; Tertiary Care Centers ; Treatment Outcome

Objective:To explore the clinical characteristics and outcomes of SARS-CoV-2 infection in kidney transplant recipients(KTRs)and examine the risk factors for severe/critical infection.Methods:A retrospective analysis was conducted for 208 adult KTRs diagnosed with SARS-CoV-2 infection between December 15, 2022, and March 15, 2023.They were assigned into two groups of mild/ordinary(n=168)and severe/critical(n=40)according to the severity of SARS-CoV-2 infection.Two groups were compared with regards to general profiles, status of baseline vaccination against COVID-19, transplant history, immunosuppressive regimens, comorbidities and treatment outcomes.For continuous variables, t or Mann-Whitney U test was utilized for comparing the inter-group differences.For categorical variables, chi-square or Fisher's exact test was employed.Bonferroni correction was applied for multiple comparisons when p value was ≤0.05.Logistic regression analysis of univariates and multivariates was conducted for identifying the risk factors for severe/critical infections.Results:The rates of hospitalization, severe illness, ICU admission, mechanical ventilation and mortality among 208 KTRs with COVID-19 were 27.4%(57/208), 19.2%(40/208), 3.4%(7/208), 5.3%(11/208)and 1.9%(4/208)respectively.Among 57 COVID-19 infected individuals, 43.9%(25/57)experienced bone marrow suppression with an incidence of anemia 36.8%(21/57)and thrombocytopenia 22.8%(13/57). The lowest counts of whole blood lymphocyte, CD4 + T lymphocyte and CD8 + T lymphocyte were 390.0(245.0, 615.0), 138.0(78.0, 293.5)and 180.0(94.7, 575.2)cells/μL respectively.The incidence of bacterial, cytomegaloviral, Pneumocystis jirovecii and other fungal infections after COVID-19 infection was 17.8%(37/208), 3.8%(8/208), 2.9%(6/208)and 2.9%(6/208)respectively.The severe/critical group had a higher incidence of other pathogen infections as compared to mild/ordinary group, including bacterial infections[62.5%(25/40)vs 7.1%(12/168), 95% CI: 47.5%~63.3%, P<0.001], cytomegaloviral infections[15.0%(6/40)vs 1.2%(2/168), 95% CI: 8.1%~19.5%, P=0.001], P.jirovecii infections[15%(6/40)vs 0(0/168), 95% CI: 9.4%~20.6%, P<0.001]and other fungal infections of Candida, Cryptococcus, Malassezia and Aspergillus fumigatus[15.0%(6/40)vs 0(0/168), 95% CI: 9.4%~20.6%, P<0.001]. The incidence of acute kidney injury(AKI)after COVID-19 infection was 13.5%(28/208)and severe/critical group had a higher incidence of AKI than mild/ordinary group[52.5%(21/40)vs 4.2%(7/168), 95% CI: 40.3% to 56.3%, P<0.001]. Univariate analysis showed that age( P=0.003), male gender( P=0.002), smoking history( P=0.012), coronary heart disease( P=0.011), diabetes mellitus( P=0.002), chronic renal insufficiency( P=0.001)and pulmonary disease history( P=0.001)were significantly different between severe/critical and mild/ordinary groups.Multivariate regression analysis revealed that comorbid chronic kidney disease( OR=3.34, 95% CI: 1.46-7.64, P=0.004)and a history of lung disease( OR=3.42, 95% CI: 1.49-7.87, P=0.004)were independent risk factors for severe/critical illness.Baseline vaccination rate against COVID-19 was 17.8%(37/208). Completion of baseline vaccination was associated with a lower risk of severe/critical COVID-19 infection( OR=0.28, 95% CI: 0.08-0.98, P=0.047). Conclusions:KTRs with severe/critical COVID-19 infections are more prone to multiple pathogen co-infections and the incidence of kidney function impairment after infection has remained relatively high.Histories of pulmonary and chronic kidney diseases are independent risk factors for severe/critical infections.Completion of baseline vaccination provides protection against severe/critical infections.