OBJECTIVE To investigate the improvement effect and potential mechanism of “Layers adjusting external application” paste on synovial fibrosis （SF） in rats with knee osteoarthritis （KOA）. METHODS Male SD rats were randomly divided into sham operation group， KOA group and Layers adjusting external application group， with 8 rats in each group. KOA model was induced by the anterior cruciate ligament disruption method in KOA group and Layers adjusting external application group. Fourteen days after modeling， the Layers adjusting external application group was given “Layers adjusting external application” paste [Sanse powder （8 g for every 100 cm2）， Compound sanhuang ointment （5 g for every 100 cm2）] on the knee joint， 8 h every day， for 28 d in total. After the last administration， the degree of synovitis and fibrosis in rats was observed， and Krenn scoring was performed in each group. The expressions of collagen Ⅰ， high mobility group protein B1 （HMGB1） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65） were detected in the synovial membrane； the contents of interleukin-1β （IL- 1β）， IL-6 and tumor necrosis factor-α （TNF-α） in serum as well as the expressions of fibrosis-related and HMGB1/Toll-like receptor 4 （TLR4）/NF-κB signaling pathway-related proteins and mRNA were detected in synovial tissue. RESULTS Compared with the sham operation group， the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement， the inflammatory cell infiltration and collagen fiber deposition were obvious； the positive expressing cells of collagen Ⅰ， HMGB1 and p-NF-κB p65 were increased significantly； the contents of IL-1β， IL-6 and TNF-α in serum， the expressions of fibrosis-related protein （transforming growth factor-β， collagen Ⅰ， tissue inhibitor of metalloproteinase 1， α-smooth muscle actin） and their mRNA as well as theexpressions of HMGB1， TLR4 protein and their mRNA， the expressions of p-NF-κB p65 protein and NF-κB p65 mRNA were all increased significantly in synovial tissues of rats （P＜0.01）. Compared with the KOA group， the pathological changes in the synovial tissue of rats in Layers adjusting external application group were significantly improved， and the above quantitative indicators were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS “Layers adjusting external application” paste could significantly improve SF in KOA rats， the mechanism of which may be associated with the inhibition of the activation of HMGB1/ TLR4/NF-κB signaling pathway.

Objective:To investigate the value of soluble interleukin-6 (IL-6) receptor (sIL-6R) level in predicting ultrafiltration insufficiency in peritoneal dialysis (PD) patients.Methods:It was a prospective cohort study. The patients who received continuous ambulatory PD and regular follow-up between November 2016 and July 2018 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled. Enzyme-linked immunosorbent assay was used to determine dialysate sIL-6R and its appearance rate (AR) was calculated. Patients were divided into high sIL-6R AR group and low sIL-6R AR group according to median value of sIL-6R AR and prospectively followed up until death, PD cessation, or the end of the study (December 31, 2022). Multiple linear regression was used to analyze the related factors of sIL-6R AR. Kaplan-Meier method and log-rank test were used to compare the survival rate difference of ultrafiltration insufficiency between high sIL-6R AR group and low sIL-6R AR group. Multivariate Cox regression and multivariate competing risk models were used to assess the risk factors associated with occurrence of ultrafiltration insufficiency.Results:A total of 198 PD patients were enrolled, including 115 (58.1%) males, with age of (54.9±13.7) years old and PD duration of 22.5 (6.6, 65.0) months. The sIL-6R AR of the cohort was 2 094.7 (1 672.4, 2 920.9) pg/min. Compared with low sIL-6R AR（<2 094.7 pg/min）group, high sIL-6R AR（>2 094.7 pg/min）group had older age ( t=-3.269, P=0.001), higher body mass index ( t=-3.248, P=0.001), proportion of combined diabetes mellitus ( χ2=8.890, P=0.003), 24 h glucose exposure ( Z=-2.257, P=0.024), 24 h ultrafiltration capacity ( Z=-2.515, P=0.012), 4 h dialysate creatinine to serum creatinine ratio ( t=-2.609, P=0.010), mass transfer area coefficient of creatinine ( Z=-2.308, P=0.021), IL-6 AR ( Z=-3.533, P<0.001) and solute glycoprotein 130 AR ( Z=-8.670, P<0.001), and lower serum albumin ( t=2.595, P=0.010) and residual renal function ( t=2.133, P=0.033). Multiple linear regression analysis showed that body mass index ( β=0.194, P=0.005), serum albumin ( β=-0.215, P=0.002) and dialysate lg[IL-6 AR] ( β=0.197, P=0.011) were independently correlated with sIL-6R AR. By the end of the study, 57 (28.8%) patients developed ultrafiltration insufficiency. Kaplan-Meier analysis showed that high sIL-6R AR group had a significantly inferior ultrafiltration insufficiency-free survival rate than that in low sIL-6R AR group (log-rank χ 2=5.375, P=0.020). Multivariate Cox regression analysis and multivariate competing risk models showed that high dialysate sIL-6R AR (>2 094.7 pg/min) was an independent influencing factor of ultrafiltration insufficiency ( HR=2.286 , 95% CI 1.254-4.165 , P=0.007 ; SHR=2.074, 95% CI 1.124-3.828, P=0.020) in PD patients. Conclusions:Dialysate sIL-6R level was associated with body mass index, serum albumin and dialysate IL-6 level. Dialysate sIL-6R may be a predictive factor of ultrafiltration insufficiency in PD patients.

Objective:To analyze the relationship between aquaporin 1 (AQP1) level and vascular calcification in patients with diabetes nephropathy.Methods:A total of 125 diabetic nephropathy patients admitted to Suzhou Hospital of Nanjing Medical University from March 2020 to March 2023 were retrospectively selected as case group. The case group was divided into group A (diabetes nephropathy stage Ⅰ and Ⅱ) with 31 cases, group B (diabetes nephropathy stage Ⅲ) with 32 cases, group C (diabetes nephropathy stage Ⅳ) with 39 cases, and group D (diabetes nephropathy stage V) with 23 cases. In these patients, 51 cases had vascular calcification, taken as the calcification group, and 74 cases had no vascular calcification, taken as the non calcification group. Sixty volunteers who underwent health examinations in the same hospital were selected as the control group. Receiver operating characteristic curve was used to analyze the predictive value of AQP1 on vascular calcification in diabetes nephropathy patients and to explore the related factors of vascular calcification in diabetes nephropathy patients.Results:Compared with the control group, AQP1 level and calcification rate in groups A, B, C and D were higher: 6.41 ± 1.04, 7.93 ± 1.23, 9.50 ± 1.52 and 11.37 ± 2.01 vs. 3.83 ± 0.56 ng/L, 6.45% (2/31), 28.13% (9/32), 51.28% (20/29) and 86.96% (20/23) vs. 0 ( P<0.05). Compared with group A, the level of AQP1 and calcification rate in groups B, C and D were higher ( P<0.05); compared with group B, the AQP1 level and calcification rate in groups C and D were higher ( P<0.05); compared with group C, the level of AQP1 and calcification rate in group D were higher ( P<0.05). Compared to the non calcification group, the levels of uric acid, homocysteine and cystatin C in calcification group were higher: (313.82 ± 38.72) μmol/L vs. (253.42 ± 30.14) μmol/L, (20.03 ± 3.01) μmol/L vs. (15.01 ± 2.71) μmol/L, (1.73 ± 0.26) mg/L vs. (1.30 ± 0.17) mg/L ( P<0.05). AQP1 was positively correlated with uric acid, homocysteine, and cystatin C ( P<0.05). The area under the curve of AQP1, uric acid, homocysteine and cystatin C in predicting vascular calcification in patients with diabetes nephropathy were 0.892, 0.803, 0.738 and 0.763, respectively. Taking whether vascular calcification occurs in patients with diabetes nephropathy as the dependent variable (no = 0, yes = 1), the variables of P<0.05 in the single factor analysis were selected for multivariate Logistic regression analysis. The results showed that uric acid, homocysteine, cystatin C and AQP1 were the main factors affecting vascular calcification in patients with diabetes nephropathy ( P<0.05). Conclusions:Serum AQP1 has a high predictive value for vascular calcification in diabetes nephropathy patients, and is expected to be used as a biomarker for early diagnosis of vascular calcification in diabetes nephropathy patients.

The historical evolution， fermentation technology and key links of Sojae Semen Praeparatum （SSP） were sorted out by consulting ancient books and modern literature， and the influencing factors and control methods of quality were analyzed and summarized in order to provide reference for the quality control of SSP. After analysis， it was found that in the fermentation process of SSP， fermentation strains， miscellaneous bacteria， temperature and humidity were all important factors affecting the quality of SSP. The condition control of "post fermentation" process has been paid more attention to in the past dynasties. In addition， the delicious SSP recognized in ancient times should be made from mold fermentation， and the breeding and application of fermented mold may be the key point to solve the quality problem of SSP. Therefore， based on the evaluation indexes of SSP in the past dynasties， it is of great significance to study and optimize the technological conditions such as strain， temperature and humidity in depth to improve the quality of SSP.

Objective To establish genotyping methods for vitamin K epoxide reductase complex subunit 1 (VKORC1)and cytochrome P450 2C9(CYP2C9)based on pyrosequencing technique to detection of warfarin metabolizing enzyme related gene polymorphisms.Methods A total of 50 peripheral blood samples from healthy adults were collected and the whole blood genomic DNA was extracted.A set of biotin-labeled amplifi-cation primers and sequencing primers were designed respectively for three SNP sites:VKORC1 -1639 G>A,CYP2C9 430C> T and CYP2C9 1075A>C.After PCR amplification of the samples,pyrophosphoric acid se-quencing was conducted.And then the signal peaks form were combined to analyze and determine each sample genotype.Genotyping results were verified by Sanger sequencing,and the consistency of the two sequencing methods was compared.Results Genotypes of the three SNPs can be clearly determined according to the ba-ses and height of the signal peaks.Among the 50 samples,there were 41 AA and nine AG for VKORC1 -1639G>A,accounting for 82% and 12% respectively,and there were 45 *1/*1,five *1/*3 for CYP2C9, accounting for 90% and 10% respectively,no CYP2C9*2 allele detected.Genotype results detected by pyrose-quencing and Sanger sequencing were consistent with each other.Conclusion In SNP genotyping,Pyrose-quencing has the advantages of convenience,time-saving,cheap with accurate and reliable results,which can quickly determine the genotypes of CYP2C9 and VKORC1.

Objective: To evaluate the safety and feasibility of laparoscopic radical antegrade modular pancreatosplenectomy(Lap-RAMPS) for left-sided pancreatic adenocarcinoma. Methods: Clinical data of total 12 patients underwent Lap-RAMPS for left-sided pancreatic adenocarcinoma at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People′s Hospital from March 2016 to August 2017 were reviewed retrospectively.There were 7 male patients and 5 female patients, with median age of 60.5 years old(47-68 years old). Abdominal enhanced CT, pancreatic MRI, PET-CT were performed on all patients to evaluate the lesion and exclude metastasis.Follow-up were done with out-patient clinic or telephone consultancy until October 2017. Results: All patients underwent pure Lap-RAMPS.The medium operative time was 250 minutes(180-445 minutes), and the blood loss was 150 ml(50-500 ml). The medium first flatus time and diet resumption time were 3.0 days(1-5 days) and 3.5 days(1-7 days) respectively.The medium postoperative hospital stay was 9 days(4-18 days). Morbidity occurred in 8 patients with gastric empty delay(n=1), bleeding(n=1), fluid collection(n=3). There was no mortality.The medium overall number of retrived lymph nodes was 15.6 and the positive rate was 41.7%. The R0 rate was 100%.The medium follow-up was 10 months.One patient was diagnosed as liver metastasis after 8 months and accepted chemotherapy.One patient died after 14 months for tumor recurrence and metastasis.Others survived without tumor recurrence or metasitasis. Conclusion Lap-RAMPS is safe and feasible with accepted oncological outcomes for selected left side pancreatic adenocarcinoma under skilled hands.

Objective To investigate the treatment efficacy,feasibility and safety of laparoscopic resection for gastric gastrointestinal stromal tumors (GISTs) larger than 5 cm.Methods The clinical data of 31 patients who underwent laparoscopic resection of large gastric GISTs between Jan 2010 and Jun 2017 at Sir Run Run Shaw Hospital and People's Hospital of Zhejiang Province were retrospectively analyzed.Results All operations were successful.Two patients were converted to open surgery.The mean tumor size was (7.2 ±0.5) cm.The mean operation time was (127 ± 12) min,intraoperative blood loss was (83 ±25) ml.The first flatus time was (2.2 ±0.8) days,the first diet resumption time was (2.4 ± 1.2) days,and the median postoperative hospital stay was (5.5 ± 1.5) days.The median follow-up time was 25 months.One patient developing liver metastasis 41 months after primary resection received oral mesylate imatinib therapy for 24 months and was still alive at the last follow-up.One patient died of lung cancer 33 months after primary operation without recurrence of gastric GIST.Conclusions Laparoscopic surgery for gastric GIST larger than 5 cm on laparoscopicaly accessible location is feasible and safe.

Objective To evaluate the safety and feasible of adjacent organ resection during laparoscopic pancreaticoduodenectomy(LPD),and summary the surgical strategies.Methods Clinical data of 15 adjacent organ resections combined with LPD from March 2013 to September 2017 were reviewed.There were 10 male and 5 female patients aging from 20 to 86 years,and the body mass index ranged from 19.6 to 34.5 kg/m2.Two patients had previous abdominal surgical history.Two patients underwent preoperative chemotherapy.Results The resected adjacent organs included liver (n =4),stomach (n =3),colon(n =6),right kidney with embolectomy and vasoplastic of inferior vena cava (n =1),and spleen artery aneurysms(n =1).The operative time ranged from 280 to 450 minutes,and the blood loss ranged from 100 to 450 ml.The total complication rate was 5/15 and no one died in 90 days after surgery.The postoperative hospital stay ranged from 10 to 42 days with medium 18 days.The pathology included adenocarcinoma of stomach and duodenum (n =1),gastric cancer invading pancreas or duodenum (n=2),ampullary adenocarcinoma with left hepatolithiasis(n=1),ampullary adenocarcinoma with a benign lesion in left liver (n =1),ampullary adenocarcinoma with single liver metastasis (n =1),ampullary adenocarcinoma(n =1),pancreatic intraductal papillary mucinous neoplasm with splenic artery aneurysms (n=1),pancreatic neuroendocrine neoplasm with colon cancer (n =1),distal common bile duct adenocarcinoma involving righ hepatic duct (n =1),pancreatic neuroendocrine neoplasm invading inferior vena cava and right renal vein(n=1),duodenal adnocarcinoma(n =1),duodenal ewing's sarcoma(n =1),duodenal intesititialoma (n =2).The follow-up was from 3 to 40 months with the medium survival of 17.5 months.Conclusions The oncological outcomes of PD combined with adjacent organ resection is acceptable.Surgical treatment for those patients with periampullary neoplasma and adjacent organ lesions should be aggressive.

Objective To evaluate the safety and feasible of adjacent organ resection during laparoscopic pancreaticoduodenectomy(LPD),and summary the surgical strategies.Methods Clinical data of 15 adjacent organ resections combined with LPD from March 2013 to September 2017 were reviewed.There were 10 male and 5 female patients aging from 20 to 86 years,and the body mass index ranged from 19.6 to 34.5 kg/m2.Two patients had previous abdominal surgical history.Two patients underwent preoperative chemotherapy.Results The resected adjacent organs included liver (n =4),stomach (n =3),colon(n =6),right kidney with embolectomy and vasoplastic of inferior vena cava (n =1),and spleen artery aneurysms(n =1).The operative time ranged from 280 to 450 minutes,and the blood loss ranged from 100 to 450 ml.The total complication rate was 5/15 and no one died in 90 days after surgery.The postoperative hospital stay ranged from 10 to 42 days with medium 18 days.The pathology included adenocarcinoma of stomach and duodenum (n =1),gastric cancer invading pancreas or duodenum (n=2),ampullary adenocarcinoma with left hepatolithiasis(n=1),ampullary adenocarcinoma with a benign lesion in left liver (n =1),ampullary adenocarcinoma with single liver metastasis (n =1),ampullary adenocarcinoma(n =1),pancreatic intraductal papillary mucinous neoplasm with splenic artery aneurysms (n=1),pancreatic neuroendocrine neoplasm with colon cancer (n =1),distal common bile duct adenocarcinoma involving righ hepatic duct (n =1),pancreatic neuroendocrine neoplasm invading inferior vena cava and right renal vein(n=1),duodenal adnocarcinoma(n =1),duodenal ewing's sarcoma(n =1),duodenal intesititialoma (n =2).The follow-up was from 3 to 40 months with the medium survival of 17.5 months.Conclusions The oncological outcomes of PD combined with adjacent organ resection is acceptable.Surgical treatment for those patients with periampullary neoplasma and adjacent organ lesions should be aggressive.

Objective To investigate the microbiological trends and antibiotic susceptibility of peritoneal dialysis(PD)-related peritonitis (PDAP).Methods All patients who developed PDAP between 2004 and 2015 in Renji Hospital,Shanghai Jiao Tong University School of Medicine were enrolled.Demographic data,results of dialysate pathogen culture and drug susceptibility test were recorded.The trend of peritonitis incidence was measured by Poisson regression and the chi-square test or Fisher exact test method was used to compare the composition of causative organisms and their antimicrobial susceptibilities over time.Results During the study period,a total of 711 episodes of PDAP were occurred in 386 patients.The culture positive rate of pathogens rose from 52.0％ in 2004 to 77.0％ in 2015 (P ＜ 0.001).The distribution of causative organisms of the culture positive peritonitis was gram-positive bacteria (270,59.5％),followed by gram-negative bacteria (129,28.4％),polymicrobial(39,8.6％),fungi (15,3.3％) and mycobacteria (1,0.2％).From 2004 to 2015,the incidence of peritonitis decreased from 0.214 to 0.160 episodes/patient·year (P=0.034).The incidence of coagulase-negative staphylococcus peritonitis decreased from 0.049 to 0.027 episodes/patient · year (P=0.025),while others had no significant change;A significant decline was observed in the sensitivity of Gram-positive strains to the first generation cephalosporin and ampicillin/sulbactam in 2010-2015 group compared with those in 2001-2009 group (61.3％ vs 88.2％,P ＜ 0.001;61.7％ vs 85.5％,P=0,001),whereas the sensitivity to vancomycin remained the same.The sensitivity of Gram-negative strains to ceftazidime and amikacin showed no significant change.As for the gram-positive peritonitis treated with cefradine as empirical treatment,compared with those in 2004-2009 group,in 2010-2015group the proportion of patients requiring to change their treatment regime was significantly higher,and the treatment course was longer.Conclusions A gradual decline is observed in the incidence of PDAP and the culture positive rate of pathogens improves.Peritonitis caused by coagulase-negative staphylococcus decreases overtime.The present empirical treatment protocols may need re-evaluation considering the decreased rate of the first generation cephalosporin sensitivity in recent years.