Objective:To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.Methods:The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model. Results:(1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500?1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300?1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500?1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them ( χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ?Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a?2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis ( χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis ( χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R 1 or R 2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma ( hazard ratio=2.62, 2.71, 95% confidence interval as 1.30?5.29, 1.30?5.69, P<0.05). Conclusions:Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R 1 or R 2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetesinduced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholineinduced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O2 for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (LNAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IRinduced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetesinduced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholineinduced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O2 for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (LNAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IRinduced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

Eight mouse hybridoma cell lines which stably secreted monoclonal antibodies ( McAbs ) against human prostate-specific antigen-α1-antichymotrypsin complex ( PSA-ACT ) were obtained through hybridoma technique. After purification, the immunological characters of 8 McAbs were identified and classified by epitopes analysis through indirect enzyme-linked immunosorbent assay ( ELISA) . A pair of McAbs was chosen from above 8 McAbs, based on which a highly sensitive, simple and rapid chemiluminescence enzyme immunoassay ( CLEIA) was developed for determination of PSA-ACT in human serums using the lumino-H2 O2 reaction catalyzed by horseradish peroxidase ( HRP) as the chemiluminescence system. Several experiment factors such as coating buffer, coating concentration, dilution ratio of PSA-ACT-HRP complex, incubation time, immunoreaction protocol and chemiluminescence reaction time were optimized. The results showed that the linear range of the proposed method for PSA-ACT determination was 0-40 ng/mL (R2=0. 9943), with the detection limit of 0. 53 ng/mL. The inter-assay relative standard deviations (RSDs) were 4. 6%-6. 6%, and intra-assay RSDs were 5 . 7%-8 . 0%. The recoveries of PSA-ACT at three spiked levels in serum samples were 95. 4%-104. 2%. The proposed method exhibited a cross-reactivity of 0. 6% with free-PSA. The proposed method is stable, sensitive, rapid and simple, and provides a foundation for the development of PSA-ACT CLEIA kit and shows great value in clinical auxiliary diagnosis of prostate cancer.

Objective To evaluate the efficacy of atrial septostomy in idiopathic pulmonary arterial hypertension(IPAH) patients complicating right ventricular failure.Methods This retrospective analysis included 5 IPAH patients (3 males,(29.3 ± 15.2) years old) with right ventricular failure which were refractory to conventional and target-specific medication in Shanghai Chest Hospital from March to July 2014.Graded balloon dilation septostomy procedures were performed in all 5 patients.Results Successful atrial septostomy was achieved in 5 attempts with no procedure-related complications.Immediately post procedure,the mean systemic oxygen saturation decreased from (98.0 ± 1.8) ％ to (86.4 ± 3.2) ％ (P =0.002),while the mean right atrial pressure decreased from(18.9 ± 1.7) mmHg(1 mmHg =0.133 kPa) to (16.0 ± 1.3)mmHg(P =0.039) and the mean cardiac index increased from (2.1 ±0.3)L · rain-1 · m-2 to (2.7 ± 0.5) L · min 1 · m-2 (p =0.029).Mean follow-up was (6.2 ± 1.8) months.Cardiac functional class (WHO) was 3 in 3 patients and 4 in 2 patients before the procedure,and increased 1 class in all patients during follow-up(P =0.062).Exercise endurance(6-min walk test)also improved from (289.2 ± 16.9)m to (320.4 ± 19.6) m (P =0.019),while B-type natriuretic peptide (BNP) level declined from (550.0 ± 35.7) ng/L to (218.0 ± 36.2) ng/L (P ＜ 0.001).Except one patient developed spontaneous closure of created defect,right to left shunt at atrial septal level was evidenced by echocardiography during follow-up in the rest 4 patients.Conclusions Atrial septostomy is safe and can improve hemodynamics and heart function in selected IPAH patients with right heart failure.Atrial septostomy can be used as a palliative treatment for IPAH and further study is warranted to evaluate the long-term efficacy of this procedure.

Bacterial cell division is strictly regulated in the formation of equal daughter cells. This process is governed by a series of spatial and temporal regulators, and several new factors of interest to the field have recently been identified. Here, we report the requirement of gluconate 5-dehydrogenase (Ga5DH) in cell division of the zoonotic pathogen Streptococcus suis. Ga5DH catalyzes the reversible reduction of 5-ketogluconate to D-gluconate and was localized to the site of cell division. The deletion of Ga5DH in S. suis resulted in a plump morphology with aberrant septa joining the progeny. A significant increase was also observed in cell length. These defects were determined to be the consequence of Ga5DH deprivation in S. suis causing FtsZ delocalization. In addition, the interaction of FtsZ with Ga5DH in vitro was confirmed by protein interaction assays. These results indicate that Ga5DH may function to prevent the formation of ectopic Z rings during S. suis cell division.
Bacterial Proteins ; chemistry ; genetics ; metabolism ; Cell Division ; Cell Shape ; Cytoskeletal Proteins ; chemistry ; genetics ; metabolism ; Mutation ; Oxidoreductases ; deficiency ; genetics ; metabolism ; Protein Binding ; Streptococcus suis ; enzymology

Objective To investigate the safety and feasibility of electrocoagulation of gallbladder artery in laparoscopic cholecystectomy ( LC) . Methods A total of 376 patients with gallbladder benign diseases underwent LC in our hospital from May 2004 to September 2013.The gallbladder artery was treated by electrocoagulation . Results Because of unclear gallbladder triangle due to abdominal adhesion , conversion to laparotomy was performed in 9 patients.In the remaining 367 patients, three-port LC with electrocoagulation of the gallbladder artery was conducted successfully .Laparoscopic appendectomy was conducted simultaneously in 12 patients.An additional fenestration and drainage of the left renal cyst was performed in 1 patient.Postoperatively, a secondary bile duct exploration was conducted in 1 patient because of bile duct obstruction caused by common bile duct stones . Conclusion The electrocoagulation of gallbladder artery is safe and feasible in LC for the treatment of gallbladder benign diseases .

Objective To identify the metabolic levels in prefrontal lobe in patients with post-concussion syndrome by proton magnetic resonance spectroscopy (1H-MRS), and to explore the relationship between metabolic levels and executive function. Methods The study was conducted in 40 patients with post-concussion syndrome and 20 normal controls. 1H-MRS on prefrontal lobe was performed in patients and controls, the NAA, Cho and Cr were measured and the ratios of NAA/Cr, Cho/Cr and NAA/(Cho + Cr) were determined. They were also evaluated executive functions by verbal fluency test (animal), Wisconsin Card Sorting Test (WSCT) and Tower of Hanoi (TOH). Results Compared with normal controls, the patients with post-concussion syndrome were significantly lower NAA/Cr and NAA/(Cho+Cr) ratios in left prefrontal lobe (P < 0.05). The NAA/Cr ratio in left prefrontal was significantly positive correlated with total scores of verbal fluency (r = 0.66, P < 0.05), categories of WSCT (r = 0.54,P < 0.05) and total score of TOH(r = 0.58, P < 0.05). The NAA/Cr ratio was significantly negative correlated with total errors (r = -0.53, P < 0.05) and persistent errors (r = -0.47, P < 0.05) of WSCT and mean executive time of TOH(r = -0.67, P < 0.05). Conclusions The metabolic levels of NAA in left prefrontal lobe in patients with post-concussion syndrome is significantly decreased , it is one cause of impaired executive functions.

Interactions between FMDV and cardiac cells are multifaceted and complex ,these interactions leads to pro-teins alterations in cardiac cells inevitably .To understand the pathogenesis of myocarditis after FMDV infection in mice ,the suckling mouse model for myocarditis induced by foot-and-mouth disease virus (FMDV) was established in this study .Suckling mice within 3 days old was selected to infect by FMDV .Myocarditis caused by FMDV in suckling mice was confirmed with clinical symptom monitor .The observation of Hematoxylin and eosin stain (H&E stain) and transmission electron microscopy (TEM) were performed after samples processing .According to conventional polymerase chain reaction (PCR) methods ,prim-ers of VP1 gene was designed ,synthesised and specific FMDV VP1 gene was amplified from the heart muscle of suckling mice . The results indicated that suckling mice appeared low spirit condition ,dyspnea ,and dull reaction within 36 hours after chal-lenge with FMDV .Infiltration of inflammatory cells and dissolution of myocardial fibers were observed with H&E stain and TEM .Special target gene of FMDV was amplified from the heart of infected group .Obvious inflammation in the heart of suck-ling mice caused by FMDV was observed .It's suggested that suckling mouse model for myocarditis induced by FMDV was es-tablished successfully ,which would lay the foundation for researches of myocarditis mechanism in young cloven-hoofed ani-mals .

Objective To evaluate the feasibility,safety,and effectiveness of pulmonary vein stenting in patients with severe puhnonary vein stenosis (PVS) after catheter ablation of atrial fibrillation (AF).Methods This retrospective analysis included 5 PVS patients (3 males,(54.1 ± 11.2) years old) confirmed by computed tomography angiography after catheter ablation of AF in Shanghai Chest Hospital from April 2010 to April 2013.After selective pulmonary vein angiography,stents were implanted in the pulmonary vein.Operation results were analyzed after the procedure.Results All of 14 serious pulmonary vein stenosis from these 5 patients were treated with primary stent implantation (diameter:7 or 8 mm,length:12-23 mm).After stenting,degree of pulmonary vein stenosis decreased from(83 ± 16) ％ to(12 ± 4) ％ (P ＜ 0.01),the minimal diameter of the stenosis was significantly increased from (1.7 ± 0.6)mm to (8.1 ± 0.7) mm (P ＜ 0.01),trans-stenotic gradient decreased from (15 ± 5) mmHg (1 mmHg =0.133 kPa) to(3 ± 2)mmHg(P ＜ 0.05),mean pulmonary pressure measured by cardiac catheter decreased from (47 ± 5) mmHg to (28 ± 4) mmHg (P ＜ 0.05).Dyspnea was improved after the procedure.There was no serious operation related complications.Six months after stenting,three patients still complained mild to moderate dyspnea,and in-stent restenosis was evidenced in seven pulmonary veins by computed tomography angiography.These stenosis was successfully dilated by repeated interventions with balloon dilation.Conclusions Stenting for severe pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation may be feasible and safe,and can improve hemodynamics and symptoms.In-stent stenosis is relatively frequent,and larger stents and early intervention may reduce the rates of in-stent restenosis.