Objective To compare the clinical results of choledocholithotomy by laparoscopic surgery and open surgery.Methods One hundred and Sixty-nine patients with cholecystoithiasis combined with choledocholithiasis were divided into laparoscopic surgery group(85 cases of laparoscopic choledocholithotomy,LCD-TD) and open surgery group(84 cases of open choledocholithotomy,OCH-TD).The clinical data in the two groups were compared and analyzed.Results The amount of intraoperative bleeding,the recover time of intestinal peristalsis after treatment,length of hospital stay,cases of postoperative pain and biliary fistulas in laparoscopic surgery group were evidently better than those of open surgery group(all P

Objective To investigate the inhibitory effect of reiniosidc C (RC) on asymmetric dimethylarginine (ADMA)-induced soluble interacellular adhesion molecule-1 (slCAM-1) expression and its mechanisms. Methods Human umbical vein endothelial cells (HUVEC 12) were cultured.The level of slCAM-1 in the conditioned medium was determined by ELISA. Changes in intracellular reactive oxygen species (ROS) levels were determined by measuring the oxidative conversion of cell permeable 2', 7'-dichlorofluorescein diacetate (DCFH-DA) to fluorescent dichlorofluorescein (DCF) in fluorospectro- photometer, and the nuclear factor-κB (NF-κB) DNA-binding activity was determined by electrophoretic mobility shift assays (EMSA). Results sICAM 1 expressions [(138.02±16.40), (194.52±11.14), (274.28±13.11)ng/L]and the generation of ROS[(75.64±5.22),(100.18±11.15),(107.23±13.45)units] in HUVEC-12 were time dependently increased by ADMA (30 μmol/L). Furthermore, thc generation of ROS [(85.33±8.68), (70.69±7.65),(59.12±4.15)units], activation of NF-κB activity and expression of sICAM-1 [(336.58±23.32),(203.27±25.18) ,(174.13±14.53)ng/L] induced by ADMA were inhibited by reinioside C (1,3,10μmol/L) in a dose-dependent manner. This effect was found to be the same by L-arginine (0.5 mmol/L) as NOS substrate and by pyrrolidine dithiocarbamate (PDTC) (10 μmol/L)as inhibitor of NF-κB.Conclusions Reinioside C attenuates the increase of sICAM-1 induced by exogenous ADMA

OBJECTIVETo investigate the effects of intragastric administration of human interferon-α (hIFN-α)-transformed Bifidobacterium on immune functions of mice.

METHODSThe E.coli-Bifidobacterium shuttle expression vector containing hIFN-α gene was constructed and transformed into Bifidobacterium. The hIFN-α-transformed Bifidobacterium suspension (1010 /ml) was prepared after induction with 0.2% L-arabinose for hIFN-α expression and administered intragastrically in male Balb/C mice at the dose of 0.1 ml every other day for 2 weeks, with the mice receiving empty vector-transformed Bifidobacteria as the negative control and those having an equal volume of saline as the blank control. The percentages of mononuclear cell subsets in the thymus, spleen and blood were detected in the mice by flow cytometry, and the serum levels of IL-4, IL-12, IFN-γ and TNF-α were assayed using mouse cytokine FlowCytomix Kit.

RESULTSThe percentages of CD3⁺CD8⁺ and CD4⁺CD8⁺ cells in the thymus, CD3⁺CD4⁺, CD3⁺CD8⁺ and CD4⁺CD8⁺ cells in the spleen, and CD3⁺CD8⁺ cells in the blood all increased significantly in IFN group as compared with those in the negative and blank control groups (P<0.01 or 0.05). The serum level of IFN-γ also increased significantly (P<0.05) while IL-4 level remained unchanged in IFN group compared with those in the two groups.

CONCLUSIONIntragastric administration of hIFN-α-transformed Bifidobacterium promotes lymphocyte proliferation and maturation and increases the serum levels of Th1 cytokines in mice.

Animals ; Bifidobacterium ; Cell Proliferation ; Genetic Vectors ; Humans ; Interferon-alpha ; pharmacology ; Interferon-gamma ; blood ; Interleukin-12 ; blood ; Interleukin-4 ; blood ; Lymphocyte Activation ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins ; pharmacology ; Spleen ; cytology ; Th1 Cells ; cytology ; Thymus Gland ; cytology ; Tumor Necrosis Factor-alpha ; blood

BACKGROUND: Implantation of bone marrow mesenchymal stem cells (BMSCs) is a potential alternative for promoting bone defects healing or osseointegration in osteoporosis. However, the reactive oxygen species (ROS) accumulated and excessive inflammation in the osteoporotic microenvironment could weaken the self-replication and multi-directional differentiation of transplanted BMSCs. METHODS: In this study, to improve the hostile microenvironment in osteoporosis, Poloxamer 407 and hyaluronic acid (HA) was crosslinked to synthetize a thermos-responsive and injectable hydrogel to load MnO2 nanoparticles as a protective carrier (MnO2 @Pol/HA hydrogel) for delivering BMSCs. RESULTS: The resulting MnO2 @Pol/HA hydrogel processed excellent biocompatibility and durable retention time, and can eliminate accumulated ROS effectively, thereby protecting BMSCs from ROS-mediated inhibition of cell viability, including survival, proliferation, and osteogenic differentiation. In osteoporotic bone defects, implanting of this BMSCs incorporated MnO2 @Pol/HA hydrogel significantly eliminated ROS level in bone marrow and bone tissue, induced macrophages polarization from M1 to M2 phenotype, decreased the expression of pro-inflammatory cytokines (e.g., TNFa, IL-1b, and IL-6) and osteogenic related factors (e.g., TGF-b and PDGF). CONCLUSION This hydrogel-based BMSCs protected delivery strategy indicated better bone repair effect than BMSCs delivering or MnO2 @Pol/HA hydrogel implantation singly, which providing a potential alternative strategy for enhancing osteoporotic bone defects healing.

Objective:To investigate the clinical value of stylized laparoscopic hemicolec-tomy for left colon cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 174 patients who underwent laparoscopic hemicolectomy for left colon cancer in the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2020 were collected. There were 106 males and 68 females, aged 59(range, 17?86)years. All patients underwent stylized laparoscopic hemicolectomy for left colon cancer. Observation indicators: (1) surgical situations; (2) postoperative complications; (3) postoperative histopathological examinations; (4) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect tumor recurrence and metastasis and survival of patients up to October 2021. Follow-up was performed once every 3 months within postoperative 2 years, once every 6 months within postoperative 2 to 5 years and once a year after postoperative 5 years, with the end point as tumor recurrence and metastasis or death of patients. Measurement data with normal distribution were represented as Mean±SD and measurement data with skewed distribution were represented as M(range) or M( Q1, Q3). Count data were described as absolute numbers or percentages. Kaplan-Meier method was used to draw survival curve and calculate survival rate. Results:(1) Surgical situations. All the 174 patients underwent stylized laparoscopic hemicolectomy for left colon cancer successfully, including 6 cases receiving preoperative enteral stent placement due to bowel obstruc-tion, 3 cases receiving defunctioning ileostomy and 1 case receiving Hartmann procedure. The operation time, volume of intraoperative blood loss, time to postoperative initial defecation and duration of postoperative hospital stay of the 174 patients were 97(80,106)minutes, 45(25,60)mL, 5(3,6)days and 7(6,8)days, respectively. (2) Postoperative complications. Twelve of the 174 patients had complications, including 4 cases with incision infection or fat liquefaction, 3 cases with anastomotic leakage, 2 cases with incomplete bowel obstruction, 1 case with abdominal hemo-rrhage, 1 case with chylous leakage and 1 case with pulmonary infection. The 2 cases with anastomotic leakage underwent ileostomy. The patient with abdominal hemorrhage underwent laparotomy to stop bleeding. One elder patient died of postoperative pulmonary infection. The other patients with complications recovered with conservative treatment. (3) Postoperative histopatho-logical examinations. Of the 174 patients, there were 27 cases in stage Ⅰ of TNM staging, 68 cases in stage Ⅱ, 77 cases in stage Ⅲ and 2 cases in stage Ⅳ. There were 9 cases with well differentiated tumor, 107 cases with moderately differentiated tumor and 58 cases with poorly differentiated tumor. The number of lymph node detected, the number of positive lymph node and tumor diameter of the 174 patients were 19(15,23), 0(0,2) and 4(3,5)cm, respectively. Of the 174 patients, there were 79 cases with lymph node metastases, 21 cases with cancerous nodules, 35 cases with vascular invasion and 29 cases with nerve invasion. (4) Follow-up. Of the 174 patients, 157 cases were followed up for 27(range, 1?70)months. Of the 157 patients who conducted follow-up, 20 cases had tumor metastasis, including 9 cases with multiple metastasis, 5 cases with liver metastasis, 4 cases with lung metastasis, 1 case with bone metastasis and 1 case with spleen metastasis. The 5-year overall survival rate and tumor free survival rate of the 157 patients were 90.9% and 80.8%, respectively.Conclusion:The stylized laparoscopic hemicolectomy for left colon cancer is safe and feasible.

Objective:To investigate the strategy and feasibility of surgery for iatrogenic perforation of colorectum following colonoscopic examination or treatment.Methods:A retrospectively descriptive study was conducted. Twenty-one patients aged from 35 to 84 years old from the Department of General Surgery of the First Affiliated Hospital of Nanjing Medical University between Jan. 2015 and Dec. 2020 were enrolled in this study. There were 15 male and 6 female patients with a median age of 64 years.Observation indicators included patient demographics, including sex, age, comorbidity, abdominal surgical history; findings and outcomes of colonoscopy, including purpose of colonoscopy, time to the diagnosis of perforation; findings and outcomes of surgical treatment, including perforation site, perforation size, surgical methods, postoperative complications.Results:Eight patients were found with diagnostic colonoscopic perforation, 13 patients with therapeutic perforation (2 patients with endoscopic mucosal resection, 7 patients with endoscopic submucosal dissection and 4 patients with stent placement). Thirteen perforation occurred during the procedure of colonoscopy. Eleven patients with perforation occurred in the sigmoid colon, 3 in the ascending colon, 3 in the rectum, 2 in the descending colon, 1 in the cecum and 1 in the hepatic flexure. The perforation size ranged from 0.3 cm to 10.0 cm with a high likelihood of a bigger perforation occurred in diagnostic colonoscopy than therapeutic colonoscopy. Seven patients received primary surgical repair with 3 patients receiving diversion. Four patients received direct colostomy in the perforation site. Six patients received segmental colectomy or radical resection with primary anastomosis, among them 2 patients received defunctioning ileostomy. Four patients received resection with the Hartmann procedure. Nine patients were performed with laparoscopic surgery with 3 patients converted to open surgery. Six patients developed postoperative complications, including 1 bowel leakage, 2 wound infection, 1 wound infection accompanied with abdominal infection, 1 kidney infection. One patient with hepatic flexure perforation after stent placement died from septic shock after the Hartmann procedure.Conclusion:With proper indication, the performance of optimal surgical treatment will save lives of patients with colonoscopic perforation.

Objective To analyze the risk factors for anastomotic leakage after low anterior resection(LAR) for rectal cancer.Methods The retrospective study of 1 336 patients with rectal cancer who underwent LAR from Jan.2013 to Dec.2017 in the Department of Colorectal Surgery,First Affiliated Hospital of Nanjing Medical University was conducted.There were 838 male and 498 female patients.The median age was 62 (53,70) years.Observation indicators:①intraoperative conditions,including the performance of preventive enterostomy,the preservation of left colic artery,the placement of transanal decompression tube;②postoperative conditions,for example,postoperative clinical symptoms and physical examination,postoperative hospital stay.Anastomotic leakage patients were graded according to the grading system of anastomotic leakage following anterior resection of the rectum proposed by the International Study Group of Rectal Cancer in 2010.Measurement data with non-normal distribution were described as median,and comparison between groups was done using Mann-Whitney U test.Ranked data were compared with rank sum test.Comparison of count data between groups were analyzed using the Chi-square test or Fisher exact test.Potential risk factors for anastomotic leakage were further analyzed with multiple logistic regression.Results Anastomotic leakage was noted in 138 (10.4％) of 1 336 patients with 93 patients (7.0％) of Grade B and 46 patients (3.4％) of Grade C respectively.The occurrence of Grade C anastomotic leakage was on the 3th day postoperatively,which was earlier than Grade B anastomotic leakage [5 (3,7) d,Z =2.746,P =0.006].There were significant differences in sex,BMI,placement of transanal decompression tube and tumor location between anastomotic leakage cases and non-anastomotic leakage cases by Chi-squared test (x2 =10.897,9.033,6.343,6.34,Z =-2.380,P ＜0.05).On multiple logistic regression analysis,male sex (OR =1.840,95 ％ CI:1.210-2.799,P =0.004),BMI ≥ 24 kg/m2 (OR =1.573,95 ％ CI:1.088-2.274,P =0.016),placement of transanal decompression tube(OR =2.418,95％ CI:1.196-4.888,P =0.014),middle rectal cancer (OR =1.536,95％ CI:O.836-2.822,P =0.167),low rectal cancer(OR =1.989,95％ CI:1.068-2.822,P =0.03),ultralow rectal cancer (OR =2.908,95％ CI:1.289-6.560,P =0.01) were independent risk factors of anastomotic leakage.Conclusion Male sex,high BMI,placement of transanal decompression tube and low rectal tumor were independent risk factors of anastomotic leakage for patients receiving LAR.

Objective To investigate the application value of superior mesenteric artery (SMA)-oriented complete mesocolic excision (CME) in the treatment of right colon cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 955 patients with right colon cancer who were admitted to the First Affiliated Hospital of Nanjing Medical University from January 2013 to June 2018 were collected.There were 514 males and 441 females,aged from 18 to 96 years,with a median age of 65 years.Of the 955 patients,377 undergoing SMA-oriented CME of right colon with the lymph node dissection along the left boundary of SMA were allocated into SMA-oriented group,and 578 undergoing superior mesenteric vein (SMV)-oriented CME of right colon with the lymph node dissection along the left boundary of SMV were allocated into SMV-oriented group.Observation indicators:(1) intraoperative and postoperative conditions;(2) postoperative complications;(3) postoperative pathological examinations;(4) follow-up and survival situations.Follow-up was performed by telephone interview and outpatient examination once every 3-6 months within 2 years after surgery and once a year after 2 years up to January 2019,using tumor recurrence and metastasis or death as the end point.Follow-up included physical examination and tumor marker test,including carcino embryonic antigen,CA19-9,chest and abdomen CT examination and enteroscopy.Measurement data with skewed distribution were described as M (P25,P75),and comparison between groups was done using the Mann-Whitney U test.Count data were described as absolute numbers or percentages,and comparison between groups was analyzed using the chi square test.Ordinal data were analyzed using the rank sum test.Kaplan-Meier method was used to calculate survival time and rate,and draw survival curve.Log-rank test was used for survival analysis.Patients with loss to follow-up were involved in survival analysis as censored data.Results (1) Intraoperative and postoperative conditions:the operation time,volume of intraoperative blood loss,duration of postoperative hospital stay were 100 minutes (90 minutes,110 minutes),50.0 mL (50.0 mL,70.0 mL),8 days (8 days,10 days) in the SMA-oriented group,and 110 minutes (90 minutes,135 minutes),50.0 mL (50.0 mL,122.5 mL),10 days (8 days,12 days) in the SMV-oriented group,showing significant differences between the two groups (Z=-5.400,-5.799,-7.461,P＜0.05).After the exclusion of 47 patients unsuitable for defecation analysis because of postoperative complications,365 in the SMA-oriented group and 543 in the SMV-oriented group were analyzed.The time to first defecation,the maximum number and the median number of daily defecation postoperatively were 5 days (3 days,5 days),2.0 (1.0,2.5),1.0 (1.0,1.0) in the SMA-oriented group,which showed no significant difference from 4 days (3 days,5 days),2.0 (1.0,3.0),1.0 (1.0,1.0) in the SMV-oriented group (Z=-1.622,-1.541,-1.024,P＞ 0.05).(2) Postoperative complications:cases with postoperative complications,cases with incisional liquefaction or infection,cases with anastomostic leakage,cases with delayed gastric emptying,cases with intra-abdominal bleeding,cases with complete or incomplete ileus,cases with anastomostic bleeding,cases with intra-abdominal infection,cases with disruption of wound,the number of death were 55,10,3,3,2,2,1,1,1,1 in the SMA-oriented group,which showed no significant difference from 83,30,13,4,3,8,3,6,2,3 in the SMV-oriented group,respectively (x2 =0.045,3.662,2.926,0.034,0.001,1.604,0.352,1.873,0.048,0.352,P＞0.05).There were 32 of 377 patients in the SMA-oriented group and 14 of 578 in the SMV-oriented group with chylous leakage,showing a significant difference between the two groups (x2 =18.312,P＜ 0.05).Patients with chylous leakage were improved after conservative treatment,without reoperation.Patients with other complications were improved after anti-infection,fluid infusion,and reoperation.Four of 955 patients died after surgery.(3) Postoperative pathological examinations:patients with stage Ⅰ,stage Ⅱ,and stage Ⅲ (pathological TNM staging),patients with high-differentiation,mid-differentiation,and low-differentiation (tumor differentiation degree),length of intestine specimen,number of positive lymph nodes,maximum tumor diameter,patients with cancer nodules,patients with vascular invasion,patients with perineural invasion were 57,174,146,30,174,173,23 cm (21 cm,26 cm),0 (0,2),5.0 cm (3.0 cm,6.0 cm),37,81,53 in the SMA-oriented group,which showed no difference from 66,280,232,33,303,242,23 cm (21 cm,25 cm),0 (0,2),5.0 cm (3.5 cm,6.0 cm),80,108,82 in the SMV-oriented group (Z=-1.020,-0.216,-0.243,-0.220,-0.814,x2=3.441,1.127,0.003,P＞0.05).The number of harvested lymph nodes was 22.0 (17.0,27.0) and 18.0 (15.0,22.0) in the SMA-oriented group and SMV-oriented group,respectively,with a significant difference between the two groups (Z=-7.800,P＜0.05).There were 202 patients extracted for further analysis.The number of harvested lymph nodes and harvested central lymph nodes was 25.0 (20.0,31.3),5.0 (3.0,8.0) of 166 patients in the SMA-oriented group,and 21.5 (18.0,28.8),1.5 (0,4.5) of 36 patients in the SMV-oriented group,respectively,showing significant differences between the two groups (Z =-1.995,-4.309,P＜0.05).(4) Follow-up and survival situations:840 of 955 patients including 346 in the SMA-oriented group and 494 in the SMV-oriented group were followed up for 1.0-73.2 months,with a median time of 31.5 months.SMA-oriented group had a higher 5-year overall survival rate than SMV-oriented group (91.8％ vs.84.9％,x2 =4.384,P＜0.05),but had no significant difference in the 5-year tumor-free survival rate compared with the SMV-oriented group (84.4％ vs.78.2％,x2=2.158,P＞0.05).Conclusion Compared with SMV-oriented CME of right colon,SMA-oriented CME of right colon is safe and feasible,with larger number of harvested lymph nodes,which can achieve complete lymph node dissection.

Metastatic pheochromocytoma and paraganglioma(MPPGL)is a rare neuroendocrine tumour in which genetic factors play an important role.In recent years,with the continuous progress of genetic testing technol-ogy,more and more susceptibility genes have been proved to be associated with MPPGL,making early identifica-tion of MPPGL possible.Recent studies have shown that genes associated with the development of MPPGL include SDHA,SDHB,SDHC,SDHD,SDHAF2,FH,MDH2,VHL,IDH1,PDH1/2,SLC25A11,GOT2,DLST,CSDE1,MAML3,H3F3A,MERTK,PCDHGC3,and KIF1B,with SDHA,SDHB,SDHC,SDHD,and SDHAF2 being the common pathogenic genes.Potential mutations affect the clinical manifestations of MPPGL,such as malignant potential and genetic prediction,which can help to better understand the clinical course and treat accordingly.Genetic testing for pheochromocytomas and paragangliomas allows for early detection of genetic syndromes and facilitates close follow-up of high-risk patients.This article provides a review of the progress of research on susceptibility genes identified in MPPGL in recent years,with a view to providing a certain theoretical basis for further related research.

Objective:To explore the effect and molecular mechanism of capsaicin receptor(TRPV1) on neuronal autophagy and depression-like behavior in mice.Methods:Using the method of random number table, 87 C57 male mice were divided into Sham operation group (Sham group), cerebral ischemia/reperfusion group (I/R group) and capsazepine(CPZ) preconditioning cerebral ischemia/reperfusion group (I/R+ CPZ group), with 28 mice in each group due to 3 incompatible.Mice in the I/R group were subjected to right middle cerebral artery occlusion (MCAO) to establish a cerebral ischemia-reperfusion model.Mice in the I/R+ CPZ group were injected with CPZ in the lateral ventricle prior to moulding.Mice in the Sham group had only wire plugs inserted and no arterial embolization was performed.The mNSS score was used to evaluate the degree of neurological deficits.The depression-like behaviour of mice was detected by the tail suspension test and forced swimming test.The infarct volume was observed by TTC staining.The pathological changes in the amygdala were observed by HE staining, and the expression of Beclin-1, LC3, p62 and p-PI3K, p-AKT and p-mTOR proteins were detected by Western blot.Statistical analysis was performed using SPSS 23.0 software.The t-test was used for comparison between two groups and one-way ANOVA was used for comparison of multiple group. Results:The neurological deficit score in I/R+ CPZ group (9.77±2.32) was significantly lower than that in I/R group (12.85±2.73) ( t=3.10, P<0.01). Compared with I/R group, the tail suspension immobility time of I/R+ CPZ Group ((93.28±50.69)s, (143.80±35.61) s; t=2.94, P<0.01) and the forced swimming immobility time ((139.50±13.33)s, (175.30±19.78)s; t=2.94, P<0.01) were significantly reduced.The results of TTC staining showed that the cerebral infarct volume in I/R+ CPZ group was significantly lower than that in I/R group ((19.30±5.19)%, (33.60±3.90)%; t=5.40, P<0.01). HE staining showed that the number of cells in the amygdala region of mice in the I/R+ CPZ group increased compared with that in the I/R group, with tighter arrangement and reduced deep staining of nuclear fixation.Western blot showed that compared with I/R group, the expression levels of autophagy related proteins Beclin-1( t=2.94, P<0.05) and LC3 ( t=3.16, P<0.05) in amygdala of I/R+ CPZ group were down-regulated, while the expression levels of p62( t=3.60, P<0.05), p-PI3K ( t=7.79, P<0.01), p-AKT ( t=4.15, P<0.01) and p-mTOR ( t=6.15, P<0.01) were up-regulated. Conclusion:Cerebral ischemia/reperfusion activates neuronal autophagy, and CPZ may regulate the PI3K-AKT-mTOR pathway, thus inhibits excessive activation of autophagy, thereby acting as a neuroprotective agent and improving post-stroke depression-like behaviour.