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Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.
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Objective@#To use the meta-analysis in evaluating the hemorrhage-prevention value of second-look endoscopy after endoscopic submucosal dissection (ESD) for early gastric cancer.@*Methods@#A literature search was conducted to identify all relevant studies comparing second-look endoscopy and non-second-look endoscopy after gastric ESD. The Medline/PubMed, Ovid, Elsevier ScienceDirect, EBSCO, CNKI and VIP databases were searched systematically. Literature inclusion criteria: (1) all the patients were diagnosed as early gastric cancer receiving ESD; (2) end point of the study included postoperative bleeding rate of ESD. Exclusion criteria: (1) papers of repeated research, review, comment, guideline, etc; (2) non-control study. Meta-analysis method was used to calculate a pooled odds ratio (OR) for developing post-ESD bleeding.@*Results@#The meta-analysis showed that post-ESD bleeding was observed in 40 of 1287 patients (3.1%) without second-look endoscopy and in 40 of 968 patients (4.1%) with second- look endoscopy (OR=1.25, 95% CI: 0.79-1.98), with no significant difference between these two groups. Subgroup analysis on research method still indicated no significant difference of post-ESD bleeding between RCT group (OR=1.45,95%CI: 0.79-2.65) and non-RCT group (OR=1.02, 95%CI: 0.50-2.08) (all P>0.05).@*Conclusion@#Based on meta analysis, second-look endoscopy can not reduce the rate of postoperative bleeding of ESD. Therefore, routine second-look endoscopy after gastric ESD may not be necessary to prevent delayed postoperative bleeding of ESD.
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Objective To study the value of CA19-9,s-ULBP2 and Dkk1 in the diagnosis of pancreatic cancer and the correlation. Methods From January 2016 to May 2017,56 patients with pancreatic cancer in our hospital were selected,45 healthy subjectsand 33 patients with benign pancreatic diseaseswere enrolled in this study.The differences of serum CA19-9,Dkk1 and s-ULBP2 expression and their relationship with clinicopatholog-ical parameters were compared between the three groups. The diagnostic value of CA19-9,s-ULBP2,Dkk1 and joint detection was analyzed.Results The serum levels of CA19-9,s-ULBP2 and Dkk1 in patients with pancreat-ic cancer were significantly higher than those in the benign pancreatic disease group and the healthy control group (P<0.05).CA19-9 and s-ULBP2 are related to TNM staging and histological differentiation,and CA19-9 is also related to tumor location.Joint test was higher than any of the individual indicators.Conclusion CA19-9,s-ULBP2 and Dkk1 are closely related to pancreatic cancer,and the combined detection of the three can improve the diag-nostic accuracy of pancreatic cancer.
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Objective To investigate the value of endoscopic ultrasonography(EUS)in the diagnosis and treatment of undetermined etiology of common bile duct (CBD) dilatation. Methods Patients, who were referred for dilated CBD but unable to identify the cause by imaging, underwent EUS for the diagnosis of etiology in Endoscopy Center of Zhongshan Hospital Affiliated to Fudan University from December 2015 to December 2016. The therapy was on the basis of diagnosis of EUS. Final diagnoses were determined by surgical pathology or follow-up for at least 3 months. Results A total of 76 patients were included in the study. The sensitivity, specificity and accuracy of EUS for patients with choledocholithiasis,patients with ampullary tumor, and patients with inflammatory stenosis were 100.0%(7/7), 100.0%(69/69), 100.0%(76/76), and 88.0%(22/25), 92.2%(47/51), 90.8%(69/76),and 90.9%(40/44), 93.8%(29/32), 90.8%(69/76), respectively. Accuracy of EUS for etiological diagnosis of CBD dilatation was 90.8%(69/76). The sensitivity,specificity and accuracy of EUS combined with tumor markers for patients with malignant CBD dilatation were 96.0%(24/25), 96.1%(49/51),and 96.1%(73/76), respectively. Conclusion EUS is an effective method for the etiological diagnosis of CBD dilatation and has guiding significance for the treatment. EUS combined with tumor markers may benefit differential diagnosis of benign and malignant CBD dilatation.
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Objective To evaluate the efficacy and safety of endoscopic submucosal dissection for the treatment of colorectal large laterally spreading tumor. Methods ESD was applied to treat 150 cases of colorectal LST with diameter larger than 4 cm. The morphological features of LST, distribution, the clinicopathological data and the en-bloc resection rate, complete resection rate, complications were retrospectively evaluated. Results There were 87 patients with LST-granular lesions and 63 patients with LST-nongranular lesions. Colorectal LST mainly distributed in the rectum for 109 cases (72.7%), sigmoid colon for 13 cases (8.7%), descending colon for 5 cases (3.3%), transverse colon for 8 cases (5.3%), ascending colon for 13 cases (8.7%), cecum for 2 cases (1.3%). There were 23 patients with low-grade neoplasia, 104 patients with high-grade intraepithelial neoplasia, 7 with intramucosal carcinoma and 16 with submucosal carcinoma. The en-bloc resection rate and complete resection rate were 92.7% (139/150) and 89.3%(134/150). Adverse events were intra-operative bleeding in 12 patients (8.0%), postoperative bleeding in 2 patients (1.3%), perforation in 3 patients (2.0%), postoperative stenosis in 3 patients (2.0%). Conclusion Colorectal large LST-NG has higher potential for malignancy. ESD is a safe and effective method to provide en-bloc and complete resection of colorectal large LST.
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Hypoxia refers to the reduction in tissue oxygen supply or utilization. It occurs in various pathological symptoms like embolism,anthracemia,and chronic obstructive sleep. At high altitude, lower partial pressure of oxygen compromises the supply of adequate oxygen to the tissues and leads to many clinical syndromes,such as acute mountain sickness,high-altitude cerebral edema,and high-altitude pulmonary edema. Histamine H3 receptor, primarily as a presynaptic receptor, is widely expressed in the central and peripheral systems. Histamine,dopamine,acetylcholine and many other neurotransmitters are regulated by histamine H3 receptor. Studies have shown that histamine H3 receptor is involved in the hypoxic response of the respiratory network. In addition,histamine,espe?cially histamine H3 receptor,participates in the regulation of cerebral ischemia in the central nervous system. In this paper,we reviewed the structure and functions of histamine H3 receptor and explained its role in the regulation of hypoxia so as to evaluate the possibility of histamine H3 receptor as a drug target for the therapy of hypoxia-induced injuries.
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Objective To identify risk factors of lymph node metastasis in superficial esophageal squamous cell carcinoma (ESCC),and to provide evidence for treatment choice under endoscope.Methods From January 2007 to December 2011,285 patients with pathologically diagnosed ESCC who received surgery and had clear record of lymph nodes resection were enrolled.The clinical pathological data of these patients were analyzed,including age,gender,smoking and drinking history,history of cancer,family history of cancer,location,tumor size,presence of esophageal,depth of infiltration,differentiation,and vascular cancer embolus.Univariate analysis (chi square test or Fisher exact probability method) and multivariate Logistic regression analysis were performed for risk factors of lymph node metastasis assessment.According to the rates of lymph node metastasis,patients were divided into three groups as follows:low risk,high risk and extremely high risk of lymph node metastasis.KaplanMeier method was used to calculate the average survival time and cumulative five years survival rate.Results Among the 285 patients with ESCC,40 (14.0 ％) patients with lymph node metastasis.The results of univariate analysis showed that location (x2 =9.333),tumor length (Fisher exact probability method),depth of infiltration (x2 =9.327),differentiation degree (Fisher exact probability method) vascular cancer embolus (Fisher exact probability method) were significantly associated with lymph node metastasis (all P＜0.05).The results of multivariate analysis indicated that tumor length over 5 cm,invasion to submucosal layer and vascular cancer embolus were independent risk factors of lymph node metastasis,and the odd ratio was 17.408(95％ confidence interval (CI) 1.557 to 194.686),3.471(95％CI 1.440 to 8.365) and 6.256(95％CI 1.787 to 21.910),respectively.The lymph node metastasis rates of patients in low risk,high risk and extremely high risk group were 5.2％(6/115),15.8％ (24/152) and 10/18,respectively;the average survival times were (69.9 ± 2.4),(63.8 ± 2.1) and (51.7 ± 1.7) months,respectively.The cumulative five years survival rates were 59 ％,51 ％ and 31％,respectively,and the difference was statistically significant (x2 6.816,P=0.033).Conclusions The risk of lymph node metastasis is high in ESCC patients with tumor length over 5 cm,invasion to submucosal layer and vascular cancer embolus,and the prognosis is poor.Lymph node metastasis should be considered when endoscopic therapy is chosen.
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Objective To compare cost-effectiveness between endoscopical esophageal variceal ligation (EVL) combined non-selective beta-receptor blocker strategies and covered-stents transjugular intrahepatic portosystemic shunt (cTIPS) in preventing esophageal variceal rebleeding in liver cirrhosis with portal hypertension.And to explore the threshold of cost-effectiveness in stents in China.Methods According to clinical practice and associated guidelines,a six state Markov-based decision analytic model was established with TreeAge Pro Suite 2014 to compare the cost-effectiveness between two interfering strategies after followed up for seven years.The parameters such as costs,life years (LY),quality-adjusted life-years (QALY) and incremental costeffectiveness ratio (ICER) were directed.Results The results of baseline research in the seven-year follow-up period indicated that the cost of endoscopical EVL combined non-selective beta-receptor blocker B was 7 444.25 United States dollar (USD)/each,and yielded 1.98 QALY.The expected cost of cTIPS was 13 151.69 USD/ each and could have 2.34 QALY.In the 7th year,ICER was 16 001.74 USD.Based on willingness-to-pay (WTP) threshold of China (19 887.00 USD),cTIPS had better cost-effectiveness than endoscopical EVL combined non-selective beta-receptor blocker B.The price of covered stents less than 5 401.52 USD had cost-effectiveness.The results of single factor sensitivity analysis indicated that rebleeding probability of endoscopical EVL combined non-selective beta-receptor blocker B group was the most influential factor in the result of model.The second important factor was the cost of cTIPS.The probabilistic sensitivity analysis reported cTIPS to be the optimal strategy at WTP of 19 887.00 USD in 83％ of the iterations.Conclusions Seven-year follow-up indicates that cTIPS may be a more cost-effective strategy than endoscopical EVL combined non-selective beta-receptor blocker B in preventing esophageal variceal rebleeding.The price of covered stents less than 5 401.52 USD which have cost-effectiveness in China.
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Objective To investigate the correlation between clinicopathological features and lymph node metastasis (LNM) in early gastric cancer (EGC).Methods From January 2006 to June 2009,the clinical data of 473 patients with EGC were collected.The data of patients including gender,age,tumor size,tumor number,general classification,differentiation degree,invasion depth,ulcer in tumor,nerve invasion,and lymphatic tumor cell embolus were analyzed.Chi-square test was performed to analyze the correlation between clinicopathological features and LNM in EGC.Logistic regression analysis was used to analyze the independent risk factor of LNM in EGC.Results Among 473 patients with EGC,77 patients had LNM and the metastasis rate was 16.3％.The metastasis rate of the female patients (24.6％,41/167) was higher than that of the male (11.8 ％,36/306).The metastasis rate of the tumors with maximum diameter over 2 cm (22.0％,39/177) was higher than that of the tumors less than 2 cm (12.8％,38/296).The metastasis rate of the elevated lesions (26.1％,6/23) was higher than that of flat and concave lesions (9.0 ％,15/167;19.8％,56/283).The metastasis rate of poorly differentiated tumors was higher than moderate differentiated and high differentiated tumors (12.7 ％,23/181; 7.1％,3/42).The metastasis rate of tumors invading into submucosa (22.9％,41/179) was higher than that of tumors invading into mucosa (12.2％,36/294).The metastasis rate of tumors with lymphatic embolus (40.7％,11/27) was higher than that of tumors without lymphatic embolus (14.8％,66/446) and the differences were statistically significant (x2 =12.960,6.873,10.704,7.382,9.277 and 12.572,all P＜0.05).The results of multifactor analyzed by Logistic regression analysis revealed that female,maximum diameter over 2 cm,poorly differentiated type and invasion to submucosa were the independent risk factors of LNM in EGC (relative risk (RR)=2.53,2.14,1.63 and 2.39,all P＜0.01).Conclusion Female,maximum diameter over 2 cm,poorly differentiated type and invasion to submucosa are the independent risk factors of LNM in EGC.
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<p><b>OBJECTIVE</b>To investigate the efficacy of tissue adhesive on intractable bleeding during endoscopic submucosal dissection(ESD) and delayed bleeding.</p><p><b>METHODS</b>A total of 9874 patients with gastrointestinal mucosal or submucosal tumors underwent ESD in our center from September 2006 to August 2013 and intractable bleeding occurred during ESD in 5 cases. Under the condition of no effective hemostasis methods, the tissue adhesive injection or spray were used to stop the bleeding. The efficacy and safety were evaluated.</p><p><b>RESULTS</b>All the 5 cases were successfully managed by the hemostasis method with tissue adhesive without any adverse event. In follow-up of two months after operation, wound healing and scar formation were observed under endoscopy.</p><p><b>CONCLUSION</b>Tissue adhesive is safe, effective and fast for intractable bleeding during ESD and delayed bleeding.</p>
Subject(s)
Humans , Dissection , Endoscopy, Gastrointestinal , Gastric Mucosa , General Surgery , Hemorrhage , Therapeutics , Intestinal Mucosa , General Surgery , Tissue Adhesives , Therapeutic Uses , Treatment OutcomeABSTRACT
Objective To explore the prognosis of endoscopic tissue adhesives injection in treating liver cirrhosis patients with esophageal gastric varices (GOV),and to evaluate the effects of various factors on bleeding after treatment.Methods A total of 157 liver cirrhosis patients with GOV treated by endoscopic tissue adhesives injection with or without ligation therapy were retrospectively analyzed.The basic information,liver function and blood biochemical values of patients at enrollment were investigated.The analysis of bleeding after treatment was conducted by Kaplan-Meier.The survival curves comparison was conducted by Log-rank test.Logistic regression model was used for multivariate analysis.The prognosis predictors were evaluated by receiver operating characteristics (ROC) curves and the area under the curve (AUC).Results Rebleeding happened in 26 of 157 patients.The median rebleeding time was 3.4 months.The results of univariate analysis indicated that there were statistical differences in FIB4 scores (Z=-1.282,P=0.100) and the inner diameter of the right portal vein (Z=-1.812,P=0.035) between bleeding group and no bleeding group.The results of multivariate analysis showed that the inner diameter of the right portal vein was independent prognostic factor of rebleeding (OR =1.733,95％ CI:1.045 to 2.874,P =0.033).Optimal diagnostic threshold was 8.5 mm (AUC=0.724,95 ％CI:0.537 to 0.910),sensitivity and specificity was 77.8％ and 66.6％ respectively.Conclusions The inner diameter of the right portal vein was one of the important factors that affected the efficacy of tissue adhesives injection in preventing bleeding and the prognosis.FIB4 score had certain reference value in predicting recurrence or bleeding after treatment.
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Objective To investigate the changes of osteopontin (OPN) expression in murine colitis induced by dextran sodium sulfate (DSS) and its role in inflammatory bowel disease (IBD).MethodsThirty-two male BALB/C mice were randomly assigned into 4 groups: control group (group A), DSS-induced murine colitis model group (group B), salazosulfapyridine treatment group (group C) and infliximab treatment group (group D). Plasma OPN concentration was measured by enzyme linked immunosorbent assay (ELISA). OPN mRNA level was detect by using reverse transcriptase polymerase chain reaction (RT-PCR) and protein expression in colonic tissues was analyzed by using Western blotting. The location expression of OPN in colonic tissues was determined by immunohistochemical staining. ResultsIn group A, B,C and D, the plasma concentrations of OPN were (5.26±1.93) ng/ml, (10.21±2.37) ng/ml, (4.58±1.83) ng/ml and (4.82±1.83) ng/ml,respectively: the mRNA levels of OPN in colonic tissues were (0.36±0.16), (0.71±0.17),(0.32±0.07) and (0. 34±0. 08), respectively; the protein levels of OPN in colonic tissues were (0.44±0.10), (0.85±0.04), (0.61±0.11) and (0.58±0.17), respectively. The OPN-positive cell numbers in lamina propria mononuclear were (46.6±10.9), (155.5±43.8), (73.1±6.8) and (70.6±8.3), respectively. The expression of OPN in group B was significantly higher than that in group A (P<0.05). Compared with group B, the expressions of OPN in group C and D were significantly decreased (all P valus <0. 05). No significant difference was detected between group C and D. Conclusions The study shows that the expression of OPN significantly increased in DSS-induced murine colitis and decreased after treated with drugs. OPN-mediated immune response contributes to DSS-induced murine colitis.
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Objective To analyse the clinical characteristics,follow up their prognsis and evaluate the treatment of patients with Crohn' s disease (CD). Methods The data of patients with CD were collected at Zhongshan Hospital of Fudan University from 2002 to 2007. The diagnosis was made according to the consensus recommended by Chinese Society of Gastroenterology. The disease severity, follow-up and prognsis were evaluated according to the consensus. Results Sixty-six CD patients were enrolled in this study. The ratio of males to females was 2.47 : 1. Age at diagnosis ranged from 12 to 76 years old, and the mean age was (32 ± 17)years old. The main gastroenterological manifestations were abdominal pain (80.3 %), diarrhea (54.6 %), fistula formation (31.8%) ; and the main systemic manifestation was fever (80.3 %) and defective nutrition. A total of 60.6 % of patients with CD had complications and 34. 8% of these patients had more than one complications. Extraintestial manifastation were presented in 7.6% of patients with CD. A total of 86.4% of patients with CD were active state cases and 57. 6% were suffered from inflammation of ileum and colon. Abdominal pain (P = 0. 011), hematochezia (P = 0. 008), fever (P = 0. 001), anemia (P = 0. 020), underweight (P = 0. 010) and heightening of CRP (P = 0. 033) were more common in patients who were in active state than those who were in slient state. During their inducing alleviate treatment, 33.3% of patients with CD were treated with aminosalicylate alone, 36.4% were treated with both aminosalicylate and glucocorticoids, 7. 6% were treated with aminosalicylate, glucocorticoids and immunosuppressant. After medicine treatment, 6.8% of the patients relieved, 62.7% turned better, 28.8% were ineffective, 1.7% died, 55.9% recurd. And 21.2% were treated by surgical operation. A total of 42.4% of patients with CD had histroy of surgical operation and 9.1% were carried on more than one surgical operation.ConclusionsActive state patients with CD had high rate of complications, low extraintestial manifestatons, rare rate of dysplasia and canceration, and high rates of surgical operation and recurring.