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.

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.

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.

OBJECTIVE:To improve the content determination for polygala xanthone Ⅲ in Polygalae Radix contained in Chi-nese Pharmacopoeia (2010 edition). METHODS:HPLC was performed on the column of Hypersil BDS C18 with mobile phase of acetonitrile-0.05% phosphoric acid(gradient elution)at a flow rate of 1.0 ml/min;detection wavelength was 320 nm,column tem-perature was 25℃,and the injection volume was 10μl. RESULTS:The linear range of polygala xanthoneⅢwas 0.029-0.928 μg/ml (r=0.999 1);RSDs of precision,stability and reproducibility tests were lower than 2.0%;recovery was 94.66%-100.90%(RSD=2.46%,n=6). CONCLUSIONS:The method is simple,stable and reproducible. Although the determination time is prolonged,it has improved the accuracy and it is more suitable for the content determination of polygala xanthoneⅢin Polygalae Radix.

Objective To compare the value of automatic breast volume scanner (ABVS) with enhanced magnetic resonance imaging(MRI) in the diagnosis of breast masses.Methods Seventy-four patients with 80 breast masses underwent preoperative ultrasound examinations including ABVS and MRI.The values of ABVS and MRI in the diagnosis of breast masses were comparatively analyzed.Results Among the 80 breast masses that were surgically removed,37 masses were benign and 43 masses were malignant.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of ABVSin the diagnosis of breast malignant masses were 94.6％,79.1％,86.3％,79.5％ and 94.4％,respectively,those of MRI were 94.6 ％,86.0 ％,90.0 ％,85.4 ％ and 94.9 ％,respectively,and those of the combination of ABVS and MRI were 94.6％,93.0％,93.8％,92.1％,and 95.2％,respectively.The sensitivity and specificity were not significant difference between ABVS and MRI in the diagnosis of breast malignant masses(P ＞0.05).The specificity of the combination ABVS and MRI in the diagnosis of breast malignant masses were significantly higher than that of ABVS (x2 =4.17,P =0.04).The sensitivity,specificity and accuracy of convergence sign in the diagnosis of breast malignant masses were 64.9 ％,97.7 ％ and 82.5 ％,respectively.Conclusions ABVS and MRI are both valuable in the diagnosis of breast masses,and the combination of ABVS and MRI is the most valuable due to high specificity.

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.

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.

Objective To evaluate the effects of different concentrations of parecoxib sodium on the rat sperm motility,capacitation and acrosome reaction in vitro.Methods The sperm samples from Sprague-Dawley rat epididymis were collected by Klinefelter diffusion method and randomly divided into 4 groups (n =18 each) using a random number table:control group (group C),and parecoxib sodium 100,500,1 000 μmol/L groups (P1-3 groups).Parecoxib sodium with the final concentrations of 100,500 and 1 000 μmol/L was added to the culture medium.The samples were then incubated for 5 h in an airtight container filled with 5 ％ CO2 at 37 ℃.Then sperm motility was examined in vitro at 37 ℃ and analyzed by the computer-assisted sperm analysis,including the sperm motility ((a + b)％),average path velocity (VAP),straight line velocity (VSL),curvilinear velocity (VCL) and amplitude of lateral head displacement (ALH).The capacitation effect was assessed by using the chlortetracycline staining and phase-contract microscopy.The acrosome reaction was evaluated by coomassie brilliant blue staining.Results The VAP,VSL,VCL and capacitation ability of the sperm were gradually decreased in C and P1-3 groups (P ＜ 0.05).Compared with group C,(a + b)％ in P2,3 groups and ALH in P2 group were significantly decreased (P ＜ 0.05).There was no significant difference in the acrosome reaction between groups (P ＞ 0.05).Conclusion Parecoxib sodium has significant inhibitory effects on the rat sperm motility and capacitation in a dose-dependent manner,while has no effect on the acrosome reaction in vitro.

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.

Objective To investigate the effects of anaesthetic concentration of sevoflurane on TM3 mouse leydig cell viability.Methods TM3 mouse leydig cells were randomly divided into 3 groups ( n =24 dishes each):control group (group C),2％ and 5％ sevoflurane groups (groups SEV1 and SEV2 ).The cells were collected after being exposed to sevoflurane or 95 ％ room air + 5 ％ CO2 for 2,4 or 6 h (T1-3) for microscopic examination with optical binocular inverted microscope.The number of live cells was counted by using cell counting kit8.Gene chips were used to indentify differentially expressed genes between group C and group SEV2 after being exposed to air and 5 ％ sevoflurane for 6 h respectively.Results The leydig cell viability was significantly decreased at T3 in group SEV2 as compared with groups C and SEV1.Morphological changes were found only in group SEV2.A total of 45 genes were identified to be differentially expressed in group SEV2 as compared with group C.The level of expression of prostaglandin-endoperoxidase synthase 2 gene (Ptgs2),chemokine (C-C motif) ligand 2(CCL2) gene and dual specificity phosphatase1 (Dusp1) gene increased by at least 4 times in group SEV2.Conclusion Sevoflurane can inhibit the cell viability of TM3 mouse leydig cell in concentration dependent manner through abnormal expression of Ptgs2,CCL2 and Dusp1 genes.