Genetic association of vitamin D receptor polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese

BACKGROUND: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. Vitamin D has been shown to exert multiple immunomodulatory effects, which acts through its own receptor (VDR). Polymorphisms of VDR had been implicated in several autoimmune diseases. In the present study, the association between Chinese patients with AIH, PBC and the polymorphisms in exon 2, intron 8 and exon 9 of vitamin D receptor genes was studied. METHODS: Four candidate gene loci were investigated in 49 patients with AIH, 58 patients with PBC, and 160 healthy controls. The VDR polymorphisms were assessed by FokI, BsmI, ApaI, and TaqI endonuclease digestion after specific polymerase chain reaction (PCR) amplification. RESULTS: The result show a significant difference in FokI polymorphism between AIH patients and controls (chi(2) = 5.47, P = 0.019), and a significant association in BsmI polymorphisms between PBC patients and controls (chi(2) = 6.52, P = 0.01). Furthermore the distribution of FokI, BsmI, ApaI, and TaqI gene types differed between Chinese healthy controls and Caucasian healthy controls. CONCLUSION: It is suggested that there is a genetic link of VDR polymorphisms to autoimmune liver diseases such as AIH and PBC in Chinese patients. Further studies are needed to elucidate the mechanisms by which VDR polymorphisms contribute to the lose of immune tolerance in autoimmune diseases.     

Adenosine-mediated bronchoconstriction and lung inflammation in an allergic mouse model

In this study, we studied the role of adenosine on airway responsiveness and airway inflammation using an allergic mouse model. Mice were sensitized by two i.p. injections of ragweed and three consecutive ragweed aerosol challenges. It was found that inhalation of adenosine causes a dose-related bronchoconstriction in this model. Ragweed sensitized and challenged mice showed increased sensitivity to airway challenge to adenosine compared to control animals. Theophylline, a non-selective adenosine receptor antagonist, blocked adenosine-induced bronchoconstriction, but was unable to inhibit bronchoconstrictor response to methacholine. Mice systemically sensitized and airway challenged with allergen showed a marked airway inflammation manifesting increases in eosinophils, lymphocytes and neutrophils, and decrease in macrophages. Twenty-four hours after airway challenge with allergen, aerosolization of adenosine further potentiated the allergen-induced airway inflammation. Cells in bronchoalveolar lavage fluid after adenosine aerosolization increased by 3.07-fold as compared to control mice, and by 1.8-fold compared to ragweed sensitized and challenged mice. The increases in eosinophils, lymphocytes, and neutrophils caused by allergen were potentiated after adenosine challenge. Unexpectedly, macrophages significantly decreased after adenosine challenge. Theophylline attenuated adenosine-enhanced airway inflammation, but could not reverse allergen-induced airway inflammation. These findings suggested that specific adenosine receptors contribute to airway responsiveness and airway inflammation associated with this model of allergic asthma.     

某铁路局沿线站点生活饮用水质调查与对策研究

目的针对某铁路局辖区供水水质现状提出保障水质安全的建议。方法于2012年4月—2013年4月对该局主要铁路干线沿途部分供水站点进行调查采样,共收集水样214份,水样检测项目共23项,检测及评价方法按照《生活饮用水标准检验方法》(GB/T 5750-2006)及《生活饮用水卫生标准》(GB 5749-2006)执行。结果该局主要铁路干线的214份水样中,合格水样89份,合格率41.59%。其中,管井直供水样187份,合格率40.11%,路外购买水样27份,合格率51.85%;水样主要不合格指标为浑浊度、氯化物、硫酸盐、溶解性总固体、总硬度、氨氮。结论该路局辖区供水水质卫生存在隐患,针对其供水行业特点,从技术和管理两方面提出保障供水卫生安全的对策及建议。     

Riboflavin concentration in corneal stroma after intracameral injection

AIM:To evaluate the enrichment of riboflavin in the corneal stroma after intracameral injection to research the barrier ability of the corneal endothelium to riboflavin in vivo.METHODS:The right eyes of 30 New Zealand white rabbits were divided into three groups. Different concentrations riboflavin-balanced salt solutions (BSS) were injected into the anterior chamber (10 with 0.5%, 10 with 1%, and 10 with 2%). Eight corneal buttons of 8.5 mm in diameter from each group were dissected at 30min after injection and the riboflavin concentrations in the corneal stroma were determined using high-performance liquid chromatography (HPLC) after removing the epithelium and endothelium. The other two rabbits in every group were observed for 24h and sacrificed. As a comparison, the riboflavin concentrations from 16 corneal stromal samples were determined using HPLC after instillation of 0.1% riboflavin-BSS solution for 30min on the corneal surface (8 without epithelium and 8 with intact epithelium).RESULTS: The mean riboflavin concentrations were 11.19, 18.97, 25.08, 20.18, and 1.13 μg/g for 0.5%, 1%, 2%, de-epithelialzed samples, and the transepithelial groups, respectively. The color change of the corneal stroma and the HPLC results showed that enrichment with riboflavin similar to classical de-epithelialized corneal collagen crosslinking (CXL) could be achieved by intracameral1% riboflavin-BSS solution after 30min; the effect appeared to be continuous for at least 30min.CONCLUSION:Riboflavin can effectively penetrate the corneal stroma through the endothelium after an intracameral injection in vivo, so it could be an enhancing method that could improve the corneal riboflavin concentration in transepithelial CXL.     

Predictive value of blood concentration of biologics on endoscopic inactivity in inflammatory bowel disease: A systematic review

BACKGROUND Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease(IBD)patients,complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics.AIM To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations.METHODS We searched PubMed/MEDLINE,Embase,and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction.RESULTS A total of 23 articles with 30 clinical studies and 1939 IBD patients were included.The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6μg/mL in IBD.Blood concentration of infliximab reaching 5.0-12.7μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease.Blood concentration of adalimumab reaching 7.2-16.2μg/mL or more could predict mucosal healing in IBD.The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8μg/mL in perianal fistulizing Crohn's disease.Blood concentration of vedolizumab surpassing 25.0μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9μg/mL.CONCLUSION Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies,whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.     

重症急性呼吸综合征患者中重症者早期预警指标研究

目的　探讨重症急性呼吸综合征 (SARS)患者中与重症发生相关的危险因素 ,寻找发生重症的早期预警指标。方法　对北京市SARS临床诊断病例数据库中转院资料完整 ,且在 2周内发生重症的 35 5例和始终未发生重症的 84 1例SARS患者进行单因素和多因素分析。结果　高龄、有基础病的患者发生重症的危险性明显增加。重症患者发生重症前表现出以下特点 :体温下降缓慢、脉搏加快、淋巴细胞计数持续 <0 9× 10 9/L、中性粒细胞高于 7 1× 10 9/L(80 % )、X线胸片异常进展较快等。采用Cox多元逐步回归发现 ,具有统计学显著性的早期预警重症发生的独立因素包括 :年龄偏大、有基础疾病、住院 2d后体温仍不能降至正常、住院 3d后中性粒细胞比值持续在 80 %以上、住院 4d后淋巴细胞计数仍持续 <0 9× 10 9/L和病程中出现脉搏持续加快达到 10 0次 /min。结论　根据SARS患者的年龄和基础病情况 ,结合临床对体温、脉搏、淋巴细胞绝对值以及中性粒细胞绝对值 (百分比 )的密切观察能够对重症SARS的发生进行早期预警。     

Expression and significance of PTEN,hypoxia-inducible factor-1 alpha in colorectal adenoma and adenocarcinoma

AIM: To investigate the expression and significance of PTEN,hypoxia-inducible factor-1 alpha (HIF-1α), and targeting gene VEGF during colorectal carciogenesis.METHODS: Total 71 cases colorectal neoplasms (9 cases of colorectal adenoma and 62 colorectal adenocarcinoma)were formalin fixed and paraffin-embedded, and all specimens were evaluated for PTEN mRNA, HIF-1α mRNA and VEGF protein expression. PTEN mRNA, HIF-1α mRNA were detected by in situ hybridization. VEGF protein was identified by citrate-microwave SP immunohistochemical method.RESULTS: There were significant differences in PTEN, HIF1α and VEGF expression between colorectal adenomas and colorectal adenocarcinoma (P＜0.05). The level of PTEN expression decreased as the pathologic stage increased.Conversely, HIF-1α and VEGF expression increased with the Dukes stage as follows: stage A (0.1029±0.0457:0.1207± 0.0436), stage B (0.1656±0.0329: 0.1572±0.0514),and stage C+D (0.2335±0.0748: 0.2219±0.0803). For PTEN expression, there was a significant difference among Dukes stage A, B, and C+D, and the level of PTEN expression was found to be significant higher in Dukes stage A or B than that of Dukes stage C or D. For HIF-1α expression,there was a significant difference between Dukes stage A and B, and the level of HIF-1α expression was found to be significantly higher in Dukes stage C+D than that of Dukes stage A or B. The VEGF expression had similar results as HIF-1α expression. In colorectal adenocarcinoma,decreased levels of PTEN were significantly associated with increased expression of HIF-1α mRNA (r=-0.36, P＜0.05)and VEGF protein (r=-0.48, P＜0.05) respectively. The levels of HIF-1 were positively correlated with VEGF expression (r=0.71, P＜0.01).CONCLUSION: Loss of PTEN expression and increased levels of HIF-1α and VEGF may play an important role in carcinogenesis and progression of colorectal adenocarcinoma.     

Pulmonary artery diastolic pressure: a simultaneous Doppler echocardiography and catheterization study

Pulmonary hypertension is an important determinant of the clinical presentation of and surgical approach to patients with heart disease. To confirm the utility of continuous wave Doppler echocardiography in assessing the pulmonary artery diastolic pressure in patients with pulmonary regurgitation, 51 patients representing the wide hemodynamic spectrum of pulmonary artery pressure underwent simultaneous determination of pulmonary artery diastolic pressure by continuous wave Doppler echocardiography and cardiac catheterization. Pulmonary artery diastolic pressure was estimated from the Doppler recordings by the end-diastolic pressure gradient obtained by the modified Bernoulli equation plus the estimated right atrial pressure. A correlation was observed (r = 0.935, SEE = 7.4 mmHg) between Doppler and catheterization pulmonary artery diastolic pressure. In addition, comparison between the mean diastolic pressure gradient across the pulmonary valve by Doppler and pulmonary artery diastolic pressure at catheterization yielded a high correlation (r = 0.947, SEE = 5.1 mmHg). These data demonstrate that continuous wave Doppler echocardiography is a useful noninvasive technique for evaluating the pulmonary artery diastolic pressure in patients with pulmonary regurgitation.     

CA19-9 as the most significant prognostic indicator of metastatic colorectal cancer

BACKGROUND/AIMS: Colorectal cancer is the third leading cause of cancer-related mortality in Taiwan. We became interested in searching for the factors predictive of survival. Serum CA19-9 (carbohydrate antigen 19-9) level has been reported as a factor predictive of survival in patients with colorectal cancer. A few articles have reported that patients with metastatic colorectal cancer who have normal (< or = 37 U/mL) serum CA19-9 levels survived significantly longer than those with higher serum CA19-9 levels. However, these reports are contradictory and lack definite conclusions. This study was carried out in an effort to evaluate the prognostic significance of serum CA19-9 levels in patients with metastatic colorectal cancer in Taiwan. METHODOLOGY: Between 1991 and 1994, a total of 128 patients with histologically confirmed metastatic colorectal cancers were evaluated retrospectively at Veterans General Hospital-Taipei. All patients had measurable metastatic lesions and life expectancies of more than 3 months. 5-Fluorouracil-based chemotherapy, either in a weekly bolus regimen or a monthly 5-day bolus schedule, were administered to all of them. Data on age, sex, performance status, location of primary tumor, extent of metastases, site of metastases, histological differentiation, serum CEA (carcinoembryonic antigen) and CA19-9 levels were analyzed before chemotherapy to determine their association with survival. Blood samples for CEA and CA19-9 measurement were analyzed using the radioimmunoassay method. Multivariate analysis by the Cox's proportional hazards regression model was performed to determine independent prognostic factors among all of the possible variables. RESULTS: By univariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.022) were identified as prognostic factors, while age, sex, location of primary tumor, site of metastasis, histological differentiation, and pre-treatment serum CEA levels were not considered significant. By multivariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.014) were still found as independent prognostic factors of these patients. CONCLUSIONS: The data from our study indicate that serum CA19-9 level is the most significant prognostic indicator of patients with metastatic colorectal cancer. It is recommended that stratification for further clinical trials for patients with metastatic colorectal cancer should be carried out according to serum CA19-9 levels.