当归龙荟片联合普芦卡必利治疗慢性功能性便秘的临床研究

目的探讨当归龙荟片联合普芦卡必利治疗慢性功能性便秘的临床疗效。方法选取2018年5月-2019年5月在北京市肛肠医院治疗的慢性功能性便秘患者122例,根据用药的差别分为对照组(61例)和治疗组(61例)。对照组口服琥珀酸普芦卡必利片,2mg/次,1次/d;治疗组在对照组基础上口服当归龙荟片,4片/次,2次/d。两组患者均经4周治疗。观察两组患者临床疗效,同时比较治疗前后两组患者临床症状评分、PAC-QOL积分、结肠传输试验积分、Bristol和SF-36评分,及血清5-羟色胺(5-HT)、血管活性肠肽(VIP)、P物质(SP)和一氧化氮(NO)水平。结果治疗后,对照组和治疗组临床有效率分别为80.33%和96.72%,两组比较差异具有统计学意义(P<0.05)。经治疗,两组症状积分均明显降低(P<0.05),且治疗组比对照组降低更明显(P<0.05)。经治疗,两组患者PAC-QOL积分和结肠传输试验积分明显降低(P<0.05),而Bristol和SF-36评分明显升高(P<0.05),且治疗组患者明显好于对照组(P<0.05)。经治疗,两组患者血清SP、5-HT水平均显著升高(P<0.05),而VIP和NO水平均明显降低(P<0.05),且治疗组患者SP、5-HT、VIP和NO水平明显优于对照组(P<0.05)。结论当归龙荟片联合普芦卡必利治疗慢性功能性便秘可有效改善患者临床症状,促进患者生活质量改善,具有一定的临床推广应用价值。     

结肠癌T-cadherin表达水平分析与5-Aza-CdR对其表达和结肠癌细胞增殖、侵袭及凋亡的影响

背景与目的：结肠癌是临床常见恶性肿瘤，探讨抑癌蛋白T-cadherin在结肠癌中的表达情况及其与患者临床病理学特征的关系，并分析5-Aza-CdR对T-cadherin表达和结肠癌细胞增殖、侵袭及凋亡的影响。方法：收集福建医科大学附属第二医院2015—2016年40例手术切除的结肠癌组织及癌旁组织新鲜样本，并经过病理学检查验证，分别提取总RNA和总蛋白质。采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）分析T-cadherin mRNA的表达，采用蛋白质印迹法（Western blot）分析T-cadherin蛋白水平，并分析T-cadherin的mRNA表达变化与患者临床病理学特征的关系。进一步以人结肠癌细胞系HT-29为研究对象，采用甲基化抑制剂5-Aza-CdR处理HT-29细胞，分别采用RTFQ-PCR和Western blot分析T-cadherin表达变化，采用细胞计数试剂盒（cell counting kit-8，CCK-8）分析细胞增殖，采用Transwell实验验证细胞侵袭能力，采用流式细胞术分析细胞凋亡。结果：T-cadherin在结肠癌组织的蛋白水平和mRNA表达均明显低于癌旁组织，其mRNA表达与淋巴结转移（F=5.316，P=0.009 3）和分化程度（F=5.807，P=0.006 4）明显相关，而与其他病理变量（包括性别、年龄、肿瘤大小和肿瘤浸润深度）无明显相关。药物5-Aza-CdR可以显著上调HT-29细胞中T-cadherin的表达水平，抑制HT-29细胞增殖、侵袭并促进细胞凋亡。结论：T-cadherin表达可能与结肠癌恶性程度密切相关，药物5-Aza-CdR处理可上调结肠癌细胞T-cadherin的表达，并抑制结肠癌细胞的增殖、迁移，促进结肠癌细胞凋亡，提示T-cadherin可能是结肠癌患者使用甲基化抑制剂5-Aza-CdR治疗的靶点。     

Nutritional status and intestinal parasites among young children from pastoralist communities of the Ethiopian Somali region

Pastoralist children in the Ethiopian Somali Regional State (ESRS) are at high risk for undernutrition and intestinal parasitic infections (IPIs). We assessed the nutritional status and its association with IPIs in 500 children <5 years of age in a clustered cross‐sectional study in Adadle district, ESRS. Stool samples were microscopically examined for IPIs and biomarkers for iron and vitamin A status, anthropometry, and food variety score (FVS) were assessed. Median (interquartile range [IQR]) FVS was 2.0 (2.0, 4.0), and 35% of children were exclusively breastfed up to age 6 months. Prevalence of stunting, wasting, underweight and mid‐upper arm circumference (MUAC) <12.5 cm was 30, 34, 40, and 16%, respectively. Median (IQR) haemoglobin, ferritin, and retinol‐binding protein concentrations were 9.5 g dL^‐1 (8.2, 10.9), 6.2 μg L^‐1 (4.0, 10.2), and 0.8 μmol L^?1 (0.67, 0.91), respectively. Prevalence of anaemia, iron, and vitamin A deficiency was 75, 91, and 30%, respectively. IPIs' prevalence was 47%; the most prevalent IPIs were Giardia lamblia (22%) and Ascaris lumbricoides (15%). Giardial infections but not A. lumbricoides increased the risk for MUAC <12.5 cm (adjusted odds ratio [aOR]: 3.50, 95% confidence interval [CI] [2.21, 5.54]). The odds for anaemia were 97% (aOR: 0.03, 95% CI [0.03, 0.07]) and 89% (aOR: 0.11, 95% CI [0.11, 0.23]) less for children with FVS >2 or with exclusive breastfeeding up to 6 months, respectively. Undernutrition and IPIs are alarmingly high in <5 years of age children in ESRS. Giardial infections and low nutritional adequacy of the diet seem to be major contributing factors to the precarious nutritional status and should be addressed by appropriate interventions.     

光叶决明中1个新的二聚苯丙素类化合物

目的对决明属植物光叶决明Cassia floribunda茎叶的化学成分进行研究。方法运用硅胶、MCI、RP-18、TLC、HPLC等多种色谱技术进行分离纯化,根据理化性质和波谱数据鉴定化合物的结构。结果从光叶决明90%乙醇提取物中分离得到18个化合物,分别鉴定为决明顺反二聚苯丙素(1)、反式对羟基肉桂酸乙酯(2)、shonanin(3)、邻苯二甲酸二丁酯(4)、1,6,8-三羟基-3-甲基蒽醌(5)、2,5-二甲基-7-羟基-色原酮(6)、2-(2′-羟丙基)-5-甲基-7-羟基色酮(7)、4′,7-二羟基-5-甲氧基黄酮(8)、柯伊利素(9)、山柰酚(10)、芹菜素(11)、3-甲氧基槲皮素(12)、6-demethoxycapillarisin(13)、7,4′-二羟基黄酮(14)、木犀草素(15)、butin(16)、甘草素(17)和圣草酚(18)。结论化合物1为新的苯丙素类化合物;化合物2～18均为首次从该植物中分离得到,其中,化合物2～4、8、9、11、13、14、16～18为首次从决明属植物中分离得到。     

Nicotinamide N-methyltransferase decreases 5-fluorouracil sensitivity in human esophageal squamous cell carcinoma through metabolic reprogramming and promoting the Warburg effect

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with poor prognosis. And different individuals respond to the same drug differently. Increasing evidence has confirmed that metabolism reprogramming was involved in the drug sensitivity of tumor cells. However, the potential molecular mechanism of 5-fluorouracil (5-FU) sensitivity remains to be elucidated in ESCC cells. In this study, we found that the 5-FU sensitivity of TE1 cells was lower than that of EC1 and Eca109 cells. Gas chromatography-mass spectrometry analysis results showed that nicotinate and nicotinamide metabolism and tricarboxylic acid cycle were significantly different in these three cell lines. Nicotinamide N-methyltransferase (NNMT), a key enzyme of nicotinate and nicotinamide metabolism, was significantly higher expressed in TE1 cells than that in EC1 and Eca109 cells. Therefore, the function of NNMT on 5-FU sensitivity was analyzed in vitro and in vivo. NNMT downregulation significantly increased 5-FU sensitivity in TE1 cells. Meanwhile, the glucose consumption and lactate production were decreased, and the expression of glycolysis-related enzymes hexokinase 2, lactate dehydrogenase A, and phosphoglycerate mutase 1 were downregulated in NNMT knockdown TE1 cells. Besides, overexpression of NNMT in EC1 and Eca109 cells caused the opposite effects. Moreover, when glycolysis was inhibited by 2-deoxyglucose, the roles of NNMT on 5-FU sensitivity was weakened. In vivo experiments showed that NNMT knockdown significantly increased the sensitivity of xenografts to 5-FU and suppressed the Warburg effect. Overall, these results demonstrated that NNMT decreases 5-FU sensitivity in human ESCC cells through promoting the Warburg effect, suggesting that NNMT may contribute to predict the treatment effects of the clinical chemotherapy in ESCC.     

Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity via inhibiting the deubiquitination activity of CSN5

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.     

哈尔滨市农村癫痫患者健康相关生命质量评价研究

目的 评价哈尔滨市农村癫痫患者健康相关生命质量并分析其影响因素。方法 通过简单随机抽样方法，随机选取哈尔滨市236例惊厥型癫痫患者，基于中国人群的EQ-5D效应值积分体系计算癫痫患者健康效应值，采用秩和检验和Tobit回归模型方法对癫痫患者健康水平影响因素进行分析。结果 调查的236名癫痫患者在5个维度有困难者占比排序为:焦虑或沮丧（42.74%）、疼痛或不适（30.77%）、日常活动（28.63%）、自己照顾自己（18.80%）、行动（16.67%），基于中国积分体系计算癫痫患者健康效应值为0.85，Tobit回归模型结果表明，职业（95%CI = 0.004～0.313，P = 0.045）、体育运动（95%CI = 0.001～0.438，P = 0.049）、最近一次发作时间（95%CI = - 0.316～- 0.020，P = 0.027）、总病程（95%CI = - 0.051～- 0.387，P = 0.011）对癫痫患者的健康效用值得分有统计学差异。结论 癫痫对患者心理方面的影响程度大于生理方面，应加大对癫痫患者心理方面的关注。脑力劳动者、体育运动的癫痫患者健康效用值相对较高，发作时间在0～3个月内、总病程较长的癫痫患者健康效用值相对较低。