A polysaccharide from the fruiting bodies of Agaricus blazei Murill induces caspase-dependent apoptosis in human leukemia HL-60 cells

Polysaccharides are the major active ingredients of fungus Agaricus blazei for treating and preventing cancer. However, there are no reports showing anti-tumor activity of A. blazei polysaccharides (ABP) on human leukemia (HL)-60 cells in vitro and in vivo. In this study, we demonstrated that ABP efficiently inhibited proliferation of cultured HL-60 cells, which was associated with the induction of apoptosis. The increase in ABP-induced apoptosis was accompanied by loss of mitochondria membrane potential (?Ψm), cytochrome c release from the mitochondria, activation of caspase-3, degradation of poly(ADP-ribose) polymerase (PARP), and the elevated ratio of Bcl-2-associated X (Bax)/B-cell lymphoma 2 (Bcl-2). Moreover, z-DEVD-fmk, a caspase-3 inhibitor, reversed the cytotoxic effects and apoptotic characteristics induced by ABP in HL-60 cells. Furthermore, we confirmed that ABP could obviously inhibit the solid cancer growth of leukemia HL-60 in tumor xenograft model. These data demonstrated that ABP effectively induced the apoptosis of HL-60 cells via a signaling cascade of mitochondrial caspase-3-dependent pathway.     

急诊肝动脉栓塞治疗原发性肝癌破裂出血36例

目的探讨急诊肝动脉栓塞治疗原发性肝癌破裂出血的效果。方法收集2007年9月～2010年9月北京军区总医院实施急诊肝动脉栓塞治疗原发性肝癌破裂出血患者36例为观察组,另随机抽取北京军区总医院2007年9月前实施保守治疗的原发性肝癌破裂出血患者26例为对照组。比较两组即时止血率、输血量、肝功能恢复率及生存率。结果观察组即时止血率、输血量和肝功能恢复率均显著优于对照组,差异均有高度统计学意义（均P〈0.01）。观察组治疗后6、12个月时生存率均显著高于对照组,差异均有高度统计学意义（均P〈0.01）。结论与保守治疗相比,急诊肝动脉栓塞具有止血成功率高、输血量少、肝功能恢复快及病死率低的优点,值得临床推广应用。     

DNA methylation suppresses liver Hamp expression in response to iron deficiency after bariatric surgery

BackgroundIron deficiency is extremely common after bariatric surgery. HEPCIDIN, encoded by Hamp, is a hormone that negatively regulates iron homeostasis.ObjectivesWe aimed to investigate the alteration of Hamp expression and related regulatory factors to explore the probable role of DNA methylation in modulating Hamp expression in the context of iron deficiency after bariatric surgery.SettingLaboratories of Diabetes Institute.MethodsRNA-seq was performed using rat liver tissue after either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy surgery to identify differentially expressed genes between the bariatric surgery and sham group. Hamp expression were measured by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The DNA methylation level was determined using MassARRAY EpiTYPER. Iron status, erythrocyte parameters, and inflammation factors were assessed.ResultsRNA-seq data showed that liver Hamp expression changed most dramatically in RYGB-operated rats. Both the mRNA expression of Hamp and the abundance of its protein product HEPCIDIN-25 decreased markedly after bariatric surgery compared with sham, while sleeve gastrectomy–operated rats showed marginally higher Hamp expression than RYGB-operated rats. The DNA methylation level of the Hamp promoter region was significant higher in RYGB-operated rats than sham, while sleeve gastrectomy rats increased slightly in DNA methylation. Consistent with the change of HEPCIDIN-25, serum iron was significantly lower for both bariatric groups than sham and particularly low in RYGB.ConclusionsOur data demonstrate that elevated DNA methylation of the Hamp promoter region suppresses its expression, this epigenetic modification likely occurs in reaction to iron deficiency after bariatric surgery, helping to maintain system iron homeostasis.     

上腔静脉频谱对大鼠肺动脉高压的评价作用

目的探讨上腔静脉频谱对野百合碱诱导的大鼠肺动脉高压的评价作用。 方法健康成年雄性SD大鼠168只,体重180~220 g,随机选取10只为正常对照组。大鼠腹腔注射2%野百合碱50 mg/kg造模,以肺动脉收缩压大于30 mmHg（1 mmHg=0.133 kPa）为模型成功的标准。第28天造模成功103只,随机选取8只进行模型检测,其余存活大鼠随机分为贝前列素组、西地那非组、波生坦组,每组24只,余23只为安慰剂组。灌胃治疗2周后进行上腔静脉超声检测及右心导管测量右心室压及肺动脉收缩压。 结果造模成功并测得肺动脉压力、进行上腔静脉超声检测的大鼠55只。大鼠模型体重减轻,肺动脉压增高,其中波生坦组肺动脉压力最高,与上腔静脉AR/S比值、上腔静脉S波相关性好。超声心动图检测上腔静脉血流频谱提示肺动脉高压大鼠AR/S增高,S波减低,与对照组比较差异有统计学意义（P<0.01）。Pearson相关示肺动脉收缩压与上腔静脉血流频谱参数AR/S明显相关（右侧AR/S：Y=50.07X＋24.62,R²=0.302,P<0.01;左侧AR/S：r=0.491,P<0.01）。从用药后的自然死亡率分析,每组死亡的大鼠出现不同程度胸腹腔积液和心包积液,以安慰剂和波生坦组较重,波生坦组在3种治疗药物中死亡率最高,但差异无统计学意义。肺组织光镜下显示：模型组、安慰剂组及各治疗组大鼠肺小动脉均出现不同程度中膜增厚,管腔变小,平滑肌增生。正常组肺小动脉未见明确异常。 结论右上腔静脉频谱AR/S与肺动脉收缩压相关性良好,可作为多普勒超声评价肺动脉高压的参数之一。     

Increased expression of LncRNA PANDAR predicts a poor prognosis in gastric cancer

Long non-coding RNAs (lncRNAs) are emerging as biomarkers and as important regulators in biological processes and tumorigenesis in cancer. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) serves as biomarkers and involves in development of multiple cancers. However, its clinical value of PANDAR in gastric cancer is still unknown. Hence, we carried out the present study aiming to identify the clinical significance of PANDAR in gastric cancer patients. We analyzed the expression levels of PANDAR in 100 paired gastric cancer tissues using Quantitative Real-time PCR. Our results showed that the expression of PANDAR was significantly increased in gastric cancer tissues compared with paired adjacent normal tissues. Furthermore, high expression of PANDAR was correlated with depth of invasion, TNM stage and lymphatic metastasis. Importantly, high expression of PANDAR could serve as an independent unfavorable prognostic role in gastric cancer. In conclusion, PANDAR may be a potential novel biomarker that predicts prognosis in gastric cancer.     

乙酰化白藜芦醇通过调节缝隙连接蛋白43表达减轻海水淹溺型急性肺损伤

目的观察海水淹溺肺损伤大鼠肺组织中缝隙连接蛋白43（Cx43）的表达变化及乙酰化白藜芦醇对其的干预作用。方法32只大鼠完全随机分为空白对照组、模型组、乙酰化白藜芦醇预处理组和乙酰化白藜芦醇组,每组8只。采用气管内滴注海水（4ml／kg）的方法制作海水淹溺型急性肺损伤大鼠模型,用ELISA法检测肺组织中TNF-仅和IL-10的含量,实时定量PCR及免疫组化的方法检测肺组织中Cx43的表达变化。结果吸人海水4h后,大鼠肺部损伤明显,TNF—α和IL-10的含量增高,Cx43在基因水平表达量增高,而蛋白水平表达降低;乙酰化白藜芦醇预处理明显减轻海水吸入导致的急性肺损伤,减少炎症因子分泌并且在基因水平和蛋白水平增加Cx43的表达。结论Cx43参与海水淹溺型急性肺损伤的发生与发展,乙酰化白藜芦醇能够通过增加Cx43的表达减轻肺损伤。     

First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advancedEGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label,randomized study

BackgroundIcotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation.Patients and methodsEligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety.ResultsBetween January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43–0.87;P = 0.006). No significant difference for OS was observed between treatments in the overall population or inEGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%;P < 0.001) and treatment-related AEs (54.1% versus 90.5%;P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group.ConclusionsFirst-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients withEGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.     

Effects of gliclazide beyond metabolic control

Evidence implicates hyperglycemia-derived oxygen free radicals as mediators of diabetic complications. Recent studies demonstrate that hyperglycemia-induced overproduction of superoxide seems the first and key event in the activation of all pathways involved in the pathogenesis of diabetic complications. Superoxide overproduction is accompanied by increased nitric oxide generation and, consequently, formation of the strong oxidant peroxynitrite, and by poly(adenosine diphosphate ribose) polymerase activation, which in turn further activates the pathways involved in the pathogenesis of diabetic complications. This process results in acute endothelial dysfunction and activation of inflammation in diabetic blood vessels that, convincingly, contribute to the development of diabetic complications. Gliclazide is an oral hypoglycemic agent that belongs to the class of sulfonylureas: basic and clinical evidences suggest that gliclazide works as an antioxidative drug, independently from its ability to reduce hyperglycemia. The availability of a compound that simultaneously decreases hyperglycemia, restoring insulin secretion, and inhibits oxidative stress produced by high glucose seems to be an interesting therapeutic prospect for the prevention of vascular complications of diabetes.     

感染性腹泻的临床诊治

本文从病原学、流行病学、诊断和治疗等方面对国内外感染性腹泻的临床诊治作一回顾性总结与评述,并指出感染性腹泻绝不是一个单纯的医学问题,而是错综复杂的社会问题;感染性腹泻是无国界的,是全人类的公害;我国应从现实情况出发,强调预防和控制措施的落实。