Efficacy and safety of riociguat in the treatment of chronic thromboembolic pulmonary arterial hypertension: A meta-analysis

Background:Riociguat is a novel soluble guanylate cyclase stimulator, and has been widely used for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (CTEPH). Some studies found that riociguat had better effects on CTEPH and proved to be safe, but the results were not utterly consistent. Therefore, the purpose of this study was to comprehensively evaluate the efficacy and safety of riociguat in the treatment of CTEPH.Methods:Randomized controlled trials on riociguat for the treatment of CTEPH were searched through such electronic databases as PubMed, Embase, Cochrane Library, Web of Science, China national knowledge internet, and Wanfang. The outcomes included exercise capacity, pulmonary hemodynamics, and side effects. The fixed-effects or random-effects models were used to analyze the pooled data, and heterogeneity was assessed by the I² test.Results:Four studies involving 520 patients were included in this meta-analysis. Compared with the placebo group, riociguat significantly improved the hemodynamic indexes and increased 6-min walking distance (P < .0001, standardized mean difference (SMD) = −0.24, 95%CI −0.35 to −0.12; P < .00001, SMD = 0.52, 95%CI 0.33 to 0.71), and decreased the Borg dyspnea score (P = .002, SMD = −0.31, 95%CI −0.51 to −0.12). In addition, riociguat could also significantly reduce the living with pulmonary hypertension scores and increase the EQ-5D scores (P = .01, SMD=−0.23, 95%CI −0.42 to −0.05; P < .00001, SMD = 0.47, 95%CI 0.27 to 0.66), but there was no significant difference in the change level of N-terminal pro-hormone B-type natriuretic peptide in patients with riociguat (P = .20, SMD = −0.24, 95%CI −0.61 to −0.13). The common adverse events of riociguat were dyspepsia and peripheral edema, and no other serious adverse reactions were observed.Conclusions:We confirmed that riociguat had better therapeutic effects in improving the hemodynamic parameters and exercise capacity in patients with CTEPH without inducing serious adverse events. This will provide a reasonable medication regimen for the treatment of CTEPH.     

Zina percutaneous screw fixation combined with endoscopic lumbar intervertebral fusion under intraoperative neuromonitoring: A case report

Introduction:Traditional open discectomy and intervertebral fusion surgery is the common strategy for lumbar disc herniation (LDH). However, it has the disadvantages of long recovery time and severe paravertebral soft tissue injury. Zina percutaneous screw fixation combined with endoscopic lumbar intervertebral fusion (ZELIF), as a novel minimally invasive surgical technique for LDH, has the advantages in quicker recovery, less soft tissue destruction, shorter hospital stays and less pain. We report a novel technique of ZELIF under intraoperative neuromonitoring (INM) for the treatment of LDH.Patient concerns:A 51-year-old male presented to our hospital with left lower extremity pain and numbness for 1 year.Diagnosis:Lumbar disc herniation (LDH).Interventions:This patient was treated with Zina percutaneous screw fixation combined with endoscopic neural decompression, endplate preparation, and intervertebral fusion through Kambin''s triangle. Each step of the operation was performed under INM.Outcomes:The follow-up period lasted 12 months; the hospitalization lasted 4 nights; the blood loss volume was 65 ml, and the time of operation was 266 min. INM showed no neurological damage during the surgery. No surgical complications, including neurological deterioration, cage migration, non-union, instrumentation failure or revision operation, were observed during the follow-up period. Visual Analogue Scale (VAS) score reduced from 7 to 1; the Oswestry Disability Index (ODI) decreased from 43 to 14; the EQ-5D score was 10 preoperatively and 15 at the final follow-up visit; the Physical Component Summary of the 36-Item Short Form Health Survey (SF-36) was 48 preoperatively and 49 at the last follow up visit; the SF-36 Mental Component Summary was 47 before surgery and decreased to 41 postoperatively.Conclusion:ZELIF under INM may represent a feasible, safe and effective alternative to endoscopic intervertebral fusion and percutaneous screw fixation, for decompressing the lumbar''s exiting nerve root directly with minimal invasion in selected patients.     

Downregulation of Serum and Distal Ileum Fibroblast Growth Factor19 in Bile Acid Diarrhoea Patients

Digestive Diseases and Sciences - Bile acid diarrhoea or BAD is a common but little recognised cause of chronic diarrhoea. Few of these patients in China have been diagnosed due to a lack of...     

Soybean allergen glycinin induced the destruction of the mechanical barrier function in IPEC-J2

Humans and animals suffer a health threat to soybean allergy. The impaired mechanism of the intestinal barrier by food/feed allergen glycinin has not been clear. The effects of epithelial metabolic activity, permeability, integrity, and the tight junction (TJ) expression induced by glycinin were conducted using porcine intestinal epithelial cells (IPEC-J2) model in this study. The results showed the decreased metabolic activity (R² = 0.964, p < 0.001) and the increased alkaline phosphatase activity (R² = 0.528, p = 0.002) linearly correlated with glycinin levels (0–4 mg/mL). The trans-epithelial electrical resistance values declined stimulated by 4 mg/mL glycinin treatment in a time-dependent manner (0, 6, 12, or 24 h, p = 0.018), and also descended after 12 or 24 h glycinin treatment in dose-dependence (0, 0.5, 1, 2, or 4 mg/mL, p < 0.001). The glycinin-induced TJ expression of claudin-3, occludin, and ZO-1 were reduced (p < 0.05).     

PCOS患者卵泡液微环境中的亚急性炎症反应

目的:回顾性分析多囊卵巢综合征(PCOS)患者及对照者卵泡液微环境中局部脂代谢紊乱及炎症反应状态及其形成机制。方法:比较2组患者外周血清脂代谢指标、性激素、炎症细胞及炎症介质水平差异;测定卵泡液中炎症介质及载脂蛋白含量;分析卵巢颗粒细胞中炎症介质及载脂蛋白基因表达。结果:PCOS患者具备典型肥胖、高脂血症及高雄激素血症,外周血中炎症细胞及各类炎症介质水平显著增加;卵泡液中同样具有显著增加的炎症细胞因子浸润,颗粒细胞内炎症介质及载脂蛋白基因表达增加。结论:PCOS组患者卵泡液内所含高水平载脂蛋白表明卵泡液内可能存在高脂蛋白状态。循环中的高脂血症及亚急性炎症各类因子可能通过血清-卵泡液屏障主动渗透。颗粒细胞通过主动摄取(例如载脂蛋白A)抑或自主合成(如炎症因子IL-1、IL-6及TNF-α等)等多种方式进行卵泡液局部微环境的稳态调节。卵子发育生理性卵泡液微环境的脂质代谢紊乱、炎症细胞浸润、高雄激素血症等均可能影响到卵母细胞和胚胎的正常发育。     

星形胶质细胞内三羧酸循环在福尔马林诱导的大鼠脊髓中枢敏化中的作用

目的:探讨星形胶质细胞内的三羧酸循环在福尔马林诱导的大鼠炎性持续性痛、慢性痛和脊髓中枢敏化中的作用。方法:在大鼠右后肢足底注射福尔马林(5%,0.05 ml)制备炎性持续性痛大鼠模型,鞘内注射100 nmol/ml氟代柠檬酸(fluorocitrate,FC)和/或5×104nmol/ml谷氨酸(L-glutamate,Glu)后,观察大鼠的行为学变化。结果:(1)急性期:与对照组相比,鞘内注射FC对大鼠自发伤害性行为(舔咬爪和缩腿反射)有抑制作用,而鞘内注射了Glu部分翻转了该抑制效应;(2)在慢性期,与对照组相比较,单次鞘内注射FC在3 h~2 d的时间点上显著提高大鼠同侧的50%爪缩阈值(P0.01,P0.05),而对侧50%爪缩阈值仅在第1 d时间点显示提高(P0.05)。随后在福尔马林注射后第9 d,再次鞘内注射FC,与对照组相比,能在3 h提高大鼠的同侧和对侧的50%爪缩阈值(P0.05),而在6 h阈值恢复到对照组水平(P0.05)。多次鞘内注射FC后,能够在3~7 d时间点上显著提高大鼠同侧的50%爪缩阈值(P0.01,P0.05),在2~7 d时间点上显著提高大鼠对侧的50%爪缩阈值(P0.01,P0.05)。随后在福尔马林注射后第9、10、11 d连续3 d鞘内注射FC,大鼠同侧的50%爪缩阈值的提高仅在鞘内注射日当天发生(P0.01,P0.05),次日即恢复到对照组水平(P0.05),而对侧的50%爪缩阈值在鞘内注射日第11 d及第12 d有所提高(P0.05),第13 d恢复到对照组水平(P0.05)。结论:星形胶质细胞内的三羧酸循环参与福尔马林诱导的急性痛和慢性痛的形成,但是在慢性痛的维持方面不起主导作用。     

中国和菲律宾少年的自杀意念现状及相关因素

目的:比较中国与菲律宾两国少年自杀意念的发生现状及其相关因素。方法:资料来源于由世界卫生组织发起的全球学校健康调查数据中的中国与菲律宾两国的数据资料。分别通过问卷调查的方式了解中国9173名和菲律宾7338名年龄为11~16岁少年的受伤、受欺负、孤独感、失眠、绝望、有无好友、吸烟、饮酒、吸毒和运动等情况,并将在过去12个月里曾认真想过自杀者认定为有自杀意念,没有认真想过自杀者为没有自杀意念。结果:中国、菲律宾的少年自杀意念发生率分别为17.4%(1544/8881)和19.3%(1371/7089)。多因素分析显示,中国少年女性(OR=1.45)、初中二、三年级(OR=1.30、OR=1.43)、受过严重的伤(OR=1.35)、受欺负(OR=1.87)、有孤独感(OR=1.47)、失眠(OR=1.55)、绝望感(OR=3.36)、饮酒(OR=1.45)及吸毒(OR=1.55)是自杀意念的危险因素,有要好朋友(OR=0.66)、经常运动(OR=0.78)则是保护因素。在菲律宾少年中,女性、年级、孤独感、失眠、吸毒都不是危险因素,而受过严重的伤、受欺负、绝望感、饮酒、有要好朋友、经常运动是危险或保护因素。结论:本研究提示中国少年自杀意念发生率低于菲律宾少年,且两国相关因素类似,但中国的危险因素偏多。因此,两国的自杀预防工作应各自采取有针对性的干预措施。     

骨原发性巨细胞血管母细胞瘤临床病理学观察

目的探讨骨原发性巨细胞血管母细胞瘤(giant cell angioblastoma,GCAB)的临床特点、影像学表现、病理学形态、免疫表型及其鉴别诊断。方法对3例骨原发性GCAB的临床资料、影像学表现、病理学形态和免疫表型进行回顾性分析。结果2例为成年女性,1例为男童。病变分别位于第2腰椎、左股骨远端和左手第3~5掌骨。患者均以局部骨疼痛就诊,其中2例伴活动受限,2例伴周围软组织肿胀。影像学显示为骨质破坏,2例累及邻近软组织。低倍镜下见组织由丛状增生的不规则形血管瘤样结节组成,结节之间为纤维结缔组织。高倍镜下,血管瘤样结节由增生的小血管和周围的胖梭形周皮细胞组成,后者可呈同心圆状围绕小血管,结节内可见散在的破骨样巨细胞。免疫表型:结节内小血管内皮细胞表达CD31和CD34,其周围的周皮细胞表达α-SMA和vimentin,破骨样巨细胞表达KP-1。结论 GCAB属于局部侵袭性的中间型血管内皮瘤。除周围软组织外,少数病例可原发于骨内,并可发生于成人。GCAB需与慢性肉芽肿性炎症、丛状纤维组织细胞瘤、簇状血管瘤和卡波西型血管内皮瘤等鉴别。     

胰岛素通过PI3K/AKT/GSK3通路促多囊卵巢综合征患者子宫内膜病变机制的研究

目的 研究多囊卵巢综合征(PCOS)胰岛素抵抗(IR)与非抵抗患者子宫内膜的PI3 K/AKT/GSK3信号通路蛋白表达情况;探讨胰岛素在PCOS患者子宫内膜病变的作用机制.方法 以2006年3月至2010年5月北京天坛医院妇产科门诊治疗的34例PCOS患者为实验组,以同期因输卵管因素不孕行诊刮术的非PCOS患者30例为对照组.实验组患者行OGTT、INS实验及性腺6项测定,根据是否存在IR将PCOS患者分为Ⅰ组(IR组)和Ⅱ组(非IR组).对实验组和对照组患者子宫内膜石蜡标本应用免疫组化方法测定PI3K(磷脂酰肌醇-3激酶)、p-AKT(PPKB,磷酸化蛋白激酶B)、GSK3(糖原合成酶激3)的表达.结果 PCOS患者的PDK表达水平要明显高于对照组(P=0.000,0.003),其中PCOS Ⅰ组最高(P=0.022).在p-AKT表达上,PCOS患者要明显高于对照组(P=0.011,0.000),其中以PCOS Ⅰ组最高(P =0.002),而在GSK3表达上,PCOS Ⅰ组,Ⅱ组和对照组三组之间差异无统计学意义(P＞0.05).结论胰岛素信号通路PI3K、p-AKT可能是IR PCOS患者子宫内膜病变的信号转导通路.     

Synthesis and Microphase Separation of PS‐b‐P(MA‐alt‐St) Block Copolymers and Their Ionomers for the Design of Polymer Crystallization Nucleation Agents

Several well‐controlled polystyrene‐block‐poly(styrene‐alt‐maleic anhydride) (PS‐b‐P(St‐alt‐MA)) functionalized block copolymers (BCs) and their sodium salt ionomers with different block ratios and molecular weights are synthesized through two‐step reversible addition–­fragmentation chain transfer (RAFT) polymerization. The atomic force microscopy (AFM) images and differential scanning calorimetry (DSC) results reveal that the prepared BCs and their ionomers microphase separate into various nanostructures depending on the block ratios. By taking advantage of the formation of amphiphilic nanostructures via the microphase, the block ionomers serve as nucleation agents to improve the crystallization rate of poly(ethylene terephthalate) (PET). The crystallization behavior of PET upon the addition of block ionomers is investigated isothermally and non‐isothermally by DSC. The results show that the block ionomers can effectively accelerate the crystallization rate of PET, which strongly depends on the molecular weights and block ratios