Microbiome‐immune‐metabolic axis in the epidemic of childhood obesity: Evidence and opportunities

Obesity epidemic responsible for increase in diabetes, heart diseases, infections and cancer shows no signs of abating. Obesity in children is also on rise, indicating the urgent need of strategies for prevention and intervention that must begin in early life. While originally posited that obesity results from the simple concept of consuming more calories, or genetics, emerging research suggests that the bacteria living in our gut (gut microbiome) and its interactions with immune cells and metabolic organs including adipose tissues (microbiome‐immune‐metabolic axis) play significant role in obesity development in childhood. Specifically, abnormal changes (dysbiosis) in the gut microbiome, stimulation of inflammatory cytokines, and shifts in the metabolic functions of brown adipose tissue and the browning of white adipose tissue are associated with increased obesity. Many factors from as early as gestation appear to contribute in obesity, such as maternal health, diet, antibiotic use by mother and/or child, and birth and feeding methods. Herein, using evidence from animal and human studies, we discuss how these factors impact microbiome‐immune‐metabolic axis and cause obesity epidemic in children, and describe the gaps in knowledge that are warranted for future research.     

金复康口服液联合培美曲塞治疗非小细胞肺癌的临床研究

目的研究金复康口服液联合注射用培美曲塞二钠治疗非小细胞肺癌的临床疗效。方法选取2016年1月—2018年1月南京市胸科医院诊治的120例非小细胞肺癌患者作为研究对象,采用随机对照表法将患者分为对照组和治疗组,每组各60例。对照组静脉滴注注射用培美曲塞二钠500 mg/m~2,静脉输注10 min以上;治疗组患者在对照组治疗的基础上口服金复康口服液,30 mL/次,3次/d。21 d为1个疗程,两组均持续治疗2个疗程。观察两组患者的临床疗效,同时比较两组治疗前后的生活质量(QOL)评分、KPS评分、无进展生存期(PFS)、总生存期(OS)和免疫功能指标水平。结果治疗后,对照组和治疗组的客观缓解率和疾病控制率比较差异无统计学意义。治疗后,两组患者QOL和KPS评分均显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组QOL评分和KPS评分显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组患者PFS和OS显著长于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者CD3+、CD4+、NK和CD4+/CD8+水平显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组免疫功能指标水平显著高于对照组,两组比较差异具有统计学意义(P0.05)。结论金复康口服液联合注射用培美曲塞二钠治疗非小细胞肺癌具有较好的临床疗效,能够改善患者生活质量,提高免疫功能,且安全性较高,具有一定临床推广应用价值。     

抗逆转录病毒药物的现状与研发

获得性免疫缺陷综合征（AIDS）是威胁人类健康的最危险疾病之一,是由人免疫缺陷病毒（HIV-1）感染引起。从HIV-1病毒发现后的30余年,已有大量的抗逆转录病毒药物投入研发,抑制病毒复制增殖周期的关键阶段。抗逆转录病毒药物延长了患者生命,同时也产生了病毒的耐药变异,因此需要开发针对耐药的新药物。简述美国已上市的抗逆转录病毒药物信息,重点关注抗逆转录病毒药物的研发进展以及非临床研究中的相关问题。     

槐杞黄颗粒联合头孢他啶对肺炎支原体肺炎患儿炎性因子及免疫功能的影响

目的 研究槐杞黄颗粒联合注射用头孢他啶对肺炎支原体肺炎患儿炎性因子及免疫功能的影响。方法 选择2015年6月—2017年6月资阳市人民医院儿科门诊的81例肺炎支原体肺炎患儿为研究对象,将患儿随机分为对照组（41例）和观察组（40例）。对照组静脉滴注注射用头孢他啶,10 mg/kg加入到5%葡萄糖注射液100 mL,2次/d;观察组在对照组治疗的基础上口服槐杞黄颗粒,10 g/次,2次/d。两组均治疗3个月。观察两组患儿的临床疗效,比较两组患儿住院时间、临床症状消退时间、炎症因子和免疫功能。结果 观察组治疗的总有效率高于对照组（95.00% vs 73.17%, P<0.05）。治疗后,观察组患儿的肺部湿啰音消退时间、发热消退时间、住院时间和咳嗽喘息消失时间均明显短于对照组,两组比较差异有统计学意义（P<0.05）。治疗后,两组的血清C反应蛋白（CRP）、白细胞介素（IL）-4以及IL-6水平均明显降低,IL-10水平均明显升高,同组治疗前后比较差异有统计学意义（P<0.05）;治疗后,观察组炎症因子水平明显优于对照组,两组比较差异有统计学意义（P<0.05）。治疗后,两组的CD4⁺/CD8⁺和CD4⁺均明显升高,CD8⁺明显降低,同组治疗前后比较差异有统计学意义（P<0.05）;治疗后,观察组免疫功能指标明显优于对照组,两组比较差异有统计学意义（P<0.05）。结论 槐杞黄颗粒联合注射用头孢他啶对肺炎支原体肺炎患儿的治疗效果优于单纯使用头孢他啶钠,可以降低炎性因子水平,提升机体免疫功能。     

生血宝合剂联合利妥昔单抗治疗自身免疫性溶血性贫血的临床研究

目的研究生血宝合剂联合利妥昔单抗注射液治疗自身免疫性溶血性贫血的临床疗效。方法选取2017年12月—2018年12月绵阳市中心医院收治的80例自身免疫性溶血性贫血患者为研究对象,将所有患者随机分为对照组和治疗组,每组各40例。对照组患者静脉注射利妥昔单抗注射液,100 mg次加入到5%葡萄糖溶液中,稀释到1 mg/mL,1次/周;治疗组在对照组基础上口服生血宝合剂,15 mL/次,3次/d。两组患者持续治疗30 d。观察两组的临床疗效,比较两组的生化指标水平、免疫功能指标。结果治疗后,对照组和治疗组的总有效率分别为77.50%、92.50%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者红细胞计数(RBC)和血红蛋白(HGB)水平均显著升高,网织红细胞百分率(Ret)水平显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组患者生化指标水平明显优于对照组,两组比较差异有统计学意义(P0.05)。治疗后,治疗组患者CD3+、CD4+、CD4+/CD8+、NK水平均显著升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组免疫功能指标水平显著高于对照组,两组比较差异有统计学意义(P0.05)。结论生血宝合剂联合利妥昔单抗注射液治疗自身免疫性溶血性贫血具有较好的治疗效果,可改善免疫功能,调节RBC、HGB、Ret水平,具有一定的临床推广应用价值。     

细菌溶解产物胶囊联合匹多莫德对儿童咳嗽变异性哮喘患儿免疫功能的影响

目的 探讨细菌溶解产物胶囊联合匹多莫德颗粒对儿童咳嗽变异性哮喘患儿免疫功能的影响。方法 选取2015年8月-2018年8月在榆林市第二医院就诊的82例儿童咳嗽变异性哮喘患儿,按照患者入院先后顺序编号,采用奇偶数法分为观察组（n=41）和对照组（n=41）。对照组给予匹多莫德颗粒,0.4 g/次,3次/d。观察组在对照组基础上给予细菌溶解产物胶囊7 mg/次,1次/d。均治疗21 d。对比两组临床疗效、肺功能、莱塞斯特咳嗽生命质量问卷（LCQ）评分及免疫功能指标情况。结果 治疗后,观察组总有效率90.24%,显著高于对照组的65.85%（P<0.05）。治疗后,两组一秒用力呼气容积（FEV1）、呼气峰流速（PEF）和FEV1/FVC均较治疗前显著升高（P<0.05）,且观察组肺功能明显高于对照组（P<0.05）。治疗后两组LCQ评分（生理、心理、社会和总分）均较治疗前显著升高（P<0.05）;且观察组LCQ评分明显高于对照组（P<0.05）。治疗后,两组白介素-4（IL-4）、肿瘤坏死因子-α（TNF-α）和血清免疫球蛋白E（IgE）均显著低于治疗前（P<0.05）;且观察组IL-4、TNF-α和IgE均显著低于对照组（P<0.05）。结论 细菌溶解产物胶囊联合匹多莫德颗粒可有效改善儿童咳嗽变异性哮喘患儿肺功能和生活质量,提高免疫功能,值得临床推广。     

平喘益气颗粒联合沙美特罗替卡松气雾剂治疗慢性阻塞性肺疾病稳定期的临床研究

目的探讨平喘益气颗粒联合沙美特罗替卡松气雾剂治疗慢性阻塞性肺疾病稳定期的临床疗效。方法选取2017年6月—2018年6月在天津市黄河医院治疗的94例慢性阻塞性肺疾病稳定期患者为研究对象,将患者按随机数表法分为对照组和治疗组,每组各47例。对照组吸入沙美特罗替卡松吸入气雾剂,2揿/次,2次/d。治疗组在对照组基础上口服平喘益气颗粒,2袋/次,3次/d。两组患者连续治疗3个月。观察两组的临床疗效,比较两组的肺功能指标、SGRQ评分、6 min步行距离、免疫功能、炎症因子。结果治疗后,对照组和治疗组的总有效率分别为76.60%、91.49%,两组比较差异有统计学意义(P0.05)。治疗后,两组第1秒用力呼气容积(FEV1)、用力肺活量(FVC)、FEV1/FVC均显著提高,同组治疗前后比较差异有统计学意义(P0.05);且治疗后治疗组FEV1、FVC、FEV1/FVC明显高于对照组,差异有统计学意义(P0.05)。治疗后,两组圣乔治呼吸问卷(SGRQ)评分显著降低,6 min步行距离显著增加,同组治疗前后比较差异有统计学意义(P0.05);且治疗后治疗组SGRQ评分低于对照组,6 min步行距离长于对照组,差异有统计学意义(P0.05)。治疗后,治疗组CD3~+、CD4~+、CD4~+/CD8~+明显高于治疗前,且治疗组CD3~+、CD4~+、CD4~+/CD8~+明显高于对照组,差异有统计学意义(P0.05)。治疗后,两组肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)水平显著下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗后治疗组炎症因子水平明显低于对照组,差异有统计学意义(P0.05)。结论平喘益气颗粒联合沙美特罗替卡松气雾剂治疗慢性阻塞性肺疾病稳定期具有较好的临床疗效,可改善患者临床症状及肺功能,调节免疫功能及相关炎症因子,提高生活质量,具有一定的临床推广应用价值。     

妇康宁颗粒的药效学研究

目的研究妇康宁颗粒剂的药效学。方法采用小鼠扭体法和热板法考察妇康宁颗粒的镇痛作用,采用小鼠耳肿胀法和大鼠纸片包埋法考察妇康宁颗粒的抗炎作用,采用小鼠凝血时间、出血时间试验考察妇康宁颗粒的止血作用,采用小鼠碳廓清试验考察妇康宁颗粒调节免疫作用。结果妇康宁颗粒对化学、物理刺激引发的疼痛具有良好的抑制作用。妇康宁颗粒剂对急性渗出性炎症和慢性增殖性炎症具有一定的抑制作用,具有剂量相关性。妇康宁颗粒剂具有一定的凝血和止血作用。妇康宁颗粒可以促进小鼠免疫器官的发育,增加小鼠单位时间清除血液异物的速度。结论妇康宁颗粒具有抗炎、止血、调节免疫作用,为临床应用提供了科学的依据。     

Minimal contribution of P-gp on the low brain distribution of naldemedine,a peripherally acting μ-opioid receptor antagonist

Naldemedine tosylate, a peripherally acting μ-opioid receptor antagonist, is indicated for treatment of opioid induced constipation in both Japan and US. Naldemedine has limited ability to affect the central analgesic effect of opioid analgesics. In this study, we investigated the contribution of P-glycoprotein (P-gp) on the brain distribution of naldemedine. Naldemedine tosylate showed acceptable oral absorption in rats. Following a single oral administration of [¹⁴C]-naldemedine tosylate to rats and ferrets, little radioactivity was detected in the region protected by the blood-brain barrier (BBB). In the assessment using Caco-2 cells, it was determined that naldemedine is a substrate for P-gp. The contribution of P-gp to the brain distribution of naldemedine was assessed using multidrug resistance 1a/b (mdr1a/b) knockout mice. While the brain-to-plasma concentration ratio (brain Kp) of naldemedine in the mdr1a/b knockout mice was 4-fold of that in the wild-type mice, the brain Kp in the mdr1a/b knockout mice was quite low (brain Kp < 0.1). These results suggest that the low brain distribution of naldemedine was due to the limited ability to cross the BBB rather than efflux by P-gp and therefore brain distribution of naldemedine would not be affected by concomitant administration of P-gp inhibitors or functional disorder of P-gp.     

Overview of the toxic effects of titanium dioxide nanoparticles in blood,liver, muscles,and brain of a Neotropical detritivorous fish

The toxicity of titanium dioxide nanoparticles (TiO₂‐NP) in the blood, liver, muscle, and brain of a Neotropical detritivorous fish, Prochilodus lineatus, was tested. Juvenile fish were exposed to 0, 1, 5, 10, and 50 mg L^?1 of TiO₂‐NP for 48 hours (acute exposure) or 14 days (subchronic exposure) to evaluate changes in hematology, red blood cell (RBC) genotoxicity/mutagenicity, liver function (reactive oxygen species (ROS) production, antioxidant responses, detoxification, and histopathology), acetylcholinesterase (AChE) activity in muscles and brain, and Ti bioaccumulation. TiO₂‐NP did not cause genetic damage to RBC, but acutely decreased white blood cells (WBC) and increased monocytes. Subchronically, RBC decreased, mean cell volume and hemoglobin increased, and WBC and lymphocytes decreased. Therefore, NP has the potential to affect immune system and increase energy expenditure, reducing the fish's ability to avoid predator and to resist pathogens. In the liver, acute exposure decreased ROS and increased glutathione (GSH) content, while subchronic exposure decreased superoxide dismutase activity and increased glutathione‐S‐transferase (GST) activity and GSH content. GSH and GST seem to play an essential role in metabolizing NP and ROS, likely increasing hepatocytes' metabolic rate, which may be the cause of observed cell hypertrophy, disarrangement of hepatic cords and degenerative morphological alterations. Although most studies indicate that the kidney is responsible for metabolizing and/or eliminating TiO₂‐NP, this study shows that the liver also has a main role in these processes. Nevertheless, Ti still accumulated in the liver, muscle, and brain and decreased muscular AChE activity after acute exposure, showing neurotoxic potential. More studies are needed to better understand the biochemical pathways TiO₂‐NP are metabolized and how its bioaccumulation may affect fish homeostasis and survival in the environment.