Identification of novel susceptibility loci for non‐syndromic cleft lip with or without cleft palate

Although several genome‐wide association studies (GWAS) of non‐syndromic cleft lip with or without cleft palate (NSCL/P) have been reported, more novel association signals are remained to be exploited. Here, we performed an in‐depth analysis of our previously published Chinese GWAS cohort study with replication in an extra dbGaP case‐parent trios and another in‐house Nanjing cohort, and finally identified five novel significant association signals (rs11119445: 3’ of SERTAD4, P = 6.44 × 10⁻¹⁴; rs227227 and rs12561877: intron of SYT14, P = 5.02 × 10⁻¹³ and 2.80 × 10⁻¹¹, respectively; rs643118: intron of TRAF3IP3, P = 4.45 × 10⁻⁶; rs2095293: intron of NR6A1, P = 2.98 × 10⁻⁵). The mean (standard deviation) of the weighted genetic risk score (wGRS) from these SNPs was 1.83 (0.65) for NSCL/P cases and 1.58 (0.68) for controls, respectively (P = 2.67 × 10⁻¹⁶). Rs643118 was identified as a shared susceptible factor of NSCL/P among Asians and Europeans, while rs227227 may contribute to the risk of NSCL/P as well as NSCPO. In addition, sertad4 knockdown zebrafish models resulted in down‐regulation of sox2 and caused oedema around the heart and mandibular deficiency, compared with control embryos. Taken together, this study has improved our understanding of the genetic susceptibility to NSCL/P and provided further clues to its aetiology in the Chinese population.     

ATPR triggers acute myeloid leukaemia cells differentiation and cycle arrest via the RARα/LDHB/ERK‐glycolysis signalling axis

Acute myeloid leukaemia (AML) remains a therapeutic challenge and improvements in chemotherapy are needed. 4‐Amino‐2‐trifluoromethyl‐phenyl retinate (ATPR), a novel all‐trans retinoic acid (ATRA) derivative designed and synthesized by our team, has been proven to show superior anticancer effect compared with ATRA on various cancers. However, its potential effect on AML remains largely unknown. Lactate dehydrogenase B (LDHB) is the key glycolytic enzyme that catalyses the interconversion between pyruvate and lactate. Currently, little is known about the role of LDHB in AML. In this study, we found that ATPR showed antileukaemic effects with RARα dependent in AML cells. LDHB was aberrantly overexpressed in human AML peripheral blood mononuclear cell (PBMC) and AML cell lines. A lentiviral vector expressing LDHB‐targeting shRNA was constructed to generate a stable AML cells with low expression of LDHB. The effect of LDHB knockdown on differentiation and cycle arrest of AML cells was assessed in vitro and vivo, including involvement of Raf/MEK/ERK signalling. Finally, these data suggested that ATPR showed antileukaemic effects by RARα/LDHB/ ERK‐glycolysis signalling axis. Further studies should focus on the underlying leukaemia‐promoting mechanisms and investigate LDHB as a therapeutic target.     

Protective Antioxidant Effects of Amentoflavone and Total Flavonoids from Hedyotis diffusa on H2O2‐Induced HL‐O2 Cells through ASK1/p38 MAPK Pathway

In this study, total flavonoids and total triterpenoid acid were extracted with ethyl acetate from Hedyotis diffusa Willd, and hepatoprotective activities of them and five compounds from total flavonoids against H₂O₂ induced hepatocyte damage on HL‐02 cells were determined. In particular, amentoflavone and total flavonoids had influence on the leakage of ALT, AST, LDH, the activities of SOD and the content of MDA. They effectively reduced the loss of MMP, the release of Cyt C, and then inhibited activation of caspase‐3/caspase‐9 cascade in hepatotoxic cells. The contents of ROS were significantly reduced to inhibit p38 in amentoflavone and flavonoids groups which decreased ASK1 and p‐p38 levels through increasing thioredoxin Trx1 and reductase TrxR1. These results suggesting that the antioxidant protection of amentoflavone and flavonoids might be reducing ROS to inhibit the H₂O₂‐induced upstream of pathway via increasing levels of Trx1 and TrxR1, which were pivotal in blocking the down streaming effectors of ASK1/p38 MAPK pathway and alleviating hepatotoxicity.     

小儿肺热咳喘口服液联合三联吸入雾化治疗法对哮喘急性发作的影响

目的:探讨小儿肺热咳喘口服液联合三联吸入雾化治疗方案对哮喘患儿的治疗效果以及对肺功能的影响作用。方法:将我院自2017年1月至2018年11月间收治的哮喘患儿210例作为研究对象,按照随机数字表法分为两组各105例,研究组患儿在布地奈德、沙丁胺醇、异丙托溴铵三联吸入雾化治疗的基础上给予小儿肺热咳喘口服液进行治疗,对照组患儿仅给予三联雾化吸入治疗,对比观察两组患儿的疗效和预后。结果:研究组临床治疗后总有效率为95.24%,明显高于对照组77.14%(P0.05);治疗后研究组咳嗽消失时间、呼吸困难消失时间和急性发作随诊时间均明显短于对照组(P0.05),两组肺部喘鸣音消失时间比较差异无统计学意义(P0.05);治疗前患儿第一秒用力呼气量(forced expiratory volume in one second,FEV1)、最大肺活量(forced vital capacity,FVC)及FEV1/FVC值、呼气峰流速值(peak expiratory flowrate,PEF)对比无统计学意义(P0.05),治疗后1 d、3 d、7 d以上指标水平均明显升高,且在治疗后7 d,研究组明显高于对照组(P0.05)。治疗期间研究组有1例出现轻度腹泻,3例食欲减退,并发症的发生率为3.81%(4/105),对照组治疗期间2例出现轻度腹泻,4例食欲减退,并发症的发生率为5.71%(6/105),两组比较无统计学意义(P0.05)。结论:使用小儿肺热咳喘口服液联合三联吸入雾化法治疗儿童哮喘急性发作,可改善患儿临床症状和肺功能,疗效显著,可推广使用。     

脐血管前置产前超声表现及临床效果分析

目的:研究脐血管前置产前超声表现及临床效果。方法:回顾性分析2017年1月至2018年12月期间本院收治的34例脐血管前置孕妇临床资料,均进行产前超声检查,将结果与产后病理结果进行比较,分析超声表现。结果:同产后病理检查结果相比较,34例孕妇的产前超声诊断准确率、误诊率分别为97.06%、2.94%,数据对比差异无统计学意义(P>0.05),产前超声检查显示的胎盘及脐带入口情况主要为帆状胎盘、脐带胎盘边缘附着、边缘性前置胎盘、低置性前置胎盘、副胎盘等。结论:产前超声检查具有较高的脐血管前置诊断准确率,可为临床分娩结局的改善提供指导,适合推广应用在临床中。     

高血压患者饮食习惯、传统制剂服用现状调查及其影响因素分析

目的:调查高血压患者饮食习惯以及传统制剂服用现状,并分析饮食习惯与高血压患病的关系以及传统制剂服用的影响因素。方法:按照简单随机抽样法,采用自制调查问卷对呼和浩特市3个镇共8个行政村成年常住农村村民进行问卷调查,调查内容包括人口学特征、饮食习惯等内容,并采用多因素logistic回归分析饮食习惯与高血压患病的关系以及高血压患者传统制剂服用的影响因素。结果:呼和浩特市高血压患病率为22.68%。多因素logistic回归结果显示,较高的BMI、高血压家族史、饮酒史、泡菜咸菜、油炸食品、红肉(猪/牛/羊肉)/动物内脏、海产品是高血压独立危险因素(OR=1.257、1.451、1.358、1.317、1.108、1.146、1.373,P<0.05),奶制品、豆制品、新鲜果蔬是高血压保护因素(OR=0.797、0.868、0.903,P<0.05)。高血压患者传统制剂服用率为16.90%。多因素logistic回归结果显示,年龄≥60岁、文化程度高中以下、不了解高血压知识是高血压患者传统制剂服用的危险因素(OR=1.342、1.545、1.142,P<0.05)。结论:呼和浩特市农村成年村民高血压患病率较高,不良饮食习惯(饮食偏咸、油腻等)是高血压独立危险因素,高龄、文化程度低、不了解高血压知识的高血压患者传统制剂服用率较高,应加强农村居民合理膳食、保持均衡饮食习惯的宣传教育以及农村高血压患者用药规范。     

乳腺癌患者改良根治术后生活质量调查及复发转移的影响因素分析

目的:调查乳腺癌患者改良根治术后生活质量,并对其复发转移的影响因素进行分析。方法:选取2012年6月～2014年6月期间于我院行改良根治术的乳腺癌患者197例,于术后3个月、术后6个月、术后12个月采用乳腺癌患者生命质量测定量表(FACT-B)评价患者生活质量。采用我院自制的调查问卷统计患者基本治疗情况,分析乳腺癌改良根治术后复发转移的影响因素。结果:本研究中,共发放197份问卷调查,回收195份,回收率为98.98%(195/197)。其中195例患者中有73例发生复发转移(复发转移组),122例未发生复发转移(未复发转移组)。195例乳腺癌患者术后3个月、术后6个月、术后12个月社会/家庭状况、生理状况、功能状况、情感状况、附加关注条目、总体生活质量等项目评分呈递增趋势(P0.05)。多因素Logistic回归分析显示,病理类型为浸润性非特殊性癌、肿瘤大小≥2 cm、临床分期为Ⅲ期、激素受体为ER及PR均阴性均是乳腺癌改良根治术后复发转移的独立危险因素(P0.05),而采用放化疗、联合化疗方案、内分泌治疗以及p53蛋白阳性表达是乳腺癌改良根治术后复发转移的独立保护因素(P0.05)。结论:乳腺癌患者行改良根治术后生活质量呈动态变化,其术后复发转移影响因素为病理类型、临床分期、肿瘤大小、激素受体、化疗方案、p53蛋白、内分泌治疗及放化疗。     

乌司他丁联合连续性肾脏替代治疗对严重脓毒症患者炎症反应和血流动力学的影响

目的:探讨乌司他丁联合连续性肾脏替代(CRRT)治疗对严重脓毒症患者炎症反应和血流动力学的影响。方法:选取2015年5月～2019年4月期间我院收治的严重脓毒症患者119例,将所有患者根据随机数字表法分为对照组(n=59)和研究组(n=60),对照组给予CRRT治疗,研究组在对照组基础上联合乌司他丁治疗,比较两组患者临床疗效、炎症反应指标、血流动力学参数,记录两组患者住院时间及28d内病死率。结果:研究组治疗7 d后的临床总有效率高于对照组(P0.05)。两组治疗7 d后血清白介素-6(IL-6)、降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)水平均下降,且研究组低于对照组(P0.05)。两组患者治疗7 d后心率、平均动脉压(MAP)、血乳酸下降,氧合指数升高(P0.05),研究组治疗7 d后氧合指数高于对照组,血乳酸则低于对照组(P0.05)。研究组住院时间短于对照组(P0.05),两组28d内病死率比较无统计学差异(P0.05)。结论:乌司他丁联合CRRT治疗严重脓毒症患者的疗效确切,可有效抑制机体炎症反应,改善血流动力学,减少住院时间,具有一定的临床应用价值。