甘草酸二铵肠溶胶囊防治肝功能损害的临床研究

本研究对甘草酸二铵肠溶胶囊防治抗结核药物对肝功能损害临床疗效的前瞻性进行分析。统计分析2013年1月至2014年12月期间的180例结核病患者的临床资料。在本次研究中,观察组患者治疗2周、1个月和2个月后的肝功能损伤发生率为1.11%、5.56%和13.33%,对照组的发生率为7.78%、17.78%和30.00%(p0.05)。观察组与对照组患者治疗后的肝功能指标(谷丙转氨酶,谷草转氨酶,总胆红素)与治疗前比较有显著差异(p0.05)。且治疗后的观察组与对照组患者的肝功能指标对比分析,有显著差异(p0.05)。通过相关分析表明抗结核疾病的治疗中,使用甘草酸二铵肠溶胶囊治疗,可以显著的降低对患者肝功能产生的损伤,促进结核疾病的顺利进行,并提高治疗成功率。     

毒蛇咬伤治疗前后肝功能变化规律探讨

目的探讨毒蛇咬伤患者治疗前后肝功能的变化情况。方法对我院2012年9月~2014年9月收治住院治疗、且明确何种蛇伤诊断的毒蛇咬伤患者作为研究对象,对患者治疗前后各时段进行6项肝功能指标检测,并按蛇种、时段及病情对检测结果进行统计分析。结果 5种毒蛇咬伤患者的6项肝功能指标在治疗前和治疗后1天大多有升高趋势,治疗后2天和4天降低,肝酶指标的下降与治疗前和治疗后1天比较有显著性差异(P0.05或P0.01)。治疗前和治疗后1天所有指标的血清水平均是重症高于轻症,而且两者比较差异有显著统计学意义(P0.05或P0.01)。各种毒蛇咬伤患者治疗前后各时段比较肝功能变化无统计学意义。结论毒蛇咬伤特别是重症患者可引起肝功能异常,以肝酶变化比较明显,胆红素变化较小。     

肝炎肝硬化患者的肝功能检验结果探讨

目的:研究探讨肝硬化患者的肝功能检验结果。方法:随机抽取我院2012年4月-2013年肝炎肝硬化患者50例(观察组)与同期来我院接受健康体检者50例(对照组)作为研究对象。两组研究人员均在晨时空腹刺激静脉血进行肝功能检验,比较两组检验人员的检验结果。结果:检查结果显示,两组研究人员的血清胆固醇(CHO)白蛋白水平(ALB)、血清胆碱酶活性(CHE)以及总胆汁酸水平(TBA)均具有差异性,数据符合统计学差异(P0.05)。结论:肝硬化患者进行肝功能检验,能够依据不同的指标,充分了解患者肝组织受损的程度,进判断患者的病情以及预后情况。     

益生菌对肝硬化自发性腹膜炎的预防及对 肝功能的影响

目的观察益生菌在肝硬化自发性腹膜炎患者中的预防效果及对肝功能的影响。方法选取福建省立医院南院2015年6月至2017年6月就诊治疗的60例肝硬化失代偿期患者为研究对象,随机平均分为对照组和益生菌组,每组30例。对照组患者采用常规保肝护肝利尿补充白蛋白治疗;益生菌组在对照组基础上加用金双歧口服,2.0g/次,3次/d,疗程3个月。比较两组患者治疗后6个月血浆内毒素(ET)、肿瘤坏死因子-α(TNF-α)、白介素6 (IL-6)、降钙素原(PCT)的水平以及肝功能指标、自发性腹膜炎(SBP)发生率和症状缓解时间的变化。结果治疗前两组患者ET、TNF-α、IL-6、PCT水平及肝功能指标比较差异无统计学意义(P0.01)。治疗后益生菌组患者ET、TNF-α、IL-6、PCT水平明显低于对照组(P0.01),肝功能指标也明显优于对照组(P0.05)。两组患者SBP发生率相比差异有统计学意义(P0.05),益生菌组患者发热缓解时间与腹部压痛缓解时间明显短于对照组(P0.05)。结论益生菌可以有效预防肝硬化失代偿期患者自发性腹膜炎的发生,改善患者肝功能并缩短发病时各症状的缓解时间。     

体外循环心脏手术患者肝功能的表达水平及腺苷蛋氨酸的干预机制研究

目的:探讨体外循环心脏手术患者肝功能的表达水平及腺苷蛋氨酸的干预机制。方法:选取2017年5月至2018年6月在海南医学院第二附属医院接受体外循环心脏手术的患者184例,根据随机数字表法分为观察组及对照组各92例,分别比较术前、术后所有患者肝功能指标水平。术后对照组患者给予生理盐水干预7d,观察组患者给予腺苷蛋氨酸干预7d,比较两组患者干预7d后肝功能指标、炎症反应指标以及心肌损伤指标水平。结果:术前患者的总胆红素(TBI)、直接胆红素(DBI)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平均显著低于术后,差异均有统计学意义(P0.05)。干预7d后观察组患者的TBI、DBI、ALT、AST、血清肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)、肌酸激酶同工酶(CK-MB)、肌钙蛋白(cTnT)水平均显著低于对照组,而白细胞介素-10(IL-10)水平显著高于对照组,差异均有统计学意义(P0.05)。观察组不良反应发生率为7.61%(7/92),与对照组的2.17%(2/92)相比,差异无统计学意义(P0.05)。结论:体外循环心脏手术会对患者肝功能造成一定程度的损害,而腺苷蛋氨酸对患者的肝功能以及心肌组织均有一定的保护作用,同时能减轻炎症反应程度,无严重药物不良反应发生。     

体外循环心脏直视手术对肝功能影响的临床研究

目的:探讨体外循环心脏直视手术对患者肝功能的影响.方法:检测60例体外循环下行心脏直视手术患者术前24小时、术后6小时、术后48小时、术后7天的血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TB)、结合胆红素(CB)等肝功能指标.结果:患者术后6小时ALT、AST、TB、CB水平显著升高(P均＜0.05);术后48小时ALT、AST水平逐渐下降,较术前无显著变化(P均＞0.05),TB、CB水平继续升高(P均＜0.05);术后7天各项肝功能指标基本恢复正常.结论:对术前肝功能异常者需行护肝治疗和缩短体外循环转流时间,对预防体外循环导致的严重肝功能损害具有重要意义.     

支链氨基酸肠内营养制剂对肝功能损害患者的影响

目的观察肝功能损害患者应用支链氨基酸肠内营养制剂后对肝功能恢复的影响。方法将我院收治的60例肝功能损害患者随机分为治疗组和对照组各30例,两组患者均于早期给予肠内营养,治疗组给予支链氨基酸肠内营养制剂,每天3~4次,每次40~45g;对照组给予普通型匀浆膳肠内营养制剂,每天3~4次,每次40~45g。两组患者分别于治疗前第1天、治疗后第14天及治疗后第30天抽血检查肝功能(谷丙转氨酶、谷草转氨酶)及血清清蛋白(ALB)和Hb等指标。结果两组患者谷丙转氨酶、谷草转氨酶指标比较差异有统计学意义(P0.05),治疗组谷丙转氨酶、谷草转氨酶指标下降明显高于对照组;两组血清清蛋白、Hb比较,治疗组明显高于对照组,差异有统计学意义(P0.05)。结论肝功能损害患者早期使用支链氨基酸能促进肝功能恢复,缩短肝功能恢复时间。     

抗结核药物易导致乙肝伴肺结核患者肝功能损伤

为了分析抗结核药物对乙肝伴肺结核患者肝功能的影响,本研究选取了2015年2月至2017年2月在我院治疗的乙肝病毒标记物阳性伴肺结核患者87例(观察组),同时选取乙肝病毒标记物阴性伴肺结核患者90例作为对照组,均给予2HREZ/4HR抗结核等治疗。通过观察两组治疗后肝损害发生以及肝功指标变化,本研究发现观察组治疗后丙氨酸转氨酶(ALT)、门冬氨酸转氨酶(AST)和总胆红素(TBil)分别为(240.06±30.44)U/L、(180.04±32.24)U/L和(51.14±6.50)mol/L,明显高于对照组(p0.05);观察组肝功能损害发生率为66.67%,明显高于对照组(p0.05);观察组中,仅HBs Ag阳性者肝功能损害发生率为26.32%,明显低于HBs Ag+HBc Ab、HBs Ag+Hbc Ab+HBe Ab和HBs Ag+Hbc Ab+Hbe Ag患者(p0.05);HBs Ag+Hbc Ab阳性者肝功能损害发生率为61.90%,明显低于HBs Ag+Hbc Ab+Hbe Ag患者(p0.05)。本研究表明,抗结核药物易导致乙肝伴肺结核患者肝功能损伤,且不同乙肝感染类型患者肝损害发生有所差异,在抗结核治疗中应注意对患者肝功能的保护。本研究为乙肝伴肺结核患者的临床药物治疗提供了一定的帮助。     

Ⅱ型糖尿病患者血糖对肝功能和血脂的影响及其意义

目的:探讨II型糖尿病患者血糖浓度对患者肝功能及血脂指标的影响及其意义。方法:选取某三级甲等医院内分泌科已确诊为II型糖尿病患者408例,根据空腹血糖浓度(FPG)分为三组:(A组,FPG8.0 mmol/L;B组,8.0≤FPG11.0 mmol/L;C组,FPG≥11 mmol/L),检测三组患者的肝功能指标及血脂指标,进而对其肝功能损害及血脂的异常情况进行分析,其数据结果应用统计学软件SPSS 17.0处理。结果:与A组及B组相比较,C组患者肝功能损伤更为严重,表现为:肝酶显著升高(P0.05);胆红素显著升高(P0.05);球蛋白显著升高(P0.05);总胆固醇、甘油三酯水平异常(P0.05)。其结果均有统计学意义。结论:II型糖尿病患者随着其血糖浓度升高可造成肝功能损伤及血脂异常,血糖监测及控制对糖尿病患者的身体健康状况具有重要意义。     

轮状病毒感染性腹泻患儿血清CRP、心肌酶谱、肝功能的检测意义

目的:探究轮状病毒感染性腹泻患儿血清C反应蛋白(CRP)、心肌酶谱、肝功能指标的检测意义。方法:选择2014年1月~2016年5月我院收治的110例轮状病毒感染致腹泻患儿及同期收治的85例细菌感染性腹泻患儿为研究对象,另外选择20名同期于我院体检的年龄、性别相匹配的健康幼儿为对照。比较三组人群血清C反应蛋白、白介素6、肌钙蛋白(hs-c Tn T)、肌酸激酶(CK)、同工酶(CL-MB)、门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)水平的差异及轮状病毒感染致腹泻患儿外损伤的发生情况。结果:轮状病毒感染(RV)组患儿下呼吸道感染、皮疹、心肌损伤以及肝功能损伤的发生率均显著高于细菌感染组(P0.05);RV组和细菌感染组组患儿的血清CRP、IL-6水平均显著高于健康对照组,RV组患儿的上述指标显著低于细菌感染组(P0.05);RV组患者肌钙蛋白(hs-c Tn T)、肌酸激酶(CK)、同工酶(CL-MB)、门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)水平均显著高于细菌感染组及健康对照组患儿(P0.05),细菌感染组患儿上述指标与健康对照组比较,差异无统计学意义(P0.05)。结论:血清CRP、心肌酶谱、肝功能指标联合检测对于早期轮状病毒感染性腹泻与细菌感染性腹泻的鉴别诊断有一定的参考价值。     

Whole-genome association studies on alcoholism comparing different phenotypes using single-nucleotide polymorphisms and microsatellites

Alcoholism is a complex disease. As with other common diseases, genetic variants underlying alcoholism have been illusive, possibly due to the small effect from each individual susceptible variant, gene x environment and gene x gene interactions and complications in phenotype definition. We conducted association tests, the family-based association tests (FBAT) and the backward haplotype transmission association (BHTA), on the Collaborative Study of the Genetics of Alcoholism (COGA) data provided by Genetic Analysis Workshop (GAW) 14. Efron's local false discovery rate method was applied to control the proportion of false discoveries. For FBAT, we compared the results based on different types of genetic markers (single-nucleotide polymorphisms (SNPs) versus microsatellites) and different phenotype definitions (clinical diagnoses versus electrophysiological phenotypes). Significant association results were found only between SNPs and clinical diagnoses. In contrast, significant results were found only between microsatellites and electrophysiological phenotypes. In addition, we obtained the association results for SNPs and microsatellites using COGA diagnosis as phenotype based on BHTA. In this case, the results for SNPs and microsatellites are more consistent. Compared to FBAT, more significant markers are detected with BHTA.     

Association of genetic and non-genetic risk factors with the development of prostate cancer in Malaysian men

There is growing global interest to stratify men into different levels of risk to developing prostate cancer, thus it is important to identify common genetic variants that confer the risk. Although many studies have identified more than a dozen common genetic variants which are highly associated with prostate cancer, none have been done in Malaysian population. To determine the association of such variants in Malaysian men with prostate cancer, we evaluated a panel of 768 SNPs found previously associated with various cancers which also included the prostate specific SNPs in a population based case control study (51 case subjects with prostate cancer and 51 control subjects) in Malaysian men of Malay, Chinese and Indian ethnicity. We identified 21 SNPs significantly associated with prostate cancer. Among these, 12 SNPs were strongly associated with increased risk of prostate cancer while remaining nine SNPs were associated with reduced risk. However, data analysis based on ethnic stratification led to only five SNPs in Malays and 3 SNPs in Chinese which remained significant. This could be due to small sample size in each ethnic group. Significant non-genetic risk factors were also identified for their association with prostate cancer. Our study is the first to investigate the involvement of multiple variants towards susceptibility for PC in Malaysian men using genotyping approach. Identified SNPs and non-genetic risk factors have a significant association with prostate cancer.     

Variants in the HEPSIN gene are associated with prostate cancer in men of European origin

There is considerable evidence that genetic factors are involved in prostate cancer susceptibility. We have studied the association of 11 single nucleotide polymorphisms (SNPs) in the HEPSIN gene (HPN) with prostate cancer in men of European ancestry. HPN is a likely candidate in prostate cancer susceptibility, as it encodes a transmembrane cell surface serum protease, which is overexpressed in prostate cancer; HPN is also located on 19q11–q13.2, where linkage is found with prostate cancer susceptibility. In this case-control association study (590 men with histologically verified prostate cancer and 576 unrelated controls, all of European descent), we find significant allele frequency differences between cases and controls at five SNPs that are located contiguously within the gene. A major 11-locus haplotype is significantly associated, which provides further support that HPN is a potentially important candidate gene involved in prostate cancer susceptibility. Association of one of the SNPs with Gleason score is also suggestive of a plausible role of HPN in tumor aggressiveness.     

Haplotype association analysis of AGT variants with hypertension-related traits: the HyperGEN study

OBJECTIVE: Function of the renin-angiotensin system is important to human hypertension, but its genetic etiology remains elusive. We set out to examine a hypothesis that multiple genetic variants in the system act together in blood pressure regulation, via intermediate phenotypes such as blood pressure reactivity. METHODS: A sample of 531 hypertensive cases and 417 controls was selected from the HyperGEN study. Hypertension-related traits including blood pressure responses to challenges to math test, handgrip and postural change (mathBP, gripBP, and postBP), and body mass index (BMI) were analyzed for association with 10 single nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT) gene. Single-marker and haplotype analyses were performed to examine the effects of both individual and multiple variants. Multiple-trait profiling was used to assess interaction of latent intermediate factors with susceptible haplotypes. RESULTS: In Blacks, two SNPs in exon 5 and 3'UTR showed significant association with gripBP, and two promoter SNPs were strongly associated with postBP. In Whites, only borderline association was found for 2 promoter SNPs with mathBP. Haplotype analyses in Blacks confirmed association with gripBP, and detected significant association of a haplotype to BMI (p=0.029). With the interactions modeled, haplotype associations found in Blacks remain significant, while significant associations to BMI (p=0.009) and gripSBP emerged in Whites. CONCLUSION: Genetic variants in regulatory regions of AGT showed strong association with blood pressure reactivity. Interaction of promoter and genic SNPs in AGT revealed collective action of multiple variants on blood pressure reactivity and BMI both in Blacks and in Whites, possibly following different pathways.     

Analysis of VEGF gene polymorphisms and serum VEGF protein levels contribution in polycystic ovary syndrome of patients

Vascular endothelial growth factor (VEGF) is a well-known factor in reproductive function and contributes to the pathogenesis of polycystic ovary syndrome (PCOS). Genetic variations in VEGFA gene were suggested to contribute alterations in VEGF secretion and PCOS. This study evaluated the association of VEGFA SNPs with altered VEGF secretion level and PCOS among ethnically-matched control women. This prospective case–control study was conducted from 2016 to 2018 and comprised of 55 women with PCOS and 52 control subjects. ELISA was used to measure VEGF levels; and various other related bio chemicals whereas the genotyping of VEGFA variants was performed through the analysis of nine SNPs of VEGF. PRL, E2, PRGE testosterone and glucose level were found to be insignificantly different. The levels of FSH, LH, LH/FSH, TT, insulin, SHBG and HOMA-IR were significantly higher in the study group. Among the nine tested variants of VEGF SNPs, two SNPs rs3025020 and rs833061, consisted of TT (Recessive and Dominant homozygous, respectively) which were marginally higher in test. The SNP rs1570360 had significantly higher GG allele (32.73%) which was recessive homozygous. There was no significant difference observed in genotype frequencies related to higher value of VEGF. The genotype frequencies for the studied SNPs were in alignment with Hardy–Weinberg equilibrium (HWE). The mean serum VEGF levels got significantly increased in PCOS group. No significant association was found between VEGF genotypes and its serum levels. VEGF levels in rs699947 (AA-major homozygous), rs3025039 (CC-major homozygous) and rs833061 (TT & CC-major & minor homozygous) genotypes were significantly higher in PCOS. The study results evidently proved that the allelic variants in genes may be a factor for PCOS and VEGF serum levels with respect to few SNP variants only. These findings indicated that VEGF may be involved in PCOS status and confirmed the previous association between genetic variants in VEGF, serum level of VEGF protein and PCOS.

     

Epidemiology and Genetic Epidemiology of the Liver Function Test Proteins

Background

The liver function test (LFT) is among the most commonly used clinical investigations to assess hepatic function, severity of liver diseases and the effect of therapies, as well as to detect drug-induced liver injury (DILI).

Aims

To determine the relative contribution of genetic and environmental factors as well as test and quantify the effects of sex, age, BMI and alcohol consumption to variation in liver function test proteins - including alanine amino transaminase (ALT), Albumin, gamma glutamyl transpeptidase (GGT), total bilirubin, total protein, total globulin, aspartate transaminase (AST), and alkaline phosphotase (ALP) - using the classical twin model.

Methods

Blood samples were collected from a total of 5380 twin pairs from the TwinsUK registry. We measured the expression levels of major proteins associated with the LFT, calculated BMI from measured weight and height and questionnaires were completed for alcohol consumption by the twins. The relative contribution of genetic and environmental factors to variation in the LFT proteins was assessed and quantified using a variance components model fitting approach.

Results

Our results show that (1) variation in all the LFTs has a significant heritable basis (h² ranging from 20% to 77%); (2) other than GGT, the LFTs are all affected to some extent by common environmental factors (c² ranging from 24% to 54%); and (3) a small but significant proportion of the variation in the LFTs was due to confounding effects of age, sex, BMI, and alcohol use.

Conclusions

Variation in the LFT proteins is under significant genetic and common environmental control although sex, alcohol use, age and BMI also contribute significantly to inter-individual variation in the LFT proteins. Understanding the underlying genetic contribution of liver function tests may help the interpretation of their results and explain wide variation among individuals.     

Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia

Many common diseases are accompanied by disturbances in biochemical traits. Identifying the genetic determinants could provide novel insights into disease mechanisms and reveal avenues for developing new therapies. Here, we report a genome-wide association analysis for commonly measured serum and urine biochemical traits. As part of the WTCCC, 500,000 SNPs genome wide were genotyped in 1955 hypertensive individuals characterized for 25 serum and urine biochemical traits. For each trait, we assessed association with individual SNPs, adjusting for age, sex, and BMI. Lipid measurements were further examined in a meta-analysis of genome-wide data from a type 2 diabetes scan. The most promising associations were examined in two epidemiological cohorts. We discovered association between serum urate and SLC2A9, a glucose transporter (p = 2 x 10(-15)) and confirmed this in two independent cohorts, GRAPHIC study (p = 9 x 10(-15)) and TwinsUK (p = 8 x 10(-19)). The odds ratio for hyperuricaemia (defined as urate >0.4 mMol/l) is 1.89 (95% CI = 1.36-2.61) per copy of common allele. We also replicated many genes previously associated with serum lipids and found previously recognized association between LDL levels and SNPs close to genes encoding PSRC1 and CELSR2 (p = 1 x 10(-7)). The common allele was associated with a 6% increase in nonfasting serum LDL. This region showed increased association in the meta-analysis (p = 4 x 10(-14)). This finding provides a potential biological mechanism for the recent association of this same allele of the same SNP with increased risk of coronary disease.     

Association of variations in TPH1 and HTR2B with gestational weight gain and measures of obesity

Serotonin is involved in appetite regulation and energy homeostasis. Recently, it has been reported that 5-hydroxytryptamine receptor 2B (Htr2b) and tryptophan hydroxylase 1 (Tph1) play major role in β-cell proliferation in mouse during pregnancy. We investigated the genetic association of HTR2B and TPH1 with risk of gestational diabetes mellitus (GDM) and measures of obesity, in 869 Korean GDM women and carefully selected 632 nondiabetic control subjects. Six single-nucleotide polymorphisms (SNPs) in HTR2B and ten SNPs in TPH1 were selected for genotyping according to their tagging status. Genetic variants in HTR2B and TPH1 were not associated with the risk of GDM. In GDM women, SNPs of TPH1 were significantly associated with weight gain during pregnancy. In nondiabetic controls, SNPs of TPH1 were associated with waist circumference and BMI. We also found that a variant of TPH1 (rs623580) was associated with BMI in a genome-wide association study comprised of 8,842 subjects. Although genetic variants in HTR2B and TPH1 were not associated with risk of GDM, we found significant association of these variants with measures of obesity. However, further replication studies in a different population are required to confirm our findings.     

The Association of Adiponectin Gene Promoter Variations with Non-Small Cell Lung Cancer in a Han Chinese Population

Recently, in vitro studies have demonstrated that adiponectin has antiangiogenic and tumor growth-limiting properties. Additionally, serum adiponectin levels have been associated with the risk of several cancers; specifically, serum adiponectin was significantly lower in lung cancer patients with advanced-stage disease. In this study, we examined the association of adiponectin gene promoter variations associated with adiponectin gene expression and plasma levels in non-small cell lung cancer (NSCLC) in a Han Chinese population. A total of 319 patients with NSCLC and 489 healthy individuals were recruited to evaluate the association of four adiponectin gene promoter single-nucleotide polymorphisms (SNPs) (SNP-12140G>A, SNP-11426A>G, SNP-11391G>A and SNP-11377C>G) with NSCLS risk. Additionally, we constructed haplotypes of these four SNPs and evaluated the association of these haplotypes with NSCLS risk. Our results showed that among these four SNPs, only SNP-12140G>A was associated with NSCLC risk(P<0.05). The haplotype analysis showed that no haplotype was associated with NSCLC after performing a Bonferroni correction (P>0.05). Additionally, an association analysis of the four SNPs stratified into pathologic stages I+II and III+IV showed that these SNPs did not exhibit significant differences between pathologic stages I+II and III+IV. Moreover, we did not observe any differences in allele and genotype frequency for these SNPs between adenocarcinoma and squamous cell carcinoma. Our results indicated that the G allele of SNP-12140may be a risk factor for NSCLC (OR = 1.516; 95% CI: 1.098–2.094) in this Han Chinese population.