目的   研究非酒精性脂肪肝老年人体质辨识及中医治未病服务对其治疗效果。方法   选择2023年1月—2024年1月贵州中医药大学第一附属医院就诊的非酒精性脂肪性肝病老年患者70例作为研究对象，根据患者就诊顺序分配为两组。对照组35例，接受常规干预；观察组35例，其在对照组基础上予中医“治未病”理念下体质辨识干预模式。比较两组干预效果，以及干预前后血脂水平、肝功能、生存质量的变化。结果   观察组的治疗总有效率91.43%，高于对照组的68.57%，差异有统计学意义（P＜0.05）。治疗前，两组各项血脂水平、肝功能、慢性肝病问卷（CLDQ）评分比较，差异无统计学意义（P＞0.05）；治疗后，两组各项血脂水平优于治疗前，各项肝功能低于治疗前，CLDQ评分高于治疗前，差异有统计学意义（P＜0.05）；治疗后，观察组的各项血脂水平优于对照组，各项肝功能低于对照组，CLDQ评分高于对照组，差异有统计学意义（P＜0.05）。结论   对非酒精性脂肪性肝病老年患者而言，中医“治未病”理念下体质辨识干预服务能够提高其治疗效果，调节血脂水平的异常，改善肝功能及生存质量，值得应用。

       Objective  To study the physical identification of nonalcoholic fatty liver in the elderly and the therapeutic effect of traditional Chinese medicine on preventing disease before arising．Methods  A total of 70 elderly patients with nonalcoholic fatty liver disease treated in the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from January 2023 to January 2024 were selected as the study objects．Patients were assigned to two groups，control group（35 cases）received  routine intervention，observation group（35 cases）received physical identification intervention based on preventing disease before arising of traditional Chinese medicine additionally．The effect of intervention and the changes of blood lipid levels，liver function and quality of life before and after intervention were compared between the two groups．Results  The total effective rate of the observation group was 91.43%，higher than that of the control group（68.57%），the difference was statistically significant（P＜0.05）．Before treatment，there were no significant differences in blood lipid levels，liver function and CLDQ scores between the two groups（P＞0.05）．After treatment，the levels of blood lipids were better than those before treatment，liver function was lower than that before treatment，CLDQ score was higher than that before treatment，the difference was statistically significant（P＜0.05）．After treatment，the blood lipid levels of the observation group was better than that of the control group，the liver function was lower than that of the control group，and the CLDQ score was higher than that of the control group，with statistical significance（P＜0.05）．Conclusions  For elderly patients with nonalcoholic fatty liver disease，the intervention service of body constitution identification under the concept of preventing disease before arising of traditional Chinese medicine can improve the therapeutic effect，regulate the abnormal blood lipid levels，improve liver function and quality of life，which is worthy of application．

非酒精性脂肪性肝病(NAFLD)是世界范围内慢性肝病的一个主要原因,约15%的NAFLD患者会发展为非酒精性脂肪性肝炎、肝纤维化、肝硬化甚至肝癌。目前其发病及进展机制尚未明确,也无有效治疗手段。因此,构建临床前NAFLD动物模型至关重要,有助于为NAFLD提供临床治疗的新方案。本文将系统分析目前已构建的NAFLD动物模型在临床前研究中的局限性,并重点总结和综述基于基因编辑在NAFLD动物模型构建中的应用及研究进展,这对于探讨NAFLD发病机制及新药研发具有重要的临床意义。

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, and about 15% of NAFLD patients will develop into nonalcoholic steatohepatitis, hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. However, the biological mechanism of the pathogenesis and progression of NAFLD is not fully understood, and there are still no effective or targeted therapies for NAFLD. Therefore, it is an urgent need to construct pre-clinical animal models of NAFLD, which will help to better understand and explore the potential therapeutic strategy in the treatment of NAFLD. Here, we summarize the recent advances and limitations of the established animal models of NAFLD and focus on the potential application and research progress of genome editing for constructing the animal models of NAFLD. There animal models will be very useful to reveal the pathologic mechanism of human NAFLD, and to screen new therapeutic drugs.

目的 探讨非酒精性脂肪肝患者昼夜节律特点并分析昼夜节律与非酒精性脂肪肝的相关性。方法 选取2017年12月—2018年12月我院门诊部及住院部非酒精性脂肪肝患者60例作为观察组,对照组抽取门诊体检正常人群60例。通过使用本院自制个人一般资料调查表、睡眠节律清晨型与夜晚型量表(MEQ)以及智能手环检测两组纳入对象的昼夜节律(饮食方式、饮食时间、活动节律、体重指数、睡眠节律等)。对比分析两组患者昼夜节律特点并分析其与非酒精性脂肪肝的相关性。结果 非酒精性脂肪肝患者在BMI、睡眠绝对夜晚型、睡眠中度夜晚型、日均运动量小于30 min、睡眠时间紊乱、睡眠时长以及深度睡眠时间等方面与对照组患者比较差异有统计学意义(P＜0.05);以非酒精性脂肪肝为应变量,以昼夜节律为自变量进行回归分析发现性别、年龄、工作性质、BMI、睡眠节律、身体锻炼、睡眠时长、深度睡眠时长与非酒精性脂肪肝呈现正相关且差异有统计学意义(OR＞1,P＜0.01)。结论 非酒精性脂肪肝患者昼夜节律一般存在失眠熬夜、睡眠时间不规律、少运动、身形丰满等特点,引发非酒精性脂肪肝相关因素包括BMI、睡眠节律、运动节律、职业性质、年龄、性别、睡眠质量等,临床上可尝试对非酒精性脂肪肝患者进行昼夜节律干预治疗,改善预后。

Objective To explore the characteristics of circadian rhythm in patients with nonalcoholic fatty liver disease(NAFLD) and to analyze the correlation between circadian rhythm and NAFLD. Methods From December 2017 to December 2018,60 patients with NAFLD in outpatient department and inpatient department of our hospital were selected as observation group,while 60 normal people were selected as control group.The circadian rhythm (dietary pattern,dietary time,activity rhythm,body mass index,sleep rhythm) of the subjects in the two groups were measured by self-made personal data questionnaire,MEQ and smart bracelet.The circadian rhythm characteristics of two groups were compared and the correlation between circadian rhythm and NAFLD was analyzed. Results There were significant differences in BMI,absolute night sleep,moderate night sleep,daily average exercise less than 30 minutes,sleep disturbance,sleep duration and deep sleep time between the patients with NAFLD and the control group (P<0.05). NAFLD was used as dependent variable and circadian rhythm as independent variable. Logistic regression analysis showed that gender,age,nature of work,BMI,sleep rhythm,physical exercise,sleep duration and deep sleep time were positively correlated with fatty liver (OR>1,P<0.01). Conclusion The circadian rhythm of NAFLD patients generally has the characteristics of insomnia,staying up late,irregular sleep time,less exercise and plump figure.The related factors causing NAFLD include BMI,sleep rhythm,motor rhythm,occupational nature,age,gender and sleep quality.In clinic,circadian rhythm intervention therapy may improve the prognosis of patients with NAFLD.

目的 通过生物信息分析途径,从分子水平揭示非酒精性脂肪性肝病（NAFLD）的发病发展机制,为NAFLD研究提供新的思路。方法 从公共数据库GEO中下载NAFLD相关的基因芯片数据GSE48452,利用Transcriptome Analysis Console软件筛选差异表达基因,FunRich软件和STRING在线分析工具对差异基因进行下一步的生物信息学分析。结果 正常组与NAFLD组差异基因52个,正常组与非酒精性脂肪性肝炎（NASH）基因64个,共同差异基因15个。这些差异表达基因参与脂质转运、胆汁酸合成、脂质和脂蛋白代谢、生物氧化等过程。通过通路分析及蛋白质相互作用分析进一步筛选出与NAFLD发病发展密切相关的18个差异表达基因。结论 通过生物信息学分析筛选出MSN、CDC45、ANXA5、PIK3CG和DTL基因可能为研究乃至阻断NAFLD发展进程的重要靶点,需进一步验证。

Objective To explore the molecular mechanism of nonalcoholic fatty liver disease （NAFLD） with bioinformatics analysis. Methods The microarray data of NAFLD were downloaded from the Gene Expression Omnibus （GEO） database and analyzed using Transcriptome Analysis Console （TAC） for screening differentially expressed genes. The further analysis of differentially expressed genes was conducted by FunRich software and the online tool STRING. Results For the comparison of control group vs. NAFLD group,52 genes have differentially expressed,while control groups vs. nonalcoholic steatohepatitis （NASH） group,64 genes have differentially expressed. 15 differentially expressed genes were found in both comparisons. These genes were involved in the biological pathway of lipid transport,bile acid biosynthesis,metabolism of lipids and lipoproteins and biological oxidations. With biological pathway analysis and protein-protein interaction analysis,18 differentially expressed genes were found closely associated with the progression of NAFLD. Conclusion MSN、CDC45、ANXA5、PIK3CG and DTL may be the important target for study the progression of NAFLD,which needs a further study to confirm.