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.

人类疾病的发生发展是环境因素与遗传学因素相互作用的结果。环境有害暴露导致的机体功能紊乱和疾病发生,与细胞内环状RNA(circRNA)的表达异常有密切关系,circRNA的功能和作用是医学研究的热点领域。circRNA是表观遗传学的一类具有环状结构的RNA分子,由于其特殊的结构和复杂的功能,在调控疾病发生和病理过程中承担着重要角色。本文系统地介绍了circRNA的来源、功能,结合作者课题组的研究成就,综述了circRNA在环境有害暴露相关疾病中的作用和机制,探讨了circRNA作为潜在生物标志物在研究中所面临的挑战。

The development of human diseases is the result of the interaction between environmental and genetic factor. Abnormal expression of cellular circular RNA (circRNA) is closely related to function disorders and diseases caused by environmental exposure. The function of circRNA is a research focus in medical science. CircRNA is the epigenetic molecular with circular structure. Because of its special structure and complex function, it plays an important role in the regulation of disease occurrence and pathological process. In this paper, the origin and functions of circRNA are systematically described. Combined with the achievements of the author's research group, the functions and mechanism of environmental exposure related diseases were reviewed. And the challenges of circRNA as a potential biomarker in research were discussed.

分泌性中耳炎（SOM）的临床特征表现为听力下降和中耳积液,与中耳化脓性炎症常伴随耳部急性感染不同,SOM常伴随耳部闷胀、轻微耳痛等,致使听力出现障碍。SOM发病机制较为复杂,可能与感染、免疫、咽鼓管功能障碍等多种因素相关,治疗方法也因此呈现出多样化的特点。本文就SOM的病因病机及其治疗方式展开综述,以期为临床及早诊断和治疗SOM提供理论依据。

The clinical characteristics of secretory otitis media（SOM）are hearing loss and effusion in the middle ear．Different from acute ear infection of suppurative inflammation in the middle ear,SOM is often accompanied by ear tightness and mild earache,resulting in hearing impairment．The pathogenesis of SOM is complex,which may be related to infection,immunity,eustachian tube dysfunction and other factors．Therefore,the treatment methods are diversified．This paper reviews the etiology,pathogenesis and treatment of SOM,in order to provide theoretical basis for clinical early diagnosis and treatment of SOM.

新生儿引起肝内胆汁淤积是由感染、遗传代谢性疾病、胃肠外营养、基因突变等各种不同病因导致胆汁形成、分泌和排泄障碍。胆汁在体内淤积会影响新生儿的生长发育,严重者出现肝纤维化、肝功能衰竭等不可逆的改变,其发病的机制涉及参与肝脏胆汁酸分泌的各种转运体、肝细胞膜转运蛋白转录和和转录后的调控等。本文归纳总结近年来国内外关于胆汁酸转运体及其转录和转录后的调控,从而为此疾病的防治提供理论依据,为将来降低其发生率和改善预后。

Neonatal intrahepatic cholestasis is caused by infection,genetic metabolic diseases,parenteral nutrition,gene mutation and other different causes leading to bile formation,secretion and excretion disorders．Bile stasis in the body will affect the growth and development of the newborn,and in severe cases,irreversible changes such as liver fibrosis and liver failure will occur．The pathogenesis of bile stasis involves various transporters involved in the secretion of bile acids in the liver,transcription and post transcription regulation of liver cell membrane transporters．In this paper,we summarized the recent studies on bile acid transporters and their transcriptional and post transcriptional regulation at home and abroad,so as to provide a theoretical basis for the prevention and treatment of this disease,and to reduce its incidence and improve its prognosis in the future.

目的 探讨噻托溴铵/奥达特罗对C、D组慢性阻塞性肺疾病（COPD）稳定期患者的临床治疗效果。方法 选取2021年1月—2021年10月期间本院收治的C、D 组COPD稳定期患者70例,按照随机数字表达均分为研究组（35例）和对照组（35例）。研究组给予噻托溴铵/奥达特罗雾化吸入治疗,对照组采取规律吸入布地奈德/福莫特罗粉治疗。均持续6个月治疗。比较2组一般资料、治疗前后肺功能指标、住院时间、mMRC评分、CAT评分、急性发作和糖皮质激素使用时间,以及不良反应。结果 治疗6个月后,研究组的肺功能指标包括第1秒用力呼气容积（FEV₁）、FEV1%预计值（FEV₁%pred）、用力肺活量（FVC）以及FEV₁/ FVC比值相比对照组均改善（均P< 0.05）。且相比对照组,研究组患者住院时间更短、治疗后mMRC评分和CAT评分更低、急性发作和糖皮质激素使用时间>30 d的例数更少（均P< 0.05）。此外,研究组患者治疗期间口干、恶心/呕吐、声音嘶哑和口腔感染的不良反应总发生率相比对照组更低。结论 噻托溴铵/奥达特罗能有效改善C、D 组COPD稳定期患者肺功能和临床症状,缩短住院时间和激素使用时间,减少急性发作和不良反应发生率,降低患者的治疗费用。

目的 观察阶梯式呼吸管理策略在改善感染性休克伴急性肺损伤（ALI）患者中的价值。方法 纳入我院2019年1月—2020年12月收治的感染性休克伴ALI患者共146例为研究对象,数字表法随机分为观察组（73例）与对照组（73例）。对照组常规护理方案,观察组阶梯式呼吸管理,对比干预前后患者心肺功能的差异。结果 观察组平均动脉压、PaCO₂水平低于对照组,心脏指数、中心静脉压、血管外肺水指数、PaO₂与氧合指数高于对照组（P<0.05）;观察组复苏成功率与临床总有效率高于对照组,复苏时间与呼吸平稳时间低于对照组（P<0.05）;观察组气管切开率、有创呼吸机使用率及呼吸机相关性肺炎与气道并发症发生率均低于对照组（P<0.05）。结论 感染性休克并急性肺损伤患者建立阶梯化呼吸管理策略能够显著改善患者的心肺功能,提高临床复苏效果,降低相关并发症风险。

Objective To observe the value of stepwise respiratory management strategy in improving patients with septic shock and acute lung injury（ALI）．Methods A total of 146 patients with septic shock and ALI treated in our hospital from January 2019 to December 2020 were included as the research objects．They were randomly divided into observation group（73 cases）and control group（73 cases）by digital table method．The control group received routine nursing plan,and the observation group received stepwise respiratory management．The differences of cardiopulmonary function before and after the intervention were compared．Results The levels of mean arterial pressure,PaCO₂ in the observation group were significantly lower than those in the control group,cardiac index,central venous pressure,extravascular lung water index,PaO₂ and oxygenation index in the observation group were significantly higher than those in the control group（P<0.05）．The success rate of resuscitation and total clinical effective rate in the observation group were significantly higher than those in the control group,and the resuscitation time and respiratory stability time in the observation group were significantly shorter than those in the control group（P<0.05）．The tracheotomy rate,the rate of using invasive ventilator and the incidence of ventilator associated pneumonia and airway complications in the observation group were lower than those in the control group（P<0.05）．Conclusions The establishment of stepwise respiratory management strategy in patients with septic shock and ALI can significantly improve their cardiopulmonary function,improve the effect of clinical resuscitation and reduce the risk of related complications.

目的 了解并分析白云区不同年龄段男性精液质量现状。方法 选取2020年1月—2021年12月在我中心就诊的已婚孕前体检男性为研究对象,开展常规精液检测,采集精液标本进行分析。结果 白云区育龄男性精液各项指标均在正常范围仅有3 176例（占比57.52%）,随年龄的增加,精液指标总活力、存活率和精子前向运动指标逐渐降低（P<0.05）。结论 26~30岁年龄段男性的精液质量各项指标正常率较其他年龄组更好（P<0.05）,是男性生育的黄金年龄。

Objective To understand and analyze the status of semen quality in men of different ages in Baiyun District of Guangzhou. Methods From January 2020 to December 2021,married men who received pre-pregnant physical examination in our center were selected as the research subjects．Routine semen testing was conducted,and samples were collected for semen analysis. Results Only 3176 cases（57.52%）of male semen data of childbearing age in Baiyun District were within the normal range．With the increase of age,total semen motility,survival rate and sperm forward motility decreased gradually（P < 0.05）. Conclusions Men in the age group of 26-30 years had higher normal rates of all indicators of semen quality than other age groups（P < 0.05）,which is the golden age of male fertility.

目的 了解广州市白云区医护人员对艾滋病感染者/患者（PLWHA）的歧视态度情况,分析其影响因素,并为降低医护人员对PLWHA的歧视态度提供建议。方法 以Lau等设计的AIDS歧视态度量表和张燕等研制的医护人员对PLWHA治疗意愿量表为主设计的调查问卷,对广州市白云区的医护人员进行随机抽样调查,对结果进行描述,研究两量表得分与HIV知识水平的相关性。结果 广州市白云区7家医疗机构并接受培训议会的医护人员AIDS歧视态度量表和治疗意愿量表平均得分分别为（46.66±10.23）分和（32.74±5.89）分,医护人员性别和接受HIV培训的AIDS歧视量表得分存在统计学差异（P<0.01）,单位、性别和接受HIV培训与否的治疗意愿量表得分存在统计学差异（P<0.05）;HIV知识水平与AIDS歧视量表得分和治疗意愿量表得分存在相关性,相关系数值r_s分别为-0.301（P<0.001）和-0.219（P<0.001）。结论 广州市白云区医护人员的性别、接受培训与否和HIV知识水平对AIDS歧视量表和治疗意愿量表得分均有影响。应加强白云区医护人员的艾滋病知识培训和各人群的权益保护,以降低医护人员对PLWHA的歧视态度。

Objective To understand the discriminatory attitudes of medical staff to people living with HIV/AIDS（PLWHA）in Guangzhou Baiyun District,analyze the influencing factors,and provide suggestions for reducing the discriminatory attitudes of medical staff to PLWHA．Methods Based on Lau's AIDS Discrimination Attitude Scale and Zhang Yan's Medical Personnel's Adjustment Questionnaire for PLWHA Treatment Willingness Scale,the questionnaire was designed to do a random sampling survey among medical personnel in Guangzhou Baiyun District,and the results were described by regression analysis,to study the correlation between the scores of the two scales and the level of HIV knowledge．Results The average scores of AIDS Discrimination Attitude Scale and Treatment Willingness Scale of medical staff in 7 medical institutions with training in Guangzhou Baiyun District were（46.66±10.23）and（32.74±5.89）respectively．There were statistical differences in AIDS discrimination scale scores of medical staff's gender and whether they received training or not（P< 0.01）,and there were statistical differences in Treatment Willingness Scale scores among institutions,gender and whether they received training or not（P< 0.05）．HIV knowledge level was correlated with the scores of AIDS Discrimination Scale and Treatment Willingness Scale,and the correlation coefficients were -0.301（P < 0.001）and -0.219（P < 0.001）．Conclusions Gender,training or not,and HIV knowledge level of medical staff in this area have an impact on the scores of the AIDS Discrimination Scale and the Treatment Willingness Scale．In order to reduce the discriminatory attitude of medical staff towards PLWHA,the AIDS knowledge and the protection of rights and interests of all groups should be strengthened.

目的 探讨容积调强（VMAT）在全脊柱骨多发转移瘤放疗中的运用,观察疗效及安全性。方法 选取 2018年1月—2021年1月本科室收治的50例全脊柱骨多发转移瘤姑息止痛放疗的临床资料,分别对全脊柱靶区设计适形放疗（CRT）和VMAT多中心计划,运用剂量体积直方图及所对应的统计表评估靶区及危及器官剂量覆盖情况,放疗结束后通过1-8周视觉模拟评分法评价近期疗效,每3个月复查全脊柱MRI观察放疗不良反应。结果 采用VMAT技术放疗靶区剂量覆盖度、靶区适形指数和剂量均匀指数均优于CRT技术（P<0.01）,照射野重叠区未见明显剂量热点和冷点。采用VMAT技术危及器官V5 Gy受照体积高于CRT（P<0.01）,除了胃、胰腺和小肠,危及器官V10 Gy受照体积高于CRT（P<0.01或P<0.05）,危及器官V20 Gy受照体积则低于CRT（P<0.01）,除了肾,危及器官V30 Gy受照体积也低于CRT（P<0.01）。采用VMAT技术时危及器官的最大受照量低于CRT（P<0.01或P<0.05）,但除了心脏、胰腺和小肠,VMAT技术的危及器官平均受照量高于CRT（P<0.01或P<0.05）。采用VMAT技术较CRT出束时间增加（P<0.01）,采用CRT时技师摆位时间较VMAT增加（P<0.05）,对于总治疗时间VMAT较CRT增加（P<0.01）。8周后评估疼痛完全缓解16例,部分缓解 22例,轻度缓解8例,无效4例,总有效率为76%。随访日期截至2021年 12月,所有配合随诊的患者3、6、9、12个月全脊柱MRI复查结果显示,VMAT技术照射野内重叠处均未见脊髓及其他组织急慢性损伤情况。结论 VMAT技术对长靶区多中心放疗剂量分布均匀,近期疗效显著,安全性良好。

Objective To investigate the application of volumetric modulated arc therapy（VMAT） in the radiotherapy for multiple bone metastases in the whole spine,and observe of efficacy and evaluation of safety．Methods The clinical data were selected from 50 patients who were treated in our department between January 2018 and January 2021 with palliative analgesic radiotherapy for multiple metastases of the whole spine．Conformal radiotherapy（CRT）and multicenter VMAT plans were respectively applied to target areas of whole spine,and dose volume histogram was used to evaluate the dose coverage of target area and organ at risk（OAR）. After radiotherapy,the short-term efficacy was evaluated by visual analog scale in between 1-8 weeks,and the whole spine MRI was reviewed every 3 months to observe the adverse reactions of radiotherapy．Results The dose coverage,target conformality index and homogeneity index of VMAT treatment were significantly better than those of CRT treatment（P<0.01）,and no obvious dose hotspots and cold spots were observed in the overlapping area of irradiation field. When VMAT treatment was applied,the exposure volume of V5 Gy in OAR was significantly higher when compared with CRT treatment（P<0.01）．Except for stomach,pancreas and small intestine,the exposure volume of V10 Gy in OAR was significantly higher for VMAT treatment when compared with CRT treatment （P<0.01 or P<0.05）．When VMAT treatment was applied,the exposure volume of V20 Gy in OAR was significantly lower when compared with CRT treatment（P<0.01）,and except for kidney,the exposure volume of V30 Gy in OAR was significantly lower when compared with CRT treatment（P<0.01）．When VMAT treatment was applied,the maximum exposure of OAR was significantly lower than that of CRT（P<0.01 or P<0.05）,however,except for the heart,pancreas and small intestine,the average exposure of VMAT treatment to OAR was higher than that of CRT （P<0.01 or P<0.05）．Compared with CRT,VMAT treatment had significantly increased beam-out time（P<0.01）,the therapist setting time of CRT was increased when compared with that of VMAT（P<0.05）,and the total treatment time of VMAT was increased when compared with that of CRT（P<0.01）. In the assessment 8 weeks after the treatments,16 patients had complete pain relief,22 had partial relief,8 had mild relief,and 4 had no effect,which total effective rate was 76%．The follow-up was ended in December 2021．There was no acute or chronic injury to the spinal cord and other tissues in the overlapping areas of the irradiation fields observed for all follow-up patients in the 3rd,6th,9th and 12th month whole-spine MRI re-examination．Conclusions VMAT has uniform dose distribution in multi-center radiotherapy for long target areas,with significant short-term efficacy and safety.