乙肝肝纤维化是由于乙肝病毒感染造成肝细胞发生凋亡或坏死,刺激肝星状细胞使之活化成为肌成纤维细胞,产生大量细胞外基质(extracellularmatrix,ECM),随着ECM的不断累积形成瘢痕组织沉积在肝组织内逐渐替代肝实质的过程.目前针对肝纤维化的发病机制尚缺乏积极有效的化学或生物药物.导师胡世平教授从事中医药防治慢性乙肝相关性疾病三十余年,积累了丰富的临床经验,在乙肝肝纤维化治疗的实践中形成了独特的诊疗思路,导师认为邪毒壅滞是乙肝肝纤维化发病的主要病机,而致病的内在因素为正气亏虚,治疗中应祛除湿热疫毒、气滞血瘀等邪气以"推陈",通过扶助正气包括调补肝气、补益脾气、滋阴养血以致新,即基于推陈致新以达到人体阴阳平和,气血津液等精微物质自生的生理状态,从而延缓、逆转肝纤维化进程.

Chronic hepatitis B is lingering and difficult to heal, and some patients are prone to secondary depression, which makes the condition more complicated.Based on the theory of liver storing blood and blood housing mood in emotional diseases and its pathological manifestations, this article believes that the core pathogenesis of depression secondary to chronic hepatitis B is liver blood deficiency, which causes the failure of blood in nourishing the soul and eventually causes the disharmony between the liver and the soul.In the clinical treatment of the patients with chronic hepatitis B,the Chinese medicines for nourishing liver, tonifying kidney, invigorating spleen, and tranquilizing mind can be used to prevent depression, thereby achieving prevention before disease onset and controlling development of existing disease.

Chronic hepatitis B(CHB)is still a malignant infectious disease that seriously threatens human health,and currently nucleos(t)ide analogues and interferon are the main treatment methods for CHB,but they cannot achieve functional cure.The development and progression of CHB are closely associated with immune function dysregulation in the host,and therefore,regulating host immunity has become a key link in the treatment of CHB.Recent studies have shown that traditional Chinese medicine exerts a therapeutic effect on CHB by regulating host immune function.This article introduces the relationship between traditional Chinese medicine theory and immunity and summarizes the theoretical basis and related studies for traditional Chinese medicine in the immune regulation of CHB,in order to provide new ideas for integrated traditional Chinese and Western medicine therapy for CHB.

目的:对安络化纤丸联合核苷类药物治疗乙型肝炎肝纤维化系统评价或Meta分析进行再评价.方法:检索中国知网(CNKI)、万方(Wanfang)、维普(VIP)、中国生物医学文献服务系统(SinoMed)、PubMed、Embase和Cochrane Library等数据库,检索时间为建库起至2022年7月,搜索安络化纤丸联合核苷类药物治疗乙型肝炎肝纤维化的系统评价或Meta分析.依照纳入和排除标准,由2 名研究人员独立筛选文献并提取文献资料,应用AMSTAR2 量表、PRISMA声明和GRADE分级系统对纳入文献的报告质量、方法学质量和证据级别进行再评价.结果:最终纳入8 篇系统评价或Meta分析文献,均为中文文献,发表时间为2015～2022年.8篇文献的AMSTAR2 评价结果均为极低质量;PRISMA 评分15.5～19.5 分,提示所纳入文献的报告有一定缺陷.评价的8 篇文献中共纳入安络化纤丸联合核苷类药物治疗慢性乙型肝炎肝纤维化患者的 65 项结局指标,其中:HA 8 项、LN 8 项、PC-Ⅲ 8 项、Ⅳ-C 8项、ALT 7 项、TBil 5 项、门静脉内径5 项、脾脏厚度5 项、AST 4 项、HBV DNA转阴率4 项、凝血酶原活动度1 项、白蛋白2 项.包括中等质量证据2 项,低质量证据12 项,极低质量证据51 项.结论:现有的证据表明安络化纤丸联合核苷酸类药物治疗乙型肝炎肝纤维化在改善患者HA、LN、PC-Ⅲ、Ⅳ-C等结局指标方面要优于对照组,但所纳入文献的方法学质量、文献质量和证据质量均偏低,需要提高系统评价或Meta分析的质量,从而为中医药治疗疾病提供高质量的循证医学证据.

目的:观察王琦教授自拟化痰祛湿方(薏脂颗粒)和益气健运方(茯元颗粒)对泡沫细胞脂质的影响,并探索其自噬机制.方法:培养RAW264.7细胞,用氧化低密度脂蛋白(ox-LDL)构建泡沫细胞模型.通过cell titer-blue法进行细胞活力测定,通过油红O染色法检测细胞脂质含量,通过蛋白质印迹法检测CD36和轻链3蛋白表达,用自噬蛋白芯片进一步研究两方对泡沫细胞自噬的影响.结果:油红O染色结果显示,ox-LDL模型组细胞脂质含量升高,泡沫细胞造模成功.两方干预后,细胞脂质含量降低.蛋白质印迹法结果显示:两方干预后CD36表达均升高,化痰祛湿方50 ng/μL组和益气健运方50 ng/μL、100 ng/μL组轻链3Ⅱ/轻链3Ⅰ水平升高.自噬芯片结果显示:与空白对照组比较,ox-LDL模型组P62升高.与ox-LDL模型组比较,化痰祛湿方组P62下降,自噬相关蛋白10上调,益气健运方组的自噬相关蛋白10、自噬相关蛋白12、自噬相关蛋白4A上调.结论:两方均可降低泡沫细胞脂质含量,可能是通过增强巨噬细胞的自噬作用从而促进脂质代谢,减少泡沫细胞的形成.

结合肿瘤患者临床特点及相关文献,从阳虚体质着手,探讨阳虚体质与原发性肝癌的病因病机、治疗、复发、预防的关系,以期为临床诊治肝癌及防治提供新思路.

Abstract Objective: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Disulfidptosis is a newly discovered mechanism of programmed cell death. However, the role of disulfidptosis - related lncRNAs (DRlncRNAs) in HCC remains unclear. The purpose of this study is to establish the prognostic model of DRlncRNAs and explore its prognostic value in HCC. Materials and methods: The relevant clinical data and RNA-seq were obtained from the Cancer Genome Atlas (TCGA) database. The DRlncRNAs were identified via univariate and multivariate Cox regression, lasso algorithm analysis, and then established the prognostic model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, principal component analysis (PCA), univariate and multivariate Cox regression analysis, functional enrichment annotation and the nomogram were used to assess the reliability of risk model. Furthermore, the potential immunotherapeutic signatures and drug sensitivity prediction were also performed. The RT-qPCR was applied to identify the expression of DRlncRNAs. Results:We constructed a prognostic model with 7 DRlncRNAs and proved the model could well predict the survival and prognosis of HCC patients. Immune correlation analysis suggested that low-risk patients had better immunotherapeutic outcomes. Drug prediction showed that Erlotinib, Gefitinib, Savolitinib, Osimertinib, Lapatinib, Afatinib and Crizotinib were more effective in low-risk patients; Sorafenib, Selumetinib, and Axitinib were more effective in high-risk patients. Finally, the expression of DRlncRNAs in normal liver and HCC cell lines were testified by RT-qPCR. Discussion and Conclusions: We constructed a risk model and provided a new direction for diagnosing and treating HCC.

目的 研究乙型肝炎病毒(hepatitis B virus,HBV)感染动物模型的造模特点,为本模型的建立和评价提供参考.方法 通过计算机检索中国知网、万方数据库、维普中文期刊服务平台及PubMed数据库近十年的相关文献,总结实验动物种类、造模方式、模型给药时间及阳性对照药、检测指标等,建立数据库进行统计分析.结果 纳入符合标准的 59 篇文献中HBV感染动物模型以C57BL/6 小鼠和BALB/c小鼠为主;最常用的造模方式为水动力高压注射法,其次为静脉注射、重组腺相关病毒载体介导的HBV感染、腹腔注射、转基因、皮下注射及先天感染;阳性对照药均为抗病毒药物,以拉米夫定最常用,给药时间多为 14 d;检测指标以血清病毒学指标为主,包括HBsAg、HBV-DNA和HBeAg,部分研究结合了肝组织病理检查及转氨酶水平来评估 HBV 感染后肝疾病进展.结论 本研究通过数据挖掘的方法筛选出应用最广泛的HBV感染动物模型的造模方法和评价指标,描述了造模的原理及具体方法,对不同的动物模型进行评估,为HBV感染动物模型的应用提供参考.

中医学认为慢性乙型肝炎由湿热疫毒之邪内侵,人体正气亏虚时发病,该病病性为本虚标实,病位在肝,涉及脾肾,病理因素包括气、血、痰、湿、毒.风药是一类具有升散宣通、畅达引导、助阳发散之性的药物,在慢性乙型肝炎的治疗中可起到疏肝畅气机、醒脾化痰湿、助阳益肾气、通瘀散癥积等作用.临床运用风药治疗本病常可取得较好的疗效.附验案1则以佐证.

目的 系统评价乌贝散类复方治疗反流性食管炎的临床疗效.方法 检索各数据库创立至2021年6月27日乌贝散类复方治疗反流性食管炎的临床随机对照试验的文献.运用RevMan 5.3软件分析乌贝散类复方治疗反流性食管炎的临床有效率、内镜下有效率、复发率和主要症状积分.结果 最终纳入12篇文献,共1 084例患者,其中观察组(乌贝散类复方治疗)552例,对照组532例.Meta分析显示:与对照组比较,运用乌贝散类复方治疗能提高反流性食管炎患者的临床有效率(RR=1.24,95％CI 1.17～1.31,P＜0.00001)和内镜下有效率(RR=1.10,95％CI1.02～1.18,P=0.02),且能有效的降低患者的复发率(RR=0.42,95％CI0.26～0.68,P=0.0004)和主要症状积分(MD=-0.54,95％CI-0.98,～-0.10,P=0.02).结论 乌贝散类复方能有效地治疗反流性食管炎,且在提高患者的临床有效率及内镜下有效率,降低患者主要症状积分和复发率等方面具有一定的优势.

近几十年来,肥胖成为了一个全球性的公共卫生问题,采取有效的手段干预肥胖显得尤为重要.研究表明肥胖与中医体质有着紧密的关联.现从古籍中肥胖与体质的相关论述,肥胖人群的体质分布特点,不同体质肥胖人群的相关指标研究,对肥胖人群进行干预的效果等几个方面进行综述,以对肥胖与中医体质的相关研究进行归纳总结,为后续研究的开展提供参考.

ObjectiveTo analyze surveys measuring the prevalence of burnout among Chinese doctors and reveal the overall prevalence, characteristics, timeline, and factors related to burnout.MethodsA comprehensive search was conducted on China National Knowledge Infrastructure, WANFANG, PubMed, EMBASE, PsycINFO and Cochrane Library databases from their inception to 28 February 2021. Random-effects meta-analyses, meta-regression and planned subgroup analyses were performed, and the standardized mean difference was adopted for comparisons between subgroups. Egger's and Begg's tests were performed to evaluate publication bias. Heterogeneity across the studies was tested using the I2 statistic. The study protocol was registered on PROSPERO (CRD42018104249).ResultsIn total, 3,210 records were reviewed; 64 studies including 48,638 Chinese doctors were eligible for meta-analysis. The prevalence of burnout increased continuously from 2008 to 2017 and decreased significantly from 2018 to 2020, a little increase from 2020 to 2021. The overall prevalence of burnout was 75.48% (95% CI, 69.20 to 81.26; I2 = 99.23%, P < 0.001), and high burnout was 9.37% (95% CI, 4.91 to 15.05, I2 = 98.88%, P < 0.001). The prevalence of emotional exhaustion was 48.64% (95% CI, 38.73 to 58.59; I2 = 99.53%, P < 0.001), depersonalization was 54.67% (95% CI, 46.95 to 62.27; I2 = 99.20%, P < 0.001), and reduced personal accomplishment was 66.53% (95% CI, 58.13 to 74.44; I2 = 99.37%, P < 0.001). Gender, marriage, professional title and specialty all influenced burnout.ConclusionsThe results showed that the total prevalence of doctor burnout in China is very high. The prevalence of burnout varies by location. Gender, marital status and professional title all affect burnout scores.

目的:从肝气虚证角度并通过网络药理学探讨黄芪-柴胡干预肝炎的作用机制.方法:检索中药系统药理学数据库与分析平台(TCMSP)等数据库,筛选黄芪-柴胡干预肝炎的活性成分和作用靶点.构建化合物-靶点-疾病网络和蛋白质-蛋白质相互作用(PPI)网络,进行拓扑学分析,筛选关键药效分子和核心靶点.对作用靶点进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析,并用Cytoscape软件构建化合物-靶点-通路网络.结果:黄芪-柴胡通过升补肝气治疗肝炎患者肝气虚证.经网络药理学分析,筛选出黄芪-柴胡14个关键药效分子,19个核心作用靶点与其干预肝炎密切相关.分子对接结果显示,度值前10的核心靶点能与黄芪-柴胡的关键活性成分形成较稳定的构象,具有良好的结合活性.GO和KE GG结果主要涉及炎症、氧化应激、细胞增殖等生物学过程.结论:黄芪-柴胡或通过槲皮素、山柰酚、芒柄花素等活性成分作用于Toll样受体、Th17细胞分化、Th1和Th2细胞分化、PI3K/AKT、MAPK、IL-17等信号通路,参与调节氧化应激反应、肝脏炎症反应、细胞增殖等生物学过程,发挥干预肝炎的作用.

目的 比较抑郁障碍(MDD)肝气郁结证及肾阳亏虚证患者脑功能与血清肿瘤坏死因子-α(TNF-α),并通过TNF-α水平与脑功能的相关性,探讨中医药治疗MDD不同中医证候类型患者可能的脑区靶点.方法 2017年10月—2020年10月在北京中医药大学第三附属医院、首都医科大学宣武医院及北京安定医院的中度MDD肾阳亏虚证、肝气郁结证患者各17例,健康对照组17例为北京中医药大学师生及北京中医药大学第三附属医院职工.同一受试者均在同一天完成静息态功能磁共振成像(rs-fMRI)及血清留取.酶联免疫吸附测定法检测血清TNF-α水平;使用SPM软件及DP ASF软件处理核磁影像数据,完成脑功能评估及相关性分析.结果 MDD肝气郁结证组及肾阳亏虚证组患者血清TNF-α 水平均高于健康对照组,且肝气郁结证组高于肾阳亏虚证组(P<0.01).与健康对照组比较,MDD肾阳亏虚证患者左侧楔前叶及左侧顶上小叶存在异常激活状态,肝气郁结证患者右侧颞上回、右侧岛叶、左侧枕下回、左侧颞下回、左侧楔叶、右侧楔前叶、左侧楔前叶存在异常激活状态.肾阳亏虚证患者血清TNF-α水平与右侧背外侧额上回、右侧额中回、左侧枕中回、左侧中央前回、左侧直回的分数低频振幅(fALFF)值正相关(P<0.05),与左侧楔前叶、右侧颞下回、右侧枕中回、右侧小脑fALFF值负相关(P<0.05).而肝气郁结证患者只有小脑fALFF值与血清TNF-α正相关(P<0.05).结论 MDD肝气郁结证及肾阳亏虚证患者脑功能及血清TNF-α水平存在差异,肾阳亏虚证患者可能更偏向于在注意力相关的脑区存在异常,且与抑郁相关的炎症反应相关性更强,主要为背外侧前额叶的异常.而肝气郁结型患者可能更偏向于视觉相关的脑区存在异常,炎症反应与脑区的相关性弱于肾阳亏虚证患者.

阴虚体质是九种基本体质类型之一,是指由于体内津液、精、血等阴液亏少,以阴虚内热等表现为主要特征的一类体质.文章以阴虚体质为研究对象,结合其常见表现,深入剖析临床常见病症及方药应用,以体统病症、以体统方药,以期为阴虚体质调体预防和治疗相关疾病起到指导作用.

目的 调查防控新型冠状病毒肺炎(新冠肺炎)疫情居家隔离期间青少年焦虑、抑郁情绪,并探讨其影响因素.方法 采用整群抽样方法,对山东、陕西、辽宁、河南、福建省的6所中学的学生以班级为单位进行焦虑、抑郁情绪的问卷调查.采用x2检验、多因素Logistic回归分析影响青少年焦虑、抑郁情绪的相关因素.结果 共纳入11430名青少年为研究对象,其中男生5818名(50.9％),女生5612名(49.1％);农村5503名(48.1％),城市5927名(51.9％);所在小区或村存在新冠肺炎病例者238名(2.1％),不存在者9703名(84.9％),不知道者1489名(13.0％).共检出焦虑情绪青少年2706例(23.6％),抑郁情绪4334例(37.9％).多因素Logistic回归显示,女生(OR=1.673)、年龄越大(OR=1.271、1.460)、班级排名较后(OR=1.193、1.575、1.699)、所在小区或村存在或不知道有无新冠肺炎病例(OR=2.320、2.197)、山东省(OR=1.806)、福建省(OR=2.036)、河南省(OR=2.406)、陕西省(OR=1.575)的青少年更容易产生焦虑情绪.女生(OR=1.577)、年龄越大(OR=1.306、1.545)、班级排名较后(OR=1.157、1.384、1.527)、所在小区或村存在或不知道有无新冠肺炎病例(OR=2.492、2.329)、山东省(OR=1.876)、福建省(OR=2.335)、河南省(OR=2.413)、陕西省(OR=1.462)的青少年产生抑郁情绪的风险更高.结论 居家隔离期间青少年焦虑、抑郁情绪检出率较高,教育部门应及时对青少年进行心理健康教育.

Objective: To evaluate the efficacy and safety of Morinda officinalis oligosaccharide (MOO) capsules for depressive disorder. Methods: Eight electronic databases were searched for relevant studies from inception to April 19, 2020. Randomized controlled trials comparing MOO capsules with antidepressants were included. Data analysis was conducted using Review Manager 5.3 software. The risk of bias was assessed using the Cochrane Risk of Bias Tool, and the quality of the studies was evaluated by two researchers using the Grading of Recommendation, Assessment, Development and Evaluations (GRADE) software. Results: Seven studies involving 1,384 participants were included in this study. The effect of MOO capsules for moderate depressive disorder was not different from that of antidepressants (risk ratio [RR] = 0.99, 95%CI 0.92-1.06). Regarding adverse events, no significant difference was found between MOO capsules and antidepressants (RR = 0.84, 95%CI 0.65-1.07). In addition, the quality of evidence related to these adverse events was rated as low. Conclusion: This systematic review suggests that the efficacy of MOO capsules in the treatment of mild to moderate depression is not inferior to that of conventional antidepressants, which may provide a new direction for clinical alternative selection of antidepressants. However, more high-quality research and detailed assessments are needed.

PURPOSE:The purpose of this study was to clarify the expression pattern of Nek2B in hepatocellular carcinoma (HCC) and its influence on malignant phenotypes of HCC through regulating SFRP1 and the Wnt/β-catenin pathway.METHODS:Nek2B levels in 64 paired HCC tissues and adjacent normal ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between Nek2B level and clinical parameters of HCC patients was analyzed. Regulatory effects of Nek2B and SFRP1 on clonality, proliferation and apoptosis of MHCC97H and Hep3B cells were determined through functional experiments. Western blot was conducted to detect protein levels of SFRP1, β-catenin, c-myc, cyclinD1 and MMP7 in HCC cells with overexpression or knockdown of Nek2B. At last, rescue experiments were performed to clarify the role of Nek2B/SFRP1 regulatory loop in aggravating the progression of HCC.RESULTS:Nek2B was upregulated in HCC tissues and cells. HCC patients expressing a high level of Nek2B were in more advanced tumor stage and had worse prognosis. Overexpression of Nek2B in MHCC97H cells enhanced clonality, 5-Ethynyl-2'- deoxyuridine (EdU)-positive ratio and suppressed apoptosis. Besides, knockdown of Nek2B in Hep3B cells yielded the opposite results. SFRP1 was downregulated in HCC, and low level of SFRP1 predicted worse prognosis of HCC. Overexpression of Nek2B downregulated SFRP1, but upregulated β-catenin, c-myc, cyclinD1 and MMP7 in HCC cells. Importantly, Nek2B/SFRP1 regulatory loop was identified to aggravate the progression of HCC.CONCLUSIONS:Nek2B is upregulated in HCC, and closely linked to tumor stage and poor prognosis in HCC patients. Through interaction with SFRP1, Nek2B aggravates the progression of HCC by activating the Wnt/β-catenin pathway.

基于周易水火"既济"与"未济"理论,从生理、病理方面探讨睡眠与心肾交感的关系,指出肾(坎)中之阳、心(离)中之阴在心肾交感的过程中发挥关键作用,枢机健运、气机通畅是心肾交感的重要条件,提出以温肾助阳、滋养心阴之法促进心肾交感,以交通心肾、健运枢机之法治疗心肾不交型失眠.