Biological basis of “depression with liver-qi stagnation and spleen deficiency syndrome”: A digital gene expression profiling study

Objective:To investigate the biological basis of“depression with liver-qi stagnation and spleen deficiency syndrome”.Methods:A digital gene expression profiling method was conducted to explore global changes in the mRNA transcriptome in a rat model of depression with liver-qi stagnation and spleen deficiency syndrome.Real-time quantitative polymerase chain reaction(q-PCR)was performed to verify the five genes most interest based on the Kyoto Encyclopedia of Genes and Genome(KEGG)analysis.Sini San,which disperses stagnated liver qi and strengthens the spleen,was administered to the model rats to observe whether it could reverse these genetic changes in the liver.Results:Forty-six differentially expressed genes were identified.Three of the five genes of most interestdHnf4a,Hnf4g and Cyp1a1dbased on KEGG analysis,were confirmed by realtime q-PCR.Sini San reduced the gene expression changes of Hnf4a,Hnf4g and Cyp1a1 in the rat model.Conclusions:Hnf4a,Hnf4g and Cyp1a1 are involved in“depression with liver-qi stagnation and spleen deficiency syndrome”.These findings indicate that depressed rats with liver-qi stagnation and spleen deficiency syndrome are at risk of liver diseases.Furthermore,our results will inform exploration of the etiology of depression and help in the development of effective therapeutic strategies.

Study on the Characteristics of Gut Microbiota in Chronic Hepatitis B(CHB)Patients with Damp Heat Syndrome and Liver Depression and Spleen Deficiency Syndrome

Objective:This study was designed to explore the characteristics of gut microbiota in CHB patients with two most common traditional Chinese medicine(TCM)Syndromes—damp heat syndrome and liver depression and spleen deficiency syndrome.Methods:According to the diagnostic criteria of Western medicine,TCM and screening exclusion criteria,65 cases of CHB with damp heat syndrome and 28 cases of CHB with liver depression and spleen deficiency syndrome were finally included in the study.All the basic information was gathered and the fresh fecal samples were collected for 16S rDNA sequencing.16S rDNA of gut microbiota was sequenced using Illumina hiseq 2,500 high-throughput sequencing platform.Based on the optimized sequence,Operational Taxonomic Units(OTU)clustering analysis and taxonomic annotation were carried out.Results:The difference in relative abundance of gut microbiota was significant between damp heat syndrome and liver depression and spleen deficiency syndrome in CHB patients.Cyanobacteria was only found in damp heat syndrome.The relative abundance of Erysipelotrichia and Subdoligranulum were higher in liver depression and spleen deficiency syndrome,while the relative abundance of Rhodospirillales,Alphaproteobacteria and Lachnospira were higher in the damp heat syndrome.LDA Effect Size(LEfSe)analysis showed that Lachnospira,Olsenella and Subdoligranulum had significant difference in species among the two TCM syndromes.Conclusion:The different characteristics of gut microbiota in the two TCM syndromes of CHB patients may play an important role in syndrome formation of TCM,which provides a new field of vision for the accurate diagnosis and treatment of TCM.

Gut microbial diversity analysis using Illumina sequencing for functional dyspepsia with liver depression-spleen deficiency syndrome and the interventional Xiaoyaosan in a rat model

AIM To investigate gut microbial diversity and the interventional effect of Xiaoyaosan(XYS) in a rat model of functional dyspepsia(FD) with liver depression-spleen deficiency syndrome. METHODS The FD with liver depression-spleen deficiency syndrome rat model was established through classic chronic mild unpredictable stimulation every day. XYS group rats received XYS 1 h before the stimulation. The models were assessed by parameters including state ofthe rat, weight, sucrose test result and open-field test result. After 3 wk, the stools of rats were collected and genomic DNA was extracted. PCR products of the V4 region of 16 S rD NA were sequenced using a barcoded Illumina paired-end sequencing technique. The primary composition of the microbiome in the stool samples was determined and analyzed by cluster analysis.RESULTS Rat models were successfully established, per data from rat state, weight and open-field test. The microbiomes contained 20 phyla from all samples. Firmicutes, Bacteroidetes, Proteobacteria, Cyanobacteria and Tenericutes were the most abundant taxonomic groups. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria in the model group was higher than that in the normal group. On the contrary, the relative abundance of Bacteroidetes in the model group was lower than that in the normal group. Upon XYS treatment, the relative abundance of all dysregulated phyla was restored to levels similar to those observed in the normal group. Abundance clustering heat map of phyla corroborated the taxonomic distribution. CONCLUSION The microbiome relative abundance of FD rats with liver depression-spleen deficiency syndrome was significantly different from the normal cohort. XYS intervention may effectively adjust the gut dysbacteriosis in FD.

Rat Models of Fatty Liver due to Liver Depression and Spleen Deficiency

[Objectives] To establish animal models of fatty liver due to liver depression and spleen deficiency that were suitable for activity discovery of traditional Chinese medicine( TCM) compounds,efficacy evaluation,new drug research and development and correspondence between prescription and syndrome of TCM. [Methods] A syndrome score scale that was suitable for evaluating the rat models was established according to the evolvement rules of etiology and pathogenesis of TCM and the modern clinical pathological mechanism. At the same time,bifendate pills and Sanqi Zhigan pills were selected as drug counterevidence for the models. Rats in model groups were given different proportions of high-fat and low-protein fodder and different concentrations of alcohol every day,and intraperitoneally injected with porcine serum twice a week. Drug groups were given with bifendate pills and Sanqi Zhigan pills( 8. 1 mg/kg,and 2. 7 g/kg) respectively for 14 consecutive days.During the experiment,general status,weight,daily fodder intake and daily water intake of the animals were observed,and TCM syndromes were scored. After the experiment,the levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),γ-glutamine transpeptidase( γ-GT),total cholesterol( TC),triglycerides( TG),low density lipoprotein-cholesterol( LDL-C),and high density lipoprotein-cholesterol( HDL-C) in serum were detected,and the pathological changes in liver tissue were observed. [Results] Compared with the control group,body weight,daily fodder and water intake of rats increased slowly in the model group,and the levels of ALT,AST,γ-GT,TC,TG and LDL-C increased significantly,while the level of HDL-C dropped. Pathological examination showed that steatosis and fat granule were observed in hepatocytes of rats in the model group. Behavioral observation found that main symptoms and minor symptoms of rats in the model group conformed to the syndrome manifestation of liver depression and spleen deficiency,which suggested that the three model groups were established successfully. Among them,three rats died in model group 1,and one rat died in model group 2. The manifestation of all the above lesions can be alleviated by drug counterevidence. [Conclusions]The animal model of fatty liver due to liver depression and spleen deficiency shows an obviously lower mortality and shorter duration and can be used for research of correlation between prescription and syndrome and its mechanism.

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin(Heart)-Pi(Spleen)Deficiency Syndrome:A Multi-centre Randomized Controlled Study

Objective:To evaluate the efficacy and safety of Jianpi Jieyu Decoction(JJD)for treating patients with mild-to-moderate depression of Xin(Heart)-Pi(Spleen)deficiency(XPD)syndrome.Methods:In this multi-center,randomized,controlled study,140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019.They were randomly divided into JJD group and paroxetine group by using a random number table,with 70 cases in each group.The patients in the JJD group were given JJD one dose per day(twice daily at morning and evening,100 m L each time),and the patients in the paroxetine group were given paroxetine(10 mg/d in week 1;20 mg/d in weeks 2-6),both orally administration for a total of 6 weeks.The primary outcome was the change of 17-item Hamilton Depression Rating Scale(HAMD-17)score at week 6 from baseline.The secondary outcomes included the Hamilton Anxiety Scale(HAMA)score,Traditional Chinese Medicine Symptom Scale(TCMSS),and Clinlcal Global Impression(CGI)scores at the 2nd,4th,and 6th weekends of treatment,HAMD-17 response(defined as a reduction in score of>50%)and HAMD-17 remission(defined as a score of 7)at the end of the 6th week of treatment.Adverse events(AEs)were also recorded.Results:From baseline to week 6,the HAMD-17 scores decreased 10.2±4.0 and 9.1±4.9 points in the JJD and paroxetine groups,respectively(P=0.689).The HAMD-17 response occurred in 60%of patients in the JJD group and in 50%of those in the paroxetine group(P=0.292);HAMD-17 remission occurred in 45.7%and 30%of patients,respectively(P=0.128).The differences of CGI scores at the 6th week were not statistically significant(P>0.05).There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week(P=0.001 and P=0.014).The HAMA scores declined 8.1±3.0 and 6.9±4.3 points from baseline to week 6 in the JJD and paroxetine groups,respectively(P=0.905 between groups).At 4th week of treatment,there was a significant difference in HAMA between the two groups(P=0.037).TCMSS decreased 11.4±5.1,and 10.1±6.8 points in the JJD and paroxetine groups,respectively(P=0.080 between groups).At the 6th week,the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group(7.14%vs.22.86%,P<0.05).Conclusion:Compared with paroxetine,JJD was associated with a significantly lower incidence of AEs in patients with mild-tomoderate depression of XPD syndrome,with no difference in efficacy at 6 weeks.(Trial registration No.Chi CTR2000040922).

基于“肝脾同调”阐析慢性肝病的中医治疗

慢性肝病是临床常见疾病,“郁、虚、湿、毒、瘀”是其核心病机,在疾病的不同阶段各有侧重,其中,以“郁、虚”为核心的肝脾失调是慢性肝病发生发展的关键。“肝脾同调”是治疗慢性肝病的基本治法,在慢性肝病不同阶段,其“肝脾同调”内涵同中有异。根据肝、脾生理病理特性,治脾明辨虚实,厘清轻重,活用运脾、健脾、温脾、醒脾、补脾等法;调肝体用并重,精准辨证,活用疏肝、缓肝、散肝、柔肝等法。临床上,治脾与调肝相辅相成,治调并举,常获良效。

俞募配穴针刺治疗肝郁脾虚型抑郁症的临床效果观察

目的:观察俞募配穴针刺治疗肝郁脾虚型抑郁症患者的临床疗效。方法:选取2022年1月至2022年12月福建中医药大学附属第二人民医院收治的肝郁脾虚型抑郁症患者100例作为研究对象,随机分为对照组和观察组,每组50例。对照组给予艾司西酞普兰口服治疗,持续用药1个月;观察组在对照组基础上联合俞募配穴针刺治疗,2 d治疗1次,持续治疗15次。比较2组患者治疗前后主要症状、抑郁程度、生命质量评分、血清5-羟色胺(5-HT)水平、肠道菌群、不良反应、复发率及临床疗效。结果:治疗后,观察组健康调查简表(SF-36)评分、血清5-HT水平、粪便标本乳酸杆菌及双歧杆菌数量高于对照组(均P<0.05),主要症状评分、汉密尔顿抑郁量表(HAMD-24)评分、粪便标本大肠埃希菌及肠球菌数量低于对照组(均P<0.05)。2组患者不良反应发生率比较差异无统计学意义(P>0.05)。观察组治疗后6个月复发率略低于对照组,但差异无统计学意义(P>0.05)。治疗后观察组总有效率高于对照组(P<0.05)。结论:俞募配穴针刺治疗肝郁脾虚型抑郁症患者疗效明确,可有效改善患者症状,减轻抑郁程度,提高生命质量,调节血清5-HT水平及改善肠道菌群分布,安全性高。

自拟疏肝健脾方对肝郁脾虚证大鼠影响及其机制

目的观察自拟疏肝健脾方对肝郁脾虚证大鼠的影响及其可能的作用机制。方法慢性捆绑束缚法制备大鼠肝郁脾虚证模型。60只大鼠随机分为正常组,模型组,疏肝健脾方高、中、低剂量组,阳性对照组,每组10只,连续21 d每日束缚3 h,束缚前30 min大鼠灌胃给药。通过记录大鼠宏观表征观察一般情况,体质量和小肠推进率观察大鼠“脾虚”情况,脾指数和胸腺指数反映大鼠免疫水平。通过旷场实验观察大鼠抑郁情绪以及糖水偏好率观察大鼠欣快感共同反映“肝郁”的情况。ELISA法检测大鼠血清中皮质酮(corticosterone,CORT)、5-羟色胺(5-hydroxytryptamine,5-HT)、去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)的含量。结果与正常组比较,模型组大鼠体质量减轻(P<0.05),总活动距离明显减少(P<0.05),活动速度减慢(P<0.05),糖水偏好率、小肠推进率、脾指数均下降(P<0.05),CORT含量、NE含量均升高(P<0.05)。与模型组比较,疏肝健脾方各剂量组大鼠总活动距离及糖水偏好率均增加(P<0.05),疏肝健脾方低剂量组小肠推进率升高、脾指数上升(P<0.05),疏肝健脾方中、低剂量组活动速度增快(P<0.05),疏肝健脾方高、低剂量组CORT含量、NE含量均降低(P<0.05),5-HT和DA含量差异无统计学意义(P>0.05)。结论疏肝健脾方可以有效改善大鼠肝郁脾虚证,其机制可能与调控下丘脑-垂体-肾上腺(hypothalamic pituitary adrenal,HPA)轴功能相关。

耳穴压豆干预在肝郁脾虚型乙肝患者中的应用效果

目的观察耳穴压豆干预在肝郁脾虚型乙肝患者中的应用效果。方法选取2023年1月至5月南昌市第九医院收治的80例自述睡眠质量下降的肝郁脾虚型乙肝患者为对象,按随机数字表法分为观察组和对照组,每组各40例。对照组接受常规护理干预,观察组在此基础上接受耳穴压豆干预,两组均干预14 d。干预前后使用匹兹堡睡眠指数评分(PSQI)、汉密顿焦虑量表(HAMA)、汉密顿抑郁量表(HAMD)、诺丁汉健康调查问卷(NHP)、自制护理满意度调查表分别评价两组患者的睡眠质量、负性心理(HAMA、HAMD)、生活质量及护理满意度。结果干预后,观察组睡眠质量优于对照组,HAMA、HAMD、NHP各维度评分低于对照组,护理满意度优于对照组,总满意度高于对照组,差异有统计学意义(P<0.05)。结论耳穴压豆干预可改善肝郁脾虚型乙肝患者睡眠质量,对减缓负性心理,提高生活质量有积极意义,患者较为满意。

乌灵胶囊联合针灸治疗肝郁脾虚证腹泻型肠易激综合征的临床疗效及安全性

目的探讨乌灵胶囊联合针灸治疗肝郁脾虚证腹泻型肠易激综合征(irritable bowel syndrome with diarrhea,IBS-D)的临床疗效及安全性。方法选取肝郁脾虚证IBS-D患者140例。按随机数字表法将所有患者分为对照组和观察组,各70例。对照组给予水疗基础治疗+口服马来酸曲美布汀胶囊和乌灵胶囊治疗,观察组在对照组的治疗基础之上联合针灸治疗。评价两组患者的综合疗效和总体证候疗效,采用肠易激综合征生活质量量表(irritable bowel syndrome quality of life scale,IBS-QOL)对肝郁脾虚证IBS-D患者治疗前和疗程结束后生活质量变化情况进行评估,采用汉密顿焦虑量表(hamilton anxiety scale,HAMA)评估患者治疗前与疗程结束后焦虑程度,采用汉密顿抑郁量表(hamilton depression scale,HAMD)评估患者治疗前与疗程结束后的抑郁程度。采用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测患者血清二胺氧化酶(diamine oxidase,DAO)、D-乳酸和肠脂肪酸结合蛋白(intestinal fatty acid binding protein,IFBP)、5-羟色胺(5-hydroxyteyptamine,5-HT)、降钙素基因相关肽(calcitonin gene related peptide,CGRP)水平。结果观察组的综合疗效97.14%(68/70)高于对照组85.71%(60/70),差异有统计学意义(χ^(2)=5.833,P<0.05);观察组的总体证候疗效98.57%(69/70)高于对照组82.86%(58/70),差异有统计学意义(χ^(2)=10.260,P<0.05);观察组疗程结束后IBS-QOL评分高于对照组,差异有统计学意义(t=4.272,P<0.05),观察组疗程结束后HAMA、HAMD评分低于对照组,差异有统计学意义(t=8.535,10.534,P<0.05);观察组疗程结束后DAO、D-乳酸、IFABP水平低于对照组,差异有统计学意义(t=7.229,13.046,7.016,P<0.05);观察组疗程结束后HT、CGRP表达水平低于对照组,差异有统计学意义(t=4.620,2.027,P<0.05);观察组患者不良反应发生率8.57%(6/70)高于对照组5.71%(4/70)(χ^(2)=0.431,P>0.05)。结论乌灵胶囊联合针灸可提升临床疗效,可有效改善IBS-D患者的生活质量和焦虑抑郁状态,同时对降低DAO、D-乳酸、IFABP、5-HT、CGRP水平,缓解胃肠道症状效果显著,且安全性较高。

逍遥散联合水飞蓟素胶囊治疗肝郁脾虚证非酒精性脂肪性肝病临床研究

目的:逍遥散联合水飞蓟素胶囊治疗肝郁脾虚证非酒精性脂肪性肝病(NAFLD)的疗效。方法:选取90例肝郁脾虚证NAFLD患者,按随机数字表法分为对照组及治疗组各45例。2组行非药物措施,对照组予以水飞蓟素胶囊口服,治疗组在对照组基础上加逍遥散治疗。2组均连续治疗12周。比较2组临床疗效,比较2组治疗前后肝功能指标[谷草转氨酶(AST)、丙氨酸转氨酶(ALT)、谷氨酰转肽酶(GGT)]值、血脂指标[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]值、血清TLR4/NF-κB信号通路相关蛋白水平[血清TOLL样受体4(TLR4)、髓样分化因子88(MyD88)、核转录因子-κB(NF-κB)]、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的变化。结果:治疗12周后,治疗组临床疗效总有效率为91.11%,对照组为73.33%,2组比较,差异有统计学意义(P<0.05)。治疗12周后,2组AST、ALT、GGT指标值均较治疗前下降(P<0.05),治疗组上述3项指标值均低于对照组(P<0.05)。治疗12周后,2组TC、TG、LDL-C水平均较治疗前下降(P<0.05),HDL-C水平均较治疗前上升(P<0.05);治疗组TC、TG、LDL-C水平均低于对照组(P<0.05),HDL-C水平高于对照组(P<0.05)。治疗12周后,2组血清TLR4、MyD88、NF-κB、IL-6、TNF-α水平均较治疗前下降(P<0.05),治疗组上述5项水平均低于对照组(P<0.05)。结论:逍遥散联合水飞蓟素胶囊对肝郁脾虚证NAFLD的疗效确切,可有效改善肝功能及血脂状况,调节血清TLR4-NF-κB信号通路,抑制炎症反应。

基于Thinc-it工具分析抑郁症不同证型患者认知功能

目的:通过Thinc-it工具探讨抑郁症不同证型患者认知功能特点。方法:从2020年6月至2022年7月宁波市第一医院心身医学科确诊为抑郁症的患者中选取肝气郁结、气郁化火、痰气郁结、心脾两虚证型患者各50例为受试者,并选取同期在医院健康体检志愿者50例为健康对照组。应用汉密尔顿抑郁量表(hamilton depression scale,HAMD)、汉密尔顿焦虑量表(hamilton anxiety scale,HAMA)对各组受试者临床症状进行评估,并分别通过Thinc-it工具进行认知功能评估,具体包括认知损害5项问卷(5-item questionnaire for cognitive impairment,PDQ-5-D)、选择反应时间任务(selection response time,CRT)、1-Back记忆任务(selection response time,1-Back)、数字符号替代测试(digit symbol substitution test,DSST)和连线测试B(line test B,TMT-B)测试。结果:抑郁症各证型组病程、HAMD评分、HAMA评分比较,痰气郁结证组和心脾两虚证组病程时间相对更长,但组间比较,差异无统计学意义(P>0.05)。郁证各证型组HAMD评分、HAMA评分高于健康对照组,差异具有统计学意义(P<0.05)。郁证各证型组PDQ-5-D评分高于健康对照组(P<0.05),郁证各证型组间比较,差异无统计学意义(P>0.05)。与健康对照组比较,郁证各证型组CRT计数减少,CRT反应时间延长,差异具有统计学意义(P<0.05)。组间比较,心脾两虚证组CRT计数高于肝气郁结证组,痰气郁结证组CRT反应时间长于肝气郁结证组,差异具有统计学意义(P<0.05)。与健康对照组比较,郁证各证型组1-Back计数减少,痰气郁结证组、心脾两虚证组1-Back反应时间延长,差异具有统计学意义(P<0.05),郁证各证型组间比较,差异无统计学意义(P>0.05)。与健康对照组比较,郁证各证型组DSST计数减少,DSST反应时间、TMT-B耗时延长,差异具有统计学意义(P<0.05)。心脾两虚证组、痰气郁结证组DSST反应时间长于肝气郁结证组、气郁化火证组,差异具有统计学意义(P<0.05)。结论:抑郁症各证型患者均存在主观认知功能、注意力、记忆力、执行功能、信息加工处理速度等方面的损害,且各证型受损程度不一,且痰气郁结证组、心脾两虚证组在注意力、执行功能、处理速度方面较肝气郁结证组和气郁化火证组受损更严重。

汪龙德运用疏肝健脾法从脾胃论治干燥综合征经验

介绍汪龙德主任医师运用疏肝健脾法从脾胃论治干燥综合征的临床经验和学术思想。认为干燥综合征的关键病机是肝郁脾虚,发病部位在肝脾,属虚实夹杂证,临证强调运用疏肝健脾法为基本治法,使肝气畅达,疏泄正常,气行血行,则瘀血渐除,气机布散津液于全身;脾胃健运,气血津液化生有源,痰饮水湿自化,则清窍腠理得以濡润。辅以清热润燥、养血生津、活血祛瘀,标本同治,可获良效。并结合案例,介绍了疏肝健脾法治疗干燥综合征的应用,以期为临床诊疗提供参考。

基于养正除积法运用杵针治疗肝郁脾虚型卒中后抑郁临床观察

目的研究基于养正除积法探讨杵针对肝郁脾虚型卒中后抑郁患者的影响。方法选择2021年3月—2022年3月广东省第二中医院脑病科门诊和病房收治的肝郁脾虚型卒中后抑郁患者80例,随机分为试验组和对照组,每组40例。对照组采用基础治疗结合草酸艾司西酞普兰治疗,试验组采用基础治疗结合杵针治疗,比较两组临床效果、汉密尔顿抑郁量表(HAMD)评分、脑卒中影响量表(SIS)评分及治疗依从性。结果试验组患者治疗总有效率为92.50%(37/40),高于对照组的75.00%(30/40),差异有统计学意义(P<0.05)。治疗后,试验组HAMD评分低于对照组,SIS评分及治疗总依从性高于对照组,差异有统计学意义(P<0.05)。结论基于养正除积法的杵针治疗可有效缓解肝郁脾虚型卒中后抑郁患者抑郁情绪,提高患者生活质量。

芒针联合中医辨证干预肝郁脾虚型溃疡性结肠炎临床疗效观察

目的评价芒针疗法联合中医辨证干预肝郁脾虚型溃疡性结肠炎的有效性和安全性。方法选择肝郁脾虚型溃疡性结肠炎患者64例,按照随机数字表法将其分为两组,分别为治疗组和对照组,治疗组根据中医辨证,给予芒针治疗,配合培土疏郁汤口服;对照组口服美沙拉嗪缓释颗粒。比较两组治疗前后的中医证候积分及治疗后临床有效率。结果治疗后,治疗组中医证候积分低于对照组,差异有统计学意义(P<0.01);治疗组的临床总有效率高于对照组,差异有统计学意义(P<0.05)。结论芒针疗法联合中医辨证干预肝郁脾虚型溃疡性结肠炎较单纯西药口服更具有优势,值得临床推广。

中西医诊治儿童性早熟研究进展

目前,越来越多的无创诊断技术正在运用到儿童性早熟的诊断中,基因检测技术促进了该病遗传病因诊断的发展。对于该病的治疗,西医主要通过病因治疗继发性性早熟,对于特发性外周性性早熟没有特殊治疗方案,目前,中枢性性早熟治疗首选促性腺激素释放激素类似物(gonadotropin-releasing hormone agonist, GnRHa)。中医认为,性早熟病机为阴虚火旺,肝郁化火,痰湿壅滞,治以滋阴降火、疏肝解郁或燥湿化痰,可改善症状,抑制骨龄快速增长。但目前中医药治疗性早熟的临床研究证据等级不高,缺少样本量大、严格且全面的临床研究,未来可通过开展多中心的随机对照、大样本研究以验证中医药治疗性早熟的疗效。网络药理学和中药成分动物实验研究证明了中药治疗性早熟的部分机制,但中药方剂成分复杂,多通过胃肠道吸收后起效,是否可以调节肠道菌群、产生特异性菌群,该菌群是否改变了机体中某些代谢产物水平从而发挥治疗作用尚无相关研究,今后可开展更多的相关机制研究。

升阳泻湿法治疗非酒精性脂肪性肝病初探

非酒精性脂肪性肝病是目前的多发病,为多因素所致,严重影响公共健康,目前对于该病的证治报道较多。该病的临床表现多数不典型,病机证候复杂,笔者汲取李东垣理论思想中升发脾之清气,以及黄元御理论思想中泻湿疏木的治法,把二者进行优化组合,拟定了升阳化湿,培土疏木为治疗大法运用于临床,立足于“湿”,分为“湿浊内蕴”和“脾虚湿困”2个证型,驭繁就简,取得了理想的临床疗效。

Appraisal of treatment outcomes in integrative medicine using metabonomics:Taking non-alcoholic fatty liver disease with spleen deficiency syndrome as an example

Objective:Appraisal of treatment outcomes in integrative medicine is a challenge due to a gap between the concepts of Western medicine(WM)disease and traditional Chinese medicine(TCM)syndrome.This study presents an approach for the appraisal of integrative medicine that is based on targeted metabolomics.We use non-alcoholic fatty liver disease with spleen deficiency syndrome as a test case.Methods:A patient-reported outcome(PRO)scale was developed based on literature review,Delphi consensus survey,and reliability and validity test,to quantitatively evaluate spleen deficiency syndrome.Then,a metabonomic foundation for the treatment of non-alcoholic fatty liver disease with spleen deficiency syndrome was identified via a longitudinal interventional trial and targeted metabolomics.Finally,an integrated appraisal model was established by identifying metabolites that responded in the treatment of WM disease and TCM syndrome as positive outcomes and using other aspects of the metabonomic foundation as independent variables.Results:Ten symptoms and signs were included in the spleen deficiency PRO scale.The internal reliability,content validity,discriminative validity and structural validity of the scale were all qualified.Based on treatment responses to treatments for WM disease(homeostasis model assessment of insulin resistance)or TCM syndrome(spleen deficiency PRO scale score)from a previous randomized controlled trial,two cohorts comprised of 30 participants each were established for targeted metabolomics detection.Twenty-five metabolites were found to be involved in successful treatment outcomes to both WM and TCM,following quantitative comparison and multivariate analysis.Finally,the model of the integrated appraisal system was exploratively established using binary logistic regression;it included 9 core metabolites and had the prediction probability of 83.3%.Conclusion:This study presented a new and comprehensive research route for integrative appraisal of treatment outcomes for WM disease and TCM syndrome.Critical research techniques used in this research included the development of a TCM syndrome assessment tool,a longitudinal interventional trial with verified TCM treatment,identification of homogeneous metabolites,and statistical modeling.

基于“土虚木郁”探讨腹泻型肠易激综合征与溃疡性结肠炎共同发病机制及证治

腹泻型肠易激综合征(IBS-D)与溃疡性结肠炎(UC)是临床较为常见的消化系统疾病,二者虽在疾病性质上有所不同,但在临床症状表现、发病机制及治疗策略等方面有诸多类似之处。基于对中医古籍的研究及临证经验的总结,众多中医学者认为“土虚木郁”是此二者疾病共同的发病机制,治疗时从肝脾论治往往可取得满意的临床疗效。多项现代医学研究表明中医“土虚木郁”与脑肠互动异常、肠道菌群-胆汁酸轴失衡等IBS-D和UC共同的病理生理学改变密切相关。该文基于中医“异病同治”理念及现代医学研究进展,以“土虚木郁”为切入点,探讨IBS-D和UC共同的发病机制及临床证治。

柴郁清肝汤治疗非酒精性脂肪性肝病肝郁脾虚证患者的疗效观察及对Th17/Treg和相关炎症因子的影响

目的:观察柴郁清肝汤治疗非酒精性脂肪性肝病(NAFLD)肝郁脾虚证患者的临床疗效及对外周血Th17/Treg和相关炎症因子的影响。方法:将60例NAFLD患者随机分为观察组(30例)和对照组(30例),其中观察组给予柴郁清肝汤治疗,对照组给予维生素E软胶囊治疗,治疗8周评价疗效;分别观察2组患者治疗前后肝功、血脂、外周血T淋巴细胞Th17、Treg的百分比及其相关炎症因子(IL-17、IL-22、IL-10)的变化。结果:治疗8周,观察组显效16例,有效12例,对照组显效8例,有效13例,2组比较差异具有统计学意义(P<0.05)。与治疗前比较,2组患者ALT、AST、GGT、ALP、TC、TG、LDL-C、Th17、IL-17和IL-22明显降低,Treg明显升高,差异具有统计学意义(P<0.05),2组间比较观察组均明显优于对照组(P<0.05)。结论:柴郁清肝汤能够有效治疗NAFLD患者,改善肝功能和血脂,调节Th17/Treg平衡及其相关炎性因子分泌是其作用机制之一。