Sixty Sprague-Dawley female rats were randomly divided into sham-operated groups and five ovariectomy (OVX) subgroups. Rats subjected to sham and OVX were treated with the vehicle, alendronate, and Zuogui Wan (ZGW) at the doses of low, medium and high lyophilized powder daily for 3 months, respectively. The gene or protein expression of NK1R, PPAR γ, and OSX were assayed by either quantitative polymerase chain reaction or Western blot analysis. The results showed that compared with the OVX group, ZGW could reduce the level of PPARγ and increase the levels of OSX and. Meanwhile, ZGW could prevent bone loss. In addition, we found ZGW upregulated for the NK1R mRNA or protein expression by promoting the expression level of transcription factor FoxO3 and increasing its binding to the NK1R promoter region -700/-200 sequence. These results suggest that the regulation of FoxO3 and NK1R played a role and contributed to the mechanism of ZGW underlying the increase in bone mass in the OVX rat model.

目的:系统评价柴胡疏肝散合四君子汤加减方治疗慢性萎缩性胃炎(chronic atrophic gastritis,CAG)的临床效果.方法:电子计算机检索中国知网(CNKI)、万方数据库(WANFANG DATA)、中国生物医学文献数据库(CBM)、中国科技期刊全文数据库(VIP)、Cochrane Library、Pubmed、Embase数据库,检索时间限定为建库至2020年8月17日,纳入所有柴胡疏肝散合四君子汤加减方治疗CAG的随机对照试验(randomized controlled trial,RCT),并运用RevMan5.3软件进行Meta分析.结果:最终纳入7项研究共606例CAG患者,Meta分析结果显示与对照组常规西药治疗方案比较,柴胡疏肝散合四君子汤加减方可提高CAG患者的临床总有效率[RR=1.23,95％CI(1.16,1.31),P<0.00001],降低CAG不良反应发生率[RR=0.18,95％CI(0.05,0.58),P=0.004]和CAG的复发率[RR=0.30,95％CI(0.13,0.70),P=0.005],差异有统计学意义;分层分析显示对照组吗丁啉、奥美拉唑、硫糖铝混悬液3种药物联合使用治疗CAG有效率高于其他2种药物合用(P<0.05),维酶素、果胶铋2种药物联合使用治疗CAG疗效最差(P<0.05);漏斗图分析结果显示不对称可能存在发表偏倚.结论:基于纳入7项研究的Meta分析结果,柴胡疏肝散合四君子汤加减方治疗CAG的临床疗效优于常规西药.

Polyphenolic acids are the widely occurring natural products in almost each herbal plant, among which rosmarinic acid (RA, C18H16O8) is well-known, and is present in over 160 species belonging to many families, especially the Lamiaceae. Aside from this herbal ingredient, dozens of its natural derivatives have also been isolated and characterized from many natural plants. In recent years, with the increasing focus on the natural products as alternative treatments, a large number of pharmacological studies have been carried out to demonstrate the various biological activities of RA such as anti-inflammation, anti-oxidation, anti-diabetes, anti-virus, anti-tumor, neuroprotection, hepatoprotection, etc. In addition, investigations concerning its biosynthesis, extraction, analysis, clinical applications, and pharmacokinetics have also been performed. Although many achievements have been made in various research aspects, there still exist some problems or issues to be answered, especially its toxicity and bioavailability. Thus, we hope that in the case of natural products, the present review can not only provide a comprehensive understanding on RA covering its miscellaneous research fields, but also highlight some of the present issues and future perspectives worth investigating later, in order to help us utilize this polyphenolic acid more efficiently, widely, and safely.

目的 探讨左归丸(Zuoguiwan,ZGW)的补肾填精、益髓壮骨的作用,促进骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)的增殖和向成骨细胞方向分化.方法 制备ZGW含药血清,设置10％FBS DMEM组、成骨诱导液组、2.5％空白大鼠血清-成骨诱导液组、2.5％ZGW含药血清-成骨诱导液组.采用MTT法观察各组对BMSCs的增殖,使用碱性磷酸酶钙钴染色法检测BMSCs向成骨细胞方向的分化能力,碱性磷酸酶(alkaline phosphatase,AKP)法检测细胞培养液中AKP的含量,Western blot检测BMSCs中Runt相关转录因子2(Runx2)、骨钙蛋白(osteocalcin,OPN)和碱性磷酸酶(alkaline phosphatase,ALP)蛋白的表达.结果 2.5％ZGW含药血清-成骨诱导液组能够促进BMSCs的快速增殖,较早地进入平台期,促进BMSCs中AKP的分泌,提高ALP含量,上调BMSCs细胞中Runx2、ALP和OPN的蛋白表达水平.结论 ZGW抗骨质疏松的分子机制,可能与调节Runx2激活ALP、OPN蛋白表达,促进BMSCs增殖和向成骨细胞方向分化有关.

目的 探讨CCK-8与MTT法在检测左归丸含药血清干预大鼠骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)增殖时所需的最佳实验条件,并比较两种方法的优缺点.方法 用左归丸含药血清进行干预P3 BMSCs,孵育结束后,分别加入CCK-8与MTT试剂,检测两种方法的最佳波长、培养时间、灵敏度和增殖时间.结果 CCK-8法与MTT法检测BMSCs的最佳波长分别为450 nm和550 nm,孵育时间分别为3 h和4 h,细胞接种密度分别为0.1×104/孔和0.25×104/孔.CCK-8法与MTT法在BMSCs接种密度分别高于0.25×104/孔和0.5×104/孔时,两种方法检测所得OD值均提早进入平台期,易出现假S型增长曲线.而当密度分别低于0.05×104/孔和0.1×104/孔时,细胞增加缓慢,难以形成S型增长曲线,不能反映出BMSCs的增殖特性.与CCK-8法相比较,在细胞密度低于0.1×104/孔或高于2×104/孔时,MTT法对BMSCs在翻倍时OD值增加的响应量无明显变化,差异无统计学意义.而细胞密度为0.25×104/孔至1×104/孔时,MTT法对BMSCs在翻倍时OD值增加的响应量明显增加,差异有统计学意义(P<0.05).结论 MTT法更适用于左归丸含药血清干预BMSCs增殖和分化的研究.

OBJECTIVE:To investigate the protective effects of Zuogui Wan (ZGW) on bone loss induced by ovariectomy (OVX) and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model.METHODS:Fifty Sprague-Dawley female rats were randomly divided into sham-operated (sham) group and four OVX subgroups. Rats subjected to sham and OVX were treated with the vehicle (OVX, 1 mL/100 g weight, n = 10), 17β-estradiol (E2, 50 μg*kg-1*d-1), and ZGW at the doses of 2.3 (ZGW-L) and 4.6 (ZGW-H) g/kg/day lyophilized powder daily for 3 months, respectively. The serum biochemical parameters of 17β-estrogen (17β-E2), tartrate-resistant acid phosphatase (TRACP-5b) and bone alkaline phosphatase (BALP) were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones. Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur. The gene or protein expression of orexin-A, orexin receptor 1 (OX1R), orexin receptor 2 (OX2R), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were assayed by either quantitative polymerase chain reaction or Western blot analysis.RESULTS:Compared with the OVX group, ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and17β-E2 (P < 0.01). Meanwhile, ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number, and arranging the trabeculae structure properly. Compared with the OVX group, it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae, and OPG in the tibiae of ZGW groups (P < 0.01, < 0.05), while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae (P < 0.01).CONCLUSION:ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.

慢性便秘发病率高,严重影响患者的生命质量,并能引发一系列严重危害.中医针对便秘病因多端、病性多样、病机多变等特点,运用灵活辨证、整体治疗思路,创制了众多有效方药,其中中成药治疗慢性便秘的优势尤为明显.现总结中医对慢性便秘的认识,分析其证治特点和用药规律,并以临床常用效方首荟通便胶囊为例,阐述中成药治疗慢性便秘的优势与应用,以期为患者提供简、便、效、廉的治疗方法.

方剂学是衔接传统中医和现代生命科学,推进中医药现代化的热点领域之一.在学科发展过程中,方剂学科经历了肇始阶段、初步发展阶段、振兴阶段及全面深化发展阶段,深刻反映了学科发展的历程.面对快速发展的新形势,方剂学正面临一些现实的困境.站在新的历史起点上,应当深入学科分化、促进学科交叉,调整学科结构、服务人才培养,加强信息化建设,完善学科队伍建设,建立健全中医药规范体系,完成科教研与企业的深度融合,有效服务社会.

骨髓抑制是恶性肿瘤放化疗中的常见不良反应之一.中医药在治疗放化疗所致的骨髓抑制中具有效果明确、不良反应小的优点.人参固本口服液由千古名方六味地黄丸与人参固本丸合方而成,是治疗放化疗骨髓抑制的有效药物.现从人参固本口服液的组方结构、功效特点和现代药理研究探究其治疗放化疗骨髓抑制的机制,以期为人参固本口服液在放化疗骨髓抑制防治中的应用提供理论指导.

目的 采用静息态功能磁共振(RS-fMRI)观察雷火灸干预原发性骨质疏松症腰背疼痛患者自发性脑活动的影响,并分析自发性脑活动与疼痛改善的相关性.方法 入组原发性骨质疏松症腰背痛患者18例,给予雷火灸治疗,取穴肝俞、肾俞、大肠俞、命门、腰阳关,每组腧穴治疗30 min,每周3次,隔日1次,持续4周.治疗4周前后采用视觉模拟评分(VAS)和RS-fMRI进行评估.结果 ①VAS治疗后较治疗前显著改善(P<0.05);②与治疗前比较,治疗后以左侧岛叶、左侧颞下回、左侧海马为代表的脑区低频振幅(ALFF)值显著降低,且ALFF值与VAS评分差值具有显著正相关.结论 雷火灸治疗能缓解原发性骨质疏松症(POP)患者慢性腰背疼痛,其调节自发性脑活动可能是重要的作用机制之一.

目的 探讨左归丸治疗绝经后骨质疏松症合并骨关节炎的可能作用机制.方法 60只雌性SD大鼠按随机数字表法分为假手术组,模型组,阿仑膦酸钠组及左归丸低、中、高剂量组,每组10只.除假手术组外,其余各组大鼠用去卵巢法建立绝经后骨质疏松症合并骨关节炎模型.造模2周后,假手术组、模型组给予蒸馏水1 ml/(kg·d)灌胃;阿仑膦酸钠组给予阿仑膦酸钠混悬液63 mg/(kg·d)灌胃;左归丸低、中、高剂量组分别给予2.42、4.84、9.68g/(kg·d)左归丸灌胃,每日1次,每周6次.12周后观察大鼠软骨组织形态学变化,检测左侧股骨远端软骨下骨骨密度(BMD),血清肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)含量,股骨中P物质(SP)和Runt相关转录因子2(Runx2)蛋白表达,下丘脑SP及其受体神经激肽1受体(NK1-R)蛋白及mRNA表达.结果 与假手术组比较,病理显示模型组大鼠软骨表面破坏、有裂隙,软骨细胞排列混乱;软骨下骨BMD降低,血清TNF-α和IL-1 β水平升高,下丘脑SP和NK1-R蛋白及mRNA表达水平下调(P＜0.05或P＜0.01),Runx2、SP表达量减少.与模型组比较,病理显示阿仑膦酸钠组及左归丸中、高剂量组大鼠软骨损伤明显改善;软骨下骨BMD明显升高,血清TNF-α和IL-1β水平显著降低,下丘脑SP和NK1-R蛋白及mRNA表达水平上调(P＜0.01);阿仑膦酸钠组及左归丸低剂量组Runx2、SP表达量增多.与左归丸低剂量组比较,左归丸中、高剂量组大鼠下丘脑NK1-R mRNA表达显著升高(P＜0.05或P＜0.01).左归丸高剂量组IL-1β水平显著低于左归丸低、中剂量组(P＜0.01).结论 左归丸可能通过上调下丘脑神经肽SP及其受体蛋白、mRNA水平,提高软骨下骨骨密度,进而纠正骨代谢失衡,是其防治绝经后骨质疏松症合并骨关节炎的作用机制之一.

小儿消积止咳口服液是目前临床治疗小儿咳嗽的常用中成药,是根据小儿咳嗽的病机特点,以疏风宣肺,化痰止咳,理脾和胃,消积化滞为制方思路,由山楂、槟榔、枳实、枇杷叶、瓜蒌、莱菔子、葶苈子、桔梗、连翘、蝉蜕制备而成.该方用药平和,配伍清疏宣通俱备,肺脾兼治,脏腑同调.多年临床实践表明其疗效显著,服用方便,口感良好,未见明显不良反应,有较好的推广应用价值.

原发性骨质疏松症(primary osteoporosis,POP)是以低骨量及骨组织微结构退化为特征的一种全身性骨病,伴有骨脆性增加,且容易发生骨折,是绝经后女性及老年人的常见病、多发病.疼痛是本病最典型的临床表现和首要就诊原因,其中70％～80％的患者表现为腰背痛,对老年人的生活质量产生了严重影响.目前很多学者从中西医康复治疗的角度进行了临床报道,虽各具特色,但疗效不一.本文就其康复治疗的最新进展进行综述.

骨质疏松症的防治是现代医学的一大难题,笔者对《黄帝内经》中“骨痿”“骨枯”“骨极”等相关内容进行梳理,把其中论及的概念、症状、病因病机、治则治法等经典原文整理分析并归纳总结,同时借鉴后世医家对该病的认识,总结出骨质疏松症应从“肝肾不足、脾肾亏虚、气滞血瘀”进行辩证论治,为临床研究提供新的思路及参考.

OBJECTIVE To compare the therapeutic effect of thunder-fire moxibustion combined with vibration training and simple vibration training on low back pain of primary osteoporosis by Young's modulus of ultrasonic wave, and seek an objective evaluating method. METHODS A total of 60 patients were randomized into an observation group and a control group, 30 cases in each one. The patients in the two groups were treated with vibration training using whole body vibration treatment bed. In the observation group, thunder-fire moxibustion was applied at Yaoyangguan (GV 3), Mingmen (GV 4), Ganshu (BL 18), Shenshu (BL 23) and Dachangshu (BL 25). The treatment was given once every other day, 3 times a week for 4 weeks. The visual analogue score (VAS), real-time shear wave elastography (RTSWE) and medical outcomes study 36-item short-form hearth survey (SF-36) were used to evaluate pain intensity, multifidus muscle tone (Young's modulus) and quality of life before treatment, after 4-week treatment and 1 month after treatment. RESULTS Compared before treatment, the VAS scores, Young's modulus of multifidus muscle and 5 dimensions of SF-36 (physical condition, body pain, general health, social function and mental health) after 4-week treatment and 1 month after treatment were significantly improved in the two groups (all P<0.05), the physiological role in the observation group after 4-week treatment and 1 month after treatment were improved (both P<0.05). In the observation group, the VAS scores, Young's modulus of multifidus muscle and 3 dimensions of SF-36 (physiological role, body pain and general health) after 4-week treatment and 1 month after treatment were superior to the control group (all P<0.05). CONCLUSION The therapeutic effect of thunder-fire moxibustion combined with vibration training is superior to simple vibration training in relieving low back pain intensity and multifidus muscle tone, and improving quality of life for primary osteoporosis. RTSWE technique can be an objective examination method to evaluate pain.

目的:探讨左归丸及其拆方治疗绝经后骨质疏松症(PMOP)的作用机制.方法:去卵巢法建立骨质疏松症模型,将40只SD大鼠平均随机分为假手术组,模型组(0.1 mL·kg-1·d-1),17β-雌二醇组(50 μg·kg-1·d-1)和左归丸补阳药低、高剂量(0.55,1.1 g·kg-1·d-1)组.灌胃给药12周后,显微CT(μ-CT)检测右侧远端股骨骨密度(BMD)及显微结构;苏木精-伊红(HE)染色观察大鼠股骨形态学变化;酶联免疫吸附法(ELISA)检测大鼠血清中Ⅰ型胶原交联羧基端肽(β-CTX)和骨特异性碱性磷酸酶(BALP)浓度;实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Western blot)检测大鼠下丘脑β2-肾上腺素能受体(β2AR),胫骨平台骨保护素(OPG)和核转录因子-κB受体激活因子配体(RANKL)蛋白及mRNA表达水平.结果:与假手术组相比,模型组大鼠BMD显著下降(P＜0.01),骨组织形态破坏;血清BALP含量降低,β-CTX含量升高(P＜0.01);下丘脑β2AR,胫骨RANKL mRNA及蛋白表达量升高(P＜0.05,P＜0.01),胫骨OPG mRNA及蛋白表达量降低(P＜0.05,P＜0.01).治疗后,与模型组比较,各用药组大鼠BMD升高(P＜0.01),骨组织形态改善;血清BALP含量升高,β-CTX含量降低(P＜0.01);下丘脑β2AR,胫骨RANKL mRNA及蛋白表达降低(P＜0.05,P＜0.01),胫骨平台OPG mRNA和蛋白表达升高(P＜0.05,P＜0.01).结论:左归丸拆方中补阳药能通过调节β2AR介导的OPG/RANKL信号通路提高去卵巢大鼠骨密度,“阳中求阴”配伍特点是左归丸治疗PMOP的关键之一.

Background: Osteoarthritis is the main cause of disability and pain. Due to limited understanding of the disease mechanism, it is generally difficult to diagnose early and eliminate sequelae. The aim of this study was to identify novel biomarkers for osteoarthritis (OA) using a bioinformatics approach. Method: The gene expression dataset GSE82107 were obtained from the Gene Expression Omnibus (GEO) database. Matrix quality assessment was performed using corrplot packages and principal component analysis. The differentially expressed genes (DEGs) picked out using GEO2R tool. Enrichment analyses were performed using The Database for Annotation, Visualization and Integrated Discovery and Gene Set Enrichment Analysis (GSEA). Weighted correlation network analysis (WGCNA) was used to find gene modules highly associated with OA. Cytoscape with Molecular Complex Detection (MCODE) plug-in was utilized to analyze protein-protein interaction of these DEGs. Receiver operator characteristic curve analysis was used to evaluate the diagnostic effectiveness of genes. Results: Samples with different conditions (HC and OA) are obviously distinguished, and the distance between biological replicates is relatively close. In total, 1676 DEGs were identified. Enrichment analysis showed that there were some gene sets related to OA pathology, such as chondrocyte development. The results of WGCNA analysis showed that 298 genes were most positive associated with OA. 10 common genes obtained were selected as candidate core genes. ROC results showed that 5 of these genes had the greatest diagnostic value. Conclusion: This is the first study to identify biomarkers related to OA by combining multiple algorithms such as GSEA, WGCNA, MCODE and ROC. We suggest that GLG1, PAPSS2, CTSK, TIMP1 and SDC1 could serve as valuable biomarkers. Further studies are needed to examine the precise role and mechanism of these genes in OA.

《辅行诀脏腑用药法要》是一部重要的敦煌遗书.该书作者陶弘景以体用辨证观将五脏系统划分为脏之体与脏之用.调节脏气的本质就是调平脏之体与脏之用之间的失衡态.《辅行诀脏腑用药法要》的病证条文均引自《黄帝内经》的不同篇章,但以《灵枢·本神》《灵枢·邪在》《素问·脏气法时论》等为主.陶弘景以“体虚为实,用虚为虚”为脏腑虚实辨证的准则,对五脏病证加以概述.文章旨在辨析陶弘景五脏体用的内涵.

目的:探讨左归丸治疗绝经后骨质疏松症的分子机制之一是通过对β2-肾上腺素能受体(β2AR)介导的核转录因子-κB受体激活因子配体(RANKL)/骨保护素(OPG)信号通路的调节.方法:通过去卵巢法建立骨质疏松模型,将40只雌性SPF级SD大鼠随机分为模型组、假手术组、雌二醇(50 μg·kg-1·d-1)组、左归丸低、高剂量(2.3,4.6 g·kg-1)组.采用酶联免疫吸附实验检测血清骨转换标志物;显微CT对右侧股骨远端骨密度水平和骨小梁微结构进行测量和分析;实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Western blot)检测胫骨和下丘脑组织中β2AR,OPG,RANK mRNA和蛋白表达水平.结果:与模型组比较,左归丸可显著降低大鼠血清中Ⅰ型胶原交联羧基端肽(β-CTX)水平(P＜0.01),增加骨特异性碱性磷酸酶(BALP)水平(P＜0.01),减少卵巢摘除诱导引起的大鼠骨量丢失,改善股骨远端骨小梁显微结构水平.同时,左归丸高、低剂量组均能显著上调胫骨组织中OPG mRNA和蛋白表达(P＜0.01),下调下丘脑组织β2AR mRNA和蛋白表达水平(P＜0.01),同时也能显著下调胫骨组织中RANKL mRNA和蛋白表达水平(P＜0.01).结论:左归丸改善围绝经期综合症,增加骨量和改善骨小梁显微结构水平的分子机制可能与对β2 AR介导的RANKL/OPG信号通路的调节有关.

左归丸是滋阴补肾、填精益髓的经典名方,体现了“阳中求阴”的配伍思路,是防治骨质疏松症(0P)的常用有效方剂之一.OP动物模型模拟了OP在人体的病理状态和发病机制,是OP防治和新药研发的重要手段.该文详细论述了左归丸防治OP的2大类常用动物模型和特点,即原发性OP动物模型,包括去卵巢法动物模型和自发性老年OP动物模型;继发性OP动物模型,包括糖皮质激素诱导性动物模型,环磷酰胺诱导性动物模型以及肾大部切除性动物模型.左归丸防治OP的效用评价,包括酶联免疫吸附测定实验检测骨吸收标记物和骨形成标记物含量,双能X射线检测骨密度,显微CT分析骨小梁数量、骨小梁分离度、骨小梁厚度、骨体积/组织体积比以及骨表面/体积比,以衡量骨微结构水平,苏木精-伊红染色法观察骨病理形态,生物力学实验测试骨最大载荷力等生物力学特性.OP动物模型的成功与否,以及左归丸的药效作用,必须与5种不同的客观评价方法结合起来进行综合衡量,才能为左归丸的基础和临床研究提供科学的参考依据.但OP动物模型有待进一步优化,以凸显左归丸治疗OP的中医病机和证候特征.