We previously described follicular unit extraction (FUE) for axillary bromhidrosis (AB). To enhance efficacy, we refined the technique into apocrine-pilosebaceous unit extraction (A-PSUE). The A-PSUE technique is carried out by extracting the follicular unit with a 1.0 mm punch, followed by a circular excision of the dermal tissue connected to the extracted follicular unit using microsurgical scissors. The excised tissue is subjected to immunofluorescence histochemical staining to evaluate the apocrine gland marker, apolipoprotein D (APOD), and the eccrine gland marker, sodium-potassium-chloride co-transporter 1 (NKCC1). Postoperative complications were documented, and odor severity was assessed using the visual analog scale (VAS), along with patient satisfaction and re-operation willingness at 6 months postoperatively. A 12-month follow-up was further conducted to evaluate long-term efficacy, with observation of symptom changes across the summer season. Thirty-one AB patients were treated. The axillary pinholes healed within five days. No significant complications occurred, except for one case of scar hyperplasia. Histology confirmed abundant skin appendages, with numerous apocrine gland clusters staining positively for APOD and NKCC1. Significant improvement in odor symptoms and patient satisfaction was observed at 6 months, and the therapeutic effect remained stable at the 12-month follow-up. The A-PSUE technique is an efficient, minimally invasive, and effective treatment for AB with a low complication rate. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

OBJECTIVE:Ferroptosis is a reactive oxygen species (ROS)- and iron-dependent form of non-apoptotic cell death process. Previous studies have demonstrated that ferroptosis participates in the development of inflammatory arthritis. However, the role of ferroptosis in rheumatoid arthritis (RA) inflammatory hypoxic joints remains unclear. This study sought to explore the underlying mechanism of ferroptosis on lipopolysaccharide (LPS)-induced RA fibroblast-like synoviocytes (FLSs).METHODS:FLSs, isolated from patients with RA, were treated with LPS and ferroptosis inducer (erastin and RSL-3), and ferroptosis inhibitor (Fer-1 and DFO), respectively. The cell viability was measured by CCK-8. The cell death was detected by flow cytometer. The proteins level were tested by Western blot. The cytosolic ROS and lipid peroxidation were determined using DCFH-DA and C11-BODIPY581/591 fluorescence probes, respectively. The small interfering RNA (siRNA) was used to knock down related proteins. The levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), iron, inflammatory cytokines (IL6 and IL8), and LDH were analyzed by commercial kits.RESULTS:Ferroptosis was activated by LPS in RA FLS with increased cellular damage, ROS and lipid peroxidation, intracellular Fe and IL8, which can be further amplified by ferroptosis inducer (erastin and RSL-3) and inhibited by ferroptosis inhibitor (Fer-1 and DFO). Mechanistically, LPS triggered ferroptosis via NCOA4-mediated ferritinophagy in RA FLSs, and knockdown of NCOA4 strikingly prevent the process of ferroptosis. Intriguingly, LPS-induced RA FLSs became insensitive to ferroptosis and NCOA4-mediated ferritinophagy under hypoxia compared with normoxia. Knockdown of HIF-1α reverted ferroptosis and ferritinophagy evoking by LPS-induced RA FLSs inflammation under hypoxia. In addition, low dose of auranofin (AUR) induced re-sensitization of ferroptosis and ferritinophagy through inhibiting the expression of HIF-1α under hypoxia.CONCLUSIONS:NCOA4-mediated ferritinophagy was a key driver of ferroptosis in inflammatory RA FLSs. The suppression of NCOA4-mediated ferritinophagy protected RA FLSs from ferroptosis in LPS-induced inflammation under hypoxia. Targeting HIF-1α/NCOA4 and ferroptosis could be an effective and valuable therapeutic strategy for synovium hyperplasia in the patients with RA.

Depression is associated with intestinal dysbiosis. Venlafaxine is a commonly used antidepressant in clinical practice as a serotonin and noradrenaline reuptake inhibitor. However, its effects on gut bacteria in depression remain unclear. Here, we established a mouse model of depression induced by chronic unpredictable mild stress (CUMS), and investigated the alterations of venlafaxine on the gut microbiota and potential key bacteria. Our data show that venlafaxine exerts antidepressant effects by restoring the serotonin (5-HT) system and glutamate (Glu) levels in CUMS mice. Moreover, we revealed that venlafaxine altered the diversity of gut bacteria in CUMS mice, and at genus level, Blautia, Oscillibacter, Tyzzerella, Butyricicoccus, and Enterorhabdus are the key bacteria responsible for venlafaxine-ameliorated depression in mice. Among these potential key bacteria, Blautia, Oscillibacter, and Butyricicoccus are correlated significantly with the 5-HT and 5-hydroxyindoleacetic acid levels; while Tyzzerella is correlated markedly with Glu levels. We further show that venlafaxine affected multiple functional metabolic pathways of gut bacteria in mice with CUMS-induced depression. Our results suggest that venlafaxine possibly ameliorates depression via modulating gut bacteria, and found the potential targets of its antidepressant effects.

Objective To observe the therapeutic effects of Jinqi Jiangtang Tablet on C57BL/6 obese mice, and predict the related mechanism of Jinqi Jiangtang Tablet in treating obesity based on network pharmacology. Methods The total of 30 SPF male C57BL/6 mice were selected and divided into normal group, model group and Jinqi Jiangtang Tablet group. Normal group was fed normal diet, model group and Jinqi Jiangtang Tablet group were fed high-fat diet, and drug intervention was given after successful model replication. Body weight, lipid level, fat content, liver and adipose tissue morphology of C57BL/6 mice were determined. The active ingredients and intersection targets of Jinqi Jiangtang Tablet in treating obesity were screened by TCMSP and GeneCards databases. The intersection targets were imported into STRING database to analyze the interaction between targets. GO analysis and KEGG pathway enrichment analysis were performed with Biocondoctor database. The protein expression of key signaling pathways was verified with Western blot based on the prediction results of network pharmacology. Results Compared with control group, the body weight and serum content of triglyceride（TG）, total cholesterol（TC） and low density lipoprotein cholesterol（LDL-C） in model group were higher（P＜0.05） while high density lipoprotein cholesterol（HDL-C） content was lower（P＜0.05）. The lipid droplet accumulation in liver tissue increased significantly, and the number and volume of adipose cells increased. Compared with model group, the body weight and serum content of TG, TC and LDL-C in Jinqi Jiangtang Tablet group were lower（P＜0.05）, while HDL-C content was higher（P ＜0.05）. The accumulation of lipid droplets in liver tissue was improved, and the number and volume of adipose cells decreased. Micro-CT showed that compared with control group, the content of white fat and brown fat in model group were significantly higher（P＜0.01）, while Jinqi Jiangtang Tablet could reduce the content of two kinds of fat（P＜0.01）. Meanwhile, Jinqi Jiangtang Tablet could improve liver and adipose tissue degeneration in obese mice. The total of 55 common targets and 79enrichment pathways of Jinqi Jiangtang Tablet for obesity were predicted by network pharmacology. KEGG enrichment analysis showed that the mechanism of action of Jinqi Jiangtang Tablet in the treatment of obesity may be closely related to fluid shear stress and AGE-RAGE signaling pathway, TNF signaling pathway and PPARγ signaling pathway in arteriosclerosis and diabetes complications. Western blot showed that compared with control group, the key proteins of PPARγ signaling pathway in adipose tissue of mice in model group were significantly up-regulated. Compared with model group, the key proteins of PPARγ signaling pathway in adipose tissue of mice in Jinqi Jiangtang Tablet group were significantly down-regulated. Conclusion Jinqi Jiangtang Tablet can effectively reduce the weight of obese mice, improve dyslipidemia, decrease the body fat content, and improve the accumulation of fat drops in liver tissue and the number and size of fat cells in adipose tissue. It may take effects in treating obesity through PPARγ signaling pathway.

Rheumatoid arthritis (RA) synovium was identified as "tumor-like" tissues because of the hypoxic microenvironment, significant cell proliferation, and invasion phenotypes. It was reported that hypoxia promoted tumor aggressiveness via up-regulated expression of fascin-1 in cancer. However, the role of fascin-1 in RA synovial hyperplasia and joint injury progression remains unknown. In the current study, we first identified that both fascin-1 and HIF-1α were highly expressed in the RA synovium, in which they were widely colocalized, compared to osteoarthritis(OA). As well, levels of fascin-1 in RA fibroblast-like synoviocytes(FLSs) were found significantly higher than those in OA FLSs. Further, it was demonstrated that the mRNA and protein levels of fascin-1 in RA FLSs were up-regulated in hypoxia (3 % O2) and experimental hypoxia induced by cobalt chloride. Mechanistically, the HIF-1α-mediated hypoxia environment activated the gene expression of the fascin-1 protein, which in turn promoted the migration and invasion of RA FLSs. Accordingly, the restoration of FLSs migration and invasion was observed following siRNA-mediated silencing of fascin-1 and HIF-1α expression. Notably, under the experimental hypoxia, we found that the expression levels of fascin-1, HIF-1α, and p-STAT3 were increased in a time-dependent manner, and fascin-1and HIF-1α expressions were dependent on p-STAT3. Our results indicated that hypoxia-induced fascin-1 up-regulation promoted RA FLSs migration and invasion through the STAT3/HIF-1α/fascin-1 axis, which might represent a novel therapeutic target for the treatment of RA.

Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which angiogenesis represents a critical early event of synovial inflammation. The present study aimed to reveal the potential molecular mechanisms of SAA/TLR4 induction of angiogenesis through NETs in RA. Materials and methods: Firstly, immunohistochemistry and immunofluorescence were used to determinate TLR4 and NETs expression in synovial tissue, respectively. ELISA was used to detect the content of SAA, MPO and NE in serum and synovial fluid of patients. DNA quantification was done by fluorescence. DNA fluorescence staining was used to compare NETs formation in RA and HC sera, and to investigate the mechanism of NETs formation induced by SAA stimulation. PicoGreen DNA testing was used to characterize the DNA in the supernatants. Also, DNA fluorescence staining to explore whether NETs formation induced by SAA was dependent or independent on NADPH oxidase pathway. MTT assay, Wound healing assay, Tube formation assay were performed to analyze human veins umbilical cells (HUVECs) proliferation, migration, and tube vessels formation, respectively under NETs or NETs + DNase stimulants. Results: Firstly, we demonstrated that TLR4 was predominantly and widely expressed in synovial tissues with elevated serum levels of SAA, compared to osteoarthritis (OA) patients, and the similar results were observed for NETs formation. Afterwards, in a series of in vitro experiments, we reported an increased MPO and NE levels, and a relatively decreased DNA level in the sera of RA patients. Set apart, the levels of MPO and NE in RA were correlated to the disease activity. Moreover, an increased spontaneous NETs formation was observed in RA patients, enhanced under SAA stimulation and regulated by TLR4 activation. And the total DNA expressed in RA patients was partly composed of NET-DNA. Also, SAA induced NETs formation dependent on NADPH pathway. Finally, our results indicated that extracted SAA-induced NETs promoted endothelial cells (ECs) migration, proliferation, and vascular tube formation. Conclusion: Our current study highlighted the role of SAA/TLR4 interaction in the induction of angiogenesis through formed NETs. Therefore, this study offers new perspectives in the understanding of RA pathogenicity and its management.

Triptolide is a natural active compound that has significant neuroprotective properties and shows promising effects in the treatment of Alzheimer's disease (AD). Recent studies have shown that autophagy occurs in AD. In this study, we determined whether autophagy regulated by triptolide ameliorates neuronal death caused by amyloid-Beta1-42 (Aβ1-42). We examined the effects of triptolide on cell viability, autophagy, apoptosis, and the protein kinase B/mammalian target of the rapamysin/70 kDa ribosomal protein S6 kinase (Akt/mTOR/p70S6K) signaling pathway in PC12 cells. The results indicated that triptolide treatment exhibited a cytoprotective effect against cell injury induced by Aβ1-42. Triptolide also reduced apoptosis and enhanced cell survival by decreasing autophagosome accumulation and inducing autophagic degradation. Furthermore, our results also showed that activating the Akt/mTOR/p70S6K mechanism was one reason for the protection of triptolide. Triptolide treatment protected against Aβ1-42-induced cytotoxicity by decreasing autophagosome accumulation, and inducing autophagic degradation in PC12 cells. These findings also suggest that the reduction of autophagosome accumulation observed in triptolide-treated cells was Akt/mTOR/p70S6K pathway dependent. Overall, triptolide exhibits a neuron protective effect and this study provides new insight into AD prevention and treatment.

中西医结合医学作为我国的特色医学,是未来医学的发展方向.随着人民群众健康需求的日益提升,中西医结合医学人才短缺的问题逐渐凸显.通过对湖南医药学院院长何清湖教授进行专访,以探讨中西医结合人才培养与专业建设的问题.何教授认为,加强中西医结合人才培养体系及专业建设,是中西医结合医学发展的关键.中西医结合人才体系的培养应注重:合理规划本科教育,按照"梯队"模式培养人才,完善人才的任用与激励机制.中西医结合专业建设的重点在于:在教学过程中探寻更适合的教育模式,围绕"新医科"理念,推动学科的交叉.何教授的观点为今后中西医结合医学的发展指明了方向.

目的:通过收集和总结文献,探讨中医、西医、中西医结合治疗慢性前列腺炎的方法,从而为进一步研究该病的治疗方法提供帮助.方法:使用计算机搜索中国学术期刊全文数据库(CNKI)、中国生物医学文献数据库(CMCC)、维普中文期刊数据库(VIP)、万方数据资源系统中国内外发表的关于治疗慢性前列腺炎的临床研究文献,整理中医、西医、中西医结合对于不同分型慢性前列腺炎的治疗方法,对中医、西医、中西医结合治疗该病的优缺点进行归纳总结.结果:共收集符合纳入标准的中医和中西医治疗慢性前列腺炎的文献133篇,排除不合格文献97篇,最终纳入36篇.最终分别总结出中医辨证论治法、内治法、外治法和中西医结合疗法4种慢性前列腺炎的治疗方法.结论:中医和西医在治疗慢性前列腺炎方面各有所长,缺点也相对明显.中医治疗和中西医结合治疗是我国特有的诊疗方法,针对慢性前列腺炎的疗效优于单纯中医治疗和西医治疗.但目前中西医结合医学还不成熟,缺乏相应的理论体系来指导中医和西医临床治疗方法的结合.

The aim of the present study is to determine whether plasma bile acids (BAs) could be used as an auxiliary diagnostic biomarker to distinguish patients with schizophrenia from healthy controls. Seventeen different BAs were quantitatively measured in plasma of 12 healthy participants and 12 patients with schizophrenia. Then, the data were subjected to correlation and linear discriminant analysis (LDA). The concentrations of cholic acid (CA), taurochenodeoxycholic acid (TCDCA) and taurodeoxycholic acid (TDCA) were significantly decreased in plasma of the schizophrenia patients. Correlation analysis showed the concentrations of CA, TCDCA and TDCA were negatively correlated with schizophrenia. In addition, LDA demonstrated that combination of CA, TCDCA and TDCA with a classification formula could predict correctly classified cases and the accuracy of prediction was up to 95.83%. Combination of the three BAs may be useful to diagnose schizophrenia in plasma samples.

生物化学是医学专业基础课程之一,具有概念繁多、内容庞杂的特点.尤其是物质代谢部分,涉及复杂的代谢路径,学生记忆和理解起来难度较大,容易产生畏难情绪.本文通过思维导图分别梳理糖、脂代谢的知识体系,同时通过类比分析比较糖脂代谢的异同点,明确二者的关联.一方面,思维导图便于学生更加直观地把握课程的逻辑主线;另一方面,类比分析能提高学生对代谢途径的理解和分析能力.以上方法的使用,提高了学生的思维能力,改善了学生学习糖、脂代谢的学习效果.

组织学与胚胎学(以下简称组胚)的课程特点、学情和教学现状等多方面因素致使其教与学分离严重,而整合医学理念则为解决上述问题提供了新思路.笔者通过教学实践,提出以下几点代表组胚教学中整合医学理念和教育改革研究的思考方向:整合中医学的整体观、整合多学科相关知识、整合思想政治教育相关内容、整合前沿学术动向,为改进组胚教学效果提供参考和借鉴.

ObjectiveThe aim of this study is to discover the possible working mechanisms of Ardisiae Japonicae Herba (AJH) on hepatoma carcinoma (HCC).MethodsIn this study, ethanol extract of AJH was prepared and used to treat HCC cell in vitro. Furthermore, a genomic wide RNA sequencing (RNA-seq) was performed to screen deregulated genes in HCC cells after the treatment of AJH extract. The gene and protein expression related to lipid metabolism in HCC cells were also investigated to validate the results obtained from RNA-seq.ResultsAJH extract could inhibit HCC cell proliferation in vitro. RNA-seq analysis has identified 1,601 differentially expressed genes (DEGs, fold change ≥ 2.0 or fold change ≤ 0.5, P < 0.05) in HCC after AJH extract treatment, which included 225 up-regulated genes and 1,376 down-regulated genes. KEGG pathway analysis of DEGs demonstrated that lipid metabolism was a potential pathway related to AJH treatment. In agreement with the RNA-seq data, qPCR and Western-blot analysis indicated that expression of genes and proteins related to lipid metabolism (SREBP1, ACC, ACLY and FASN) were significantly down-regulated in AJH treatment group as compared with the control group. Furthermore, AJH extract could also decrease lipid contents and cellular free fatty acid levels in HCC cells.ConclusionEthanol extract of AJH could inhibit HCC cell proliferation in vitro, the possible mechanism may be related to the inhibition of lipid metabolism.

Lipid metabolism disorder caused by the upregulation of lipogenic genes is a typical feature of prostate cancer. The synthesis of fatty acids is enhanced to accelerate the development of prostate cancer and is considered as a potential therapeutic target. Epicatechin gallate, an active compound of green tea, has been reported to modulate lipid metabolism. In this research, the potential role of epicatechin gallate in prostate cancer cells was evaluated. The results indicated that epicatechin gallate downregulates the expression of acetyl-CoA carboxylase, ATP citrate lyase, and fatty acid synthase in prostate cancer cells and prostate xenograft tissues, suggesting that epicatechin gallate can inhibit de novo fatty acid synthesis. Moreover, epicatechin gallate significantly restrains the migration rather than the viability of prostate cancer cells. PI3K/AKT/mTOR signaling pathway, which exhibits regulatory effect on lipogenesis, is also inhibited under epicatechin gallate treatment, while pretreatment with AKT activator SC79 or mTOR activator MHY1485 blocks the inhibitory effect of epicatechin gallate on the expression of lipogenic genes and the migration of prostate cancer cells. In conclusion, this study revealed that epicatechin gallate impairs the synthesis of fatty acids via inhibition PI3K/AKT/mTOR signaling pathway and then attenuates the migration of prostate cancer cells.

中西医结合诊疗模式目前在中国通过各级医疗单位逐步推广,现已成为提高人民健康水平、促进中国健康事业发展的重要推动力,在临床及科研等多方面取得了重要成果.何清湖教授以多年医疗经验为出发点,分享对于中西医结合诊疗模式现状的看法,对中西医结合的发展前景作出评价.

Microscopic polyangiitis (MPA) is a systemic autoimmune disease that primarily affects the small and medium blood vessels. Endothelial injury is one of the pathological hallmarks of MPA. However, the pathogenesis for this has not yet been fully elucidated. Exosomal microRNAs (miRNAs) have recently emerged as a new molecular pattern involved in the endothelial injury in other diseases. Hence, we speculated that MPA plasma-derived exosomes (MPA-exo) could induce the endothelial injury, which was likely to be aroused by the dysregulated exosomal miRNAs in MPA. In the present study, plasma-derived exosomes were isolated and identified. MPA-exo could be internalized by human renal glomerular endothelial cells (HRGECs) in vitro and induced HRGECs injury. Subsequently, a series of differentially expressed miRNAs in MPA-exo were identified by high-throughput sequencing analysis. Further bioinformatics analysis for the target genes of these differentially expressed miRNAs showed a potential mechanism for their possible role in MPA endothelial injury. Notably, we revealed a considerable correlation between miR-185-3p, miR-125a-3p, and clinical parameters. In conclusion, the current study revealed that differentially expressed miRNAs in MPA-exo are associated with the endothelial injury. Our results suggested that these miRNAs and their target genes might be involved in the inflammation process of MPA.

目的 探讨人参皂苷Rg3对前列腺癌细胞PC3和DU145细胞增殖的调节作用.方法 100μmol/L人参皂苷Rg3处理体外培养的前列腺癌细胞PC3和DU145,使用CCK-8实验检测细胞的增殖能力;DCFH-DA活性氧荧光探针试剂盒检测人参皂苷Rg3处理的DU145细胞中活性氧(ROS)水平;JC-1法检测PC3和DU145细胞线粒体膜电位的去极化;RT-PCR和免疫印迹法检测PC3和DU145细胞中氧化还原相关蛋白的表达差异.结果 CCK-8实验结果表明,100μmol/L人参皂苷Rg3能够显著抑制PC3细胞增殖,而对DU145细胞的增殖没有显著调节作用;DCFHDA活性氧荧光探针试剂盒检测结果表明,人参皂苷Rg3能够显著上调DU145细胞和PC3细胞中ROS水平;JC-1检测实验表明,人参皂苷Rg3能够诱导PC3和DU145细胞中线粒体膜电位去极化;RT-PCR和免疫印迹实验表明,抗氧化蛋白谷胱甘肽过氧化物酶-1(GPX-1)和超氧化物歧化酶2(SOD2)在DU145细胞中的表达显著高于PC3细胞.结论 人参皂苷Rg3对PC3和DU145细胞的增殖表现出不同的调节作用,可能与细胞中抗氧化蛋白的表达差异有关.

BACKGROUND AND PURPOSE:Sleep deprivation compromises learning and memory in both humans and animals, and can be reversed by administration of modafinil, a drug promoting wakefulness. Dysfunctional autophagy increases activation of apoptotic cascades, ultimately leading to increased neuronal death, which can be alleviated by autophagy inhibitors. This study aimed to investigate the alleviative effect and mechanism of modafinil on the excessive autophagy occurring in the hippocampus of mice with deficiency of learning and memory induced by sleep deprivation.EXPERIMENTAL APPROACH:The Morris water maze was used to assess the effects of modafinil on male C57BL/6Slac mice after 48-hr sleep deprivation. The HT-22 hippocampal neuronal cell line was also used. Nissl staining, transmission electron microscope, immunofluorescence, Western blot, transient transfection, and autophagy inducer were used to study the effect and mechanism of modafinil on hippocampal neurons with excessive autophagy and apoptosis.KEY RESULTS:Modafinil improved learning and memory in sleep-deprived mice, associated with the inhibition of excessive autophage and apoptosis and an enhanced activation of the PI3K/Akt/mTOR/P70S6K signalling pathway in hippocampal neurons. These effects of modafinil were abolished by rapamycin. In addition, modafinil suppressed the aberrant autophagy and apoptosis induced by rapamycin and reactivated PI3K/Akt/mTOR/P70S6K signals in HT-22 cells.CONCLUSIONS AND IMPLICATIONS:These results suggested that modafinil alleviated impaired learning and memory of sleep-deprived mice potentially by suppressing excessive autophagy and apoptosis of hippocampal neurons. This novel mechanism may add to our knowledge of modafinil in the clinical treatment of impaired memory caused by sleep loss.

脂代谢紊乱是前列腺癌(PCa)的一个标志性特征.固醇调节元件结合蛋白(SREBPs)是调节细胞脂类代谢的重要转录因子,能够调控脂肪酸和胆固醇合成关键基因的表达.研究表明SREBPs可能是作为治疗前列腺癌的潜在靶点.总结了SREBPs在前列腺癌发生发展中的作用机制,以及靶向SREBPs治疗前列腺癌的研究进展.