Characterization of distinct microbiota associated with androgenetic alopecia patients treated and untreated with platelet-rich plasma(PRP)

Background:Androgenic alopecia(AGA)is the most common type of hair loss in men,and there are many studies on the treatment of hair loss by platelet-rich plasma(PRP).The human scalp contains a huge microbiome,but its role in the process of hair loss remains unclear,and the relationship between PRP and the microbiome needs further study.Therefore,the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota composition.Methods:We performed PRP treatment on 14 patients with AGA,observed their clinical efficacy,and collected scalp swab samples before and after treatment.The scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3-V4 region of the 16 s RNA gene and sequencing for bacterial identification.Results:The results showed that PRP was effective in the treatment of AGA patients,and the hair growth increased significantly.The results of relative abundance analysis of microbiota showed that after treatment,g_Cutibacterium increased and g_Staphylococcus decreased,which played a stable role in scalp microbiota.In addition,g_Lawsonella decreased,indicating that the scalp oil production decreased after treatment.Conclusions:The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing.

Exogenous testosterone therapy on choroid in androgen deficiency

AIM:To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency.METHODS:Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers were included in the study.The eyes were scanned for subfoveal choroidal thickness(SFCT),choroidal vascularity index(CVI),choroidstromal area(C-SA),choroid-luminal area(C-LA),choroidstromal to luminal area ratio(CSLR),and the choroidal parameters within central 1500μm of the macula(CVI1500,C-LA1500,C-SA1500,and CSLR1500)by enhanced-depth imaging optical coherence tomography(EDI-OCT)at baseline,6th and 18th weeks of the exogenous testosterone treatment.RESULTS:The mean SFCT values of the androgen deficient groups and healthy controls were 307.7±27.0 and 303.2±37.2μm(P=0.8).However,CVI,C-SA,CSLR,CVI1500,C-LA1500,and CSLR1500 were significantly different between the groups(all P<0.01).At the 6th week visit after exogenous testosterone treatment,SFCT,CVI,C-LA,and C-SA were significantly decreased,and these parameters returned to baseline levels at the 18th-week visit(all P>0.05).However,CVI1500 and LA1500 significantly increased at the end of the follow-up period(P<0.001).CONCLUSION:CVI is lower in androgen-deficient patients than in healthy subjects.The alterations in the choroid during the testosterone peak are transient in the treatment of patients with androgen deficiency.However,the increase in CVI within the central 1500μm of the macula persists even after 4mo.

Androgen signaling inhibits de novo lipogenesis to alleviate lipid deposition in zebrafish

Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males.However,the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood,especially in teleosts.In this study,cyp17a1-/-zebrafish(Danio rerio)exhibited excessive visceral adipose tissue(VAT),lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis(DNL)enzymes.The assay for transposase accessible chromatinwithsequencing(ATAC-seq)results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/-fish compared to cyp17a1+/+male fish,including stearoyl-CoA desaturase(scd)and fatty acid synthase(fasn).Androgen response element(ARE)motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+male fish but not in cyp17a1-/-fish.Both androgen receptor(ar)-/-and wildtype(WT)zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue,lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis enzymes.The Ar agonist BMS-564929 reduced the content of VAT and lipid content,and down-regulated acetyl-CoA carboxylase a(acaca),fasn,and scd expression.Mechanistically,the rescue effect of testosterone on cyp17a1-/-fish in terms of phenotypes was abolished when ar was additionally depleted.Collectively,these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish,thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.

Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

Androgen Receptor Promotes Lung Cancer Metastasis by Modifying the miR23a-3p/EPHB2 Pathway

Objective This study aimed to investigate the reasons behind the lower survival rates in male lung cancer patients than in female lung cancer patients.Methods Through various techniques,such as Argonaute immunoprecipitation,luciferase assays,and ChIP,this study confirmed the positive effects of androgen receptor(AR)on lung cancer cell invasion across different in vitro cell lines and in vivo mouse models.Results The findings suggest that AR enhanced the invasion of lung cancer cells by modifying EPHB2 signals at the protein expression level,which in turn required changes in miRNA-23a-3p.Restoring miRNA-23a-3p could counteract the intensified invasion of lung cancer cells mediated by AR.Conclusion This study revealed that AR may facilitate the lung cancer matastasis by modulating miRNA-23a-3p/EPHB2 signaling and that targeting this signaling pathway could provide new approaches to inhibit lung cancer metastasis.

The Pathogenesis and Treatment Progress of Androgenic Alopecia

Androgenic alopecia, also known as seborrheic alopecia, is the most common hair loss disorder in dermatology clinics, mainly characterized by hair follicle miniaturization and progressive hair loss. The etiology and pathogenesis of androgenic alopecia are not clear, but may be related to heredity and androgen metabolism. Currently, minoxidil and finasteride are the only two drugs approved by the U.S. Food and Drug Administration (FDA) for AGA treatment, other treatments include oral minoxidil, hair transplantation, low energy laser therapy (LLLT), platelet-rich plasma (PRP), Chinese medicine microneedles, and combination therapy. With the development of medicine and science, we have ushered in the era of biologics and targeted therapy. In recent years, a variety of signaling pathways for androgenic alopecia have been found, which may provide a basis for targeted therapy for androgenic alopecia.

Re-Densification Effect of Pressure-Injected Peptide-Hyaluronic Acid Combination on Male Androgenic Alopecia

Introduction: Mechanism of male androgenic alopecia (MAGA) is complex and leads to an excessive hair shedding and decreased hair density. Oral, topical, and injectable autologous treatments demonstrate ability to stimulate hair re-growth, but the response is suboptimal or plateaus off. Synthetic combination of the peptide complex and hyaluronic acid (P-HA) demonstrated hair regrowth in alopecia patients. Electronically-operated pneumatic injections (EPI) generate micro-trauma in the dermis and under wound-healing conditions may enhance regeneration effect of P-HA. Methods: Subjects seeking improvement of their male pattern hair loss (Hamilton-Norwood type 2-4) received the P-HA treatments through EPI. The course included 4 treatments every two weeks over the 8-week period. In 6 months, the hair growth was assessed comparative to baseline by global clinical photography and digital phototrichograms. The treatment safety and tolerability were documented through the whole study period. Results: Twelve men (30-45 years old) completed the treatment course with high tolerability and without adverse events. Post-treatment assessment of the previously bald areas showed improved coverage on the clinical photographs. The phototrichograms demonstrated statistically significant increase in terminal hair density by 36%, cumulative hair thickness by 37%, and follicular units by 20%;all contributing to a 38% increase in cumulated hair density (all p Conclusion: Electronic pneumatic injections are well tolerated and can be safely used for the needle-free administration of the peptide-hyaluronic acid combination in MAGA therapy. We achieved significant hair re-densification in the balding scalp. The exact role of the EPI-induced impact in the hair re-growth mechanism remains to be ascertained. .

Specific alterations of regional myocardial work in strength-trained athletes using anabolic androgenic steroids compared to athletes with genetic hypertrophic cardiomyopathy

Background:Strength-trained athletes using anabolic androgenic steroids(AAS)have left ventricular(LV)hypertrophy and myocardial fibrosis that can lead to sudden cardiac death.A similar feature was described in athletes with hypertrophic cardiomyopathy(HCM),which complicates the diagnosis for clinicians.In this context,we aimed to compare the LV function of the 2 populations by measuring global and regional strain and myocardial work using speckle-tracking imaging.Methods:Twenty-four strength-trained asymptomatic athletes using AAS(AAS-Athletes),22 athletes diagnosed with HCM(HCM-Athletes),and 20 healthy control athletes(Ctrl-Athletes)underwent a resting echocardiography to assess LV function.We evaluated LV global and regional strains and myocardial work,with an evaluation of the constructive work(CW),wasted work,and work efficiency(WE).Results:Compared to Ctrl-Athletes,both AAS-Athletes and HCM-Athletes had a thicker interventricular septum,with maj ored values in HCM-Athletes.LV strain was reduced in AAS-Athletes and even more in HCM-Athletes.Consequently,global WE was significantly diminished in both AAS and HCM-Athletes(93%±2%in Ctrl-Athletes,90%±4%in AAS-Athletes,and 90%±5%in HCM-Athletes(mean±SD);p<0.05).Constructive work and WE regional analysis showed specific alterations,with the basal septal segments preferentially affected in AAS-Athletes,and both septal and apical segments affected in HCM-Athletes.Conclusion:The regional evaluation of myocardial work reported specific alterations of the major LV hypertrophy induced by the regular use of AAS compared to the LV hypertrophy due to HCM.This finding could help clinicians to differentiate between these 2 forms of pathological hypertrophy.

Clinical Study on Application of Xinrun Tongluo Method Based on the Theory of Collateral Diseases in Treating Androgenic Baldness of Blood Heat Wind Dryness Syndrome

[Objectives]To explore the intervention effect of the representative formula of Xinrun Tongluo method,Liangxue Xiaofeng Powder,on the incidence of androgenic alopecia in the syndrome of blood heat and wind dryness.[Methods]A total of 72 patients with androgenic alopecia in Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine from October,2022 to June,2023 were randomly divided into a control group(36 cases,treated with Western medicine)and a treatment group(36 cases,treated with Chinese herbal formula+Western medicine).The short-term and long-term efficacy of the two groups of patients was compared.[Results]The hair microscopic signs and short-term and long-term efficacy of the treatment group were significantly better than those of the control group before and after treatment,with a statistically significant difference(P<0.05).[Conclusions]The representative formula of Xinrun Tongluo method is Liangxue Xiaofeng Powder,which has better clinical efficacy as an auxiliary Western medicine in the treatment of androgenic alopecia patients with blood heat and wind dryness syndrome,and is worthy of further promotion and application in clinical practice.

Defective Expression of the Gap Junction Protein Pannexin-1 Channel Contributes to the Formation of PCOS-Realted Androgenetic Alopecia

Objective: To determine serum pannexin-1 channel levels and their association with hair loss in women with PCOS diagnosed with female androgenetic alopecia (FAGA). Materials and Methods: Thirty-five women with PCOS who presented with diffuse and treatment-resistant progressive hair loss and were diagnosed with FAGA were included in the study. 25 patients who were diagnosed with female androgenetic alopecia but did not have PCOS were considered as the control group. PCOS and control groups were matched by age. Follicular miniaturization, displacement of terminal hairs with vellus hairs, and a diffuse decrease in hair density were accepted as FAGA in the trcihoscopy examination of the vertex and bitempoaral area. On the third day of the menstrual cycle serum FSH, LH, testosterone, PRL and insulin levels were measured. Insulin resistance was calculated with HOMA-IR. Serum pannexin-1 channel levels of each group were mesured with ELISA. Results: Serum pannexin 1 channels levels of FAGA group due to PCOS were found to be significantly higher than FAGA patients in the control group (2.72 ± 1.09 ng/mL vs 1.65 ± 0.97 ng/mL, p < 0.01). Serum LH, insulin and testosterone levels of PCOS group were significantly higher than controls. HOMA-IR values were significantly higher and >2.5 in the PCOS group compared to the controls. PRL values were similar except for one patient with elevated PRL. Serum FSH values were the same in both groups. A positive and significant correlation was found between pannexin 1 channels levels and HOMA-IR and serum testosterone levels (r = 0.650, p Conclusions: In addition to hyperandrogenemia, increased pannexin 1 channel levels may play a role in the etiology of PCOS associated FAGA, as it impairs the communication between the skin and hair follicle.

9例儿童雄激素不敏感综合征临床特点和遗传学特点分析

目的 分析雄激素不敏感综合征(androgen insensitivity syndrome, AIS)患者的临床资料和遗传学结果。方法 收集2017—2022年在江西省儿童医院就诊的9例AIS患者临床资料,完善相关实验室检查及性腺、腹股沟彩超,并进行基因突变检测。结果 9例患者染色体均为男性核型,其中7例患者的社会性别为女性,2例为男性;所有患者就诊原因均有腹股沟斜疝(或伴有性别模糊),均发现AR基因突变,病例1为新突变(p.R608fs*18)。66.6%(6/9)的AIS患者突变位于配体结合域(ligand binding domain, LDB),80%(4/5)的完全型雄激素不敏感综合征患者突变位于LBD,50.0%(2/4)的部分型雄激素不敏感综合征患者突变位于LBD。55.5%(5/9)AIS患者突变类型为错义突变。结论 错义突变为AR基因常见突变类型,LBD是AIS的主要突变部位,外生殖器表现为女性患者,如发现腹股沟斜疝,应常规行性腺及腹股沟彩超检查以排外AIS。

1565 nm非剥脱点阵激光在雄激素性秃发中的临床疗效观察

目的探讨1565 nm非剥脱点阵激光联合外用米诺地尔及口服非那雄胺治疗雄激素性秃发(AGA)患者的效果及安全性。方法将75例Hamilton-Norwood分级Ⅱ—Ⅲ级男性AGA患者随机分为对照组1、对照组2和试验组,各25例。对照组1给予外用5%米诺地尔酊治疗,对照组2在对照组1基础上同时口服非那雄胺片,试验组除上述口服及外用治疗外,进行1565 nm非剥脱点阵激光治疗。在治疗前和治疗第24周时,采用7点总体评分量表评价毛发总体疗效;皮肤毛发镜测定毛发直径和毛发密度。治疗后调查患者满意度,并记录不良反应的发生情况。结果试验组毛发总体疗效优于对照组1和对照组2。治疗前,3组患者毛发直径和毛发密度差异均无统计学意义(P>0.05);治疗后,3组患者毛发直径和毛发密度均升高,试验组治疗后毛发直径和毛发密度均高于对照组1和对照组2(P<0.05)。试验组患者满意度优于对照组1和对照组2。试验组患者行激光治疗时出现可耐受的疼痛及灼烧感,症状均于数小时内自行缓解,各组均无严重不良反应发生。结论1565 nm非剥脱点阵激光、5%米诺地尔和非那雄胺联合疗法治疗AGA的疗效明显优于单纯使用米诺地尔和非那雄胺药物治疗。

不同比例雌雄激素诱导大鼠前列腺炎症、纤维化的研究

目的研究不同比例浓度雌雄激素对前列腺组织炎症、纤维化程度的影响。方法取4月龄SD雄性大鼠84只,随机分并对78只大鼠行双侧睾丸切除手术去势模型,同时对去势大鼠皮下注射不同浓度雌雄激素,1个月后取大鼠前列腺组织,通过HE染色和Masson染色分别观察前列腺炎症及纤维化程度。结果雌激素能诱导前列腺组织炎症浸润及纤维化,且随雌激素浓度增加而加重,而雄激素在一定程度上能缓解炎症、纤维化程度,其缓解程度与雄激素浓度比例正相关。结论雌激素能诱导前列腺组组织炎症、纤维化,雄激素能改善前列腺炎症及纤维化,其作用与浓度密切相关。

雄性激素对老年男性认知功能影响(综述)

在观察性研究中,男性雄性激素水平与整体认知、记忆、执行功能和空间表现之间存在正相关,雄性激素水平和多种认知功能与年龄增长呈负相关。关于雄性激素对认知功能影响的机理也有被报道。雄性激素补充治疗是否能改善老年男性认知功能的结论也不相同,有些研究认为睾酮补充治疗能够改善雄性激素缺乏男性的认知功能,有些结论与之相反,这需要今后更大规模的随机对照试验来进一步证实睾酮治疗在预防认知能力下降和痴呆等方面的作用。

多囊卵巢综合征患者外周血微RNA-320a-3p的表达及意义

目的探讨多囊卵巢综合征(PCOS)患者外周血微RNA(miR)-320a-3p的表达水平及miR-320a-3p调控PCOS的可能机制。方法选择2021年7月至2022年7月就诊于焦作市人民医院的149例PCOS患者为研究对象(PCOS组),另选择月经周期规律(28~35 d)、无高雄激素临床或生化表现、超声检查未发现卵巢多囊样变的健康志愿者18例为对照组。收集并比较2组受试者临床资料。应用实时荧光定量聚合酶链式反应检测2组受试者血浆中miR-320a-3p表达水平,采用Pearson偏相关分析血浆中miR-320a-3p表达与临床指标的相关性,受试者操作特征曲线分析miR-320a-3p对PCOS的预测价值,双荧光素酶报告基因测定评估miR-320a-3p与雄激素受体的关系。结果2组受试者的年龄、臀围、促卵泡激素(FSH)、催乳素(PRL)、高密度脂蛋白胆固醇(HDL-C)比较差异无统计学意义(P>0.05)。PCOS组患者的体质量指数、腰围、总睾酮(TT)、抗米勒管激素(AMH)、黄体生成素(LH)、空腹胰岛素(FINS)、空腹血糖(FBG)、餐后2 h血糖(2 h BG)、胰岛素抵抗稳态模型(HOMA-IR)、总胆固醇、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)显著高于对照组,雌二醇(E_(2))水平显著低于对照组(P<0.05)。PCOS组患者血浆中miR-320a-3p相对表达量显著低于对照组(P<0.05)。miR-320a-3p水平与TT呈中度负相关(r=-0.594,P<0.05);与腰围、FINS、2h BG、HOMA-IR、LDL-C呈低度负相关(r=-0.293、-0.208、-0.227、-0.208、-0.208,P<0.05);与臀围、AMH、FSH、E_(2)、PRL、FBG、TG、HDL-C无明显相关性(r=-0.079、0.020、-0.042、0.089、0.005、-0.141、-0.116、0.059,P>0.05)。miR-320a-3p预测PCOS的曲线下面积为0.968(95%置信区间为0.922~1.000,P<0.05),截断值为0.515,敏感度为0.917,特异度为0.789,约登指数为0.706。miR-320a-3p能够负调控雄激素受体。结论PCOS患者外周血中miR-320a-3p呈异常低表达,其可能通过负向调控雄激素受体使TT水平升高来参与PCOS的发生发展,对PCOS具有较高的预测价值。

血清白细胞介素-35表达水平与前列腺癌全雄激素阻断治疗预后的相关性分析

目的 探究血清白细胞介素-35(IL-35)表达水平与前列腺癌全雄激素阻断(MAB)患者预后的相关性。方法 收集2017年4月至2020年4月在本院接受MAB治疗的60例前列腺癌患者为研究对象。测定患者治疗前血清IL-35水平。依据随访结果,用受试者工作特征(ROC)曲线确定IL-35最佳截断值,并以此将纳入者分为低IL-35组和高IL-35组。比较2组病理特征,Kaplan-Meier生存曲线和Cox回归模型分析血清IL-35与患者预后的相关性。结果 以3年随访是否死亡为结局绘制ROC曲线,所得IL-35最佳截断值147.73 pg/ml[曲线下面积(95%CI)=0.667(0.517,0.818,P<0.001)],并以此为临界点将患者分为低IL-35组(<147.73 pg/ml)和高IL-35组(≥147.73 pg/ml)。高IL-35组中Gleason评分>7分(58%和29%)、肿瘤T分期中T4期(74%和44%)和伴淋巴结转移(68%和39%)者占比均显著高于低IL-35组(P<0.05)。KaplanMeier生存曲线显示,低IL-35组患者无进展生存(PFS)[(32±4)个月和(23±4)个月]和总生存[(32±3)个月和(24±4)个月]情况均优于高IL-35组患者(χ^(2)=11.988、8.617,P<0.05);单因素和多因素Cox回归模型分析显示,血清IL-35水平[HR值(95%CI)=1.044 (1.017,1.073)]、[HR值(95%CI)=1.035(1.006,1.064)];Gleason评分[HR值(95%CI)=2.218 (1.449,6.307)]、[HR值(95%CI)=3.056 (1.649,9.447)];临床T分期[HR值(95%CI)=2.056(1.553,5.984)]、[HR值(95%CI)=1.900(1.237,11.622)]和伴淋巴结转移[HR值(95%CI)=2.415(2.084,7.445)]、[HR值(95%CI)=4.147(1.081,15.910)]均是影响MAB治疗的前列腺癌患者无进展生存期(PFS)和总生存情况的独立危险因素(P<0.05)。结论 治疗前血清IL-35水平异常升高是影响前列腺癌患者MAB治疗预后的独立危险因素。

蔓柏生发方改善小鼠的雄激素性脱发可能与肠道菌群相关:基于16S rDNA分析

目的基于16S rDNA技术探索蔓柏生发方对雄激素性脱发(AGA)小鼠的肠道菌群影响。方法将36只C57BL/6小鼠随机分成6组:空白对照组、模型对照组、阳性药物组以及蔓柏生发方高、中、低组,每组6只。剔除所有小鼠脊背部2 cm×3 cm面积的毛发,除空白对照组外,其他组使用丙酸睾酮稀释液在小鼠背部脱毛区域进行皮下多点注射制备AGA模型,每只总剂量为0.1 mg/d。空白对照组和模型对照组在小鼠剃毛处外涂生理盐水,每只1.0 mL/d;阳性药物组涂5%米诺地尔酊,每只1.0 mL/d;蔓柏生发方高、中、低组分别灌胃不同浓度的蔓柏生发方(5.0 g/kg、2.5 g/kg、1.25 g/kg),连续给药30 d。30 d后留取脱毛区皮肤进行病理学观察,收集小鼠粪便进行16S rDNA分析。结果与模型组相比,蔓柏生发方组毛囊数量均明显增多,其中高剂量组可见毛囊呈现生长期样形态,接近空白组毛囊形态。多样性分析结果显示,与空白组比较,模型组肠道菌群丰富度、多样性明显下降,而蔓柏生发方对模型小鼠的肠道菌群丰富度有良好的上调作用,同时其作用具有浓度依赖性,高剂量组对菌群的调控作用最为显著。肠道菌群的α多样性指数在模型组与蔓柏生发方组之间存在显著差异(P<0.05)。结论蔓柏生发方能显著提高AGA小鼠肠道菌群的丰富度和多样性,其对AGA模型小鼠脱毛的治疗作用可能与其调节肠道微生物多样性有关。

神经复元方对H_(2)O_(2)诱导的大鼠海马神经元损伤后雄激素受体活化的影响

[目的]探究神经复元方对过氧化氢(H_(2)O_(2))诱导的SD大鼠海马神经元损伤中雄激素受体(AR)的活化影响,探讨其治疗卒中后抑郁的作用机制。[方法]取新生24 h的SD大鼠的海马组织,分离原代大鼠海马神经元,通过微管相关蛋白2(MAP-2)免疫荧光鉴定细胞。对SD大鼠给予神经复元方灌胃处理,分离血清,获得空白血清和含药血清,再利用细胞计数试剂(CCK8)检测确定含药血清的最佳处理浓度。使用100μmol/L的H_(2)O_(2)对大鼠海马神经元细胞处理致损伤,分为空白血清组、损伤模型+空白血清组、损伤模型+含药血清组、损伤模型+氟西汀4组。利用蛋白质免疫印迹法(Western blot)和免疫荧光检测各组AR蛋白磷酸化及非磷酸化的情况。[结果]与空白血清组相比,损伤模型+空白血清组的AR、p-AR蛋白表达显著下降。与损伤模型+空白血清组相比,损伤模型+含药血清组和损伤模型+氟西汀组的AR、p-AR蛋白表达上升。[结论]神经复元方对H_(2)O_(2)诱导的SD大鼠海马神经元损伤有一定修复作用,能够促进AR活化,提示AR可能为神经复元方治疗脑卒中后抑郁的重要靶蛋白。

4例46,XY性发育障碍患者遗传学分析

目的:探讨4例46,XY性发育障碍发生的分子机制。方法:收集患者临床病历资料,采集其肝素抗凝外周血进行淋巴细胞培养,染色体G显带技术制备并分析染色体核型,提取外周血DNA行SRY基因检测和测序,SRY基因检测结果阴性者外送标本行性发育相关基因靶向测序,生物信息学方法分析测序结果。结果:查体显示4例患者社会性别均为女性,而外周血淋巴细胞核型分析结果提示核型均为男性(46,XY),社会性别与生物学性别不一致;性别决定基因SRY均为阳性,测序结果提示病例1为SRY基因编码区第5位碱基缺失(c.del5A),病例2为SRY基因编码区第5位碱基发生错义突变(c.5A>T),病例3为SRY基因编码区第6位碱基缺失(c.del6A),病例4的SRY基因检测范围内未见突变位点,靶向测序结果提示雄激素受体基因(AR)编码区发生错义突变(c.2117 A>G);生物信息学软件Mutation taster提示c.del5A、c.del6A和c.2117 A>G等3种突变可能导致疾病发生,c.5A>T突变可能为人群多态现象;Raptor X蛋白质三维结构预测软件分析结果显示SRY基因c.5A>T突变对SRY蛋白的三维构象没有影响,而AR基因c.2117 A>G突变可导致AR蛋白的三维结构明显变化,并增加两个氢键;PolyPhen-2显示SRY基因c.5A>T和AR基因c.2117A>G突变为可能致病;ClinvAR软件分析结果提示4种突变均未见临床病例报道。结论:基因突变可能是导致患者性器官发育异常的原因,基因检测有助于明确诊断以及家庭再生育咨询。

HSD17B6的主要功能及其在内分泌代谢和肿瘤中的作用

羟基类固醇脱氢酶是醛酮还原酶和短链脱氢酶⁃还原酶超家族的成员,对于类固醇激素在体内发挥正常功能起着至关重要的作用。HSD17B6是羟基类固醇脱氢酶中的一种,在体内主要参与雄激素的代谢和生物合成,产生雌激素受体β的高亲和力配体,进而可能影响体内糖脂代谢,造成内分泌及生殖系统的紊乱与疾病的发生。HSD17B6表达异常也与机体免疫功能有关,可参与肿瘤的发生与发展,作为潜在生物标志物用于肿瘤的诊断与评估,为药物或靶向治疗提供参考信息。尽管其对疾病影响的精细机制尚不明确,但HSD17B的功能丧失可能对机体造成不同程度的损伤。本文就HSD17B6在代谢病和肿瘤方面的作用进行综述。