Analysis of the relationship between liver-qi stagnation and premature ovarian failure based on exosomes

The incidence of premature ovarian failure,which is related to women’s excessive pressure and mental tension,has increased in recent years.Premature ovarian failure has become one of the diseases that seriously disturb women’s physical and mental health,and its incidence can be regarded as liver depression and qi stagnation.Patients have an increasing demand for treatment,not only for fertility with the improvement of social living standards and the development of healthcare technology.Exosomes,as small membrane vesicles containing complex RNA and proteins,have the function of mediating cell communication and transmitting information in the pathological state caused by liver-qi stagnation.Exosomes in the hypoxic microenvironment can protect cells from damage and promote the pathological process.Moreover,exosomes in an inflammatory environment can play an active anti-inflammatory role.Exosomes can reduce the apoptosis of granulosa cells by expressing miRNA and so on to restore ovarian function.The purpose of treating premature ovarian failure can be achieved in this way.This paper introduced the relationship between the three,discussed the guiding significance of Chinese medicine theories in the treatment of exosomes and premature ovarian failure,and provided new research ideas for the treatment of integrated traditional Chinese medicine and western medicine.

Deficit of mitochondria-derived ATP during oxidative stress impairs mouse MII oocyte spindles

尽管在母亲的老化和不孕的氧化应力的角色被建议了,内在的机制充分没被理解。现在的学习被设计在氧化应力下面在中期 II (MII ) 卵母细胞决定在 mitochondrial 功能和锭子稳定性之间的关系。MII 老鼠卵母细胞当面与 H2O2 被对待或渗透转变毛孔(PTP ) 的缺席块 ers cyclosporin A (CsA ) 。另外,抗氧化剂 N-acetylcysteine (NAC ) , F0/F1 synthase 禁止者 oligomycin A,线粒体 uncoupler 羰基氰化物 4-trifluoro-methoxyphenylhydrazone (FCCP ) 或加 2.5 公里 Ca2+(Th+2.5 公里 Ca2+) 的 thapsigargin 在机械学的研究被使用。卵母细胞锭子和染色体的词法分析被执行并且 mitochondrial 膜潜力(DeltaPsim ) ,细胞质的免费的钙集中([Ca2+] c ) 并且在卵母细胞以内的细胞质的 ATP 内容也是 assayed。在一时间 -- 并且 H2O2 剂量依赖者举止,锭子在卵母细胞以后被发现的 meiotic 的混乱与 H2O2 被对待,它被预告的处理与 NAC 阻止。H2O2 的管理导致了 DeltaPsim 的驱散,的增加[Ca2+] 在细胞质的 ATP 的 c 和减少铺平。到 H2O2 处理的卵母细胞的这些有害回答能被孵化前与 CsA 堵住。类似于驱散的 H2O2,两 oligomycin A 和 FCCP DeltaPsim,减少的细胞质的 ATP 内容和拆卸的 MII 卵母细胞锭子,当时高[Ca2+] c 独自没在锭子形态学上有效果。在结论,在导出线粒体的 ATP 的减少可以在氧化应力期间引起老鼠 MII 卵母细胞锭子的拆卸,大概由于 mitochondrial PTP 的开始。

Dynamic changes in the systemic immune responses of spinal cord injury model mice

Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord injury.The spinal cord in mice was completely transected at T8.Changes in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+T-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory T-cells were observed during the acute phase.These systemic immune alterations were gradually restored to basal levels during the sub-acute phase.During the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase.All experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital,China(approval No.2019 AE01040)on June 25,2019.

Efficacy of Qizi Yusi Pill on Pregnancy Outcomes in Women of Advanced Reproductive Age:A Multicenter,Randomized,Double-Blind,Placebo-Controlled Trial

Objective:To evalvate efficacy of Qizi Yusi Pills(QYP),a Chinese medicine compound preparation,on in vitro fertilization-embryo transfer(IVF-ET)in women of advanced reproductive age.Methods:This multicenter,randomized,double-blind,placebo-controlled trial was conducted from June 2018 to October2019.A total of 124 patients were randomly allocated to either the QYP group or the placebo group using a stratified block randomization design,with 62 patients in each group.All patients completed controlled ovarian stimulation using a standard gonadotropin-releasing hormone agonist(GnRH-a)long protocol.As the QYP group,QYP was administered while the control group received placebo.QYP and placebo were administered for a total of 24 to 30 days from the day of GnRH-a pituitary downregulation to transvaginal oocyte retrieval.Both medications were taken orally at doses of 10 g three times each day.The primary outcome was cumulative pregnancy rate,and the secondary outcomes were periodic medication,follicular status,serum hormone and endometrial receptivity.Follow-up continued until 4 weeks after delivery.Maternal and neonatal complications,such as gestational diabetes,were also observed.Results:Overall,119 patients completed the study,60 in the QYP group and 59 in the placebo group.Per protocol(PP)analysis revealed that 6-month cumulative pregnancy rate in the QYP group was significantly higher than that in the placebo group[43.33%(26/60)vs.25.42%(15/59),P=0.040].Additionally,more oocytes were retrieved from the QYP group than those from the placebo group(8.95±3.12 vs.7.85±1.91,P=0.022).Moreover,the endometrial thickness of HCG day in the QYP group was significantly higher than that in the placebo group(11.78±2.27 mm vs.10.68±2.07 mm,P=0.012).Maternal and neonatal complications between the two groups were not significantly different(P>0.05).Intention-to-treat analysis was in line with PP results.Conclusions:QYP can enhance ovarian reserve capacity and ovarian response,and possibly promote endometrial receptivity.QYP effectively improves cumulative pregnancy rates in older patients(≥35 years)undergoing IVF-ET.(Registration No.ChiCTR1800014427).

Genetically engineered FGF1-sericin hydrogel material treats intrauterine adhesion and restores fertility in rat

Endometrial injury can cause intrauterine adhesions(IUA)and induce the formation of endometrial fibrosis,leading to infertility and miscarriage.At present,there is no effective treatment method for severe IUA and uterine basal injury with adhesion area larger than one-third of the uterus.In this study,we prepared FGF1 silk sericin hydrogel material(FGF1-SS hydrogel)to treat endometrial injury and prevent endometrial fibrosis.Compared with the silk sericin hydrogel material(WT-SS hydrogel),FGF1-SS hydrogel significantly promotes the cell migration and infiltration ability of endometrial stromal cells(ESCs).More importantly,FGF1-SS hydrogel can release FGF1 stably for a long time and inhibit the ESCs injury model forms fibrosis through the TGF-β/Smad pathway.In the IUA rat model,FGF1-SS hydrogel treatment effectively restored the number of uterine glands and uterine wall thickness in rats,with a fertility rate of 65.1%66.4%.The results show that FGF1-SS hydrogel is expected to be a candidate to prevent IUA.

Xiaoyi Yusi decoction(消异育嗣汤)improves in vitro fertilization and embryo transfer outcomes in patients with endometriosis

OBJECTIVE:To investigate the effect of—Xiaoyi Yusi decoction(XYYSD,消异育嗣汤),a Traditional Chinese Medicine(TCM),on in vitro fertilization and embryo transfer(IVF-ET)in patients with endometriosis,and to study the mechanism underpinning the action.METHODS:Women who underwent IVF-ET were divided into three groups by simple randomization:the treatment(n=32;with TCM treatment),patient(n=28;with endometriosis alone),and control(n=33;with male factor alone)groups.The luteal phase short-acting gonadotropin-releasing hormone agonist prolonged protocol was used in all three groups.To compare the changes in TCM scores and reproductive outcomes before and after TCM intervention in patients with endometriosis,partial least-squares discriminant analysis was used to analyze the follicular fluid samples of each group and screen and compare metabolites using the MetaboA nalyst software.RESULTS:The clinical data indicated that following TCM intervention,kidney deficiency and blood stasis symptom patterns improved dramatically in patients with endometriosis and that their clinical pregnancy rate increased significantly(71.9%vs 57.1%,P<0.05).Metabolomics showed that the two groups of samples were separated before and after TCM intervention.After TCM intervention,the intervention group was close to the control group,indicating that the TCM had a certain effect.Pathway analysis revealed that after TCM intervention,the metabolism of glycerin phospholipid,pyruvate,and citric acid was regulated.CONCLUSIONS:Through the pyruvate and glycerophospholipid metabolism pathways and tricarboxylic acid cycle,the TCM XYYSD successfully improved kidney deficiency and blood stasis symptom pattern,as well as the clinical reproductive outcomes of patients with endometriosis-related infertility.

Clinical efficacy of Chinese herbal compound in the treatment of infertility with kidney deficiency:A meta-analysis

Objective:Based on the current evidence system to evaluate the effect of traditional Chinese medicine compound on the clinical efficacy of infertility patients with kidney deficiency.Methods:Search the China Knowledge Resources Database(CNKI),Chinese Science and Technology Journal Database(VIP),China Academic Journal Database(Wanfang),PubMed,EMBASE,Ovid.The included studies are randomized controlled trials.The experimental group is Chinese medicine compound or Chinese medicine compound combined with western medicine,and the control group is western medicine.Two reviewers independently extracted and evaluated the literature data according to the Cochrane manual standards,and used Rev Man5.3 software for data synthesis and Meta-analysis.Results:32 studies were selected,a total of 2715 cases of infertility patients.The clinical pregnancy rate of the experimental group and the control group[n=29,OR(95%CI)=2.47(2.07,2.96),P<0.00001],the clinical total effective rate[n=20,OR(95%CI)=3.77(2.83,5.03),P<0.00001],TCM syndrome score[n=14,MD(95%CI)=4.34(3.08,5.61),P<0.00001],ovulation rate[n=20,OR(95%CI)=2.21(1.85,2.63),P<0.00001],the occurrence rate of two-way BBT[n=11,OR(95%CI)=2.65(2.02,3.48),P<0.00001].The GRADE scoring results show that the level of evidence is low and very low.Conclusion:Traditional Chinese medicine compound can increase the clinical pregnancy rate and clinical total effective rate of infertility with kidney deficiency syndrome,improve the scores of Chinese medical syndromes,increase its ovulation rate and the occurrence rate of BBT bidirectional type,and confirm the clinical efficacy of Chinese medicine compound from the perspective of evidence-based medicine.

Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve:A Prospective,Open-Labeled,Randomized and Controlled Study

Objective:To explore the effects of Zishen Yutai Pills(ZYPs)on the quality of oocytes and embryos,as well as pregnancy outcomes in patients with diminished ovarian reserve(DOR)receiving in vitro fertilizationembryo transfer(IVF-ET).The possible mechanisms,involving the regulation of bone morphogenetic protein 15(BMP15)and growth differentiation factor 9(GDF9),were also investigated.Methods:A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio.The patients in the treatment group(60 cases)received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone(Gn RH)antagonist protocol.The patients in the control group(60 cases)received the same protocol but without ZYPs.The primary outcomes were the number of oocytes retrieved and high-quality embryos.Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes.Adverse events were assessed by comparison of the incidence of ectopic pregnancy,pregnancy complications,pregnancy loss,and preterm birth.Contents of BMP15 and GDF9 in the follicle fluids(FF)were also quantified with enzymelinked immunosorbent assay.Results:Compared with the control group,the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group(both P<0.05).After treatment with ZYPs,a significant regulation of serum sex hormones was observed,including progesterone and estradiol.Both hormones were up-regulated compared with the control group(P=0.014 and 0.008),respectively.No significant differences were observed with regard to pregnancy outcomes including implantation rates,biochemical pregnancy rates,clinical pregnancy rates,live birth rates,and pregnancy loss rates(all P>0.05).The administration of ZYPs did not increase the incidence of adverse events.The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group(both P<0.05).Conclusions:ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET,resulting in increments of oocytes and embryos,and up-regulation of BMP15 and GDF9 expressions in the FF.However,the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes(Trial reqistration No.Chi CTR2100048441).

Effect of Electro-acupuncture on Expression of IRS-1/PI3K/GLUT4 Pathway in Ovarian Granulosa Cells of Infertile Patients with Polycystic Ovary Syndrome-Insulin Resistance of Phlegm-Dampness Syndrome

Objective:To evaluate the effect of electro-acupuncture(EA)in infertile patients with phlegmdampness polycystic ovary syndrome-insulin resistance(PCOS-IR).Methods:Seventy-six PCOS-IR patients who underwnet in vitro fertilization and embryo transfer(IVF-ET)were equally assigned to two groups according to a random digital table:the EA group and the control group,with 38 cases in each group.Before undergoing IVF,the two groups were treated with EA or pseudo-acupuncture,respectively,for 3 menstrual cycles.The intervention was 25 min twice a week until the day of oocyte collection.The selected acupoints were Zhongwan(RN 12),Tianshu(ST 25),Daheng(SP 15),Daimai(GB 26),Qihai(CV 6),Guanyuan(CV 4),and bilateral points including Xuehai(SP 10),Fenglong(ST 40),Zusanli(ST 36),and Yinlingquan(SP 9).Evaluation of phlegm-dampness syndrome score and IR score were carried out before and after treatment.Additionally,the number of oocytes retrieved,transplantable embryo rate,high-quality embryo rate,clinical pregnancy rate and live birth rate were compared between the two groups.Real-time polymerase chain reaction analysis was used to monitor the m RNA expression of the insulin receptor substrate(IRS-1),phosphatidylinositiol 3-kinase(PI3 K)and glucose transport factor 4(GLUT4)in ovarian granulosa cells.Results:EA treatment reduced the phlegm-dampness syndrome score as well as the IR scores compared with the control group(P<0.05).No significant differences in the number of oocytes retrieved and clinical pregnancy rate between the two groups(P>0.05).Moreover,the transplantable embryo rate[49.0%(284/580)vs.41.9%(273/652)],high-quality embryo rate[36.6%(104/284)vs.27.8%(76/273)],and live birth rate[50%(19/38)vs.26.3%(10/38)]in the EA group were significantly higher than in the control group(P<0.05).Gene expression analyses revealed significantly elevated IRS-1,PI3 K and GLUT4 m RNA in ovarian granulosa cells of the EA group compared with the control group(P<0.05).Conclusions:EA may ameliorate the effects of phlegm-dampness syndrome and ovarian IR in PCOS-IR patients.Mechanistically,this effect might be through an upregulation of the IRS-1/PI3 K/GLUT4 signaling pathway,which may result in improved oocyte quality and embryonic development potential.(Registration No.Chi CTR1800015453)

Effect of Quyu Jiedu Granule(祛瘀解毒颗粒) on Micro-environment of Ova in Patients with Endometriosis

Objective:To observe the effect of Quyu Jiedu Granules(祛瘀解毒颗料,QJG) on the micro-environment of ova in patients with endometriosis(EM).Methods:Twenty EM patients who received in vitro fertilization and embryo transfer(IVF-ET) were randomized equally into a treated group and a control group. Further,20 patients who received IVF-ET due to oviduct factors were enrolled into a non-endometriosis group. The dosage of gonadotrophic hormone used,the number of ova attained,fertilization rate and clinical pregnancy ra...

Low dose hormone therapy in reproductive endocrinology in China

The human endocrine system normally functions in abalanced physiological state. Any excess or deficiencywill cause an endocrine imbalance and result in hyper-orhypo-function, requiring readjustment by hormonesuppression or supplementation in order to reestablish anormal physiological balance.

RNF187 governs the maintenance of mouse GC-2 cell development by facilitating histone H3 ubiquitination at K57/80

RING finger 187(RNF187),a ubiquitin-ligating(E3)enzyme,plays a crucial role in the proliferation of cancer cells.However,it remains unclear whether RNF187 exhibits comparable functionality in the development of germline cells.To investigate thepotential involvement of RNF187 in germ cell development,we conducted interference and overexpression assays using GC-2 cells,a mouse spermatocyte-derived cell line.Our findings reveal that the interaction between RNF187 and histone H3 increases theviability,proliferation,and migratory capacity of GC-2 cells.Moreover,we provide evidence demonstrating that RNF187 interactswith H3 and mediates the ubiquitination of H3 at lysine 57(K57)or lysine 80(K80),directly or indirectly resulting in increasedcellular transcription.This is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediatinghistone H3 ubiquitination,thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of genetranscription.These discoveries provide a new theoretical foundation for further comprehensive investigations into the functionof RNF187 in the reproductive system.