In this study,we used a network meta-analysis(NMA)to compare the effectiveness of medicines and supplements for idiopathic male infertility and to identify the best treatment.Medline,Excerpta Medica Database(EMBASE),O...In this study,we used a network meta-analysis(NMA)to compare the effectiveness of medicines and supplements for idiopathic male infertility and to identify the best treatment.Medline,Excerpta Medica Database(EMBASE),Ovid,and China National Knowledge Infrastructure(CNKI),were searched for the period from January 1990 to June 2021 using the keywords"male infertility,""medical therapy,""supplement/nutrient therapy,"and related terms.Randomized controlled trials(RCTs)investigating medicines(mainly follicle-stimulating hormone(FSH),androgen,and clomiphene/tamoxifen)or supplements(mainly zinc,selenium,vitamin C or E,carnitine,coenzyme Q10(CoQ10),or combined treatment)for idiopathic infertile men were selected for meta-analysis.Preferred reporting items for systematic reviews and meta-analysis(PRISMA)was used for data extraction,and a risk-of-bias tool and grades of recommendation,assessment,development,and evaluation(GRADE)system adapted to the NMA were employed to assess the quality of the evidence.The primary outcomes were live birth and spontaneous pregnancy rate(SPR).The secondary outcomes were sperm parameters(including concentration,progressive motility,and morphology)and side effects.In total,65 RCTs involving 7541 men with sperm abnormalities but normal hormone levels were included.A total of 36 studies reported SPR but only three reported live birth rates.The quality of the included studies was found to be moderate to high.Compared with a placebo or being untreated,carnitine plus vitamins significantly improved SPR(relative risk(RR)=3.7,95%confidence interval(95%CI),1.6-8.5);fatty acids significantly increased sperm concentrations(mean difference(MD)=12.5×10^(6)mL-1,95%CI,3.1×10^(6)-22.0×10^(6));and selective estrogen receptor modulator(SERM)plus CoQ10 significantly improved sperm progressive motility(MD=11.0%,95%CI,0.1%-21.9%)and normal sperm morphology(MD=11.0%,95%CI,4.6%-17.4%).The most optimal intervention was carnitine plus vitamins and fatty acids for SPR and sperm concentrations,respectively,even after excluding trials at a high risk of bias.Compared with a placebo or being untreated,FSH(RR=4.9,95%CI,1.1-21.3)significantly increased SPR,whereas SERM plus kallikrein increased sperm concentration(MD=16.5×10^(6)mL^(-1),95%CI,1.6×10^(6)-31.4×10^(6)),and SERM plus CoQ10 significantly improved sperm progressive motility(MD=11.3%,95%CI,7.3%-15.4%)and normal morphology(MD=11.2%,95%CI,5.4%-16.9%)in men with oligoasthenozoospermia(OA).In terms of side effects,fatty acids and pentoxifylline were associated with foul breath and/or a bad taste(RR=8.1,95%CI,1.0-63.5)and vomiting(RR=8.0,95%CI,1.0-63.0),respectively.In conclusion,the optimal treatment for male infertility for live birth is still unknown.Carnitine plus vitamins and FSH are likely to be better than other therapies in achieving successful spontaneous pregnancy in couples overall and in cou ples with men with OA,respectively.The efficacy of other treatments on pregnancy outcomes warrants further verification.展开更多
The mammalian epididymis not only plays a fun dame ntal role in the maturati on of spermatozoa,but also provides protecti on agai nst various stressors.The foremost among these is the threat posed by oxidative stress,...The mammalian epididymis not only plays a fun dame ntal role in the maturati on of spermatozoa,but also provides protecti on agai nst various stressors.The foremost among these is the threat posed by oxidative stress,which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids,proteins,and nucleic acids.In mice,the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5(GPX5)as a major luminal scavenger in the proximal caput epididymidal segment.Accordingly,the loss of GPX5^-/-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx57 mice.To explore the underlying mechanism,we have conducted transcriptomic analysis of caput epididymidal epithelial cells from aged(13 months old)Gpx5^-/-m mice.This analysis revealed the dysregulation of several thousand epididymal mRNA transcripts,in eluding the downregulation of a subgroup of piRNA pathway gen es,in aged Gpx5^-/-mice.In agreeme nt with these fin dings,we also observed the loss of piRNAs,which potentially bind to the P-element-induced wimpy testis(PlWI)-like proteins PIWIL1 and PIWIL2.The absence of these piRNAs was correlated with the elevated mRNA levels of their putative gene targets in the caput epididymidis of Gpx5^-/-mice.Importantly,the oxidative stress response genes tend to have more targeting piRNAs,and many of them were among the top increased genes upon the loss of GPX5^-/-.Taken together,our findings suggest the existence of a previously uncharacterized somatic piRNA pathway in the mammalian epididymis and its possible invoIvement in the aging and oxidative stress-mediated responses.展开更多
Endometriosis is a common and benign angiogenesisdependent gynecological disorder,which refers to the proliferation and growth of endometrium-like tissues with neovasculature formation outside of the uterus.1 Availabl...Endometriosis is a common and benign angiogenesisdependent gynecological disorder,which refers to the proliferation and growth of endometrium-like tissues with neovasculature formation outside of the uterus.1 Available medical treatments for endometriosis containing hormonal and non-hormonal treatments had been limited for longterm usage by their side effects.2 Ideal medical treatment for endometriosis with efficacy to relieve symptoms and suppress endometriotic lesion growth and minimal side effects has been longing for decades.3 Angiogenesis is a promising therapeutic target for endometriosis.展开更多
基金supported by the National Public Welfare Projects for Chinese Medicine(201507001)to Xiao Ke WuTheme-based Research Scheme(T13-602/21-N)from Research Grant Councilthe Health and Medical Research Fund(06170246)from Food and Health Bureau to Chi Chiu Wang。
文摘In this study,we used a network meta-analysis(NMA)to compare the effectiveness of medicines and supplements for idiopathic male infertility and to identify the best treatment.Medline,Excerpta Medica Database(EMBASE),Ovid,and China National Knowledge Infrastructure(CNKI),were searched for the period from January 1990 to June 2021 using the keywords"male infertility,""medical therapy,""supplement/nutrient therapy,"and related terms.Randomized controlled trials(RCTs)investigating medicines(mainly follicle-stimulating hormone(FSH),androgen,and clomiphene/tamoxifen)or supplements(mainly zinc,selenium,vitamin C or E,carnitine,coenzyme Q10(CoQ10),or combined treatment)for idiopathic infertile men were selected for meta-analysis.Preferred reporting items for systematic reviews and meta-analysis(PRISMA)was used for data extraction,and a risk-of-bias tool and grades of recommendation,assessment,development,and evaluation(GRADE)system adapted to the NMA were employed to assess the quality of the evidence.The primary outcomes were live birth and spontaneous pregnancy rate(SPR).The secondary outcomes were sperm parameters(including concentration,progressive motility,and morphology)and side effects.In total,65 RCTs involving 7541 men with sperm abnormalities but normal hormone levels were included.A total of 36 studies reported SPR but only three reported live birth rates.The quality of the included studies was found to be moderate to high.Compared with a placebo or being untreated,carnitine plus vitamins significantly improved SPR(relative risk(RR)=3.7,95%confidence interval(95%CI),1.6-8.5);fatty acids significantly increased sperm concentrations(mean difference(MD)=12.5×10^(6)mL-1,95%CI,3.1×10^(6)-22.0×10^(6));and selective estrogen receptor modulator(SERM)plus CoQ10 significantly improved sperm progressive motility(MD=11.0%,95%CI,0.1%-21.9%)and normal sperm morphology(MD=11.0%,95%CI,4.6%-17.4%).The most optimal intervention was carnitine plus vitamins and fatty acids for SPR and sperm concentrations,respectively,even after excluding trials at a high risk of bias.Compared with a placebo or being untreated,FSH(RR=4.9,95%CI,1.1-21.3)significantly increased SPR,whereas SERM plus kallikrein increased sperm concentration(MD=16.5×10^(6)mL^(-1),95%CI,1.6×10^(6)-31.4×10^(6)),and SERM plus CoQ10 significantly improved sperm progressive motility(MD=11.3%,95%CI,7.3%-15.4%)and normal morphology(MD=11.2%,95%CI,5.4%-16.9%)in men with oligoasthenozoospermia(OA).In terms of side effects,fatty acids and pentoxifylline were associated with foul breath and/or a bad taste(RR=8.1,95%CI,1.0-63.5)and vomiting(RR=8.0,95%CI,1.0-63.0),respectively.In conclusion,the optimal treatment for male infertility for live birth is still unknown.Carnitine plus vitamins and FSH are likely to be better than other therapies in achieving successful spontaneous pregnancy in couples overall and in cou ples with men with OA,respectively.The efficacy of other treatments on pregnancy outcomes warrants further verification.
基金This research was supported by the National Basic Research Program of China(Grant No.2014CB943103)National Natural Science Foundation of China(Grant No.31471104,No.31671203,No.31301225,No.31301226,No.31701119,and No.31571192)and was partly realized under the frame of the France-China scientific exchange programs"Xu Guangqi"and"Cai Yuanpei"of the"Partenariat Hubert CurienM attributed to J RD and YLZ The authors thank Prof.Winnie Wai Chi Shum,Prof.Xiaodong Sun,Ms.Aihua Liu,Dr.Chaobao Zhang,Dr.Zhen Lin,Dr.Xueting Luo,and the Bio-Med Big Data Center,CAS-MPG Partner Institute for Computational Biology,Shanghai Institutes for Biological Sciences,and Chinese Academy of Sciences for their kind support.
文摘The mammalian epididymis not only plays a fun dame ntal role in the maturati on of spermatozoa,but also provides protecti on agai nst various stressors.The foremost among these is the threat posed by oxidative stress,which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids,proteins,and nucleic acids.In mice,the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5(GPX5)as a major luminal scavenger in the proximal caput epididymidal segment.Accordingly,the loss of GPX5^-/-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx57 mice.To explore the underlying mechanism,we have conducted transcriptomic analysis of caput epididymidal epithelial cells from aged(13 months old)Gpx5^-/-m mice.This analysis revealed the dysregulation of several thousand epididymal mRNA transcripts,in eluding the downregulation of a subgroup of piRNA pathway gen es,in aged Gpx5^-/-mice.In agreeme nt with these fin dings,we also observed the loss of piRNAs,which potentially bind to the P-element-induced wimpy testis(PlWI)-like proteins PIWIL1 and PIWIL2.The absence of these piRNAs was correlated with the elevated mRNA levels of their putative gene targets in the caput epididymidis of Gpx5^-/-mice.Importantly,the oxidative stress response genes tend to have more targeting piRNAs,and many of them were among the top increased genes upon the loss of GPX5^-/-.Taken together,our findings suggest the existence of a previously uncharacterized somatic piRNA pathway in the mammalian epididymis and its possible invoIvement in the aging and oxidative stress-mediated responses.
基金supported by the National key Research and Development Program of China (2019YFC1709500)the National Collaboration Project of Critical Illness by Integrating Chinese Medicine and Western Medicine+8 种基金the Project of Heilongjiang Province Innovation Team “Tou Yan”the Yi-Xun Liu and Xiao-Ke Wu Academician Workstationthe Innovation Team of Reproductive Technique with Integrative Chinese Medicine and Western Medicine in Xuzhou City, ChinaHeilongjiang University of Chinese Medicine from the National Clinical Trial BaseHeilongjiang Provincial Clinical Research Center for Ovary Diseasesthe Research Grant Council (T13-602/21-N, C5045-20EF, and 14122021)Food and Health Bureau in Hong Kong, China (06171026)supported by a National Health and Medical Research Council (NHMRC) Investigator grant (GNT1176437)travel support from Merck.
基金the Strategic Seed Funding for Collaborative Research Scheme(SSFCRS)of the Chinese University of Hong Kong(CUHK,China)(No.0670/22)the National Natural Science Foundation of China(No.82260948).
文摘Endometriosis is a common and benign angiogenesisdependent gynecological disorder,which refers to the proliferation and growth of endometrium-like tissues with neovasculature formation outside of the uterus.1 Available medical treatments for endometriosis containing hormonal and non-hormonal treatments had been limited for longterm usage by their side effects.2 Ideal medical treatment for endometriosis with efficacy to relieve symptoms and suppress endometriotic lesion growth and minimal side effects has been longing for decades.3 Angiogenesis is a promising therapeutic target for endometriosis.
