BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical valu...BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical value.AIM To identify potential DNA methylation markers specific to ADE and CRC.METHODS Here,we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.RESULTS Comparing 22 CRC and 25 ADE samples,global methylation was higher in the former,but both showed similar methylation patterns regarding differentially methylated gene positions,chromatin signatures,and repeated elements.High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC.Combined with RNA-seq gene expression data,we identified 14 methylation-regulated differentially expressed genes,of which only AGTR1 and NECAB1 methylation had prognostic significance.CONCLUSION Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC,suggesting prognostic biomarkers for CRC.展开更多
BACKGROUND Epidermal growth factor receptor(EGFR)is a transmembrane protein that is differentially expressed in gestational diabetes mellitus(GDM).Endothelial dy-sfunction is a hallmark of GDM and plays a key role in ...BACKGROUND Epidermal growth factor receptor(EGFR)is a transmembrane protein that is differentially expressed in gestational diabetes mellitus(GDM).Endothelial dy-sfunction is a hallmark of GDM and plays a key role in its pathogenesis.EGFR is associated with endothelial dysfunction in the context of various diseases.How-ever,the exact mechanism by which EGFR causes endothelial dysfunction in GDM is unknown,particularly its regulation at the transcriptional and protein levels.METHODS Quantitative real-time polymerase chain reaction was used to detect the ex-pression of EGFR and H19.Western blotting was used to detect the expression of endothelial cell dysfunction markers.A cell counting kit 8 assay was used to assess cell viability,flow cytometry was used to assess apoptosis,scratch and Transwell assays were used to assess cell migration,and a tube formation assay was used to assess cell vascular formation.Hematoxylin-eosin staining was used to observe histopathological changes in the placentas of the mice.RESULTS In this study,EGFR was upregulated in clinical samples,GDM animal models and GDM cell models,and the knockdown of EGFR could mitigate the effect of streptozotocin(STZ)and high glucose(HG);promoted the proliferation,migration and vascularization of human umbilical vein endothelial cells(HUVECs);inhibited cell apoptosis and the expression of endothelial cell dysfunction markers(vascular cell adhesion molecule-1,tumor necrosis factor-α,vascular endothelial growth factor-A,and intercellular cell adhesion molecule-1);and alleviated the process of GDM in vivo.Mechanistically,EIF4A3 binding to long noncoding RNA H19 increased the stability of EGFR messenger RNA,thereby promoting HG-induced HUVECs dysfunction or STZ-induced endothelial cell dysfunction in GDM mice.In addition,ERRFI1 also regulated the expression of EGFR,and ERRFI1 inhibited EGFR activity by binding to EGFR,thereby inhibiting HG-induced HUVECs dysfunction.CONCLUSION Our study revealed that EGFR can accelerate the development of GDM by promoting endothelial cell dysfunction.展开更多
Parthenogenetic embryonic stem cells（pE SCs）, as ＂seed cells＂ for regenerative medicine, are an effective way to build patient-specific pluripotent stem cells, due to the fact that characteristics of self-renewal ...Parthenogenetic embryonic stem cells（pE SCs）, as ＂seed cells＂ for regenerative medicine, are an effective way to build patient-specific pluripotent stem cells, due to the fact that characteristics of self-renewal and pluripotent are similar to embryonic stem cells（ESCs）. Parthenogenetic activation can be performed at meiosis I or meiosis II describing the embryos with distinct patterns of homozygosity and heterozygosity.Heterozygous pE SCs are expected to be used for autologous transplantation, while homozygous pE SCs enable to be used for allogeneic gene therapy in theory but is hampered by immunological barriers defined by the recognition of natural killer（NK）cells. In this review, we describe the mechanism of deriving heterozygous and homozygous pE SCs, and summarize the advantages and limitations of pE SCs in the area of cell therapy.展开更多
Collecting baseline information on how laboratories perform testing is a reasonable first step towards establishing intra- and inter-laboratory standardization and quality control for semen analysis. We carried out a ...Collecting baseline information on how laboratories perform testing is a reasonable first step towards establishing intra- and inter-laboratory standardization and quality control for semen analysis. We carried out a survey of the laboratories performing the testing in China's Mainland. A questionnaire, composed of 36 questions covering all aspects of semen analysis, was designed, and a copy was distributed to each of the 145 laboratories. Of these, 118 laboratories completed the questionnaires. The survey results showed that semen volume was measured visually in 53.6% （59/110） of the responding laboratories, and 70.9% （73/103） of laboratories analysed incompletely liquefied semen without any treatment. In addition, both manual-microscopic and computer-assisted semen-analysis systems were applied to analyse sperm concentration, motility and morphology. However, more than five methods were employed in routine sperm staining. An enzyme-linked immunosorbent assay was commonly used for determining whether antisperm antibodies were present. Several seminal biochemical markers were analysed in only 27.1% （32/118） of the responding laboratories. Generally, there was a lack of intra- and inter-laboratory quality control measures for semen analysis in all laboratories responding to this survey. In conclusion, the methods of semen analysis and the interpretation of test results in the surveyed laboratories differed markedly. In particular, many laboratories employed methods other than those recommended by the World Health Organization Laboratory Manual for the Examination of Human Semen and Sperm- cervical Mucus Interaction （1999）. These findings suggest an urgent need for the standardization of semen analysis with acceptable quality controls for each parameter to make the results repeatable and meaningful.展开更多
Objective:In this paper,we will discuss if the CETP polymorphism contributes to the centenarians in Hainan island.Methods:We tested the Taq IB and I405 V polymorphisms of CETP gene among 276 centenarians and 301 match...Objective:In this paper,we will discuss if the CETP polymorphism contributes to the centenarians in Hainan island.Methods:We tested the Taq IB and I405 V polymorphisms of CETP gene among 276 centenarians and 301 matched healthy individuals by AS-PCR and analyzed the data with SPSS software package(Version 19.0).Results:Our data indicated that allele B1 and V have the significant differences between centenarians and healthy control groups with P<0.001.Further analysis implied that genotypes B1B1(P<0.001,OR=0.148,95% CI=0.095-0.230) and VV(P<0.001 and OR=0.353,95% CI=0.237-0.525) were significantly different between centenarians and matched controls.The combination of B and V,such as B1B1-II(P<0.001,OR=0.128,95% CI=0.049-0.329),B1B1-IV(P<0.001,OR=0.115,95% CI=0.056-0.237),B1B2-VV(P<0.05,OR=0.534,95% CI=0.310-0.920),and B2B2-VV(P<0.001,OR=0.198,95% CI=0.086-0.453) have significant differences between centenarians and matched healthy individuals from Hainan.Conclusion:Our results implied that allele B1B1 and VV,as well as the combination B1B1-II,B1B1-IV,B1B2-VV and B2B2-VV may contribute to the longevity in centenarians of Hainan,south of China.展开更多
MicroRNAs(miRNAs)are mediators of the aging process.The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility.Twenty-seven donors were divide...MicroRNAs(miRNAs)are mediators of the aging process.The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility.Twenty-seven donors were divided into three groups by age(Group A,n=8,age:20–30 years;Group B,n=10,age:31–40 years;and Group C,n=9,age:41–55 years)for high-throughput sequencing analysis.Samples from 65 individuals(22,22,and 21 in Groups A,B,and C,respectively)were used for validation by quantitative real-time polymerase chain reaction(qRT-PCR).A total of 2160 miRNAs were detected:1223 were known,937 were newly discovered and unnamed,of which 191 were expressed in all donors.A total of 7,5,and 17 differentially expressed microRNAs(DEMs)were found in Group A vs B,Group B vs C,and Group A vs C comparisons,respectively.Twenty-two miRNAs were statistically correlated with age.Twelve miRNAs were identified as age-associated miRNAs,including hsa-miR-127-3p,mmu-miR-5100_L+2R-1,efu-miR-9226_L-2_1ss22GA,cgr-miR-1260_L+1,hsa-miR-652-3p_R+1,pal-miR-9993a-3p_L+2R-1,hsa-miR-7977_1ss6AG,hsa-miR-106b-3p_R-1,hsa-miR-186-5p,PC-3p-59611_111,hsa-miR-93-3p_R+1,and aeca-mir-8986ap5_1ss1GA.There were 9165 target genes of age-associated miRNAs.Gene Ontology(GO)analysis of the target genes identified revealed enrichment of protein binding,membrane,cell cycle,and so on.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways,such as signaling pathways regulating stem cell pluripotency,metabolic pathways,and the Hippo signaling pathway.This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.展开更多
Piwi-interacting RNAs(piRNAs)is a novel class of non-coding RNAs.However,changes in piRNA expression profiles in recurrent spontaneous abortion(RSA)have not yet been investigated.The aim of this study was to identify ...Piwi-interacting RNAs(piRNAs)is a novel class of non-coding RNAs.However,changes in piRNA expression profiles in recurrent spontaneous abortion(RSA)have not yet been investigated.The aim of this study was to identify differentially expressed piRNAs in deciduas of RSA patients.Decidua tissues were collected by curettage from recruited RSA patients and normal early pregnant(NEP)women with their informed consent.Small RNA sequencing was used to evaluate the differences in piRNA expression profiles between RSA and NEP.The present results demonstrated that the counts of total piRNA reads in RSA samples were increased compared with those in NEP samples(0.21%vs.0.11%).Differential expression analysis identified 29 upregulated piRNAs and 18 downregulated piRNAs in RSA samples.RT-qPCR further confirmed that the expression levels of uniq-109625,uniq-89328,uniq-50651 and uniq-4569 were decreased in 8 RSA tissues,compared with 13 NEP tissues.Otherwise,pi-22628 and uniq-173406 were increased in 8 RSA tissues.Based on GO term and KEGG pathway analysis,we speculate that these piRNAs regulate RSA by targeting extracellular matrix component pathway,cell adhesion pathway and focal adhesion pathway.PiRNAs may be involved in RSA pathogenesis by target genes function on adhesion and extracellular matrix component.展开更多
Objective To relieve long-term malnutrition caused by a malignant tumor affecting the pylorus and to prolong the patient survival.Methods A patient presented with complete pyloric obstruction due to pyloric tumors,and...Objective To relieve long-term malnutrition caused by a malignant tumor affecting the pylorus and to prolong the patient survival.Methods A patient presented with complete pyloric obstruction due to pyloric tumors,and achieved good therapeutic effects through nutritional support and effective chemotherapy.Results After about 40 days of treatment,all physiological indicators were improving.After chemotherapy,the pyloric tumor shrank and the complete obstruction was relieved.The patient was able to eat and drink normally.Conclusion Nutritional support,combined with chemotherapy,may effectively treat complete pyloric obstruction caused by advanced tumors.展开更多
Gonadotropin-releasing hormone （GnRH） is secreted from neurons within the hypothalamus and is necessary for reproductive function in all vertebrates. GnRH is also found in organs outside of the brain and plays an im...Gonadotropin-releasing hormone （GnRH） is secreted from neurons within the hypothalamus and is necessary for reproductive function in all vertebrates. GnRH is also found in organs outside of the brain and plays an important role in Leydig cell steroidogenesis in the testis. However, the signalling pathways mediating this function remain largely unknown. In this study, we investigated whether components of the mitogen-activated protein kinase （MAPK） pathways are involved in GnRH agonist （GnRHa）-induced testis steroidogenesis in rat Leydig cells. Primary cultures of rat Leydig cells were established. The expression of 3β-hydroxysteroid dehydrogenase （3β-HSD） and the production of testosterone in response to GnRHa were examined at different doses and for different durations by RT-PCR, Western blot analysis and radioimmunoassay （RIA）. The effects of GnRHa on ERK1/2, JNK and p38 kinase activation were also investigated in the presence or absence of the MAPK inhibitor PD-98059 by Western blot analysis. GnRHa induced testosterone production and upregulated 3β-HSD expression at both the mRNA and protein levels; it also activated ERK1/2, but not JNK and p38 kinase. Although the maximum effects of GnRHa were observed at a concentration of 100 nmnol L-1 after 24 h, activation of ERKI/2 by GnRHa reached peak at 5 min and it returned to the basal level within 60 min. PD-98059 completely blocked the activation of ERKI/2, the upregulation of 3β-HSD and testosterone production. Our data show that GnRH positively regulates steroidogenesis via ERK signalling in rat Leydig cells. ERK1/2 activation by GnRH may be responsible for the induction of 3β-HSDgene expression and enzyme production, which may ultimately modulate steroidogenesis in rat Leydig cells.展开更多
This multi-center, cross-sectional study investigated the association between serum testosterone （T） levels, serum sex hormone-binding globulin （SHBG） levels, and the risk of metabolic syndrome （MS） in 3332 adul...This multi-center, cross-sectional study investigated the association between serum testosterone （T） levels, serum sex hormone-binding globulin （SHBG） levels, and the risk of metabolic syndrome （MS） in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T （TT） and SHBG than those without MS （P 〈 0.001）. There was no significant difference in serum free T （FT） levels between subjects with and without MS （P = 0.627）. In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index （BMI）, smoking and drinking status, and serum TT （odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P 〈 0.01）. However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status （OR 0,981, 95% CI 0.960-1.007）. Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.This multi-center, cross-sectional study investigated the association between serum testosterone （T） levels, serum sex hormone-binding globulin （SHBG） levels, and the risk of metabolic syndrome （MS） in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T （TT） and SHBG than those without MS （P 〈 0.001）. There was no significant difference in serum free T （FT） levels between subjects with and without MS （P = 0.627）. In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index （BMI）, smoking and drinking status, and serum TT （odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P〈 0.01）. However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status （OR 0,981, 95% CI 0.960-1.007）. Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.展开更多
Objective To explore the effects of electroacupuncture(EA)on pregnancy outcomes after assisted reproduction and mitochondrial function of granulosa cells(GCs)in patients with polycystic ovary syndrome(PCOS)and phlegm-...Objective To explore the effects of electroacupuncture(EA)on pregnancy outcomes after assisted reproduction and mitochondrial function of granulosa cells(GCs)in patients with polycystic ovary syndrome(PCOS)and phlegm-dampness syndrome.Methods In this randomized controlled trial,90 infertile women with PCOS and phlegm-dampness syndrome were recruited between August 2022 and December 2022.Patients were randomly assigned to the EA and control groups using a random sequence of codes in the order of enrolment,with 45 in in each group.Both groups underwent the ovarian stimulation protocol.The patients in the EA group received EA therapy including Zhongwan(CV 12),Qihai(CV 6),bilateral Xuehai(SP 10),Sanyinjiao(SP 6),Yinlingquan(SP 9),Tianshu(ST 25),Zusanli(ST 36),and Fenglong(ST 40),and the patients in the control group was treated with pseudo-acupuncture.The intervention was 25 min twice a week for a total of 6 times until the trigger day after menstruation had ended in the cycle before oocyte retrieval.The primary outcomes were clinical pregnancy rate(CPR)and the number of high-quality embryos.The secondary outcomes were(1)pregnancy-related indicators,including fresh embryo transfer rate(ETR),ovarian hyperstimulation syndrome(OHSS)rate,early pregnancy loss rate(ePLR),ectopic pregnancy rate,live birth rate(LBR),and cumulative CPR;(2)mitochondrial autophagy and mitochondrial membrane potential(MMP)in GCs;and(3)scoring for Chinese medicine syndrome.Adverse events to assess clinical safety were also monitored.Results The cumulative CPR was significantly higher in the EA group(42/45,93.3%)than in the control group(38/45,84.4%,P=0.036).The number of high-quality embryos and fresh ETR in the EA group were higher than those in the control group(3.80±1.65 vs.2.44±1.34,P<0.001;46.7%vs 24.4%,P=0.028).Ectopic pregnancies were not observed in either group.There were no significant differences in the fresh CPR,OHSS rate,ePLR or LBR between the two groups(P>0.05).Compared with the control group,the EA group showed lower expression levels of miR-146a-5p mRNA and P62 protein in GCs and higher levels of MMP and the LC3-II/LC3-I protein ratio(all P<0.01).The phlegm-dampness syndrome scores of the EA group were significantly lower than those of the control group(P<0.01).Conclusions EA significantly improved pregnancy outcomes in patients with PCOS and phlegm dampness syndrome.Mechanistically,this effect may be related to EA in decreasing miR-146a-5p mRNA expression,promoting mitochondrial autophagy in GCs,and improving mitochondrial function,which may contribute to improved oocyte quality.(Trial registration No.ChiCTR2200062915)展开更多
Background The 3q26 chromosome region, where the human telomerase RNA gene （hTERC） is located, is a biomarker for cervical cancer and precancerous lesions. The aim of this study was to confirm the value of measurin...Background The 3q26 chromosome region, where the human telomerase RNA gene （hTERC） is located, is a biomarker for cervical cancer and precancerous lesions. The aim of this study was to confirm the value of measuring hTERC gene gain in predicting the progression of cervical intraepithelial neoplasia grade Ⅰ or Ⅱ （CIN-Ⅰ and -Ⅱ, respectively） to CIN-Ⅲ and cervical cancer. Methods Liquid-based cytological samples from 54 patients with CIN-Ⅰ or CIN-Ⅱ lesions were enrolled in this study. Follow-up was performed with colposcopy and biopsy within 24 months after the diagnosis of CIN-Ⅰ or CIN-Ⅱ. Copy numbers of the hTERC gene were measured by fluorescence in situ hybridization with a dual-color probe mix containing the hTERC gene probe （labeled red） and the control, the chromosome 3 centromere-specific probe （labeled green）.Results All patients whose lesions progressed from CIN-Ⅰ or CIN-Ⅱ to CIN-Ⅲ displayed a gain of the hTERC gene, whereas patients where the hTERC gene was not amplified did not subsequently progress to CIN-Ⅲ or cervical cancer. The signal ratio pattern per cell was recorded as N：N （green： red）. The numbers of cells with the signal ratio pattern of 4：4 or N：≥5 in patients whose lesions progressed to CIN-Ⅲ were significantly higher than those whose lesions did not progress. Significantly, none of the patients with a 4：4 signal ratio pattern regressed spontaneously.Conclusions In conclusion, measurement of hTERC gene gain in CIN-Ⅰ or CIN-Ⅱ patients using liquid-based cytological samples could be a useful biomarker to predict the progression of such cervical lesions. In addition, a 4：4 or N：≥5 signal ratio pattern may indicate the unlikeness of spontaneous regression of CIN-Ⅰ or CIN-Ⅱ lesions.展开更多
In the case of a previous offspring with trisomy 21, recurrence risk for Down syndrome is about 1%. It may be due to chance, but the possibility of germline mosaicism for trisomy 21 in one of the parents has important...In the case of a previous offspring with trisomy 21, recurrence risk for Down syndrome is about 1%. It may be due to chance, but the possibility of germline mosaicism for trisomy 21 in one of the parents has important implications for the recurrence. Here we report a young healthy mother, who has a second pregnancy of trisomy 21.展开更多
The clinical findings frequently presented in trisomy 4q syndrome including mental retardation, developmental delay and multiple abnormalities such as microcephaly, acrocephaly, as well as malformed ears, high/broad/d...The clinical findings frequently presented in trisomy 4q syndrome including mental retardation, developmental delay and multiple abnormalities such as microcephaly, acrocephaly, as well as malformed ears, high/broad/depressed nasal bridge, teeth and thumb anomalies. It has been proposed that trisomy 4q is caused by a familial balanced translocation or a de novo imbalance. We reported a new case of trisomy 4q with a karyotype of 46, XY, der（5）t（4;5）（q27;q35） and this karyotye was reported for the first time. His phenotype included severe mental retardation, growth retardation, facial and thumb anomalies. Detected by cytogenetic investigation, comparative genomic hybridization, multicolor fluorescence in situ hybridization, the duplicated region from 4q27 to 4qter was confirmed. Trisomy 4q is a rare clinical finding. To our knowledge, this is the eighth case with duplicated fragment spanning from 4q27 to 4qter. Comparing the karyotypic and phenotypic correlation with those previously described, we reported a new case with partial trisomy 4q syndrome.展开更多
基金the National Natural Science Foundation of China,No.81960504the“Xingdian Talents”Support Project of Yunnan Province,No.RLQB20200002+2 种基金the Medical Discipline Reserve Talents of Yunnan Province,No.H-2018015the Applied Basic Research Projects-Union Foundation of Kunming Medical University,No.2017FE467(-132)the Talent Introduction Project of Hubei Polytechnic University,No.21xjz34R。
文摘BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical value.AIM To identify potential DNA methylation markers specific to ADE and CRC.METHODS Here,we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.RESULTS Comparing 22 CRC and 25 ADE samples,global methylation was higher in the former,but both showed similar methylation patterns regarding differentially methylated gene positions,chromatin signatures,and repeated elements.High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC.Combined with RNA-seq gene expression data,we identified 14 methylation-regulated differentially expressed genes,of which only AGTR1 and NECAB1 methylation had prognostic significance.CONCLUSION Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC,suggesting prognostic biomarkers for CRC.
基金Supported by the Youth Talent Program of Yunnan“Ten-thousand Talents Program”,No.YNWR-QNBJ-2018-169the Science Project of Yunnan Science and Technology Department,No.202201AY070001-068.
文摘BACKGROUND Epidermal growth factor receptor(EGFR)is a transmembrane protein that is differentially expressed in gestational diabetes mellitus(GDM).Endothelial dy-sfunction is a hallmark of GDM and plays a key role in its pathogenesis.EGFR is associated with endothelial dysfunction in the context of various diseases.How-ever,the exact mechanism by which EGFR causes endothelial dysfunction in GDM is unknown,particularly its regulation at the transcriptional and protein levels.METHODS Quantitative real-time polymerase chain reaction was used to detect the ex-pression of EGFR and H19.Western blotting was used to detect the expression of endothelial cell dysfunction markers.A cell counting kit 8 assay was used to assess cell viability,flow cytometry was used to assess apoptosis,scratch and Transwell assays were used to assess cell migration,and a tube formation assay was used to assess cell vascular formation.Hematoxylin-eosin staining was used to observe histopathological changes in the placentas of the mice.RESULTS In this study,EGFR was upregulated in clinical samples,GDM animal models and GDM cell models,and the knockdown of EGFR could mitigate the effect of streptozotocin(STZ)and high glucose(HG);promoted the proliferation,migration and vascularization of human umbilical vein endothelial cells(HUVECs);inhibited cell apoptosis and the expression of endothelial cell dysfunction markers(vascular cell adhesion molecule-1,tumor necrosis factor-α,vascular endothelial growth factor-A,and intercellular cell adhesion molecule-1);and alleviated the process of GDM in vivo.Mechanistically,EIF4A3 binding to long noncoding RNA H19 increased the stability of EGFR messenger RNA,thereby promoting HG-induced HUVECs dysfunction or STZ-induced endothelial cell dysfunction in GDM mice.In addition,ERRFI1 also regulated the expression of EGFR,and ERRFI1 inhibited EGFR activity by binding to EGFR,thereby inhibiting HG-induced HUVECs dysfunction.CONCLUSION Our study revealed that EGFR can accelerate the development of GDM by promoting endothelial cell dysfunction.
文摘Parthenogenetic embryonic stem cells（pE SCs）, as ＂seed cells＂ for regenerative medicine, are an effective way to build patient-specific pluripotent stem cells, due to the fact that characteristics of self-renewal and pluripotent are similar to embryonic stem cells（ESCs）. Parthenogenetic activation can be performed at meiosis I or meiosis II describing the embryos with distinct patterns of homozygosity and heterozygosity.Heterozygous pE SCs are expected to be used for autologous transplantation, while homozygous pE SCs enable to be used for allogeneic gene therapy in theory but is hampered by immunological barriers defined by the recognition of natural killer（NK）cells. In this review, we describe the mechanism of deriving heterozygous and homozygous pE SCs, and summarize the advantages and limitations of pE SCs in the area of cell therapy.
文摘Collecting baseline information on how laboratories perform testing is a reasonable first step towards establishing intra- and inter-laboratory standardization and quality control for semen analysis. We carried out a survey of the laboratories performing the testing in China's Mainland. A questionnaire, composed of 36 questions covering all aspects of semen analysis, was designed, and a copy was distributed to each of the 145 laboratories. Of these, 118 laboratories completed the questionnaires. The survey results showed that semen volume was measured visually in 53.6% （59/110） of the responding laboratories, and 70.9% （73/103） of laboratories analysed incompletely liquefied semen without any treatment. In addition, both manual-microscopic and computer-assisted semen-analysis systems were applied to analyse sperm concentration, motility and morphology. However, more than five methods were employed in routine sperm staining. An enzyme-linked immunosorbent assay was commonly used for determining whether antisperm antibodies were present. Several seminal biochemical markers were analysed in only 27.1% （32/118） of the responding laboratories. Generally, there was a lack of intra- and inter-laboratory quality control measures for semen analysis in all laboratories responding to this survey. In conclusion, the methods of semen analysis and the interpretation of test results in the surveyed laboratories differed markedly. In particular, many laboratories employed methods other than those recommended by the World Health Organization Laboratory Manual for the Examination of Human Semen and Sperm- cervical Mucus Interaction （1999）. These findings suggest an urgent need for the standardization of semen analysis with acceptable quality controls for each parameter to make the results repeatable and meaningful.
基金supported by the National Science Foundation of China(No.31501018 and 81260510)social development project of Hainan Province (SF201401)
文摘Objective:In this paper,we will discuss if the CETP polymorphism contributes to the centenarians in Hainan island.Methods:We tested the Taq IB and I405 V polymorphisms of CETP gene among 276 centenarians and 301 matched healthy individuals by AS-PCR and analyzed the data with SPSS software package(Version 19.0).Results:Our data indicated that allele B1 and V have the significant differences between centenarians and healthy control groups with P<0.001.Further analysis implied that genotypes B1B1(P<0.001,OR=0.148,95% CI=0.095-0.230) and VV(P<0.001 and OR=0.353,95% CI=0.237-0.525) were significantly different between centenarians and matched controls.The combination of B and V,such as B1B1-II(P<0.001,OR=0.128,95% CI=0.049-0.329),B1B1-IV(P<0.001,OR=0.115,95% CI=0.056-0.237),B1B2-VV(P<0.05,OR=0.534,95% CI=0.310-0.920),and B2B2-VV(P<0.001,OR=0.198,95% CI=0.086-0.453) have significant differences between centenarians and matched healthy individuals from Hainan.Conclusion:Our results implied that allele B1B1 and VV,as well as the combination B1B1-II,B1B1-IV,B1B2-VV and B2B2-VV may contribute to the longevity in centenarians of Hainan,south of China.
基金This work was supported by the Central Public Interest Scientific Institution Basal Research Fund of National Research Institute for Family Planning(No.2021GJZ09)the CAMS Innovation Fund for Medical Sciences(CIFMS,No.2018-I2M-1-004)。
文摘MicroRNAs(miRNAs)are mediators of the aging process.The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility.Twenty-seven donors were divided into three groups by age(Group A,n=8,age:20–30 years;Group B,n=10,age:31–40 years;and Group C,n=9,age:41–55 years)for high-throughput sequencing analysis.Samples from 65 individuals(22,22,and 21 in Groups A,B,and C,respectively)were used for validation by quantitative real-time polymerase chain reaction(qRT-PCR).A total of 2160 miRNAs were detected:1223 were known,937 were newly discovered and unnamed,of which 191 were expressed in all donors.A total of 7,5,and 17 differentially expressed microRNAs(DEMs)were found in Group A vs B,Group B vs C,and Group A vs C comparisons,respectively.Twenty-two miRNAs were statistically correlated with age.Twelve miRNAs were identified as age-associated miRNAs,including hsa-miR-127-3p,mmu-miR-5100_L+2R-1,efu-miR-9226_L-2_1ss22GA,cgr-miR-1260_L+1,hsa-miR-652-3p_R+1,pal-miR-9993a-3p_L+2R-1,hsa-miR-7977_1ss6AG,hsa-miR-106b-3p_R-1,hsa-miR-186-5p,PC-3p-59611_111,hsa-miR-93-3p_R+1,and aeca-mir-8986ap5_1ss1GA.There were 9165 target genes of age-associated miRNAs.Gene Ontology(GO)analysis of the target genes identified revealed enrichment of protein binding,membrane,cell cycle,and so on.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways,such as signaling pathways regulating stem cell pluripotency,metabolic pathways,and the Hippo signaling pathway.This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.
基金Supported by the National Natural Science Foundation of China Grants(No.81801523)the Natural Science Foundation of Guangdong Province(Nos.2017A030313789,2018A030313528,2019A1515011984)+3 种基金the Science and Technology Planning Foundation of Guangzhou City(201904010017,202102080102)Guangdong Province Medical Research Funding(No.A2021269)the Family Planning Research Institute Innovation Team of Guangdong Province grants(C-03)the Family Planning Research Institute of Guangdong Province Grants(S2018010).
文摘Piwi-interacting RNAs(piRNAs)is a novel class of non-coding RNAs.However,changes in piRNA expression profiles in recurrent spontaneous abortion(RSA)have not yet been investigated.The aim of this study was to identify differentially expressed piRNAs in deciduas of RSA patients.Decidua tissues were collected by curettage from recruited RSA patients and normal early pregnant(NEP)women with their informed consent.Small RNA sequencing was used to evaluate the differences in piRNA expression profiles between RSA and NEP.The present results demonstrated that the counts of total piRNA reads in RSA samples were increased compared with those in NEP samples(0.21%vs.0.11%).Differential expression analysis identified 29 upregulated piRNAs and 18 downregulated piRNAs in RSA samples.RT-qPCR further confirmed that the expression levels of uniq-109625,uniq-89328,uniq-50651 and uniq-4569 were decreased in 8 RSA tissues,compared with 13 NEP tissues.Otherwise,pi-22628 and uniq-173406 were increased in 8 RSA tissues.Based on GO term and KEGG pathway analysis,we speculate that these piRNAs regulate RSA by targeting extracellular matrix component pathway,cell adhesion pathway and focal adhesion pathway.PiRNAs may be involved in RSA pathogenesis by target genes function on adhesion and extracellular matrix component.
基金This work was supported by the National Natural Science Foundation of China(81870458)the Yunnan Engineering Technology Center of Digestive Disease(2018DH006)+2 种基金the Yunling Scholar(YLXL20170002)the Education Department of Yunnan Province(2019Y0352)the Health Department of Yunnan Province(2018NS0084).
文摘Objective To relieve long-term malnutrition caused by a malignant tumor affecting the pylorus and to prolong the patient survival.Methods A patient presented with complete pyloric obstruction due to pyloric tumors,and achieved good therapeutic effects through nutritional support and effective chemotherapy.Results After about 40 days of treatment,all physiological indicators were improving.After chemotherapy,the pyloric tumor shrank and the complete obstruction was relieved.The patient was able to eat and drink normally.Conclusion Nutritional support,combined with chemotherapy,may effectively treat complete pyloric obstruction caused by advanced tumors.
文摘Gonadotropin-releasing hormone （GnRH） is secreted from neurons within the hypothalamus and is necessary for reproductive function in all vertebrates. GnRH is also found in organs outside of the brain and plays an important role in Leydig cell steroidogenesis in the testis. However, the signalling pathways mediating this function remain largely unknown. In this study, we investigated whether components of the mitogen-activated protein kinase （MAPK） pathways are involved in GnRH agonist （GnRHa）-induced testis steroidogenesis in rat Leydig cells. Primary cultures of rat Leydig cells were established. The expression of 3β-hydroxysteroid dehydrogenase （3β-HSD） and the production of testosterone in response to GnRHa were examined at different doses and for different durations by RT-PCR, Western blot analysis and radioimmunoassay （RIA）. The effects of GnRHa on ERK1/2, JNK and p38 kinase activation were also investigated in the presence or absence of the MAPK inhibitor PD-98059 by Western blot analysis. GnRHa induced testosterone production and upregulated 3β-HSD expression at both the mRNA and protein levels; it also activated ERK1/2, but not JNK and p38 kinase. Although the maximum effects of GnRHa were observed at a concentration of 100 nmnol L-1 after 24 h, activation of ERKI/2 by GnRHa reached peak at 5 min and it returned to the basal level within 60 min. PD-98059 completely blocked the activation of ERKI/2, the upregulation of 3β-HSD and testosterone production. Our data show that GnRH positively regulates steroidogenesis via ERK signalling in rat Leydig cells. ERK1/2 activation by GnRH may be responsible for the induction of 3β-HSDgene expression and enzyme production, which may ultimately modulate steroidogenesis in rat Leydig cells.
文摘This multi-center, cross-sectional study investigated the association between serum testosterone （T） levels, serum sex hormone-binding globulin （SHBG） levels, and the risk of metabolic syndrome （MS） in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T （TT） and SHBG than those without MS （P 〈 0.001）. There was no significant difference in serum free T （FT） levels between subjects with and without MS （P = 0.627）. In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index （BMI）, smoking and drinking status, and serum TT （odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P 〈 0.01）. However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status （OR 0,981, 95% CI 0.960-1.007）. Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.This multi-center, cross-sectional study investigated the association between serum testosterone （T） levels, serum sex hormone-binding globulin （SHBG） levels, and the risk of metabolic syndrome （MS） in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T （TT） and SHBG than those without MS （P 〈 0.001）. There was no significant difference in serum free T （FT） levels between subjects with and without MS （P = 0.627）. In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index （BMI）, smoking and drinking status, and serum TT （odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P〈 0.01）. However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status （OR 0,981, 95% CI 0.960-1.007）. Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.
基金Supported by National Natural Science Foundation of China(No.81774355)Natural Science Foundation of Shandong Province(No.ZR2022QH033)。
文摘Objective To explore the effects of electroacupuncture(EA)on pregnancy outcomes after assisted reproduction and mitochondrial function of granulosa cells(GCs)in patients with polycystic ovary syndrome(PCOS)and phlegm-dampness syndrome.Methods In this randomized controlled trial,90 infertile women with PCOS and phlegm-dampness syndrome were recruited between August 2022 and December 2022.Patients were randomly assigned to the EA and control groups using a random sequence of codes in the order of enrolment,with 45 in in each group.Both groups underwent the ovarian stimulation protocol.The patients in the EA group received EA therapy including Zhongwan(CV 12),Qihai(CV 6),bilateral Xuehai(SP 10),Sanyinjiao(SP 6),Yinlingquan(SP 9),Tianshu(ST 25),Zusanli(ST 36),and Fenglong(ST 40),and the patients in the control group was treated with pseudo-acupuncture.The intervention was 25 min twice a week for a total of 6 times until the trigger day after menstruation had ended in the cycle before oocyte retrieval.The primary outcomes were clinical pregnancy rate(CPR)and the number of high-quality embryos.The secondary outcomes were(1)pregnancy-related indicators,including fresh embryo transfer rate(ETR),ovarian hyperstimulation syndrome(OHSS)rate,early pregnancy loss rate(ePLR),ectopic pregnancy rate,live birth rate(LBR),and cumulative CPR;(2)mitochondrial autophagy and mitochondrial membrane potential(MMP)in GCs;and(3)scoring for Chinese medicine syndrome.Adverse events to assess clinical safety were also monitored.Results The cumulative CPR was significantly higher in the EA group(42/45,93.3%)than in the control group(38/45,84.4%,P=0.036).The number of high-quality embryos and fresh ETR in the EA group were higher than those in the control group(3.80±1.65 vs.2.44±1.34,P<0.001;46.7%vs 24.4%,P=0.028).Ectopic pregnancies were not observed in either group.There were no significant differences in the fresh CPR,OHSS rate,ePLR or LBR between the two groups(P>0.05).Compared with the control group,the EA group showed lower expression levels of miR-146a-5p mRNA and P62 protein in GCs and higher levels of MMP and the LC3-II/LC3-I protein ratio(all P<0.01).The phlegm-dampness syndrome scores of the EA group were significantly lower than those of the control group(P<0.01).Conclusions EA significantly improved pregnancy outcomes in patients with PCOS and phlegm dampness syndrome.Mechanistically,this effect may be related to EA in decreasing miR-146a-5p mRNA expression,promoting mitochondrial autophagy in GCs,and improving mitochondrial function,which may contribute to improved oocyte quality.(Trial registration No.ChiCTR2200062915)
文摘Background The 3q26 chromosome region, where the human telomerase RNA gene （hTERC） is located, is a biomarker for cervical cancer and precancerous lesions. The aim of this study was to confirm the value of measuring hTERC gene gain in predicting the progression of cervical intraepithelial neoplasia grade Ⅰ or Ⅱ （CIN-Ⅰ and -Ⅱ, respectively） to CIN-Ⅲ and cervical cancer. Methods Liquid-based cytological samples from 54 patients with CIN-Ⅰ or CIN-Ⅱ lesions were enrolled in this study. Follow-up was performed with colposcopy and biopsy within 24 months after the diagnosis of CIN-Ⅰ or CIN-Ⅱ. Copy numbers of the hTERC gene were measured by fluorescence in situ hybridization with a dual-color probe mix containing the hTERC gene probe （labeled red） and the control, the chromosome 3 centromere-specific probe （labeled green）.Results All patients whose lesions progressed from CIN-Ⅰ or CIN-Ⅱ to CIN-Ⅲ displayed a gain of the hTERC gene, whereas patients where the hTERC gene was not amplified did not subsequently progress to CIN-Ⅲ or cervical cancer. The signal ratio pattern per cell was recorded as N：N （green： red）. The numbers of cells with the signal ratio pattern of 4：4 or N：≥5 in patients whose lesions progressed to CIN-Ⅲ were significantly higher than those whose lesions did not progress. Significantly, none of the patients with a 4：4 signal ratio pattern regressed spontaneously.Conclusions In conclusion, measurement of hTERC gene gain in CIN-Ⅰ or CIN-Ⅱ patients using liquid-based cytological samples could be a useful biomarker to predict the progression of such cervical lesions. In addition, a 4：4 or N：≥5 signal ratio pattern may indicate the unlikeness of spontaneous regression of CIN-Ⅰ or CIN-Ⅱ lesions.
文摘In the case of a previous offspring with trisomy 21, recurrence risk for Down syndrome is about 1%. It may be due to chance, but the possibility of germline mosaicism for trisomy 21 in one of the parents has important implications for the recurrence. Here we report a young healthy mother, who has a second pregnancy of trisomy 21.
文摘The clinical findings frequently presented in trisomy 4q syndrome including mental retardation, developmental delay and multiple abnormalities such as microcephaly, acrocephaly, as well as malformed ears, high/broad/depressed nasal bridge, teeth and thumb anomalies. It has been proposed that trisomy 4q is caused by a familial balanced translocation or a de novo imbalance. We reported a new case of trisomy 4q with a karyotype of 46, XY, der（5）t（4;5）（q27;q35） and this karyotye was reported for the first time. His phenotype included severe mental retardation, growth retardation, facial and thumb anomalies. Detected by cytogenetic investigation, comparative genomic hybridization, multicolor fluorescence in situ hybridization, the duplicated region from 4q27 to 4qter was confirmed. Trisomy 4q is a rare clinical finding. To our knowledge, this is the eighth case with duplicated fragment spanning from 4q27 to 4qter. Comparing the karyotypic and phenotypic correlation with those previously described, we reported a new case with partial trisomy 4q syndrome.
