Incidence of second primary cancers in patients with retinoblastoma: a systematic review and meta-analysis.

Introduction: This systematic review and meta-analysis aimed to examine the risk of second primary cancers (SPCs) among retinoblastoma (Rb) patients, both hereditary and nonhereditary. Previous studies have reported on the long-term risk of SPCs in these patient populations, but a comprehensive synthesis of the existing evidence is lacking. Methods: A systematic search was conducted in PubMed, EMBASE, and Cochrane Library from inception to 12 March 2023, supplemented by manual screening. Eligible studies were identified, and data were extracted. The primary outcome measure was the standardized incidence ratios (SIRs) of SPCs in Rb patients. Summary estimates were calculated using random or fixed effects models. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Results: Ten studies, including nine high-quality studies, were included in this review. The summary estimate of SIR for SPCs among hereditary Rb patients was 17.55 (95% CI=13.10-23.51), while the pooled estimate of SIR for SPCs among nonhereditary Rb patients was 1.36 (95% CI=0.90-2.04). Significant differences in SIRs for different SPC types were observed (P=0.028), including nasal cavity tumor (SIR=591.06, 95% CI=162.79-2146.01), bone tumor (SIR=442.91, 95% CI=191.63-1023.68), soft tissue sarcoma (SIR=202.93, 95% CI=114.10-360.93), CNS (SIR=12.84, 95% CI=8.80-18.74), and female breast cancer (SIR=3.68, 95% CI=2.52-5.37). Chemotherapy and radiation therapy were associated with an increased risk of SPCs among hereditary Rb patients. Discussion: The findings of this review indicate that hereditary Rb patients have a significantly elevated risk of developing SPCs, whereas nonhereditary Rb patients do not show the same risk. Furthermore, significant differences were observed in the SIRs of different SPC types. Treatment techniques, specifically chemotherapy and radiation therapy, were associated with an increased risk of SPCs among hereditary Rb patients. These findings highlight the importance of radiation protection for Rb patients and the need for further research and tailored management strategies for this high-risk population.

A comprehensive meta-analysis to identify susceptibility genetic variants for precocious puberty.

PURPOSE: Currently, several genetic variants in ERα gene (rs2234693 and rs9340799), ERß gene (rs1256049 and rs4986938), KISS1 gene (rs4889, rs1132506 and rs5780218), LIN28B gene (rs314263, rs314276 and rs314280), and MKRN3 gene (rs2239669) have been repeatedly explored for their contribution to precocious puberty (PP) susceptibility. However, the results remain conflicting rather than conclusive. We here performed a meta-analysis to identify the real susceptibility genetic variants for PP. METHODS: After screening by inclusion criteria, 20 related studies were finally included in this meta-analysis. The odds ratios and 95% confidence intervals were calculated to assess the strength of association. Sensitive analysis, publication bias, and trial sequential analysis (TSA) were performed to evaluate the stability and reliability of results. RESULTS: Rs2234693, rs9340799, and rs1256049 were significantly associated with PP susceptibility (p < 0.0084). Stratified analysis according to ethnicity showed that rs2234693 and rs9340799 were significantly associated with PP susceptibility in Asian and Chinese populations. Stratified analysis according to PP subtype showed that rs2234693 and rs9340799 were significantly associated with idiopathic central PP susceptibility in Asian and Chinese populations (p < 0.0084). The results of publication bias, sensitivity analysis, and TSA provided solid evidence for the association between these three variants and PP susceptibility. CONCLUSIONS: Rs2234693 and rs9340799 in ERα gene and rs1256049 in ERß gene may serve as susceptive factors for PP development. The present finding should be confirmed in replication studies and reinforced in functional studies, which will ultimately improve the feasibility of the application of these three PP-susceptible loci in clinical practice.

DNA strand displacement and TdT-Mediated DNA extension for swift, convenient, and quantitative evaluation of sperm DNA integrity and its clinical implications.

DNA integrity is crucial for the clinical pregnancy outcome and offspring health, while detection methods currently used (comet assay, TUNNEL assay, SCSA, etc.) can only provide the ratio of positive sperms at the cellular level and are unable to quantitatively detect the breakpoints at the DNA molecular level. Herein, we developed a detection system based on terminal deoxynucleotidyl transferase and DNA strand displacement fluorescent probe, which could efficiently and conveniently measure the number of 3'-OH (equivalent to the number of breakpoints). We further investigated the use of this technique in assisted reproduction after completing the principle verification, system optimization, and research on analytical performance. The detection system was shown to have a good linear range from 0.01 nM to 4 nM, using single-stranded DNA with 3'-OH end as the calibrator. The system underwent thorough optimization for stability and accuracy. In comparison to the widely accepted index DFI detected by SCSA, the new system demonstrated reasonable correlation and better prediction efficiency. Its applicability was also proven through its use in assisted reproductive technology procedures.

The balance between NANOG and SOX17 mediated by TET proteins regulates specification of human primordial germ cell fate.

BACKGROUND: Human primordial germ cells (hPGCs) initiate from the early post-implantation embryo at week 2-3 and undergo epigenetic reprogramming during development. However, the regulatory mechanism of DNA methylation during hPGC specification is still largely unknown due to the difficulties in analyzing early human embryos. Using an in vitro model of hPGC induction, we found a novel function of TET proteins and NANOG in the hPGC specification which was different from that discovered in mice. METHODS: Using the CRISPR-Cas9 system, we generated a set of TET1, TET2 and TET3 knockout H1 human embryonic stem cell (hESC) lines bearing a BLIMP1-2A-mKate2 reporter. We determined the global mRNA transcription and DNA methylation profiles of pluripotent cells and induced hPGC-like cells (hPGCLCs) by RNA-seq and whole-genome bisulfite sequencing (WGBS) to reveal the involved signaling pathways after TET proteins knockout. ChIP-qPCR was performed to verify the binding of TET and NANOG proteins in the SOX17 promoter. Real-time quantitative PCR, western blot and immunofluorescence were performed to measure gene expression at mRNA and protein levels. The efficiency of hPGC induction was evaluated by FACS. RESULTS: In humans, TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) impaired the NODAL signaling pathway and impeded hPGC specification in vitro, while the hyperactivated NODAL signaling pathway led to gastrulation failure when Tet proteins were inactivated in mouse. Specifically, TET proteins stimulated SOX17 through the NODAL signaling pathway and directly regulates NANOG expression at the onset of hPGCLCs induction. Notably, NANOG could bind to SOX17 promoter to regulate its expression in hPGCLCs specification. Furthermore, in TKO hESCs, DNMT3B-mediated hypermethylation of the NODAL signaling-related genes and NANOG/SOX17 promoters repressed their activation and inhibited hPGCLC induction. Knockout of DNMT3B in TKO hESCs partially restored NODAL signaling and NANOG/SOX17 expression, and rescued hPGCLC induction. CONCLUSION: Our results show that TETs-mediated oxidation of 5-methylcytosine modulates the NODAL signaling pathway and its downstream genes, NANOG and SOX17, by promoting demethylation in opposition to DNMT3B-mediated methylation, suggesting that the epigenetic balance of DNA methylation and demethylation in key genes plays a fundamental role in early hPGC specification.

Diurnal rhythm of human semen quality: analysis of large-scale human sperm bank data and timing-controlled laboratory study.

STUDY QUESTION: Can we identify diurnal oscillations in human semen parameters as well as peak times of semen quality? SUMMARY ANSWER: Human semen parameters show substantial diurnal oscillation, with most parameters reaching a peak between 1100 and 1500 h. WHAT IS KNOWN ALREADY: A circadian clock appears to regulate different physiological functions in various organs, but it remains controversial whether diurnal rhythms occur in human semen parameters. STUDY DESIGN, SIZE, DURATION: The medical record of a provincial human sperm bank (HSB) with 33 430 semen samples collected between 0800 and 1700 h from 1 March 2010 to 8 July 2015 was used to analyze variation in semen parameters among time points. A laboratory study was conducted to collect semen samples (n = 36) from six volunteers at six time points with identical time intervals (2 days plus 4 h) between 6 June and 8 July in 2019, in order to investigate the diurnal oscillation of semen parameters in vivo, with a strictly controlled abstinence period. Therefore, the sperm bank study with a large sample size and the in vivo study with a strictly controlled abstinence period in a 24-h time window could be compared to describe the diurnal rhythms in human semen parameters. PARTICIPANTS/MATERIALS, SETTING, METHODS: Samples were obtained from potential HSB donors and from participants in the laboratory study who were volunteers, recruited by flyers distributed in the community. Total sperm count, sperm concentration, semen volume, progressive motility and total motility were assessed using computer-aided sperm analysis. In addition, sperm chromatin integrity parameters (DNA fragmentation index and high DNA stainability) were assessed by the sperm chromatin structure assay, and sperm viability was measured with flow cytometry in the laboratory study. MAIN RESULTS AND THE ROLE OF CHANCE: The 33 430 samples from the HSB showed a temporal variation in total sperm count, sperm concentration, semen volume, progressive motility and total motility (all P < 0.001) between 0800 and 1700 h. Consequently, the eligibility of semen samples for use in ART, based on bank standards, fluctuated with time point. Each hour earlier/later than 1100 h was associated with 1.14-fold risk of ineligibility. Similarly, the 36 samples taken during the 24-h time window showed diurnal oscillation. With the pre-collection abstinence period strictly controlled, most semen parameters reached the most favorable level between 1100 and 1500 h. LIMITATIONS, REASONS FOR CAUTION: Some of the possible confounding factors, such as energy intake, which might influence semen quality or diurnal rhythms, were not adjusted for in the analyses. In addition, the findings should be considered with caution because the study was conducted in a specific population, time and place, while the timing of oscillations could differ with changing conditions. WIDER IMPLICATIONS OF THE FINDINGS: The findings could help us to estimate semen quality more precisely and to obtain higher quality sperm for use in ART and in natural conception. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Natural Science Foundation of China (81871208) and National Key R&D Program of China (2017YFC1002001). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Evaluation of Sperm DNA Integrity by Mean Number of Sperm DNA Breaks Rather Than Sperm DNA Fragmentation Index.

BACKGROUND: Sperm DNA integrity is crucial for normal fertilization, implantation, and embryo development. Several assays are available to assess sperm DNA fragmentation but are limited by high price, complicated processes, and low accuracy. METHODS: We developed a secondary amplification detection system based on terminal deoxynucleotidyl transferase and endonuclease IV, which could efficiently measure the number of 3'-OH (equivalent to the number of breakpoints). We applied this detection system in single stranded DNA with standard concentrations to obtain the standard curve. We then broke the double stranded genomic DNA by ultrasound and enzyme digestion and used the detection system to monitor the increase of DNA breakpoints. Finally, we used this method to measure the mean number of sperm DNA breakpoints (MDB) in 80 sperm samples. RESULTS: We successfully measured the number of 3'-OH in single stranded DNA with standard concentration and obtained the standard curve. The linear range for the number of DNA breakpoints was from 0.1 nM to 15 nM. The detection method was successfully validated on λ DNA and 80 human sperm samples. The results of real clinical samples revealed that the mean number of DNA breakpoints (MDB) had a stronger relevance with the sperm motility and clinical pregnancy outcomes than the commonly used parameter of DNA fragmentation index (DFI). CONCLUSION: We have developed a straight-forward method for direct measurement of the mean number of DNA breakpoints in sperms. The method has advantages of short time-consumption, simple operation, high analytical sensitivity, and low requirement for instrumentation, which makes it conducive to clinical application. The proposed new parameter (MDB) could be a more direct, accurate and clinically significant indicator for evaluating the sperm DNA integrity.

Replication study and meta-analysis of selected genetic variants and polycystic ovary syndrome susceptibility in Asian population.

PURPOSE: Polycystic ovary syndrome (PCOS) is a highly complex disorder influenced by genetic and environmental factors. Previous association studies have identified multiple PCOS-susceptible loci, but there is no consistent conclusion, which calls for further investigations. METHODS: In the present case-control study, FSHR gene variants (rs2268361, rs6165, and rs6166), LHCGR gene variant (rs13405728), THADA gene variant (rs13429458), DENND1A gene variants (rs10818854 and rs2479106), and INSR gene variants (rs2059807 and rs1799817) were genotyped with Sanger sequencing in a total of 400 PCOS women and 480 healthy women. RESULTS: After Bonferroni correction, our results showed that rs13405728, rs13429458, rs2479106, rs10818854, and rs2059807 were significantly associated with PCOS risk in Chinese women. To improve the statistical strength, a further meta-analysis in Asian population was conducted. Although rs6166 and rs1799817 were not associated with PCOS risk in the present study, they were identified to be strongly associated with PCOS risk in the pooled Koreans and Chinese respectively. No significant association with PCOS risk was consistently found for rs2268361 or rs6165. Moreover, the pooled results further confirmed the significant association with PCOS risk for rs13405728, rs13429458, rs2479106, rs10818854, and rs2059807. CONCLUSIONS: Collectively, the rs6166, rs13405728, rs13429458, rs2479106, rs10818854, rs2059807, and rs1799817 may indeed be the genetic risk factors for PCOS in Asian population, which requires further investigation using larger independent sets of samples in different ethnic populations.

[Functional polymorphism sites in non-coding regions of folate metabolism-related genes in the reproductive-aged population of Hubei Province].

Objective: To investigate the distribution of the functional polymorphisms in the non-coding regions of folate metabolism-related genes in the reproductive-aged population of Hubei Province. METHODS: Using Sanger sequencing, we examined the polymorphisms of the genes MTR (rs28372871 and rs1131450), MTRR (rs326119) and CBS (rs2850144) in 790 subjects before and during pregnancy from April 2020 to March 2021. We compared the distributions of the four loci between different populations. RESULTS: The distributions of the four genotypes of rs28372871, rs1131450, rs326119 and rs2850144 all conformed to the Hardy-Weinberg equilibrium (HWE). Statistically significant differences were observed in the polymorphism distribution of rs28372871 between Hubei and Jiangsu (P < 0.05), in that of rs1131450 between Hubei and Shanghai (P < 0.05), and in that of rs2850144 between Hubei and Yazd, Iran (P < 0.01). CONCLUSIONS: This was the first investigation on the distribution of MTR, MTRR and CBS gene polymorphisms in the reproductive-aged population of Hubei Province. The effects of the functional loci in both encoding and non-coding regions of folate metabolism-related genes have to be comprehensively considered so as to formulate an appropriate folate-supplementary protocol.

The association study between CYP24A1 gene polymorphisms and risk of liver, lung and gastric cancer in a Chinese population.

Recently, four single nucleotide polymorphisms (rs2585428, rs4809960, rs6022999 and rs6068816) in CYP24A1 gene were extensively studied for their associations with cancer risk. However, these studies included only a few types of cancer, which calls for further investigations. In view of this, we here conducted a case-control study to explore the associations between these four CYP24A1 gene polymorphisms and risk of liver, lung and gastric cancer in a Chinese population. A total of 480 liver cancer patients, 550 lung cancer patients, 460 gastric cancer patients and 800 normal controls were recruited in this study. The genotyping of CYP24A1 gene polymorphisms was applied with Sanger sequencing assay. Single-locus analysis demonstrated that rs6022999 was significantly associated with risk of liver and lung cancer, while rs6068816 was significantly associated with the risk of gastric cancer. Haplotype analysis revealed that haplotype GTAT was associated with an increased risk of liver cancer and a decreased risk of lung cancer, and haplotype ATGC was associated with a decreased risk of lung cancer. The further meta-analysis of rs6068816 and lung cancer risk showed that rs6068816 was not associated with lung cancer risk in Chinese population, which confirmed our present finding. Conclusively, rs6022999 may be a genetic biomarker for liver and lung cancer susceptibility in Chinese population, and rs6068816 may be used to predict gastric cancer risk in Chinese population.

Corrigendum: Induced Pluripotent Stem Cells Derived From Two Idiopathic Azoospermia Patients Display Compromised Differentiation Potential for Primordial Germ Cell Fate.

[This corrects the article DOI: 10.3389/fcell.2020.00432.].

Induced Pluripotent Stem Cells Derived From Two Idiopathic Azoospermia Patients Display Compromised Differentiation Potential for Primordial Germ Cell Fate.

At present, the etiology of most non-obstructive azoospermia (NOA) remains unclear. In vitro generation of patient-specific induced pluripotent stem cells (iPSCs) is an effective approach for exploring the mechanisms of human disease. Here, we established iPSCs from two patients with idiopathic NOA and differentiated them into primordial germ cell-like cells (PGCLCs) in vitro. Compared with iPSCs derived from normal fertile men, the NOA patient-specific iPSCs show decreased efficiency of PGCLC formation in vitro. Particularly, the embryoids derived from NOA patient-specific iPSCs show defects in the expression of early primordial germ cell (PGC) genes. The transcriptome analysis reveals the expression patterns of key human PGC genes are generally similar in PGCLCs differentiated from all iPSC lines, and the differentially expressed genes were enriched with gene ontology (GO) of cell cycle and apoptosis regulation. Moreover, the PGCLCs derived from NOA patient-specific iPSCs might have initiated epigenetic reprogramming at a very early stage. Thus, the NOA patient-specific iPSCs exhibit poor response to germ cell induction in vitro, which may be related to the regulation of apoptotic process. These findings provide a foundation for future research on mechanism of male infertility.

A rare karyotype of nonmosaic isodicentric (Y) (p11.31) with azoospermia and short stature.

Chromosome aberration is one of the common causes of male infertility. Isodicentric chromosome is a chromosomal aberration in which two arms of a chromosome are identical in morphology and genetics and connected by two centromeres. We firstly reported a case of infertile male with nonmosaic 46, X, idic (Y) (qter-p11.31::p11.31-qter) but with the sex-determining region Y (SRY). The broken site is the chromosome Y (p11.31). The patients' clinical phenotype was azoospermia and short stature. Fluorescence in situ hybridisation (FISH), chromosomal microarray comparative genomic hybridisation (array CGH) and related molecular analysis were performed. Azoospermia of this case may be caused by the abnormal chromosome structure, which leads to abnormal chromosome synapsis in spermatogenesis. Loss of genes in PAR1 and gain of genes copies in azoospermia factor (AZF) region on the Y chromosome may also contribute to the pathogenesis of azoospermia.

Generation of an iPSC line (HUSTi002-A) from fibroblasts of a patient with Sertoli cell-only syndrome carrying c.731_732delAT in PIWIL2 gene.

Sertoli cell-only syndrome (SCOS) is a severe phenotype of male infertility; autosomal gene defects are thought to be the causes for this disease. The iPSC line generated from a SCOS patient carrying a mutation in PIWIL2 gene expresses pluripotent markers, has a normal karyotype and the mutation c.731_732delAT in PIWIL2 gene and is able to differentiate into three germ layers. This cell line will help to study the pathogenesis of SCOS, and the roles of PIWIL2 in human germ cells development and spermatogenesis.

Lack of association between interleukin-22 gene polymorphisms and cancer risk: a case-control study and a meta-analysis.

BACKGROUND: Interleukin-22 (IL22) has been implicated in inflammation and tumorigenesis. The association between IL22 gene polymorphisms and cancer risk has been widely explored. However, the limited sample sizes of previous studies may produce inadequate statistical power and conflicting results, which calls for further investigations. In this study, we recruited a total of 1490 cancer patients (480 liver cancer patients, 550 lung cancer patients, and 460 gastric cancer patients) and 800 normal controls to explore the associations between IL22 gene polymorphisms (rs1179251, rs2227485, rs2227511, and rs2227473) and cancer risk. METHOD: The genotyping was performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. RESULTS: Our results showed that none of the four IL22 gene polymorphisms was associated with the risk of liver, lung or gastric cancer in Hubei Han Chinese population. To improve the statistical strength, a meta-analysis was further conducted. The results further confirmed our present findings and showed that rs1179251, rs2227485, and rs2227473 were not associated with cancer risk in total or stratified analysis. CONCLUSION: Consequently, the rs1179251, rs2227485, rs2227511, and rs2227473 polymorphisms may not be associated with cancer risk. However, further investigations using larger samples in different ethnic populations are required.

Association study between CYP24A1 gene polymorphisms and cancer risk.

CYP24A1, an essential gene in regulation of vitamin D, has been reported to play an important role in enhancing immune activity and inhibiting tumorigenesis. Previous studies proposed that rs2585428, rs4809960, rs6022999 and rs6068816 in CYP24A1 gene might be greatly associated with cancer risk. To validate the findings, we here investigated the associations of these four polymorphisms and colorectal cancer (CRC) risk in a central Chinese population (426 colon cancer patients, 361 rectal cancer patients and 800 healthy controls). The genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Our results revealed that the rs4809960 and rs6022999 were strongly associated with the CRC risk, especially with the colon cancer risk. Moreover, the analysis of haplotypes consisting of rs2585428(G > A), rs4809960(T > C), rs6022999(A > G) and rs6068816(C > T) indicated that haplotype ATGC significantly decreased the CRC risk, especially the colon cancer risk. Haplotype GCAT significantly increased the CRC risk, especially the rectal cancer risk. However, haplotype ACAC was only found to be associated with increased risk of CRC. To improve the statistical strength, an updated meta-analysis was further performed. The results showed that rs2585428 was associated with cancer risk in Caucasian population, rs4809960 was associated with breast cancer risk in Caucasian population, and rs6022999 was associated with cancer risk in Asian population. Collectively, the rs4809960 and rs6022999 may be the genetic biomarkers for prediction of colon cancer risk in Chinese population, the rs2585428 and rs6022999 may link to cancer susceptibility in Caucasian population and in Asian population respectly.

The effectiveness and safety of acupuncture for the treatment of myasthenia gravis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: No systematic reviews of acupuncture as a treatment for myasthenia gravis (MG) have been published in English. The aim of our study is to evaluate the efficacy and safety of acupuncture as a treatment for MG. METHODS: We searched for randomized controlled trials (RCTs) in seven main electronic databases. Unpublished articles, including conference papers and Chinese doctoral and master's theses, were also included as supplementary sources. The primary outcome was the relative clinical score (RCS) response rate. We performed a meta-analysis using RR and MD with 95% CI. RESULTS: Thirteen RCTs involving a total of 775 participants were included. Most included trials had a high risk of bias in allocation concealment and blinding. Eleven RCTs used acupuncture as an adjuvant to medication, and this treatment showed a significant improvement in the RCS response rate compared to medication alone (RR: 1.42; 95% CI: 1.06-1.91; P=0.02). The subgroup analysis based on the treatment duration showed a significant effect on the RCS response rate when the treatment duration was longer than 12 weeks (RR: 2.02; 95% CI: 1.31-3.12; P=0.001). In contrast, there was no significant effect of treatment with a duration less than 8 weeks (RR: 1.14; 95% CI: 0.91-1.44; P=0.26). Four RCTs showed a significant difference in the absolute clinical score (ACS) (RR: 3.42; 95% CI: 1.23-5.61; P=0.002). The acupuncture group reported better outcomes. No severe adverse events corresponding to acupuncture were reported. CONCLUSIONS: This meta-analysis suggests that acupuncture as an integrative therapy has a significant positive effect in treating MG. Acupuncture may enhance the efficacy of medication in MG patients. The safety of acupuncture requires further investigation. The clinical significance of these changes needs to be investigated by further studies using rigorous designs and longer follow-up times.

PEX10, SIRPA-SIRPG, and SOX5 gene polymorphisms are strongly associated with nonobstructive azoospermia susceptibility.

PURPOSE: Male infertility is a multifactorial syndrome encompassing a wide variety of disorders. A previous Chinese genome-wide single-nucleotide polymorphism (SNP) association studies have identified four SNPs (rs12097821 in PRMT6 gene, rs2477686 in PEX10 gene, rs6080550 in SIRPA-SIRPG, and rs10842262 in SOX5 gene) as being significantly associated with risk factors for nonobstructive azoospermia (NOA). However, the results were not fully repeated in later studies, which calls for further investigations. METHODS: We here performed a case-control study in a central Chinese population to explore the association between the four SNPs and male infertility, which included 631 infertile men (NOA and oligozoospermia) and 720 healthy fertile men. The genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. RESULTS: The results showed that rs12097821 and rs10842262 were strongly associated with the risk of NOA but not total male infertility or oligozoospermia, while rs2477686 and rs6080550 were not associated with the risk of total male infertility, NOA, or oligozoospermia. To improve the statistical strength, a meta-analysis was conducted. The results suggested that rs2477686, rs6080550, and rs10842262 were significantly associated with male infertility, especially with NOA, while rs12097821 was only found to be associated with total male infertility. CONCLUSIONS: Collectively, the rs2477686, rs6080550, and rs10842262 may indeed be the genetic risk factors for NOA, which requires further investigation using larger independent sets of samples in different ethnic populations.

A comprehensive study of CD44 rs 187115 variant and cancer risk in a central Chinese population.

The rs187115, an intronic variant of CD44 gene, has been previously reported to play a potential role in genetic susceptibility to cancer. Here, we comprehensively examined the association between CD44 rs187115 variant and cancer risk (breast cancer, cervical cancer, lung cancer, gastric cancer, liver cancer, colon cancer, and rectal cancer) in a central Chinese population. The rs187115 variant was genotyped with the polymerase chain reaction-restriction fragment length polymorphism assay. In this study, we observed that rs187115 was associated with the risk of cervical, lung, and liver cancer, but not with the risk of breast, gastric, colon, rectal or colorectal cancer. Of note, the G allele and G allele genotypes of rs187115 conferred an increased risk of cervical, lung, and liver cancer. To improve the statistical strength, a followed meta-analysis was conducted. The results demonstrated that rs187115 was significantly associated with cancer risk, and the significant association remained in the stratification analysis by ethnicity, genotyping method, and cancer type. Collectively, the CD44 rs187115 variant may be associated with the risk of cervical, lung, and liver cancer in the central Chinese population, and may be used as a potential biomarker for cancer predisposition in the Asian population, especially in the Chinese population.

The association of POLR2E rs3787016 polymorphism and cancer risk: a Chinese case-control study and meta-analysis.

How single nucleotide polymorphisms in long non-coding RNAs are involved in cancer susceptibility remains poorly understood. We hypothesized that polymerase II polypeptide E (POLR2E) rs3787016 polymorphism, identified in a genome-wide association study of prostate cancer, might be a common genetic risk factor for cancer risk. To address this issue, we here conducted a case-control study to investigate the association of POLR2E rs3787016 polymorphism with risk of liver and lung cancer (including 800 normal controls, 480 liver cancer patients, and 550 lung cancer patients), followed by a meta-analysis. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. Although no significant association was found for rs3787016 with risk of liver or lung cancer, the further stratified analysis identified that rs3787016 contributed to liver cancer risk particularly for over than 60 years individuals who drink. Moreover, the meta-analysis demonstrated that rs3787016 was associated with overall cancer risk and prostate cancer risk. Collectively, the POLR2E rs3787016 polymorphism may be a valuable biomarker for cancer predisposition.

[Correlation of sperm DNA fragmentation index with age and semen parameters in infertile men].

OBJECTIVE: To explore the correlation of the sperm DNA fragmentation index (DFI) with age, sperm concentration and sperm motility in infertile men. METHODS: We collected semen samples from 531 infertile males in our hospital from January 2016 to June 2017. We determined the semen parameters using the computer-assisted semen analysis system, measured the sperm DFI by sperm chromatin structure assay, and analyzed the correlation of the sperm DFI with the age, sperm concentration and sperm motility of the patients. RESULTS: With the increase of age, the infertile males showed a significantly decreased proportion of the sperm with a DFI ≤15% and elevated proportion of the sperm with a DFI ≥25%, with a positive correlation between age and sperm DFI (r = 0.653, P < 0.01). With the increase of sperm concentration and motility, however, the proportion of the sperm with a DFI ≤15% was remarkably increased while that of the sperm with 15%