Sperm retrieval outcomes of contralateral testis in men with nonobstructive azoospermia and unsuccessful unilateral microdissection testicular sperm extraction.

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Novel predictors for livebirth delivery rate in patients with idiopathic non-obstructive azoospermia based on the clinical prediction model.

Objective: To build a prediction model for live birth delivery per intracytoplasmic sperm injection (ICSI) in iNOA patients by obtaining sperm by microdissection testicular sperm extraction (mTESE). Methods: A retrospective cohort study of 377 couples with iNOA male partners treated with 519 mTESE-ICSI cycles was conducted from September 2013 to July 2021 at the Reproductive Medical Centre of Peking University Third Hospital. Following exclusions, 377 couples with iNOA male partners treated with 482 mTESE-ICSIs were included. A prediction model for live birth delivery per ICSI cycle was built by multivariable logistic regression and selected by 10-fold cross-validation. Discrimination was evaluated by c-statistics and calibration was evaluated by the calibration slope. Results: The live birth delivery rate per mTESE-ICSI cycle was 39.21% (189/482) in these couples. The model identified that the presence of motile sperm during mTESE, bigger testes, higher endometrial thickness on the day of human chorionic gonadotrophin (hCG) administration (ET-hCG), and higher quality embryos are associated with higher live birth delivery success rates. The results of the model were exported based on 10-fold cross-validation. In addition, the area under the mean ROC curve was 0.71 ± 0.05 after 10-fold cross-validation, indicating that the prediction model had certain prediction precision. A calibration plot with an estimated intercept of -1.653 (95% CI: -13.403 to 10.096) and a slope of 1.043 (95% CI: 0.777 to 1.308) indicated that the model was well-calibrated. Conclusion: Our prediction model will provide valuable information about the chances of live birth delivery in couples with iNOA male partners who have a plan for mTESE-ICSI treatment. Therefore, it can improve and personalize counseling for the medical treatment of these patients.

Outcomes after HSCT for mucolipidosis II (I-cell disease) caused by novel compound heterozygous GNPTAB mutations.

Background: Mucolipidosis type II (MLII), or I-cell disease, is a rare lysosomal storage disease (LSD) caused by variants in the GNPTAB gene. MLII patients exhibit clinical phenotypes in the prenatal or neonatal stage, such as marked dysmorphic features, cardiac involvement, respiratory symptoms, dysostosis multiplex, severe growth abnormalities, and mental and motor developmental abnormalities. The median age at diagnosis for MLII is 0.7 years, the median survival is 5.0 years, and the median age at death is 1.8 years. No cure for MLII exists. Methods: Sanger sequencing of the GNPTAB gene identified the compound heterozygous mutations c.673C > T in exon 7 and c.1090C > T in exon 9, which were novel double heterozygous mutations first reported in China. For the first time, we describe our experience in the use of HSCT for MLII. Our patient underwent HSCT with cells from a 9/10 human leukocyte antigen (HLA)-matched unrelated donor at 12 months of age. Myeloid neutrophil and platelet engraftment occurred on Days 10 and 11, respectively. Results: The patient's limb muscle tension was significantly reduced, and his gross and fine motor skills were improved four months after transplantation. DST(Developmental Screen Test) results showed that the patient's fine motor skills and mental development were improved compared with before HSCT. Conclusion: MLII is a very severe lysosomal storage disease, to date, only 3 cases have been reported on the use of HSCT to treat MLII. Our data show that HSCT is a potential way to prolong the life of patients and improve their quality of life. Due to the lack of comparable data and time, the exact benefit remains unclear in MLII patients. Longer-term follow-up and in-depth prospective studies are indispensable.

A retrospective cohort study of geographic differences in the semen of 1,012 sperm donors in China.

Background: Male reproductive health has become a serious public health concern, and semen quality is essential to male reproduction. We aimed to investigate geographical differences in the semen quality of sperm donors from northern and southern China by enrolling donors across the country. Methods: A total of 1,012 sperm donors were enrolled in this study between 2015 and 2019. Donors were first divided into two parts based on their birthplace according to the "Qinling-Huaihe" line, and secondly, by their residential latitude. Finally, donors were re-classified into two groups (typically north and south) which contained 667 samples. Results: Statistically significant differences in sperm concentration were observed among men from different latitudes in China (P=0.04). The sperm concentrations of males from 18° to 27° north latitude were significantly lower than those from 36° to 45° and 45° to 54° [median 131, 134, and 146, respectively, P=0.021 (18° to 27° vs. 36° to 45°) and P=0.01 (18° to 27° vs. 45° to 54°)]. Conclusion: We hypothesize environmental pollution and mental stress due to the increased population size may be the main factors underlying differences in the sperm quality of men in northern and southern China.

Psychological status of infertile men during the Coronavirus Disease 2019 Pandemic in China: a cross-sectional investigation.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has had a widespread and profound impact on people's mental health. The factors associated with mental symptoms among men diagnosed with infertility, a disease closely related to psychological conditions, remain unclear. The aim of this study is to investigate the risk factors associated with mental symptoms among infertile Chinese men during the pandemic. RESULTS: A total of 4,098 eligible participants were recruited in this cross-sectional, nationwide study, including 2,034 (49.6%) with primary infertility and 2,064 (50.4%) with secondary infertility. The prevalence of mental health conditions was 36.3%, 39.6%, and 6.7% for anxiety, depression, and post-pandemic stress, respectively. Sexual dysfunction is associated with a higher risk with adjusted odds ratios (ORs) of 1.40 for anxiety, 1.38 for depression, and 2.32 for stress. Men receiving infertility drug therapy displayed a higher risk for anxiety (adjusted OR, 1.31) and depression (adjusted OR, 1.28) symptoms, while those receiving intrauterine insemination had a lower risk of anxiety (adjusted OR, 0.56) and depression (adjusted OR, 0.55) symptoms. CONCLUSION: The COVID-19 pandemic has had a significant psychological impact on infertile men. Several psychologically vulnerable populations were identified, including individuals with sexual dysfunction, respondents receiving infertility drug therapy, and those experiencing control measures for COVID-19. The findings provide a comprehensive profile of the mental health status of infertile Chinese men during the COVID-19 outbreak and provide potential psychological intervention strategies.

RéSUMé: CONTEXTE: L'épidémie de maladie à coronavirus 2019 (COVID-19) a eu un impact étendu et profond sur la santé mentale des gens. Les facteurs associés aux symptômes mentaux chez les hommes diagnostiqués comme infertiles, une maladie étroitement liée aux conditions psychologiques, restent flous. L'objectif de cette étude est d'étudier les facteurs de risque associés aux symptômes mentaux chez les hommes chinois infertiles pendant la pandémie. RéSULTATS: Au total, 4 098 participants admissibles ont été recrutés dans cette étude transversale à l'échelle nationale, dont 2 034 (49,6%) présentaient une infertilité primaire et 2 064 (50,4%) une infertilité secondaire. La prévalence des problèmes de santé mentale était respectivement de 36,3 %, 39,6 % et 6,7 % pour l'anxiété, la dépression, et le stress postpandémique. La dysfonction sexuelle est associée à un risque plus élevé avec des odds ratios ajustés (OR) de 1,40 pour l'anxiété, 1,38 pour la dépression et 2,32 pour le stress. Les hommes recevant un traitement médicamenteux contre l'infertilité présentaient un risque plus élevé de symptômes d'anxiété (OR ajusté, 1,31) et de dépression (OR ajusté, 1,28), alors que ceux dont le traitement consistait à faire des inséminations intra-utérines présentaient un risque plus faible de symptômes d'anxiété (OR ajusté, 0,56) et de dépression (OR ajusté, 0,55). CONCLUSIONS: La pandémie de COVID-19 a eu un impact psychologique important sur les hommes infertiles. Plusieurs populations psychologiquement vulnérables ont été identifiées, notamment les personnes souffrant de dysfonction sexuelle, les hommes recevant un traitement médicamenteux contre l'infertilité, et ceux subissant des mesures de contrôle de la COVID-19. Les résultats fournissent un profil complet de l'état de santé mentale des hommes Chinois infertiles pendant l'épidémie de COVID-19 et fournissent des stratégies potentielles d'intervention psychologique.

Microdeletions and vertical transmission of the Y-chromosome azoospermia factor region.

Spermatogenesis is regulated by several Y chromosome-specific genes located in a specific region of the long arm of the Y chromosome, the azoospermia factor region (AZF). AZF microdeletions are the main structural chromosomal abnormalities that cause male infertility. Assisted reproductive technology (ART) has been used to overcome natural fertilization barriers, allowing infertile couples to have children. However, these techniques increase the risk of vertical transmission of genetic defects. Despite widespread awareness of AZF microdeletions, the occurrence of de novo deletions and overexpression, as well as the expansion of AZF microdeletion vertical transmission, remains unknown. This review summarizes the mechanism of AZF microdeletion and the function of the candidate genes in the AZF region and their corresponding clinical phenotypes. Moreover, vertical transmission cases of AZF microdeletions, the impact of vertical inheritance on male fertility, and the prospective direction of research in this field are also outlined.

Combined oncolytic adenovirus carrying MnSOD and mK5 genes both regulated by survivin promoter has a synergistic inhibitory effect on gastric cancer.

Gastric cancer (GC) is one of the major causes of cancer-related mortality. The use of oncolytic virus for cancer gene-virotherapy is a new approach for the treatment of human cancers. In this study, a novel Survivin promoter-driven recombinant oncolytic adenovirus carrying mK5 or MnSOD gene was constructed, which was modified after deletion of the E1B gene. Human plasminogen Kringle 5 mutant (mK5) and manganese superoxide dismutase (MnSOD) are both potential tumor suppressor genes. By constructing Ad-Surp-mK5 and Ad-Surp-MnSOD oncolytic adenoviruses, we hypothesized that the combination of the two viruses would enhance the therapeutic efficacy of GC as compared to the one virus alone. The results of the in vitro experiments revealed that the combination of adenovirus carrying mK5 and MnSOD gene exhibited stronger cytotoxicity to GC cell lines as compared to the virus alone. Additionally, the virus could selectively kill cancer cells and human somatic cells. Cell staining, flow cytometry, and western blot analysis showed that the combination of two adenoviruses containing therapeutic genes could promote the apoptosis of cancer cells. In vivo experiments further verified that Ad-Surp-mK5 in combination with Ad-Surp-MnSOD exhibited a significant inhibitory effect on the growth of GC tumor xenograft as compared to the virus alone, and no significant difference was observed in the bodyweight of treatment and the normal mice. In conclusion, the combination of our two newly constructed recombinant oncolytic adenoviruses containing mK5 or MnSOD therapeutic genes could significantly inhibit gastric cancer growth by inducing apoptosis, suggestive of its potential for GC therapy.

FAM9B serves as a novel meiosis-related protein localized in meiotic chromosome cores and is associated with human gametogenesis.

Meiosis is a complex process involving the expression and interaction of numerous genes in a series of highly orchestrated molecular events. Fam9b localized in Xp22.3 has been found to be expressed in testes. However, FAM9B expression, localization, and its role in meiosis have not been previously reported. In this study, FAM9B expression was evaluated in the human testes and ovaries by RT-PCR, qPCR, and western blotting. FAM9B was found in the nuclei of primary spermatocytes in testes and specifically localized in the synaptonemal complex (SC) region of spermatocytes. FAM9B was also evident in the follicle cell nuclei and diffusely dispersed in the granular cell cytoplasm. FAM9B was partly co-localized with SYCP3, which is essential for both formation and maintenance of lateral SC elements. In addition, FAM9B had a similar distribution pattern and co-localization as γH2AX, which is a novel biomarker for DNA double-strand breaks during meiosis. All results indicate that FAM9B is a novel meiosis-associated protein that is co-localized with SYCP3 and γH2AX and may play an important role in SC formation and DNA recombination during meiosis. These findings offer a new perspective for understanding the molecular mechanisms involved in meiosis of human gametogenesis.

Roles of CatSper channels in the pathogenesis of asthenozoospermia and the therapeutic effects of acupuncture-like treatment on asthenozoospermia.

Rationale: Idiopathic asthenozoospermia (iAZS) is one of the major causes of male infertility and has no effective therapeutic treatment. Understanding the potential mechanisms that cause it may be helpful in seeking novel targets and treatment strategies for overcoming the problem of low sperm motility in iAZS individuals. Methods: Computer-assisted semen analysis (CASA) was utilized to assess the sperm motility. RT-qPCR, Western blot, immunofluorescence staining, and calcium imaging analysis were performed to examine the expression and function of CatSper channels. Hyperactivation and acrosome reaction were used to evaluate the functional characteristics of epididymal sperm. In vivo fertility assay was applied to determine the fertility of rats. CatSper1 knockdown and overexpression experiments were performed to confirm the roles of CatSper channels in the pathogenesis of iAZS and the therapeutic effects of electroacupuncture (EA) treatment on AZS model rats. Results: Here, we reported a functional down-regulation of CatSper channel from CatSper1 to CatSper 4 in the sperm of both iAZS patients and ornidazole (ORN)-induced AZS model rats, and an impaired sperm function characterized by a reduction of protein tyrosine phosphorylation, hyperactivation, and acrosome reaction in the epididymal sperm of AZS rats. Knockdown of CatSper1 in the testis tissues is sufficient to induce AZS in normal rats, and this action was validated by the reversal effects of CatSper1 overexpression. Transcutaneous electrical acupoint stimulation (TEAS) and electroacupuncture (EA) at 2 Hz frequency improve the sperm motility via enhancing the functional expression of CatSper channels in the sperm. Gene silencing CatSper1 in the sperm abolishes the therapeutic effects of 2 Hz-EA treatment on AZS rats. Conclusions: We conclude that a functional down-regulation of CatSper channel in the sperm may be a contributor or a downstream indicator for a portion of AZS, especially iAZS, while 2 Hz-TEAS or EA treatment has a therapeutic effect on iAZS through inducing the functional up-regulation of CatSper channels in the sperm. This study provides a novel mechanism for the pathogenesis of some AZS especially iAZS, and presents a potential therapeutic target of CatSper for iAZS treatment. Acupuncture treatment like TEAS may be used as a promising complementary and alternative medicine (CAM) therapy for male infertility caused by iAZS in clinical practice.

Clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection with fresh or cryopreserved sperm in patients with nonobstructive azoospermia.

We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI) treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia (NOA). A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles (Group A). Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles (Group B). We compared patient characteristics, embryonic development, and pregnancy outcomes between Groups A and B. There was no statistical difference in the patient characteristics, and no differences were observed with fertilization or quality embryo rates between Groups A and B. The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B (both P < 0.05). In conclusion, fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.

Sperm retrieval rates and clinical outcomes for patients with different causes of azoospermia who undergo microdissection testicular sperm extraction-intracytoplasmic sperm injection.

The aim of our study was to compare the sperm retrieval rates (SRRs) and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI). We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI. Patients with azoospermia were classified into Group A (Klinefelter syndrome, n = 284, 125 cycles), Group B (azoospermia Y chromosome factor c [AZFc] microdeletion, n = 91, 64 cycles), Group C (cryptorchidism, n = 52, 39 cycles), Group D (previous mumps and bilateral orchitis, n = 23, 23 cycles), and Group E (idiopathic azoospermia, n = 319, 96 cycles). Clinical characteristics, SRR, embryonic development, and pregnancy outcomes of the patients were compared between all groups. Patients in Group D had the highest and most successful SRR. The average SRR for all patients was 46.0%. The rates of clinical pregnancy, implantation, and live birth in Group D were 78.3%, 65.0%, and 74.0%, respectively, which were higher than those in all other groups (P < 0.05). Group B patients had the lowest clinical pregnancy, implantation, and live birth rates of all groups (P < 0.05). No differences were found in the miscarriage rate or birth defects among the groups (P > 0.05). Patients with orchitis had the highest SRR and best clinical outcomes. Although AZFc microdeletion patients had a higher SRR, their clinical outcomes were worse.

AF cell derived exosomes regulate endothelial cell migration and inflammation: Implications for vascularization in intervertebral disc degeneration.

AIMS: The intervertebral disc is the largest avascular organ of the body. Vascularization of the disc has been typically regarded as a pathological feature of intervertebral disc degeneration (IDD). However, the underlying mechanism of vascularization in IDD is still unclear. The current study aimed to investigate the role of AF cell derived exosome (AF-exo) in the interaction with human umbilical vein endothelial cells (HUVECs) and its potential role in the regulation of vascularization in IDD. MAIN METHODS: Human AF tissues were obtained from patients with IDD and idiopathic scoliosis. The AF-exo were isolated and identified by transmission electron microscopy (TEM), nanoparticle trafficking analysis (NTA) and Western blotting. Then, the AF-exo were used for HUVECs cultures. The migration of HUVECs was observed in 2D and 3D cultures. The inflammatory phenotype of HUVECs was examined by Real-time PCR and enzyme-linked immunosorbent assay (ELISA). Additionally, apoptosis of HUVECs were analyzed by flow cytometry. KEY FINDINGS: Here, we for the first time found that AF cells could secrete AF-exo and that the AF-exo could be phagocytosed by HUVECs. Additionally, we found that degenerated AF-exo exerted pro-vascularization effect on HUVECs by promoting cell migration (in 2D and 3D cultures) and inflammatory factor expression including IL-6, TNF-α, MMP-3, MMP-13 and VEGF, whereas the application of non-degenerated AF-exo demonstrated inverse effects. SIGNIFICANCE: These results showed that AF-exo is an essential regulator mediating intercellular communication between AF cells and HUVECs, suggesting its important role in vascularization in the intervertebral disc.

Establishing the lower limits of total serum testosterone among Chinese proven fertile men who received treatment of assisted reproductive technology.

Testosterone (T) plays a crucial role in spermatogenesis because extremely low levels of intratesticular T lead to correspondingly low serum levels of total T (tT), severe disorders of spermatogenesis, and male sterility. However, there is little consensus on the lower limits of serum tT in proven fertile men undergoing assisted reproductive technology treatments in Chinese or other Asian populations. We aimed to establish the reference range of serum tT based on a population of 868 fertile Chinese men undergoing in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) treatments. We defined a fertile man as having had a live baby with his partner as recorded in our IVF registration system. The lower limits of serum tT were established using a Siemens IMMULITE 2000 chemiluminescent system. The 1st, 2.5th, and 5th percentiles and their 95% confidence intervals (CIs) were 3.6 (95% CI: 2.7-4.1) nmol l-1, 4.3 (95% CI: 4.1-5.0) nmol l-1, and 5.6 (95% CI: 4.8-5.8) nmol l-1, respectively. Using the linear correlation of serum tT between the Siemens platform and a liquid chromatography-tandem mass spectrometry platform, the calculated lower limits of serum tT were also established for fertile Chinese men undergoing IVF/ICSI-ET treatments, which will benefit the clinical diagnosis and treatment of male infertility during such procedures.

Altered microRNA profiles of testicular biopsies from patients with nonobstructive azoospermia.

Many studies have shown that microRNAs (miRNAs) play vital roles during the spermatogenesis. However, little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia (NOA). Using microarray technology, the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined. Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs. The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the results of which were then validated with a larger sample size. Correlations between the miRNA expression levels and clinical characteristics were analyzed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia. Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups. Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis, cell cycle, and mitotic prometaphase. In the subsequent qRT-PCR assays, the selected miRNA expression levels were consistent with the microarray results, and similar validated results were obtained with a larger sample size. Some clinical characteristics were significantly associated with the expression of certain miRNAs. In particular, we identified a combination of two miRNAs (miR-10b-3p and miR-34b-5p) that could serve as a predictive biomarker of azoospermia. This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis. These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.

Serum E-selectin concentration is associated with risk of metabolic syndrome in females.

OBJECTIVES: Traits of metabolic syndrome (MetS) and biomarkers of inflammation and endothelial dysfunction were examined. We investigated the differences of various biomarkers among individuals with or without Mets in a gender-specific manner. The gender-specific associations between E-selectin and MetS were further evaluated. METHODS: A total of 205 patients were recruited from the outpatient clinics of Tri-Service General Hospital, Taipei, Taiwan. Inclusion criteria were age between 20-75 years and BMI < 35 kg/m2. Demographic, anthropometric and MetS index data were compared between genders. Markers of inflammation and endothelial dysfunction were compared between individuals with or without MetS by gender. RESULTS: Age-adjusted E-selectin values showed significant positive correlations with BMI, waist-hip ratio, fasting plasma glucose, systolic and diastolic blood pressure, triglycerides, TNF-α, hsCRP and ICAM-1, and inverse correlation with HDL cholesterol. E-selectin levels were positively correlated with numbers of MetS components in females (P < 0.001) but not in males (P = 0.125). CONCLUSIONS: Increased E-selectin levels are significantly associated with increased MetS risk in females, but not in males.

Risk Assessment of Laparoscopic Cholecystectomy in Liver Cirrhotic Patients with Clinically Significant Portal Hypertension: A Retrospective Cohort Study.

Objective: This study was aimed to evaluate the correlation between clinically significant portal hypertension (CSPH) and postoperative complications and risk predictors of postoperative complications. Methods: The retrospective study was conducted to identify the effect. The cirrhotic patients were divided into two groups, those with or without CSPH. The intraoperative and postoperative conditions were evaluated. Multivariate logistic regression analysis was performed to identify potential risk predictors for postoperative complications in cirrhotic patients with CSPH. Results: The cirrhotic patients with CSPH who underwent laparoscopic cholecystectomy (LC) had postoperative hospitalization than the patients without CSPH. However, the incidence of postoperative complications between two groups showed no significant difference. The results of multivariate analysis showed that male, gallbladder wall >3 mm, size of stones ≥1 cm, scores of Model for end-stage liver disease (MELD) ≥10, and operation time >60 minutes were the potential risk predictors for postoperative complications. Conclusions: CSPH did not increase the incidence of postoperative complications in cirrhotic patients who underwent LC, but increased conversion rate and prolonged postoperative hospitalization. Furthermore, our study showed that gender, sizes of gallbladder wall and stones, scores of MELD, and operation time were the important postoperative risk predictors for cirrhotic patients with CSPH.

Long-Term Efficacy of Laparoscopic Radiofrequency Ablation in Early Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Objective: The aim of this study was to investigate the long-term efficacy of laparoscopic radiofrequency ablation (LRFA) in early hepatocellular carcinoma (HCC) compared with other surgical procedures. Methods: A literature search of Cochrane library, PubMed, and Embase through October 2018 was conducted by two investigators (J.-F.G. and F.Y.) independently. The quality of included studies was estimated by the Newcastle-Ottawa Scale. Review Manager 5.3 software was used for meta-analysis, and either fixed- or random-effects model was used according to the heterogeneity of included studies. The chi-square test was used for heterogeneity analysis of included studies, and subgroup analysis was conducted to estimate the heterogeneity between each study and also to estimate the efficacy of different studies. Results: A total of 11 studies involving 1691 patients were included in this analysis. Patients undergoing hepatic resection (HR) had higher 3-, 5-year overall survival rate, 3-year disease-free survival rate, and lower local recurrence rate than those undergoing LRFA. However, patients undergoing LRFA had higher 3-, 5-year overall survival rate than those undergoing other minimally invasive ablation, although there was no statistical difference in local recurrence rate or disease-free survival rate. Conclusion: HR is still an ideal choice for early HCC. If minimally invasive ablation is an alternative treatment, LRFA will be better than other minimally invasive options.

Ambient ozone pollution is associated with decreased semen quality: longitudinal analysis of 8945 semen samples from 2015 to 2018 and during pollution-control period in Beijing, China.

Previous studies suggest that air pollution has a negative effect on semen quality. However, most studies are cross-sectional and the results are controversial. This study investigated the associations between air pollutants (PM2.5, PM10, SO2, NO2, CO, and O3) and semen quality among sperm donation candidates, especially when the air pollution was artificially controlled in Beijing, China. We analyzed 8945 semen samples in the human sperm bank of Peking University Third Hospital (Beijing, China) from October 2015 to May 2018. Air pollution data during the entire period (0-90 days prior) and key stages (0-9, 10-14, and 70-90 days prior) of sperm development were collected from the China National Environmental Monitoring Centre. The association between air pollutants and semen parameters (sperm concentration and progressive motility) was analyzed by a mixed model adjusted for age, abstinence duration, month, and average ambient temperature. Only O3during key stages of 0-9 days and 10-14 days and the entire period was negatively associated with sperm concentration between 2015 and 2018 (P < 0.01). During the period of air pollution control from November 2017 to January 2018, except for the increase in O3concentration, other five pollutants' concentrations decreased compared to those in previous years. In this period, the sperm concentration decreased (P < 0.001). During the pollution-control period, O3exposure 10-14 days prior was negatively associated with sperm concentration (95% CI: -0.399--0.111; P < 0.001). No significant association was found between the other five pollutants and semen quality during that period. Our study suggested that only O3exposure was harmful to semen quality. Therefore, O3should not be neglected during pollution control operation.

Novel DPY19L2 variants in globozoospermic patients and the overcoming this male infertility.

Globozoospermia has been reported to be a rare but severe causation of male infertility, which results from the failure of acrosome biogenesis and sperm head shaping. Variants of dpy-19-like 2 (DPY19L2) are highly related to globozoospermia, but related investigations have been mainly performed in patients from Western countries. Here, we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations, as revealed by whole-exome sequencing. Patient 3 (P3) contained a heterozygous variant (c.2126+5G>A), P6 contained a homozygous nonsense mutation (c.1720C>T, p.Arg574*), P8 contained compound heterozygous variants (c.1182-1184delATC, p.Leu394_Ser395delinsPhe; c.368A>T, p.His123Arg), and P9 contained a heterozygous variant (c.1182-1184delATCTT, frameshift). We also reported intracytoplasmic sperm injection (ICSI) outcomes in the related patients, finding that ICSI followed by assisted oocyte activation (AOA) with calcium ionophore achieved high rates of live births. In summary, the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.