A meta-analysis and systematic review of photodynamic therapy for diabetic foot ulcers.

BACKGROUND: Diabetic foot ulcer (DFU) is a chronic and challenging condition, addressed through various treatments including photodynamic therapy (PDT) and standard of care (SOC), yet lacking consensus on the optimal approach. This study presents a comprehensive meta-analysis of randomized controlled trials to evaluate the efficacy and safety of PDT versus SOC in managing DFU. METHODS: An extensive literature search was conducted across PubMed, Embase, and the Cochrane Library databases to identify RCTs that compared the effectiveness of PDT with SOC in treating DFU. The primary metrics evaluated included changes in ulcer area, wound healing indices, and pain levels experienced by the patients. RESULTS: This meta-analysis incorporated data from 6 RCTs, encompassing 458 patients with 467 DFUs. The analysis indicated that while PDT led to a faster reduction in ulcer size compared to SOC, the difference was not statistically significant [mean difference (MD): 2.73cm², 95% Confidence Interval (CI) -2.98 to 8.44; p>0.05]. However, a notable improvement was observed in the wound healing rate in the PDT group [MD: 29.26%, 95% CI 7.24 to 51.28; p=0.01]. Based on the Visual Analog Scale (VAS), pain assessment revealed no significant difference between the two treatment groups [MD: 2.35, 95% CI -2.36 to 7.06; p=0.33]. CONCLUSION: The study suggests that PDT might offer an enhanced healing rate for DFUs compared to SOC alone, potentially leading to improved patient outcomes. Importantly, our findings highlight the superiority of photodynamic therapy in accelerating ulcer healing without an associated increase in complications. PROSPERO: 2023 CRD42023493930.

A detection model of testis-derived circular RNAs in serum for predicting testicular sperm retrieval rate in non-obstructive azoospermia patients.

BACKGROUND: Microdissection testicular sperm extraction is an effective method to retrieve sperm from non-obstructive azoospermia patients. However, its successful rate is less than 50%. OBJECTIVES: To identify the predictive value of circular RNAs in serum for sperm retrieval rate in non-obstructive azoospermia patients. MATERIALS AND METHODS: 180 non-obstructive azoospermia patients were recruited in this study, including 84 individuals with successful sperm retrieval and 96 individuals with failed sperm retrieval. Our study contained two phases. First, 20 patients, selected from the 180 patients, were included in screening cohort. In this cohort, the top 20 circular RNAs from our previous testicular circRNA profiles were verified between successful and failed sperm retrieval groups using real-time polymerase chain reaction. Six circular RNAs with the most significantly different expressions were selected for further verification. Second, the 180 patients were included as discovery cohort to verify the six circular RNAs. Circular RNAs were extracted from serum in each participant. Logistic regression analysis was further performed to identify the predictive value and the area under the curve analysis was used to evaluate diagnostic efficiency, sensitivity, and specificity. RESULTS: Six circular RNAs including hsa_circ_0058058, hsa_circ_0008045, hsa_circ_0084789, hsa_circ_0000550, hsa_circ_0007422, and hsa_circ_0004099 showed aberrant expressions between the successful and failed sperm retrieval group. In addition, both single-circular RNA panels and multi-circular RNA panels were finally verified to be significant in predicting sperm retrieval rate. Notably, multi-circular RNAs panels demonstrated better predictive abilities compared with single-circRNA panels, and the combined panel of six-circular RNAs (risk score = 1.094×hsa_circ_0058058+0.697×hsa_circ_0008045+0.718×hsa_circ_0084789-0.591×hsa_circ_0000550-0.435×hsa_circ_0007422-1.017×hsa_circ_0004099-1.561) exhibited the best predictive ability in the present study with an AUC of 0.977, a sensitivity of 91.7% and a specificity of 86.5%. A higher risk score indicated a higher risk of failure in sperm retrieval. DISCUSSION AND CONCLUSION: Our study was the first to report that testis-derived circular RNAs in serum have the ability to predict sperm retrieval rate in non-obstructive azoospermia patients, whether it is a single-circular RNA or a combination of multi-circular RNAs.

GRPR down-regulation inhibits spermatogenesis through Ca2+ mediated by PLCß/IP3R signaling pathway in long-term formaldehyde-exposed rats.

Formaldehyde (FA), which is known as an air pollutant, has been proven to induce male infertility. However, the underlying mechanism of FA-induced male infertility remains elusive. In this study, 24 male SD rats were exposed to different levels of FA (0, 0.5, 2.46, and 5 mg/m3) for eight consecutive weeks. Through HE staining and sperm smear, we observed that FA exposure resulted in spermatogenic injury and the sperm quality decreased in rats. The qRT-PCR and Western blot analysis further revealed that GRPR was down-regulated in testicular tissues of FA-exposed rats as well as primary spermatogenic cells. Meanwhile, ZDOCK uncovered an interaction between GRPR and PLCß. In addition, the CCK8, Fluo 3-AM and Flow cytometry results showed that FA exposure suppressed the expression of GRPR, PLCß and IP3R, consequently reducing the Ca2+ concentration in spermatogenic cells, inducing apoptosis and inhibiting proliferation of spermatogenic cells. Moreover, rescue experiments confirmed that promoting GRPR could improve intracellular Ca2+ concentration by upregulating PLCß and IP3R, partially reducing the apoptosis and promoting the proliferation of FA-treated spermatogenic cells. These findings revealed that GRPR participates in spermatogenesis through Ca2+ mediated by the PLCß/IP3R signaling pathway in FA-exposed rats.

STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1.

The novel oncogene STYK1/NOK plays critical roles in cancer development. However, its regulation during cell division is less defined. In this paper, we show that over-expression of STYK1/NOK caused mitotic arrest and cytokinesis defects. The protein level of STYK/NOK fluctuated during the cell cycle, with a peak at mitosis and a quick reduction upon mitotic exit. The cell cycle-related expression pattern of STYK1/NOK resembled the one of aurora kinases and polo-like kinase 1. Depletion of APC3 led to accumulation of STYK1/NOK and to the G2/M arrest. Co-immunoprecipitation experiment demonstrated the direct interaction of STYK1/NOK with CDH1. Overexpression of CDH1 shortened the half-life of STYK1/NOK. The kinase domain, but not the five D boxes, of STYK1/NOK was responsible for the interaction with CDH1. Altogether, our data demonstrated for the first time that STYK1/NOK could affect cell division, probably by directly targeting key components of APC/C such as CDH1 at late mitosis. Current study may provide a vital mechanistic clue for understanding the roles of STYK1/NOK in mitosis and cytokinesis during STYK1NOK mediated genomic instability and oncogenesis.

Wearable Sensor-Based Monitoring of Environmental Exposures and the Associated Health Effects: A Review.

Recent advances in sensor technology have facilitated the development and use of personalized sensors in monitoring environmental factors and the associated health effects. No studies have reviewed the research advancement in examining population-based health responses to environmental exposure via portable sensors/instruments. This study aims to review studies that use portable sensors to measure environmental factors and health responses while exploring the environmental effects on health. With a thorough literature review using two major English databases (Web of Science and PubMed), 24 eligible studies were included and analyzed out of 16,751 total records. The 24 studies include 5 on physical factors, 19 on chemical factors, and none on biological factors. The results show that particles were the most considered environmental factor among all of the physical, chemical, and biological factors, followed by total volatile organic compounds and carbon monoxide. Heart rate and heart rate variability were the most considered health indicators among all cardiopulmonary outcomes, followed by respiratory function. The studies mostly had a sample size of fewer than 100 participants and a study period of less than a week due to the challenges in accessing low-cost, small, and light wearable sensors. This review guides future sensor-based environmental health studies on project design and sensor selection.

Semen Quality Following Long-term Occupational Exposure to Formaldehyde in China.

Importance: The potential effects of long-term occupational exposure to formaldehyde (FA) on human semen quality is not clear. Objective: To assess whether long-term occupational exposure to FA is associated with semen quality. Design, Setting, and Participants: This population-based cohort study was conducted from June 1 to June 30, 2021, in Xi'an, China. Participants were adults aged 23 to 40 years who had lived in the study area for 24 months or longer. Data analysis was performed from September 1 to October 1, 2021. Exposures: Long-term occupational exposure to FA was measured using a formaldehyde detector, and the FA exposure index (FEI) was calculated as follows: FEI = final concentration of FA (mg/m3) × work time during a workday (hour) × cumulative workdays (year). Main Outcomes and Measures: Semen samples were collected by masturbation after 3 to 7 days of abstinence and were then assessed by the computer-automated semen analysis system, Baso-Papanicolaou staining, and sperm-chromatin structure assay. Results: A total of 205 men (mean [SD] age, 29.49 [3.64] years), with 124 individuals in the FA exposure group (mean [SD] FEI, 73.72 [54.86]) and 81 age-matched controls, were included in the final analysis. Long-term personal occupational exposure to FA was significantly associated with poor semen quality. Specifically, a 1-unit increase in FEI was associated with a change of -0.99% (95% CI, -1.00% to -0.98%) in total sperm motility, -0.99% (95% CI, -0.99% to -0.97%) in progressive sperm motility, -0.05% (95% CI, -0.08% to -0.02%) in curvilinear velocity, -0.07% (95% CI, -0.10% to -0.04%) in straight line velocity, -0.07% (95% CI, -0.10% to -0.04%) in time-average velocity, -0.98% (95% CI, -0.99% to -0.93%) in normal sperm morphology, -0.24% (95% CI, -0.35% to -0.11%) in seminal neutral glucosidase, -0.61% (95% CI, -0.66% to -0.56%) in seminal plasma zinc, 0.52% (95% CI, 0.15% to 1.02%) in beat cross frequency, and 0.10% (95% CI, 0.06% to 0.14%) in the DNA fragmentation index. These associations remained significant after adjusting for confounding factors. Furthermore, subgroup analysis found that high levels of oxidative stress might promote the associations between FA exposure and semen quality. Conclusions and Relevance: This study found an association between long-term occupational exposure to FA and semen quality. This deterioration was dose and time dependent and might be induced by oxidative stress.

Rno_circRNA_008646 regulates formaldehyde induced lung injury through Rno-miR-224 mediated FOXI1/CFTR axis.

Formaldehyde (FA) serves as a prevailing air pollutant, which has seriously threatened public health in recent years. Of all the known health effects, lung injury is one of the most severe risks. However, little is known about the circRNAs related molecular mechanism in the development of lung injury induced by FA. This study was designed to explore the potential roles of dysregulated circRNAs as well as its mechanism in FA-induced lung injury. In the present study, 24 male SD rats were exposed to formaldehyde (control, 0.5, 2.46 and 5 mg/m3) for 8 h per day for 8 weeks to induce lung injury. We used H&E staining to evaluate the histopathological changes of lung injury indifferent groups. The expression of circRNAs in lung tissue was detected by real-time PCR. Meanwhile, circRNA/miRNA/mRNA interaction networks were predicted by bioinformatics analysis. Our study revealed that formaldehyde exposure resulted in abnormal histopathological changes in lung tissues. Moreover, the expression of rno_circRNA_008646 was significantly higher in lung tissues of formaldehyde exposure rats than in control. Bioinformatics analysis showed that one potential target miRNA/mRNA for rno_circRNA_008646 was rno-miR-224/Forkhead Box I1 (FOXI1). Besides, luciferase report gene confirmed that there was targeted binding relationship between rno_circRNA_008646 and rno-miR-224, rno-miR-224 and FOXI1. Further verification experiments indicated that the expression of rno_circRNA_008646 was negatively correlated rno-miR-224, while it was positively correlated with FOXI1. JASPAR database showed transcription factor FOXI1 located in promotor of CF Transmembrane Conductance Regulator (CFTR). Both FOXI1 and CFTR were up-regulated in lung tissues after formaldehyde exposure. In conclusion, our findings suggested that formaldehyde may induce lung injury, and this may be caused by up-regulatedrno_circRNA_008646, which medicated rno-miR-224/FOXI1/CFTR axis.

Increasing prevalence of myopia and the impact of education in primary-school students in Xi'an, north-western of China.

Purpose: The present study was performed to detect the prevalence of myopia among primary-school students in Xi'an, north-western of China. Methods: The present study was a school-based study with students aged from 6 to 13 years old. All the individuals underwent ophthalmological examination and spherical equivalent (SE) of refractive error were measured with non-cycloplegic refraction. Myopia was defined as a SE of ≤ -0.5 diopters (D), and further divided into three stratified groups based on SE: low myopia (≤ -0.5 to >-3.0 D), moderate myopia (≤ -3.0 to >-6.0 D), and high myopia (≤ -6.0 D). Relative risk factors, including age, sex, grade and ethnicity were investigated using questionnaire. Results: A total of 4,680 individuals were eligible for this survey and 4,654 (99.4% participation rate) were finally included (51.2% boys). The mean age of participants was 8.756 ± 1.727 years. The whole city-level prevalence of total myopia was 57.1% (95% CI: 55.7-58.6%). Additionally, the prevalence of low, moderate, and high myopia was 45.0% (95% CI: 43.5-46.4%), 11.1% (95% CI: 10.2-12.0%), and 1.0% (95% CI: 0.7-1.3%), respectively. Moreover, grade (education level) instead of age, sex and ethnicity was the most essential risk factor for prevalence of overall myopia (OR = 1.844, 95% CI: 1.605-2.119), and an increase of prevalence by 84.4% per grade was seen. Furthermore, similar associations of grade were significant with low myopia (OR = 1.613, 95% CI: 1.385-1.877) and moderate myopia (OR = 2.186, 95% CI: 1.693-2.823), meanwhile, prevalence of low myopia and moderate myopia demonstrated an increase of prevalence by 61.3 and 118.6% per grade, respectively. None of the factors included in the present study was significant risk factor for high myopia. Conclusions: The present study investigated a non-negligible high prevalence of myopia among primary-school students in Xi'an, north-western of China, and a gradual increasing in proportion with education level.

Circular RNA-CDR1as is involved in lung injury induced by long-term formaldehyde inhalation.

OBJECTIVE: Formaldehyde (FA) is known to induce lung injury, but the underlying molecular mechanism remains largely unclear. CDR1as is an important member of the circular RNAs (circRNAs) family and functions as miRNA sponges with gene-regulatory potential. Our earlier circRNA microarray data showed CDR1as was highly expressed in lung tissue exposed to FA. However, the mechanism of circRNA-CDR1as mediates the FA-exposed lung injury is still unclear. This study aimed to explore the role of CDR1as in lung injury. MATERIALS AND METHODS: In this study, FA was inhaled at doses of 0.5, 2.46, and 5 mg/m3, respectively. After exposure 8 weeks, lung histopathological examination, lung injury score, and IL-1ß in bronchoalveolar lavage fluid (BALF) were determined. The expressions of CDR1as, rno-miR-7b and Atg7 were detected and the potential interaction of circRNA/miRNA/mRNA was predicted by bioinformatics analysis, including drawing circRNA/miRNA/mRNA interaction network, GO and KEGG analysis. RESULTS: Our results indicated FA inhalation upregulated the expression of CDR1as in lung tissues in a dose-dependent manner while the expression of rno-miR-7b decreased and Atg7 increased. Moreover, the alteration of CDR1as was positively correlated with lung injury. DISCUSSION AND CONCLUSIONS: CircRNA/miRNA/mRNA prediction further explained the possible effect mechanisms of CDR1as. These data implicated that CDR1as might be a critical regulator involved in lung injury induced by FA.

The expression of Beclin-1 in testicular tissues of non-obstructive azoospermia patients and its predictive value in sperm retrieval rate.

BACKGROUND: Beclin-1 is an autophagy gene and higher levels suggest mammalian testicular damage. Our study aims at exploring the role of Beclin-1 in non-obstructive azoospermia (NOA) patients and clarifying the predictive value of Beclin-1for sperm retrieval in microdissection testicular sperm extraction (micro-TESE). METHODS: In the present study, 62 NOA patients were finally recruited. Serum hormone including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol II (E2), testosterone (T) and prolactin (PRL), as well as testicular volume were measured. Testicular histopathology was diagnosed by two independent pathologists. The expression of Beclin-1 was detected by real-time PCR in testicular tissue. RESULTS: Our study illustrated that Beclin-1 was differently expressed in three pathological types of NOA. Compared with hypospermatogenesis (HS, P=0.002) or maturation arrest (MA, P=0.049), Beclin-1 showed significantly up-regulated in Sertoli cell-only syndrome (SCOS) group. Moreover, Beclin-1 expression was obviously positive related with serum LH (rho =0.269, P=0.036), meanwhile significantly negative correlation with testicular volume (rho =-0.370, P=0.003), serum T (rho =-0.326, P=0.010), Johnsen score (rho =-0.318, P=0.012), and pathologic type (rho =-0.452, P<0.001). Furthermore, a logistic regression model demonstrated that Beclin-1 is an important predictor of failed sperm retrieval (OR =0.001, P=0.007), which exhibited a pretty AUC =78.6 (P=0.001). CONCLUSIONS: Beclin-1 may play a critical role in spermatogenesis. Elevated Beclin-1 may be obviously associated with lower chances of positive sperm retrieval.

Rno_circRNA_016194 might be involved in the testicular injury induced by long-term formaldehyde exposure via rno-miR-449a-5p mediated Atg4b activation.

Although circular RNAs (circRNAs) can function as microRNAs (miRNAs) sponges to participate in spermatogenesis, little is known about the functions of circRNAs in testis exposed to formaldehyde. In this study, twenty-four male SD rats (6-8 weeks) were randomly assigned to four groups, including a control group, 0.5, 2.46, and 5 mg/m3 formaldehyde exposure groups, inhaling formaldehyde for eight consecutive weeks. The RT-qPCR was used to detect the expression of rno_circRNA_016194; the testicular injuries were observed by testicular histopathology. Our study illustrated up-regulated rno_circRNA_016194 was dose-dependent with formaldehyde. Simultaneously, the testicular histopathology showed an obvious damages in the 2.46 and 5 mg/m3 formaldehyde exposure rats. Combined with bioinformatics analysis, the rno-miR-449a-5p was predicted and verified that its expression decreased in the testis exposed to formaldehyde. Meanwhile, the testicular morphometry changes were contrary to the expression of rno_circRNA_016194 and consistent with rno-miR-449a-5p. Moreover, bioinformatics analysis also prompted the potential downstream target gene for rno_circRNA_016194/rno-miR-449a-5p was Atg4b, and Atg4b expression was up-regulated in rats exposed to formaldehyde verifying by Western blot. Collectively, the rno_circRNA_016194 might be involved in formaldehyde-induced male reproductive toxicity and become potential therapeutic targets for male occupational exposure to formaldehyde.

Temporal trends in semen concentration and count among 327 373 Chinese healthy men from 1981 to 2019: a systematic review.

STUDY QUESTION: Are there temporal trends of sperm concentration (SC) and total sperm count (TSC) in Chinese healthy males from 1981 to 2019? SUMMARY ANSWER: Our result indicated a temporal decrease in SC and TSC among 327 373 healthy Chinese men in the recent four decades. WHAT IS KNOWN ALREADY: A review of 61 papers reported a temporal decline in SC and TSC from 1938 to 1990. This trend was later confirmed by a systematic review of 185 published papers from 1981 to 2013. However, the majority of the included individuals were from western countries. In China, whether SC and TSC have declined remains controversial. STUDY DESIGN, SIZE, DURATION: This systematic review of published articles used data extracted from Pubmed, Science Direct, Embase, China-National-Knowledge-Infrastructure (CNKI) and Wanfang Data to assess changes in SC and TSC in China from 1981 to 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 111 studies including 327 373 individuals who provided semen samples from 1981 to 2019 were extracted for the present analysis. Study selection and data extraction were performed by two independent researchers. The trends in SC and TSC were analysed using liner-regression and meta-regression before and after adjusting for potential covariates. Moreover, subgroups, categorised based on geographic region, fertility status or recruitment source, were also analysed. MAIN RESULTS AND THE ROLE OF CHANCE: SC declined significantly (slope liner-regression = -0.748 million/ml/year; P = 0.005; slope meta-regression = -0.824 million/ml/year; P < 0.001) between 1981 and 2019 in China. Trends for TSC was similar to that for SC (slope liner-regression = -2.073 million/year; P = 0.032; slope meta-regression = -2.188 million/year; P = 0.003). In subgroup meta-regression analyses, males with definite fertility had continuous declines in SC (slope northern group=-2.268, P = 0.009; slope southern group=-1.014, P = 0.009) and TSC (slope northern group=-9.675, P = 0.010; slope southern group=-3.215, P = 0.042). However, in the unselected group, where fertility status was unknown, the obvious downward trend in SC was only seen in males from Northern regions (slope = -0.836, P = 0.003). Another subgroup analysis demonstrated that obvious decreases in SC (slope = -1.432, P < 0.001) and TSC (slope=-4.315, P = 0.001) were only seen in volunteer groups but not in pre-pregnancy examination groups and other recruitment groups. The results changed minimally in multiple sensitivity analyses. LIMITATIONS, REASONS FOR CAUTION: The validity of the meta-analysis results was limited mainly by the quality of the included studies. Additionally, our study spanned many decades and the recommended criteria for some semen parameter assessments have significantly changed, which may bring about some unavoidable bias. Moreover, the data remain insufficient especially in some provinces of China. WIDER IMPLICATIONS OF THE FINDINGS: The present study is the first study to report significant decreases in SC and TSC in 327 373 healthy Chinese men between 1981 and 2019, indicating a serious reproductive health warning. Further studies on the causes of the declines are urgently needed. STUDY FUNDING/COMPETING INTEREST(S): D.Z. is supported by the National Natural Science Funding of China, Natural Science Funding of Shaanxi Province, Science Funding of Health Department, Shaanxi Province, Fundamental Research Funds for the Central University and the Project of Independent Innovative Experiment for Postgraduates in Medicine in Xi'an Jiaotong University. The authors have no conflicts of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Long-term exposure to formaldehyde induced down-regulation of SPO11 in rats.

Objective: Formaldehyde, a ubiquitous environmental contaminant, has long been suspected of causing male reproductive injury, but the underlying molecular mechanism remains largely unknown. SPO11 is a meiosis-related gene, whose absence can cause spermatogenesis arrest. Materials and methods: The present study aimed to explore the role of SPO11 in male reproductive injury induced by long-term formaldehyde exposure, so as to further understand the molecular mechanism of formaldehyde-induced male reproductive toxicity. Adult male Sprague-Dawley rats (n = 24, 245 ± 22 g) were randomly divided into four groups of six (n = 6) and were exposed to formaldehyde gas at doses of 0 (control), 0.5, 2.46 and 5 mg/m3, respectively, via inhalation for 8 consecutive weeks. Results and dissussion: The expression levels of SPO11 were detected in testicular tissues by real-time quantitative polymerase chain reaction, immunofluorescence, and Western blot. The results indicated that the expression of SPO11 was inhibited by formaldehyde exposure in a dose-dependent manner. Furthermore, the histopathological results showed that testicular seminiferous tubules were atrophied, spermatogenic cells were decreased and the lumina were oligozoospermic in the 2.46 and 5 mg/m3 formaldehyde exposure groups. Combined with the morphometric results, we found that the downregulated expression levels of SPO11 were consistent with the changes of testicular seminiferous tubule diameter and seminiferous epithelium height in testicular tissue, suggesting that SPO11 might be one of the main targets of formaldehyde reproductive toxicity. Conclusions: In conclusion, our findings indicated that SPO11 might be related to male reproductive injuries induced by long-term formaldehyde exposure.

Over-expression of hsa_circ_0000116 in patients with non-obstructive azoospermia and its predictive value in testicular sperm retrieval.

BACKGROUND: Non-obstructive azoospermia (NOA), identified in approximately 10% of infertile males, is a multifactorial disease whose molecular mechanisms remain unknown. OBJECTIVES: The aim of this study was to identify the role of hsa_circ_0000116 in NOA and illustrate its predictive value in testicular sperm retrieval. MATERIALS AND METHODS: The study included 78 individuals, 58 with NOA and 20 with obstructive azoospermia (OA). Serum hormones including testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and estradiol II (E2) were measured. Testicular histopathology was analyzed by at least two pathologists. The expression of hsa_circ_0000116 in testicular tissue samples was detected using real-time PCR, and the circRNA-miRNA-mRNA networks were predicted using bioinformatics analysis. RESULTS: Our study illustrated that the expression of hsa_circ_0000116 was significantly higher in testicular tissue samples of NOA patients than in that of OA patients. Moreover, hsa_circ_0000116 was aberrantly expressed in three different pathological types of NOA: It was significantly up-regulated in patients with Sertoli cell-only syndrome (SCOS) when compared to patients with hypospermatogenesis (HS). In addition, the expression of hsa_circ_0000116 was negatively correlated with Johnsen score, while it was positively correlated with serum FSH level. A multivariate logistic regression model demonstrated that a high level of hsa_circ_0000116 was associated with a low rate of successful testicular sperm retrieval. Bioinformatics analysis and verification experiments showed that one of the most probable potential target miRNA for hsa_circ_0000116 was hsa-miR-449a. Further analysis indicated that hsa_circ_0000116 may be affecting the fertility function through a hsa_circ_0000116-miR-449-autophagy-related competing endogenous RNA (ceRNA) network. DISCUSSION AND CONCLUSION: We report for the first time that hsa_circ_0000116 may play pivotal roles in regulating spermatogenesis and may also be a potential biomarker for the diagnosis and treatment of NOA, while acting as a predictive tool for the rate of successful testicular sperm retrieval in NOA patients.

Is vanishing twin syndrome associated with adverse obstetric outcomes of ART singletons? A systematic review and meta-analysis.

PURPOSE: The objective of our meta-analysis was to estimate the effect of VTS on obstetric outcomes of ART singletons. METHODS: PubMed, Embase, MEDLINE, and ClinicalTrials.gov were searched up to January 2019 to find studies reporting the obstetric outcomes of ART singletons with VTS. Dichotomous data were expressed as odds ratios (OR) with 95% confidence intervals (CI). Continuous data were expressed as weighted mean difference (WMD) with 95% CI. RESULTS: A total of 17 observational studies encompassing more than 60,000 ART singletons were included in this meta-analysis. The impact of VTS on singletons was highly dependent on the definition of VTS, precisely, the vanishing timing and intrauterine growth stage. When VTS happened at or before 14 weeks, regardless of intrauterine growth stage, there were no differences in terms of gestational age (GA) [WMD = - 0.08, 95% CI = - 0.27, 0.10], preterm birth (< 37 weeks) (PTB) [OR = 1.23, 95% CI = 0.89, 1.70], and low birth weight (< 2.5 kg) (LBW) [OR = 1.56, 95% CI = 1.00, 2.43] in original singletons versus singleton with VTS. On the contrary, VTS occurred after 14 weeks was associated with significantly shorter GW and lower BW, as well as higher risks of PTB and LBW. When the sac reduced in VTS was an empty gestational sac, there would be no differences in GW, PTB, and LBW between singletons versus singletons with VTS, whereas the loss of a fetus with cardiac-activity was associated with adverse obstetric outcomes. CONCLUSIONS: This meta-analysis suggests whether or not VTS is harmful to obstetric outcomes is highly dependent on the vanishing timing and intrauterine growth stage.

Association between X-ray repair cross-complementing group 1 Arg399Gln polymorphism and male infertility: An update meta-analysis.

Numerous studies concentrate on the association between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphism and male infertility; however, the results remain inconclusive and inconsistent. Hence, this meta-analysis was conducted to get a precise estimation of the correlation. PubMed, Web of Science, Embase, Scopus and China National Knowledge Infrastructure (CNKI) databases were searched to identify the all relevant studies before 3 May 2020. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the strength of the association. Finally, six studies with 1,886 cases and 1,212 controls were included in our study. The result indicated that XRCC1 Arg399Gln polymorphism was significantly associated with male infertility under allelic model (A-allele vs. G-allele: OR = 1.183, p = .003), heterozygote genetic model (AA vs. GA: OR = 1.256, p = .027), recessive genetic model (AA vs. GG + GA: OR = 1.279, p = .012) and dominant genetic model (AA + GA vs. GG: OR = 1.218, p = .026). In addition, in Asian subgroup, statistic correlation remained significant in allelic model (A-allele vs. G-allele: OR = 1.145, p = .025) with rare heterogeneity (I2  = 0%). In summary, our meta-analysis suggested that XRCC1 Arg399Gln polymorphism was significantly associated with male infertility and the A-allele might be a risk factor for this disease, especially in Asians.

Pregnancy outcomes after day 5 versus day 6 blastocyst-stage embryo transfer: A systematic review and meta-analysis.

AIM: To compare the pregnancy outcomes after day 5 blastocyst-stage embryo transfers (BET) versus day 6 BET following vitrified-warmed cycle and to evaluate whether the number of embryos transferred and the chromosomal status of embryo influence effect estimates. METHODS: A literature search (PubMed, Embase and MEDLINE) up to January 2019 was conducted to identify studies where women with day 6 BET were compared to women with day 5 BET. Only studies published in English language, on peer-reviewed journal were considered eligible. The following subgroup analyses were performed: (i) number of embryos transferred and (ii) chromosomal status of embryo. RESULTS: From a total of 1956 articles identified, 23 observational studies were included in the meta-analysis. We observed that day 6 BET were associated with lower implantation rate (risk ratio, RR: 1.17, 95% confidence interval, CI: 1.10-1.24), clinical pregnancy rate (RR: 1.17, 95% CI: 1.10-1.24), ongoing pregnancy rate (RR: 1.15, 95% CI: 1.07-1.24) and live birth rate (RR: 1.22, 95% CI: 1.11-1.33) than day 5 BET following vitrified-warmed cycle. The subgroup analysis found that the superiority of day 5 BET compared with day 6 BET is influenced by the number of embryos transferred and chromosomal status of embryos. CONCLUSION: Current evidence shows that day 5 BET is superior to day 6 BET following vitrified-warmed cycle in clinical practice. Due to the overall low quality of available evidence, more larger and well-conducted studies are needed to compare the pregnancy outcomes between day 5 and day 6 BET before drawing a clear conclusion.

CircRNA expression profile and functional analysis in testicular tissue of patients with non-obstructive azoospermia.

BACKGROUND: Non-obstructive azoospermia (NOA) is a multifactorial disorder whose molecular basis remains largely unknown. Circular RNAs (CircRNAs), a novel class of endogenous RNAs, have been recognized to play important roles in many biological processes. However, little is known about the expression patterns and functions of circRNAs in human testes involved in NOA. METHODS: In this study, the testicular circRNA expression profile were explored in NOA patients and the controls by high-throughput circRNA microarray. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm the microarray data. Bioinformatics analyses including the circRNA/miRNA/mRNA interaction network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict the functions of differentially expressed circRNAs. RESULTS: A total of 368 differentially down-regulated and 526 up-regulated circRNAs were detected in NOA patients. These findings have been verified by qRT-PCR on 6 selected circRNAs. Among these differentially expressed circRNAs, the hsa_circRNA_0023313 was obviously up-regulated in testicular tissue of NOA patients. The most likely potential target miRNA for hsa_circRNA_0023313 include hsa-miR-520d-3p, hsa-miR-373-3p, hsa-miR-372-3p, hsa-miR-302c-3p and hsa-miR-130b-5p. Function analysis indicated that hsa_circRNA_0023313 was ubiquitin-protein transferase activity and chromatin binding. KEGG analysis revealed that the top five pathways related to hsa_circRNA_0023313 were endocytosis, meiosis, FoxO signaling pathway, ubiquitin mediated proteolysis and AMPK signaling pathway. CONCLUSIONS: This is the first report that the testicular circRNA expression profile is altered in NOA patients indicating circRNAs might play important roles in regulating spermatogenesis and be potential biomarkers for the diagnosis and treatment of NOA.

Vitrification and conventional freezing methods in sperm cryopreservation: A systematic review and meta-analysis.

OBJECTIVE: The objective is to systematically review and synthesize the literature on the efficacy with two different cryopreservation methods used for human spermatozoa and evaluate whether vitrification protocol and quality of sperm influence effect estimates. DESIGN: The following electronic databases were searched up to September 2017: Pubmed, Embase and Web of Science. The search strategy used the following the relevant medical subject heading (MeSH) terms, keywords, and word variants for: sperm parameters, conventional freezing, and vitrification. Queries were limited to those involving humans. Randomized controlled trials (RCTs) that published in English languages were considered eligible. Studies and references were included if they reported total motility, progressive motility, morphology, or DNA fragmentation index (DFI) for vitrified or conventional cryopreserved human spermatozoa. Patients recruited in RCTs considering sperm vitrification as one of the experimental arms and conventional freezing (including slow freezing or vapor fast freezing) sperm control as the other. Studies that had high risks of allocation concealment were excluded when performing sensitivity analysis. We specified 2 subgroup variables, including vitrification protocol and quality of spermatozoa cryopreserved, to investigate sources of heterogeneity. A meta-analysis was performed using a random effects (I2 > 50%) or fixed effects (I2 < 50%) model to calculate weighted mean differences (MD) and 95% CI. RESULT(S): The search yielded a total of 2428 articles and 13 RCTs were included for analysis. They involved 486 vitrified and 486 conventional cryopreserved sperm samples. Four sperm parameters were reported as mean differences and based on adjusted estimates in all included studies. Meta-analysis of these studies showed significantly higher total motility [weighted mean differences (WMD) 6.98; 95% confidence interval (CI) 2.94; 11.02; P < 0.0001] and progressive motility [WMD 4.59; 95% CI 0.78; 8.39; P = 0.02] of past-thawed sperm following vitrification compared with conventional freezing methods. However, DNA fragmentation index (DFI) [WMD -1.18; 95% CI -2.81; 0.45; P = 0.16] and morphology [WMD 0.11; 95% CI -0.42; 0.63; P = 0.69] of past-thawed sperm are similar between two freezing groups. Subgroup analysis shown that the vitrification protocol and quality of spermatozoa are potential risk factors for the efficacy of vitrification. Higher past-thawed sperm parameters following the cryoprotectants-free (CPAs-free) vitrification were observed, as well as a lower past-thawed sperm parameters with the cryoprotectants-presence (CPAs-presence) vitrification, which could reflect the CPAs related cytotoxicity. Meanwhile, vitrification had higher ability in preservation of high quality of spermatozoa compared with vitrification of low quality spermatozoa. CONCLUSION(S): According to the results of present meta-analysis, vitrification is superior to conventional freezing methods in preservation of spermatozoa, regarding total and progressive motility. However, the efficacy of vitrification is influence by using different vitrification protocol and cryopreservation of different quality spermatozoa. It is must emphasized that the results of present meta-analysis is limited by the small number of studies of variable vitrification protocol. Further well conducted studies are required to confirm the efficacy of vitrification in cryopreservation of spermatozoa, in addition, allow the examination of the two cryopreservation methods in terms of pregnancy achievement and determination of the role of clinical variable on efficacy of vitrification.

Formaldehyde inhalation triggers autophagy in rat lung tissues.

Formaldehyde (FA), a ubiquitous environmental contaminant, has long been suspected of causing lung injury. However, the molecular and cellular mechanisms underlying this phenomenon remain elusive. The aim of this study was to elucidate the role of autophagy in lung injury induced by FA inhalation. In this study, lung weight coefficient, interleukin 8 in bronchoalveolar fluid, and histopathological examination were used to evaluate the lung injury. Moreover, electron microscopy, Western blotting for the ratio of LC3-II/LC3-I were used to detect autophagy in lung tissues. Our results indicated that the lung toxicity of FA inhalation is dose dependent. Lung weight coefficient, inflammatory response, and histopathological structure in the 0.5 mg/m3 FA exposure group showed no obvious changes compared with the control. However, exposure to 5 and 10 mg/m3 FA produced lung injury including pulmonary edema, histological changes, and inflammatory responses. Furthermore, the alterations of autophagy correlated with lung injury. Taken together, these data indicate that FA exposure triggers autophagy of alveolar epithelial cells, which might play a pivotal role in lung injury.