Targeting a thrombopoietin-independent strategy in the discovery of a novel inducer of megakaryocytopoiesis, DMAG, for the treatment of thrombocytopenia.

Thrombocytopenia is a thrombopoietin (TPO)-related disorder with very limited treatment options, and can be lifethreatening. There are major problems with typical thrombopoietic agents targeting TPO signaling, so it is urgent to discover a novel TPO-independent mechanism involving thrombopoiesis and potential druggable targets. We developed a drug screening model by the multi-grained cascade forest (gcForest) algorithm and found that 3,8-di-O-methylellagic acid 2- O-glucoside (DMAG) (10, 20 and 40 µM) promoted megakaryocyte differentiation in vitro. Subsequent investigations revealed that DMAG (40 mM) activated ERK1/2, HIF-1b and NF-E2. Inhibition of ERK1/2 blocked megakaryocyte differentiation and attenuated the upregulation of HIF-1b and NF-E2 induced by DMAG. Megakaryocyte differentiation induced by DMAG was inhibited via knockdown of NF-E2. In vivo studies showed that DMAG (5 mg/kg) accelerated platelet recovery and megakaryocyte differentiation in mice with thrombocytopenia. The platelet count of the DMAG-treated group recovered to almost 72% and 96% of the count in the control group at day 10 and 14, respectively. The platelet counts in the DMAG-treated group were almost 1.5- and 1.3-fold higher compared with those of the irradiated group at day 10 and 14, respectively. Moreover, DMAG (10, 25 and 50 mM) stimulated thrombopoiesis in zebrafish. DMAG (5 mg/kg) could also increase platelet levels in c-MPL knockout (c-MPL-/-) mice. In summary, we established a drug screening model through gcForest and demonstrated that DMAG promotes megakaryocyte differentiation via the ERK/HIF1/NF-E2 pathway which, importantly, is independent of the classical TPO/c-MPL pathway. The present study may provide new insights into drug discovery for thrombopoiesis and TPO-independent regulation of thrombopoiesis, as well as a promising avenue for thrombocytopenia treatment.

Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial.

PURPOSE: To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. METHODS: One hundred apparently healthy adults aged 18-65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 µg folic acid, 8 mg vitamin B6, 6.4 µg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. RESULTS: Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference - 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (ß = -1.680, P = 0.004) and betaine (ß = -1.421, P = 0.020) after 12 weeks of supplementation. CONCLUSIONS: Daily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website: https://clinicaltrials.gov/ct2/show/NCT03720249 .

Development of chlorine dioxide sustained-release device using carboxymethyl cellulose-polyvinyl alcohol-ß-cyclodextrin ternary hydrogel and a new sustained-release kinetic model.

Owing to unique physiochemical and biological properties as well as the ability to be combined with a wide variety of materials for both biocompatibility and hydrophilia, carboxymethyl cellulose (CMC) is an excellent choice as a carrier. Loading Chlorine dioxide (ClO2) into biodegradable carrier for its good disinfection performance and high safety factors has attracted significantattention. Therefore, in this study, we used ClO2 as a model drug, and a sustained-ClO2-gas-release gel was developed from degradable materials, such as carboxymethyl cellulose (CMC), polyvinyl alcohol (PVA), and ß-cyclodextrin (ßCD), through a simple and benign crosslinking strategy. Notably, the gel had sustained-release property in a wide temperature range of 4-35 â„ƒ and released ClO2 gas effectively for more than 30 days. Furthermore, a loss factor was proposed based on the incomplete release of the drug in the sustained release process to a chieve a good fit with the gas diffusion process. A new diffusion model was designed based on the Korsmeyer-Peppas model, and an excellent fit was obtained. This sustained-ClO2-gas-release gel provides theoretical and technical guidance for the development of sustained-disinfectant-release agents for use in space and offers new insights into the sustained release model of skeleton-soluble hydrogels. Supplementary Information: The online version contains supplementary material available at 10.1007/s10570-023-05070-6.

[mRNA Expression Profile Changes in Angiotensin-â ¡-Induced Atrial Myocardial Fibrosis in Rats].

Objective: To study the differences between the mRNA expression profile in angiotensin Ⅱ (Ang Ⅱ)-induced fibrotic cardiomyocytes and that of normal cardiomyocytes and the relevant signaling pathways. Methods: Six 8-week-old male Sprague-Dawley (SD) rats were randomly assigned to a control group and an Ang Ⅱ group, with 3 rats in each group. Rats in the control group were injected via caudal vein with 0.9% normal saline at 2 mg/kg per day, while rats in the Ang Ⅱ group were injected with Ang Ⅱ via caudal vein at 2 mg/kg per day. The medications were continuously administered in the two groups for 14 days. The degree of myocardial fibrosis was determined by Masson's Trichrome staining and the content of collagen Ⅰ was determined by immunohistochemistry. High throughput sequencing was performed to measure the mRNA expression of rat cardiomyocytes in the two groups and to screen for differentially-expressed mRNAs. The differentially-expressed mRNAs were analyzed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results: Compared with those of the control group, the degree of myocardial fibrosis and the content of collagen Ⅰ in Ang Ⅱ group were significantly higher ( P<0.05). Through sequencing, 313 differentially-expressed mRNAs were identified, with 201 being up-regulated and 112 being down-regulated. Go and KEGG analyses showed that these differentially-expressed mRNA were involved in a variety of biological regulatory functions and pathways of myocardial fibrosis. Conclusion: Ang Ⅱ can cause myocardial fibrosis in rats. There are significant differences in mRNA expression between fibrotic cardiomyocytes and normal cardiomyocytes. The differentially expressed mRNAs may play an important role in biological processes, including immune response, cell remodeling, and extracellular matrix deposition.

[Characteristics of the left heart structure and function in 86 term neonates with intrauterine growth restriction]. / 86ä¾‹å®«å† ç”Ÿé•¿å—é™è¶³æœˆæ–°ç”Ÿå„¿çš„å·¦å¿ƒç»“æž„åŠåŠŸèƒ½åˆ†æž.

OBJECTIVES: To study the left heart structure and functional characteristics of term neonates with intrauterine growth restriction (IUGR). METHODS: This study included 86 term neonates with IUGR admitted to the Neonatal Ward of Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2022 as the IUGR group, as well as randomly selected 86 term neonates without IUGR born during the same period as the non-IUGR group. The clinical data and echocardiographic data were compared between the two groups. RESULTS: The analysis of left heart structure and function showed that compared with the non-IUGR group, the IUGR group had significantly lower left ventricular mass, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, end-diastolic interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic volume, left ventricular end-systolic volume, and stroke volume (P<0.05) and significantly higher ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness, proportion of neonates with a mitral peak E/A ratio of ≥1, and cardiac index (P<0.05). The Spearman correlation analysis suggested that stroke volume was positively correlated with birth weight and body surface area (rs=0.241 and 0.241 respectively; P<0.05) and that the ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness was negatively correlated with birth weight and body surface area (rs=-0.229 and -0.225 respectively; P<0.05). CONCLUSIONS: The left ventricular systolic function of neonates with IUGR is not significantly different from that of neonates without IUGR. However, the ventricular septum is thicker in neonates with IUGR. This change is negatively correlated with birth weight and body surface area. The left ventricular diastolic function may be impaired in neonates with IUGR.

Lactobacillus rhamnosus GG colonization in early life regulates gut-brain axis and relieves anxiety-like behavior in adulthood.

Evidence reveals that gut dysbiosis is involved in bidirectional interactions in gut-brain axis and participates in the progress of multiple disorders like anxiety. Gut microbes in early life are crucial for establishment of host health. We aimed to investigate whether early life probiotics Lactobacillus rhamnosus GG (LGG) colonization could relieve anxiety in adulthood through regulation of gut-brain axis. Live or fixed LGG was gavaged to C57BL/6 female mice from day 18 of pregnancy until natural birth, and newborn mice from day 1 to day 5 respectively. In this study, we found that live LGG could be effectively colonized in the intestine of offspring. LGG colonization increased intestinal villus length and colonic crypt depth, accompanied with barrier function protection before weaning. Microbiota composition by 16S rRNA sequencing showed that some beneficial bacteria, such as Akkermansia and Bifidobacteria, were abundant in LGG colonization group. The protective effect of LGG on gut microbiota persisted from weaning to adulthood. Intriguingly, behavioral results assessed by elevated plus mazed test and open field test demonstrated relief of anxiety-like behavior in adult LGG-colonized offspring. Mechanically, LGG colonization activated epithelial growth factor receptor (EGFR) and enhanced serotonin transporter (SERT) expression and modulated serotonergic system in the intestine, and increased brain-derived neurotrophic factor and γ-aminobutyric acid receptor levels in the hippocampus and amygdala. Blocking EGFR blunted LGG-induced the increased SERT and zonula occludens-1 expression. Collectively, early life LGG colonization could protect intestinal barrier of offspring and modulate gut-brain axis in association with relief of anxiety-like behavior in adulthood.

Discovery of a novel megakaryopoiesis enhancer, ingenol, promoting thrombopoiesis through PI3K-Akt signaling independent of thrombopoietin.

Thrombocytopenia, a most common complication of radiotherapy and chemotherapy, is an important cause of morbidity and mortality in cancer patients. However, there are still no approved agents for the treatment of radiation- and chemotherapy-induced thrombocytopenia (RIT and CIT, respectively). In this study, a drug screening model for predicting compounds with activity in promoting megakaryocyte (MK) differentiation and platelet production was established based on machine learning (ML), and a natural product ingenol was predicted as a potential active compound. Then, in vitro experiments showed that ingenol significantly promoted MK differentiation in K562 and HEL cells. Furthermore, a RIT mice model and c-MPL knock-out (c-MPL-/-) mice constructed by CRISPR/Cas9 technology were used to assess the therapeutic action of ingenol on thrombocytopenia. The results showed that ingenol accelerated megakaryopoiesis and thrombopoiesis both in RIT mice and c-MPL-/- mice. Next, RNA-sequencing (RNA-seq) was carried out to analyze the gene expression profile induced by ingenol during MK differentiation. Finally, through experimental verifications, we demonstrated that the activation of PI3K/Akt signaling pathway was involved in ingenol-induced MK differentiation. Blocking PI3K/Akt signaling pathway abolished the promotion of ingenol on MK differentiation. Nevertheless, inhibition of TPO/c-MPL signaling pathway could not suppress ingenol-induced MK differentiation. In conclusion, our study builds a drug screening model to discover active compounds against thrombocytopenia, reveals the critical roles of ingenol in promoting MK differentiation and platelet production, and provides a promising avenue for the treatment of RIT.

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.

Evaluation of deep learning approaches for modeling transcription factor sequence specificity.

As a key component of gene regulation, transcription factors (TFs) play an important role in a number of biological processes. To fully understand the underlying mechanism of TF-mediated gene regulation, it is therefore critical to accurately identify TF binding sites and predict their affinities. Recently, deep learning (DL) algorithms have achieved promising results in the prediction of DNA-TF binding, however, various deep learning architectures have not been systematically compared, and the relative merit of each architecture remains unclear. To address this problem, we applied four different deep learning architectures to SELEX-seq and HT-SELEX data, covering three species and 35 families. We evaluated and compared the performance of different deep neural models using 10-fold cross-validation. Our results indicate that the hybrid CNN + DNN model shows the best performances. We expect that our study will be broadly applicable to modeling and predicting TF binding specificity when more high-throughput affinity data are available.

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.

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.

An electrodeless atmospheric microwave plasma jet for efficient degradation of antibiotic norfloxacin.

Plasma technology is increasingly being used for the degradation of residual antibiotics in aquatic environments. However, the electrodes in conventional plasma generators are subject to erosion, which can pollute the reaction system and shorten its lifetime. To overcome these drawbacks, we developed an electrodeless high-flow atmospheric microwave plasma jet (MPJ) for fast and efficient degradation of residual norfloxacin (NOR), a typical fluoroquinolone antibiotic that is frequently detected in the aquatic environment owing to its widespread use in the treatment of various infectious diseases. Stable plasma was generated through a low-cost magnetron with the assistance of injection-locking technology. The degradation efficiency of NOR (20 mg/L) reached 98.27 ± 1.03% at 6 min and the mineralisation efficiency reached 68.67 ± 3.21% at 15 min. The fast degradation process of the NOR solution contributes to the large cross-section (approximately 153 mm2) of the plasma in direct contact with the solution. Hydroxyl radical (•OH) scavengers were used to identify the generated oxidising species, which indicated that their non-selective oxidation plays a major role in NOR degradation. Three main possible degradation pathways and mechanisms were proposed, namely the attack of •OH on the piperazine ring, quinolone ring, and benzene ring. The NOR solution was not toxic to Escherichia coli after 20 min of degradation. Thus, the high-flow atmospheric MPJ is an effective technology for the degradation of antibiotics in aqueous solutions.

Pulmonary valve annular and right ventricular outflow tract size as predictions values for moderate to severe pulmonary regurgitation after repaired Tetralogy of Fallot.

OBJECTIVE: This study sought to investigate the variation of right heart structure pre- and post-operation as risk factors for moderate to severe pulmonary regurgitation (PR) after repaired Tetralogy of Fallot and the best "cutoff" values for the transannular patch (TAP). METHODS: We collected surgical, echocardiographic, and computed tomographic data of Teralogy of Fallot (TOF) patients over two years and calculated z-score values based on the echocardiographic data. Based on the PR level after follow-up, the patients were divided into two groups, trivial to mild PR and moderate to severe PR. A multivariate logistic regression analysis was performed, and the receiver operating characteristic curve analysis was used to find the best "cutoff" value for risk factors. RESULTS: A total of 104 TOF patients were included in our cohort study. From the multivariate analysis, correction strategy (P = .002), difference in zRVOT (OR 1.974, 95% CI 1.354 to 2.878, P < .0001), and zPVA (OR 3.605, 95% CI 1.980 to 6.562, P < .0001) were the significant risk factors for moderate to severe PR. The "cutoff" value for the difference in zPVA that could predict moderate to severe PR in the TAP group was 3, and the optimal "cutoff" value for TAP was -1.4. CONCLUSIONS: The TAP is a risk factor for significant PR after surgery. We recommend the optimal "cutoff" value for TAP is -1.4 calculated using Shan-Shan Wang's data set. During the procedure, to limit the RVOT resection and restrict the enlargement of pulmonary annulus within a variation of z-score as 3 would reduce significant PR.

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.

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.

Recurrent granular cell tumor of the thyroid: a case report and literature review.

BACKGROUND: Granular cell tumor (GCT) of the thyroid is a rare benign tumor of Schwann cell origin with a favorable prognosis and only 10 cases have been reported so far in scientific literature. The present case study describes the first case of recurrent thyroid GCT. CASE PRESENTATION: Our case describes a 20-year-old woman who had undergone lobectomy for GCT of the thyroid 4 years ago. Hematoxylin-eosin (HE) staining revealed that the lesion was composed of epithelioid cells with an abundance of eosinophilic granular cytoplasm. Immunohistochemical analysis showed that tumor cells tested positive for S-100 protein and negative for desmin. Both histological and immunohistochemical analyses supported the diagnosis of recurrent GCT of the thyroid. CONCLUSIONS: Our case suggested that a tumor-free margin excision and post-operative follow-up are necessary for the treatment of GCT of the thyroid.

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.

Orbital angular momentum modes emission from a silicon photonic integrated device for km-scale data-carrying fiber transmission.

We experimentally demonstrate orbital angular momentum (OAM) modes emission from a high emission efficiency OAM emitter for 20-Gbit/s quadrature phase-shift keying (QPSK) carrying data transmission in few-mode fiber (FMF). The device is capable of emitting vector optical vortices carrying well-defined OAM efficiently with the efficiency of the device >37%. Seven modes propagate through a 2-km two-mode and a 3.6-km three-mode FMF with measured optical signal-to-noise ratio (OSNR) penalties less than 4 dB at a bit-error rate (BER) of 2 × 10-3. The demonstrations with favorable performance pave the way to incorporate silicon photonic integrated devices as transceivers in an OAM-enabled optical fiber communication link.