Exploring the relationship between IGHMBP2 gene mutations and spinal muscular atrophy with respiratory distress type 1 and Charcot-Marie-Tooth disease type 2S: a systematic review.

Background: IGHMBP2 is a crucial gene for the development and maintenance of the nervous system, especially in the survival of motor neurons. Mutations in this gene have been associated with spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot-Marie-Tooth disease type 2S (CMT2S). Methods: We conducted a systematic literature search using the PubMed database to identify studies published up to April 1st, 2023, that investigated the association between IGHMBP2 mutations and SMARD1 or CMT2S. We compared the non-truncating mutations and truncating mutations of the IGHMBP2 gene and selected high-frequency mutations of the IGHMBP2 gene. Results: We identified 52 articles that investigated the association between IGHMBP2 mutations and SMARD1/CMT2S. We found 6 hotspot mutations of the IGHMBP2 gene. The truncating mutations in trans were all associated with SMARD1. Conclusion: This study provides evidence that the complete LOF mechanism of the IGHMBP2 gene defect may be an important cause of SMARD1.

The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress.

Introduction: The immune-related lncRNAs (IRLs) are critical for the development of cervical cancer (CC), but it is still unclear how exactly ILRs contribute to CC. In this study, we aimed to examine the relationship between IRL and CC in detail. Methods: First, the RNAseq data and clinical data of CC patients were collected from The Cancer Genome Atlas (TCGA) database, along with the immune genes from the Import database. We used univariate cox and least absolute shrinkage and selection operator (lasso) to obtain IRLs for prediction after screening the variables. According to the expression levels and risk coefficients of IRLs, the riskscore were calculated. We analyzed the relationship between the model and oxidative stress. We stratified the risk model into two as the high and low-risk groups. We also evaluated the survival differences, immune cell differences, immunotherapeutic response differences, and drug sensitivity differences between the risk groups. Finally, the genes in the model were experimentally validated. Results: Based on the above analyses, we further selected four IRLs (TFAP2A.AS1, AP000911.1, AL133215.2, and LINC02078) to construct the risk model. The model was associated with oxidative-stress-related genes, especially SOD2 and OGG1. Patients in the high-risk group had a lower overall survival than those in the low-risk group. Riskscore was positively correlated with resting mast cells, neutrophils, and CD8+ T-cells. Patients in the low-risk group showed a greater sensitivity to immunosuppression therapy. In addition, we found that patients with the PIK3CA mutation were more sensitive to chemotherapeutic agents such as dasatinib, afatinib, dinaciclib and pelitinib. The function of AL133215.2 was verified, which was consistent with previous findings, and AL133215.2 exerted a pro-tumorigenic effect. We also found that AL133215.2 was closely associated with oxidative-stress-related pathways. Discussion: The results suggested that risk modeling might be useful for prognosticating patients with CC and opening up new routes for immunotherapy.

Genomic Analysis of an Escherichia coli Sequence Type 167 Isolate Harboring a Multidrug-Resistant Conjugative Plasmid, Suggesting the Potential Transmission of the Type Strains from Animals to Humans.

Purpose: The E. coli ST167 clone is the globally dominant ST among extraintestinal pathogenic E. coli (ExPEC) and is frequently associated with carbapenem resistance. This study reports genomic characterization of a pandrug-resistant E. coli ST167 isolate (ECO3183) and the possibility of the type strains' transmission. Materials and Methods: Antibiotic susceptibility testing was performed using disk diffusion and the VITEK 2 automated system. The E. coli ECO3183 genome was sequenced. We used the genome to analyze the phylogenetic relationship, phylogenetic group, sequence type (ST), acquired antibiotic resistance genes (ARGs), IS elements, genomics islands, the replicon type and transferability of the plasmids. The conjugative transfer of plasmids was assessed using filter mating experiments. Results: ECO3183 contained a 4.87-Mb chromosome and two plasmids [pECO3183-1 (167.63 Kb) and pECO3183-2 (46.16 Kb)]. It belonged to phylogenetic group A, clonal complex 10 (CC10), and ST167. ECO3183 is a pandrug-resistant strain nonsusceptible to 24 tested antimicrobials representing 8 different antimicrobial classes. Among 55 E. coli isolates phylogenetically related to ECO3183, 47% (26/55) were from humans, while 35% (19/55) were from animals. Further analysis revealed that among 1140 ST167 isolates (in the EnteroBase database), 4% (47/1140) originated from environments, 17% (192/1140) were isolated from humans, and 78% (890/1140) were obtained from animals. The pECO3183-1 contained two identical repeats of a 9633 bp region (IS6100-sul1-ΔaadA16-dfrA27-arr-3-aac(6')-Ib-cr-IS26) and a 17.88-kb resistance island (sul2-aph(3″)-Ib-aph(6)-Id-IS26-Δaph(3')-Ia-IS26-tet(A)-ΔfloR-ΔISVsa3-IS26-Δaac(3)-IId-IS26-mph(A)), and these three regions contained most of ECO3183 carrying ARGs. It was identified as a conjugative plasmid, which confers MDR resistance and has the potential to spread. Conclusion: ECO3183 exhibited pandrug-resistance phenotype that was mediated by pECO3183-1 carrying MDR ARGs and pECO3183-2 carrying blaNDM-5. Source analysis of strains indicated that ST167 E. coli might be transmitted between species from animals to humans, which needs continued monitoring.

A necroptosis-related gene signature to predict prognosis and immune features in hepatocellular carcinoma.

BACKGROUND AND AIM: Necroptosis plays an important role in hepatocellular carcinoma (HCC) development, recurrence, and immunotherapy tolerance. We aimed to build a new prognostic necroptosis-related gene signature that could be used for survival and immunotherapy prediction in HCC patients. METHODS: We found that necroptosis was associated with HCC progression and survival outcomes and was involved in the immune infiltration of HCC. Multiple bioinformatics methods including WGCNA, LASSO-Cox regression, stepwise Cox regression, and Random Forest and Boruta model analysis, were used to establish a prognostic profile related to necroptosis. The necroptosis-related gene signature was validated in ICGC and GSE14520 datasets. RESULTS: This five-gene signature showed excellent predictive performance and was an independent risk factor for patients' overall survival outcome in the three cohorts. Moreover, this signature was an exact predictor using fewer genes than previous gene signatures. Finally, qRT-PCR and immunohistochemical staining investigations were performed in previously collected fresh frozen tumor tissues from HCC patients and their paracancerous normal tissues, and the results were consistent with the bioinformatics results. We found that LGALS3 not only affected the proliferation and migration ability of HepG2 cells but also affected necroptosis and the expression of inflammatory cytokines. CONCLUSION: In summary, we established and validated an individualized prognostic profile related to necroptosis to forecast the therapeutic response to immune therapy, which might offer a potential non-apoptotic therapeutic target for HCC patients.

Association between HIF-1α, BNIP3, and autophagy in the chorionic villi of missed abortion.

AIM: To investigate the expression of autophagy mediated by the hypoxia-inducible factor 1α (HIF-1α)/BNIP3 signaling pathway in villus tissues of missed abortion and HTR-8/SVneo cells and to elucidate the association of HIF-1α and BNIP3 in autophagy of missed abortion. METHODS: Villus tissues from 30 healthy women with induced abortion and 35 patients with missed abortion were collected, and HTR-8/SVneo cells were cultured under hypoxia and transfected with HIF-1α-siRNA. Real-time polymerase chain reaction was utilized to measure the mRNA levels of HIF-1α and BNIP3; Western blotting was performed to determine the protein levels of HIF-1α, BNIP3, LC3 II/I, and Beclin 1 in villus tissues and HTR-8/SVneo cells. Cellular invasion activity was detected by transwell matrigel assay. The level of autophagy was confirmed by transmission electron microscopy of autophagosome formation. RESULTS: The mRNA levels of HIF-1α and BNIP3 were significantly lower in the missed abortion villi than in the induced abortion samples. The protein levels of HIF-1α, BNIP3, Beclin 1, and LC3II/I were significantly decreased in villus tissues from missed abortion, and autophagosomes were significantly decreased in villus tissues from missed abortion. Under hypoxia, the mRNA expression of HIF-1α and BNIP3 was inhibited after silencing HIF-1α by RNAi, while the protein expression of HIF-1α, BNIP3, Beclin1, and LC3II/I was significantly downregulated. The number of invading cells was significantly decreased, and autophagosomes were significantly decreased after silencing HIF-1α by RNAi in HTR-8/SVneo cells. CONCLUSIONS: Autophagy mediated by the HIF-1α/BNIP3 signaling pathway in villous trophoblast cells may be associated with the progression and development of missed abortion.

Allelic phenotype prediction of phenylketonuria based on the machine learning method.

BACKGROUND: Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase (PAH) gene. Our study aimed to predict the phenotype using the allelic genotype. METHODS: A total of 1291 PKU patients with 623 various variants were used as the training dataset for predicting allelic phenotypes. We designed a common machine learning framework to predict allelic genotypes associated with the phenotype. RESULTS: We identified 235 different mutations and 623 various allelic genotypes. The features extracted from the structure of mutations and graph properties of the PKU network to predict the phenotype of PKU were named PPML (PKU phenotype predicted by machine learning). The phenotype of PKU was classified into three different categories: classical PKU (cPKU), mild PKU (mPKU) and mild hyperphenylalaninemia (MHP). Three hub nodes (c.728G>A for cPKU, c.721 for mPKU and c.158G>A for HPA) were used as each classification center, and 5 node attributes were extracted from the network graph for machine learning training features. The area under the ROC curve was AUC = 0.832 for cPKU, AUC = 0.678 for mPKU and AUC = 0.874 for MHP. This suggests that PPML is a powerful method to predict allelic phenotypes in PKU and can be used for genetic counseling of PKU families. CONCLUSIONS: The web version of PPML predicts PKU allele classification supported by applicable real cases and prediction results. It is an online database that can be used for PKU phenotype prediction http://www.bioinfogenetics.info/PPML/ .

Combined analysis of bulk and single-cell RNA sequencing reveals novel natural killer cell-related prognostic biomarkers for predicting immunotherapeutic response in hepatocellular carcinoma.

Introduction: Natural killer (NK) cells play an irreplaceable and important role as a subtype of innate immune cells in the contemporary setting of antitumor immunity. Methods: We chose a total of 1,196 samples for this analysis from the public dataset's six separate cohorts. To identify 42 NK cell marker genes, we first carried out a thorough study of single-cell RNA sequencing data from the GSE149614 cohort of hepatocellular carcinoma (HCC). Results: Using the NK cell marker genes in the TCGA cohort, we next created a seven-gene prognostic signature, separating the patients into two categories with distinct survival patterns. This signature's prognostic prediction ability was well verified across several validation cohorts. Patients with high scores had higher TIDE scores but lower immune cell infiltration percentages. Importantly, low-scoring patients had superior immunotherapy response and prognosis than high-scoring patients in an independent immunotherapy cohort (IMvigor210). Finally, we used CD56 and TUBA1B antibodies for immunohistochemical labeling of HCC tissue sections, and we discovered a lower number of CD56+ cells in the HCC tissue sections with high TUBA1B expression. Discussion: In summary, our research created a unique prognostic profile based on NK cell marker genes that may accurately predict how well immunotherapy would work for HCC patients.

Age- and sex-specific reference intervals for complete blood count parameters in capillary blood for Chinese neonates and infants: A prospective study.

BACKGROUND: The reference intervals (RIs) of laboratory tests are essential for disease diagnosis, therapy monitoring, and health assessment. They are also significant for clinicians to discriminate between subjects with disease and healthy subjects. However, RIs for complete blood count (CBC) parameters in capillary blood for children are deficient. This study aimed to establish capillary blood RIs for blood cell parameters in neonates and infants from birth to 2 years of age in Zhengzhou. METHODS: We prospectively collected a total of 1840 capillary blood specimens from healthy subjects from birth to 2 years of age. Hematology RIs were established by analyzing capillary blood sample data, and RIs and 90 % confidence intervals (CIs) were calculated according to Clinical and Laboratory Standards Institute (CLSI) C28-A3 guidelines. RESULTS: RIs were established for hematological parameters of capillary blood in neonates and infants from birth to 2 years of age. The levels of almost all hematological parameters, except for the lymphocyte (LYMPH), platelet (PLT), and thrombocytocrit (PCT) parameters, peaked in the first month after birth and then decreased to lower levels within 6 months. There were significant sex differences in most erythrocyte-related parameters, with higher levels in males than in females. Erythrocyte-related parameters showed an increasing tendency with increasing age after the second month. Neutrophil (NEUT) levels were high on the third day of life, declined to a nadir in the first month, and then slowly increased with age. LYMPH levels were low at birth and began to increase after birth, peaked at approximately-six months of age and then gradually declined with age. PLT and PCT levels showed an increasing trend during the first month, while the other parameters showed a decreasing trend. All platelet-related and leukocyte-related parameters showed no significant difference with sex. CONCLUSION: We provide comprehensive age- and sex-specific RIs, including RIs for neonates in Henan. Our study provides more comprehensive reference ranges for Child Health Hospital and children's medical institutions, which may facilitate preliminary screening, diagnosis, and therapy.

The association of γδT lymphocytes with cystic leukomalacia in premature infants.

Background: Periventricular leukomalacia (PVL) is an essential cause of cerebral palsy in preterm infants, and cystic PVL (cPVL) is the most severe form of the disease. The pathogenesis of cPVL is complex, and immune imbalances and inflammatory responses may play an essential role in it. Objective: This study aimed to investigate the correlation between peripheral blood lymphocyte subsets, especially γδT cells with the pathogenesis of cPVL in preterm infants. Methods: Peripheral blood from preterm infants with GA < 32 weeks and BW < 1,500 g was used in this study and was collected at 34 weeks corrected gestational age and within 24 h after the diagnosis with cranial MRI or cranial ultrasound. The infants were divided into cPVL groups and control groups. Flow cytometry was used to detect peripheral blood γδT, CD3+, CD4+, CD8+, and the proportion of total lymphocytes. Multiplex cell assays were used to detect the concentration of extracellular serum cytokines IL-6, IL-2, IL-8, IL-17A, IL-10, IL-1RA, eotaxin (CCL11), MCP-1 (CCL2), CXCL1, G-CSF, and IFNγ. A follow-up visit was carried out when the patient was 3 years old. Results: After correcting for confounding factors, the proportion of peripheral blood γδT in the cPVL group was significantly lower than that in the control group (ß: 0.216; 95% CI: 0.058-0.800, P < 0.022). Peripheral blood γδT (AUC: 0.722, P=0.006) and multivariate binary regression model (AUC: 0.865, P < 0.000) have good diagnostic values for cPVL. Peripheral blood γδT has some predictive power for neurodevelopmental outcomes in preterm infants (AUC: 0.743, P = 0.002). Conclusion: It seems that peripheral blood γδT cells are inversely correlated with cPVL, which is not only a risk factor for cPVL disease but also neurodevelopmental outcomes in preterm infants. However, the causality of cPVL and various lymphocytes is unclear and needs further study.

Identification of phenylketonuria patient genotypes using single-gene full-length sequencing.

BACKGROUND: Phenylketonuria (PKU) is a common, autosomal recessive inborn error of metabolism caused by PAH gene variants. After routine genetic analysis methods were applied, approximately 5% of PKU patients were still not diagnosed with a definite genotype. METHODS: In this study, for the first time, we identified PKU patients with unknown genotypes via single-gene full-length sequencing. RESULTS: The detection rate of PKU genotype increased from 94.6 to 99.4%, an increase of approximately 5%. The variants c.1199 + 502A > T and 1065 + 241C > A were found at a high frequency in Chinese PKU patients. CONCLUSION: Our study suggest that single-gene full-length sequencing is a rapid, efficient and cost-effective tool to improve the genotype detection rate of PKU patients. Moreover, we provides additional case data to support pathogenicity of deep intronic variants in PAH.

Red blood cell distribution width at admission predicts outcome in critically ill patients with kidney failure: a retrospective cohort study based on the MIMIC-IV database.

PURPOSE: We aimed to explore whether red blood cell distribution width (RDW) could serve as a biomarker to predict outcomes in critically ill patients with kidney failure in this study. MATERIALS AND METHODS: This retrospective study was conducted with the Medical Information Mart for Intensive Care IV (MIMIC-IV).A total of 674 patients were divided into three groups based on tertiles of RDW. We used the generalized additive model, Kaplan-Meier curve, and Cox proportional hazards models to evaluate the association between RDW and clinical outcomes. We then performed subgroup analyses to investigate the stability of the associations between RDW and all-cause mortality. RESULTS: Nonlinear and J-shaped curves were observed in the generalized additive model. Kaplan-Meier analysis showed that patients with elevated RDW had a lower survival rate. The Cox regression model indicated that high levels of RDW were most closely associated with ICU mortality and 30-day mortality (HR = 4.71, 95% CI: 1.69-11.64 and HR = 6.62, 95% CI: 2.84-15.41). Subgroup analyses indicated that the associations between RDW and all-cause mortality were stable. CONCLUSIONS: Elevated levels of RDW were associated with an increased risk of all-cause mortality, and RDW could be an independent prognostic factor for kidney failure.

Reference intervals for coagulation parameters in non-pregnant and pregnant women.

Established reference intervals (RIs) of coagulation parameters generally based on the general population are not applicable to specific women. In order to accurately evaluate the coagulation status of non-pregnant women and pregnant women, specific RIs should be established. Our study recruited 465 non-pregnant women and 1972 pregnant women aged 20-45 years. Eight tests including antithrombin (AT), protein C (PC), free protein S (fPS), lupus anticoagulant (LA), D-dimer, fibrin/fibrinogen degradation products (FDP), coagulation factor VII (FVII), and factor VIII (FVIII) were performed on ACL TOP automated coagulation instrument. The RIs for these tests were established in non-pregnant and pregnant women at different gestational weeks. Compared to the non-pregnant group, the medians of AT and fPS were lower, while the medians of PC, LA normalized ratio, D-dimer, FDP, FVII, and FVIII were higher. During pregnancy, AT and fPS activity showed a decreasing trend, with the increase of gestational age. PC activity, LA normalized ratio, D-dimer concentrations, FDP concentrations, FVII, and FVIII activity presented an increasing trend, with the increase of gestational age. The non-pregnant women-specific RIs and the gestational age-specific RIs of AT, PC, fPS, LA normalized ratio, D-dimer, FDP, FVII, and FVIII needed to be established for accurate clinical diagnoses.

WNT3 hypomethylation counteracts low activity of the Wnt signaling pathway in the placenta of preeclampsia.

Preeclampsia is a hypertensive disorder of pregnancy. Many studies have shown that epigenetic mechanisms may play a role in preeclampsia. Moreover, our previous study indicated that the differentially methylated genes in preeclampsia were enriched in the Wnt/ß-catenin signaling pathway. This study aimed to identify differentially methylated Wnt/ß-catenin signaling pathway genes in the preeclamptic placenta and to study the roles of these genes in trophoblast cells in vitro. Using an Illumina Infinium HumanMethylation 850 K BeadChip, we found that the Wnt signaling pathway was globally hypermethylated in the preeclamptic group compared with the term birth group, but hypomethylated in the preeclamptic group compared with the preterm birth group. Among all Wnt/ß-catenin signaling pathway factors, WNT3 was the most significantly differentially expressed gene and was hypomethylated in the preeclamptic group compared to the nonhypertensive groups, namely, the preterm birth group and term birth group. This result was confirmed by pyrosequencing. Through quantitative real-time PCR and western blot analysis, the WNT3 gene was found to be highly expressed in preeclamptic placental tissues, in contrast to other WNT factors, which were previously reported to be expressed at low levels in placental tissues. Additionally, in the HTR8/SVneo cell line, knockdown of WNT3 suppressed the Wnt/ß-catenin signaling pathway, consistent with the findings for other WNT factors. These results prompted us to speculate that the WNT3 gene counteracts the low activation state of the Wnt signaling pathway in the preeclamptic placenta through methylation modification.

Correlation Analysis between GDM and Gut Microbial Composition in Late Pregnancy.

The prevalence of GDM is very high worldwide. The specific pathogenesis of GDM is currently not very clear. Recent research suggests that changes in the intestinal flora during pregnancy play a key role in it. Therefore, this study is aimed at exploring the characteristics of the intestinal flora of patients with gestational diabetes in the third trimester of pregnancy and at finding the intestinal flora with significant differences in healthy pregnant women to provide a basis for future clinical attempts of using intestinal microecological agents to treat gestational diabetes mellitus (GDM). We sequenced the V3-V4 regions of the 16S ribosomal ribonucleic acid (rRNA) gene from stool samples of 52 singleton pregnant women at >28 weeks of gestation. Our results showed that there were significant differences between the NOR group vs. GDM group and the G group vs. LG group among Bacteroides, Firmicutes, and Firmicutes/Bacteroides. At the species level, there were significant differences in the abundance of eight species in the NOR and GDM groups. Among them, the relative abundance of Clostridium_spiroforme, Eubacterium_dolichum, and Ruminococcus_gnavus was positively correlated with FBG, and Pyramidobacter_piscolens was negatively correlated with FBG, whereas there were significant differences in the abundance of five species in the G and LG groups. Functional analysis showed that there were differences in the biosynthesis and metabolism of polysaccharides, digestive system, classification, and degradation of the intestinal microbes between the NOR and GDM groups and between the G and LG groups. These results indicated that the gut microbes between GDM patients in the third trimester of pregnancy and healthy controls had essential characteristic changes and might be involved in the regulation of patients' blood glucose levels.

Analysis of the screening results of 24040 potential sperm donors in a human sperm bank in Henan Province, China: a 14-year retrospective cohort study.

STUDY QUESTION: Is there a relation between the characteristics of potential sperm donors and the acceptance rate of these potential donors? SUMMARY ANSWER: A relatively higher acceptance rate was observed for potential sperm donors who were aged ≤ 35 years, were married, had children, and who had received higher education, and acceptance rates were also higher during spring and winter than summer and autumn. WHAT IS KNOWN ALREADY: Recruiting donors to a sperm bank program is difficult and slow owing to the high rates of rejection and dropout. STUDY DESIGN, SIZE, DURATION: A total of 24040 potential sperm donors were screened by the Henan Human Sperm Bank from 2006 to 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Potential sperm donors were recruited using the following baseline requirement: height of 168 cm or taller; age 22-45 years; currently attending or had graduated from high school or above. Men who met the criteria for age, height, and education level were invited for semen quality screening. The acceptable criteria for semen samples included liquefaction time < 60min, volume ≥ 2mL, sperm concentration ≥ 60 × 106/mL, progressive motility ≥ 60%, post-thaw motility ≥ 40%, pre-freezing total motile sperm per vial > 30 × 106/mL, post-thaw total motile sperm per vial > 12 × 106/mL, and freeze-thaw survival rate ≥ 60%. Any potential sperm donors meeting the minimum criteria for acceptable semen quality on two consecutive semen samples were scheduled for clinical assessment, physical examination, and laboratory tests. The reasons for sperm donor rejection were analyzed. The characteristics of accepted and rejected donors were compared using the chi-square test, and multivariate logistic regression analyses were conducted to identify factors associated with the acceptance rate of potential sperm donors and the positive rate of sexually transmitted diseases (STDs). MAIN RESULTS AND THE ROLE OF CHANCE: Only 23.38% (5620/24040) of potential sperm donors were accepted. The top four reasons for rejection were suboptimal semen quality (90.27%), STDs (6.26%), dropped out (2.65%), and chromosomal abnormalities (0.35%). The most common reason for the rejection of donors with an STD was a positive test for mycoplasmas (49.05%), followed by hepatitis B virus (27.56%), Chlamydia trachomatis (4.68%), and Escherichia coli (3.03%). n this study, the acceptance rate for men aged ≤ 35 years was significantly higher than that for men aged >35 years (P < 0.05). The acceptance rates were also significantly higher for men with a higher education than for men with lower education, married men than unmarried men, and men with children than men without children (P < 0.05). Moreover, acceptance rates were significantly higher during spring and winter than during summer (P <0.05) but were not significantly higher during autumn than during summer (P >0.05). LIMITATIONS, REASONS FOR CAUTION: This study was not performed to analyze the effect of lifestyle habits, such as alcohol consumption and cigarette smoking, on the acceptance rate of potential sperm donors. WIDER IMPLICATIONS OF THE FINDINGS: Only a small proportion of potential sperm donors were accepted in this anonymous sperm donor program. New strategies for sperm donor recruitment may be required to improve the acceptance rate. In the future, we may have to target potential sperm donors who are aged ≤ 35 years and who received higher education in order to improve the acceptance rate. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Joint Construction Project of Henan Medical Science and Technology Research Plan under grant number LHGJ20190389. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Relationship Among Traditional Semen Parameters, Sperm DNA Fragmentation, and Unexplained Recurrent Miscarriage: A Systematic Review and Meta-Analysis.

Several studies have explored the relationship among traditional semen parameters, sperm DNA fragmentation (SDF), and unexplained recurrent miscarriage (RM); however, the findings remain controversial. Hence, we conducted a meta-analysis to explore the relationship among traditional semen parameters, SDF, and unexplained RM. Multiple databases, including PubMed, Google Scholar, MEDLINE, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI), were searched to identify relevant publications. From the eligible publications, data were extracted independently by two researchers. A total of 280 publications were identified using the search strategy. According to the inclusion/exclusion criteria, 19 publications were eligible. A total of 1182 couples with unexplained RM and 1231 couples without RM were included in this meta-analysis to assess the relationship among traditional semen parameters, SDF, and unexplained RM. Our results showed that couples with unexplained RM had significantly increased levels of SDF and significantly decreased levels of total motility and progressive motility compared with couples without RM, although significant differences were not observed in the semen volume, sperm concentration, and total sperm count between couples with and without RM. The SDF assay may be considered for inclusion in evaluations of couples with unexplained RM.

The association of γδ-T cells with bronchopulmonary dysplasia in premature infants.

BACKGROUND: As the survival rate of premature infants increases, the incidence of bronchopulmonary dysplasia (BPD), a chronic complication of premature infants, is also higher than before. The pathogenesis of BPD is complicated, and immune imbalance and inflammatory response may play important roles in it. OBJECTIVE: To investigate the correlation between lymphocyte subsets in peripheral blood, especially γδ-T cells, and BPD of preterm infants. MATERIALS AND METHOD: The study was carried out with the peripheral blood of premature infants (GA < 32 weeks, BW < 1500 g), which were collected at 24 h or 3-4 weeks after birth. The infants were divided into non-BPD groups and BPD groups that were classified as mild or moderate and severe in preterm infants based on the magnitude of respiratory support at 28 days age and 36 weeks postmenstrual age. The γδ-T, CD3+, CD4+, CD8+ and total lymphocyte subsets in peripheral blood were detected by flow cytometry. RESULTS: The percentages of T lymphocyte subsets in peripheral blood were not different between BPD and non-BPD within 24 h after birth. And no significant difference was found in T lymphocyte subsets among neonates with BPD of different severities. However, the infants who developed BPD had a significant increase in γδ-T cells compared to non-BPD ones within 3-4 weeks after birth. CONCLUSIONS: It seems that γδ-T cells in peripheral blood are correlated with BPD. However, the causality of BPD and various lymphocytes remains unclear, which need to be further studied.

Serum anion gap at admission predicts all-cause mortality in critically ill patients with cerebral infarction: evidence from the MIMIC-III database.

BACKGROUND: Recent studies reported that serum anion gap could be regarded as a prognostic biomarker for patients admitted to intensive care units. However, the association between AG and mortality in cerebral infarction patients remained largely unknown. METHODS: Relevant clinical data were collected from Medical Information Mart for Intensive Care III. Patients were divided into three groups according to tertiles of AG. Kaplan-Meier curve and Cox proportional hazards models were used to evaluate the association between AG levels and all-cause mortality. Subgroup analyses were performed to verify the predictive role of AG on mortality. RESULTS: Kaplan-Meier analysis showed that patients with higher AG had shorter survival time. Cox regression model indicated high AG as an independent risk factor of 30-day, 60-day and 180-day all-cause mortality (30-day: HR = 2.45, 95% CI = 1.21-4.97, 60-day: HR = 2.04, 95% CI = 1.07-3.89, and 180-day: HR = 1.85, 95% CI = 1.02-3.36). However, no significance was observed between AG and 365-day all-cause mortality (HR = 1.56, 95% CI = 0.87-2.78). CONCLUSIONS: High AG was associated with increased risk of all-cause mortality, and AG could be an independent short-term prognostic factor for cerebral infarction.