Safety and efficacy of GLP-1 and glucagon receptor dual agonist for the treatment of type 2 diabetes and obesity: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This study aimed to investigate the effects of randomized, placebo-controlled trials involving the GLP-1 and glucagon receptor dual agonists, mazdutide, and cotadutide, on glycaemic control and body weight changes in individuals with type 2 diabetes mellitus (T2DM), obesity, or both. METHODS: We conducted searches in Medline, PubMed, Scopus, the Cochrane database, and Web of Science up to March 5, 2024. The primary outcomes assessed were changes in HbA1c level and percentage changes in body weight from baseline (CFB). RESULTS: Eleven studies and four unpublished trials were included. The pooled meta-analysis revealed a significant reduction in HbA1c (MD = -0.63%; 95% CI = [-0.82, -0.44]; P < 0.00001), fasting plasma glucose (MD = -1.71 mmol/L; 95% CI = [-2.31, -1.10]; P < 0.00001), and percentage change in body weight (MD = -4.16%; 95% CI = [-5.41, -2.92]; P < 0.00001). Safety analysis revealed no significant change in serious adverse events (OR = 1.03; 95% CI = [0.61, 1.75]; P = 0.91), but there were significantly higher odds of treatment-emergent adverse events (OR = 2.52; 95% CI = [1.92, 3.30]; P < 0.00001) and vomiting (OR = 6.05; 95% CI = [3.52, 10.40]; P < 0.00001). CONCLUSION: These results suggest that mazdutide and cotadutide are effective for glycaemic control and weight reduction in individuals with T2DM, obesity, or both.

The effect of COVID-19 vaccine to the Omicron variant in children and adolescents: a systematic review and meta-analysis.

Background: Omicron (B.1.1.529), a variant of SARS-CoV-2, has emerged as a dominant strain in COVID-19 pandemic. This development has raised concerns about the effectiveness of vaccination to Omicron, particularly in the context of children and adolescents. Our study evaluated the efficacy of different COVID-19 vaccination regimens in children and adolescents during the Omicron epidemic phase. Methods: We searched PubMed, Cochrane, Web of Science, and Embase electronic databases for studies published through March 2023 on the association between COVID-19 vaccination and vaccine effectiveness (VE) against SARS-CoV-2 infection in children and adolescents at the Omicron variant period. The effectiveness outcomes included mild COVID-19 and severe COVID-19. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was prospectively registered in PROSPERO (CRD42023390481). Results: A total of 33 studies involving 16,532,536 children were included in the analysis. First, in children and adolescents aged 0-19 years, the overall VE of the COVID-19 vaccine is 45% (95% confidence interval [CI]: 40 to 50%). Subgroup analysis of VE during Omicron epidemic phase for different dosage regimens demonstrated that the VE was 50% (95% CI: 44 to 55%) for the 2-dose vaccination and 61% (95% CI: 45 to 73%) for the booster vaccination. Upon further analysis of different effectiveness outcomes during the 2-dose vaccination showed that the VE was 41% (95% CI: 35 to 47%) against mild COVID-19 and 71% (95% CI: 60 to 79%) against severe COVID-19. In addition, VE exhibited a gradual decrease over time, with the significant decline in the efficacy of Omicron for infection before and after 90 days following the 2-dose vaccination, registering 54% (95% CI: 48 to 59%) and 34% (95% CI: 21 to 56%), respectively. Conclusion: During the Omicron variant epidemic, the vaccine provided protection against SARS-CoV-2 infection in children and adolescents aged 0-19 years. Two doses of vaccination can provide effective protection severe COVID-19, with booster vaccination additionally enhancing VE.

Novel variations in TENT5D lead to teratozoospermia in infertile patients.

PURPOSE: Teratozoospermia is the main pathogenic factor of male infertility. However, the genetic etiology of teratozoospermia is largely unknown. This study aims to clarify the relationship between novel variations in TENT5D and teratozoospermia in infertile patients. MATERIALS AND METHODS: Two infertile patients were enrolled. Routine semen analysis of patients and normal controls was conducted with the WHO guidelines. Whole-exome sequencing (WES) was conducted to identify pathogenic variants in the two patients. Morphology and ultrastructure analysis of spermatozoa in the two patients was determined by Papanicolaou staining, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The functional effect of the identified variants was analyzed by immunofluorescence staining and western blotting. The expression of TENT5D in different germ cells was detected by immunofluorescence staining. RESULTS: Two new hemizygous variations, c.101C > T (p.P34L) and c.125A > T (p.D42V), in TENT5D were detected in two patients with male infertility. Morphology analysis showed abnormalities in spermatozoa morphology in the two patients, including multiple heads, headless, multiple tails, coiled, and/or bent flagella. Ultrastructure analysis showed that most of the spermatozoa exhibited missing or irregularly arranged '9+2' structures. Further functional experiments confirmed the abrogated TENT5D protein expression in patients. In addition, both p.P34L and p.D42V substitutions resulted in a conformational change of the TENT5D protein. We precisely analyzed the subcellular localization of TENT5D in germ cells in humans and mice. And we found that TENT5D was predominantly detected in the head and flagellum of elongating spermatids and epididymal spermatozoa. CONCLUSIONS: Our results showed further evidence of a relationship between TENT5D mutation and human male infertility, providing new genetic insight for use in the diagnosis and treatment of male infertility.

Associations between extreme temperature exposure and hypertensive disorders in pregnancy: a systematic review and meta-analysis.

BACKGROUND: Hypertensive disorders in pregnancy (HDP) are a major cause of maternal mortality and morbidity. Recent studies indicated that pregnant women are the most vulnerable populations to ambient temperature influences, but it affected HDP with inconsistent conclusions. Our objective is to systematically review whether extreme temperature exposure is associated with a changed risk for HDP. METHOD: We searched PubMed, EMBASE, Web of Science and Cochrane Library databases. We included cohort or case control studies examining the association between extreme temperature exposure before or during pregnancy and HDP. Heat sources such as saunas and hot baths were excluded. We pooled the odds ratio (OR) to assess the association between extreme temperature exposure and preeclampsia or eclampsia. RESULTS: Fifteen studies involving 4,481,888 patients were included. Five studies were included in the meta-analysis. The overall result demonstrated that in the first half of pregnancy, heat exposure increases the risk of developing preeclampsia or eclampsia and gestational hypertension, and cold exposure decreases the risk. The meta-analysis revealed that during the first half of pregnancy, heat exposure increased the risk of preeclampsia or eclampsia (OR 1.54, 95% confidence interval (CI): 1.10, 2.15), whereas cold exposure decreased the risk (OR 0.90, 95% CI: 0.84, 0.97). CONCLUSION: The ambient temperature is an important determinant for the development of HDP, especially for preeclampsia or eclampsia. The effects of extreme temperatures may be bidirectional during the different trimesters of pregnancy, which should be evaluated by future studies. This review provided hints of temperature regulation in HDP administration.

Identification of CFAP52 as a novel diagnostic target of male infertility with defects of sperm head-tail connection and flagella development.

Male infertility is a worldwide population health concern. Asthenoteratozoospermia is a common cause of male infertility, but its etiology remains incompletely understood. No evidence indicates the relevance of CFAP52 mutations to human male infertility. Our whole-exome sequencing identified compound heterozygous mutations in CFAP52 recessively cosegregating with male infertility status in a non-consanguineous Chinese family. Spermatozoa of CFAP52-mutant patient mainly exhibited abnormal head-tail connection and deformed flagella. Cfap52-knockout mice resembled the human infertile phenotype, showing a mixed acephalic spermatozoa syndrome (ASS) and multiple morphological abnormalities of the sperm flagella (MMAF) phenotype. The ultrastructural analyses further revealed a failure of connecting piece formation and a serious disorder of '9+2' axoneme structure. CFAP52 interacts with a head-tail coupling regulator SPATA6 and is essential for its stability. Expression of microtubule inner proteins and radial spoke proteins were reduced after the CFAP52 deficiency. Moreover, CFAP52-associated male infertility in humans and mice could be overcome by intracytoplasmic sperm injection (ICSI). The study reveals a prominent role for CFAP52 in sperm development, suggesting that CFAP52 might be a novel diagnostic target for male infertility with defects of sperm head-tail connection and flagella development.

Cumulative evidence of the genetic association between SP-B C1580T polymorphisms and risk of neonatal respiratory distress syndrome.

Objective: Surfactant protein SP-B, an important protein in pulmonary surfactant, is required for the stabilization of surfactant films in the lung and maintenance of postnatal lung function. Although the association between SP-B polymorphisms and the risk of neonatal respiratory distress syndrome (RDS) has been evaluated, the results have been inconsistent. We investigated the association between SP-B polymorphisms and the risk of neonatal RDS.Methods: Relevant studies were systematically searched in PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) electronic databases until June 2022. Data were collected independently by two reviewers and converted to odds ratios (ORs) with 95% confidence intervals (CIs). Meta-analysis, subgroup analysis, sensitivity analysis, and publication bias assessment were performed using Stata 12.1 software and Review Manager 5.3.Results: Fourteen studies were included. SP-B C1580T polymorphism was significantly associated with neonatal RDS in five genetic models (T vs. C: OR = 0.70, 95% CI 0.57-0.86, I2 = 78%; TT vs. CC: OR = 0.63, 95% CI 0.53-0.86, I2 = 39%; CT vs. CC: OR = 0.65, 95% CI 0.50-0.84, I2 = 54%; TT + CT vs. CC: OR = 0.62, 95% CI 0.49-0.78, I2 = 59%; TT vs. CC + CT: OR = 0.78, 95% CI 0.67-0.91, I2 = 43%). The CT and TT genotypes may decrease the risk of RDS in neonates. Subgroup analyses revealed that the association of SP-B C1580T polymorphism with neonatal RDS was stable, independent of preterm birth and Hardy-Weinberg equilibrium. In addition, the Han Chinese were more likely to be affected by SP-B C1580T polymorphisms than Caucasians and Finnish.Conclusions: Our findings suggest that SP-B C1580T polymorphism may be a protective factor against neonatal RDS.

Timing of Intravenous Prophylactic Antibiotic Agents for Cesarean Delivery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Prophylactic antibiotic administration has been used to reduce infectious morbidities in cesarean deliveries. However, no consensus on the timing has been reached. We performed this review to compare maternal and neonatal infectious morbidities of antibiotic administration before skin incision and after cord clamping. Methods: PubMed, EMBASE, MEDLINE, Cochrane Library, and Web of Science databases were searched. Only randomized controlled trials (RCTs) comparing the use of antibiotic agents pre-operatively and after cord clamping were included. Characteristics and results of the included studies were extracted, and risks of bias were assessed. A fixed-effect model was applied to estimate the relative risks (RRs) for outcomes. Results: Sixteen RCTs, including 8,027 women and 7,131 newborns, met the selection criteria. Pre-operative administration of antibiotic agents was associated with a reduction in the risk of endometritis (RR, 0.52; 95% confidence interval [CI], 0.37-0.72) and wound complications (RR, 0.54; 95% CI, 0.42-0.69), compared with administration after cord clamping. No differences were observed in the rate of febrile illness (RR, 0.79; 95% CI, 0.59-1.05), urinary tract infection (RR, 0.92; 95% CI, 0.64-1.32), neonatal intensive care unit (NICU) admission (RR, 0.94; 95% CI, 0.79-1.12), and neonatal sepsis (RR, 0.83; 95% CI, 0.61-1.14). Conclusions: The present study showed that prophylactic antibiotic agent administration before skin incision can reduce the risk of endometritis and wound complications while not increasing that of NICU admission and neonatal sepsis compared with administration after cord clamping.

Identification of biallelic variations of CEP70 in patients with male infertility.

Introduction: Male infertility is a severe health issue caused by complex and multifactorial pathological conditions. Genetic factors are a major cause of male infertility. CEP70, a centrosomal protein, has been reported to play an important role in male reproduction in mice. However, the role of CEP70 in human male infertility is limited. Methods: Whole exome sequencing and Sanger sequencing were used to identify the genetic cause of the infertile patients. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy were further conducted to explore morphological and ultrastructural defects in spermatozoa from the patient. Immunofluorescence staining was used to detect the pathogenicity of the identified variants and the particular expression of CEP70 in testis. Results: In this study, we identified biallelic mutations of CEP70 in two unrelated infertile male individuals with oligoasthenoteratozoospermia that followed a recessive inheritance pattern. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy showed that morphological and ultrastructural defects in the acrosome and flagellum of sperm from the patient in a pattern strikingly similar to that in Cep70-/- male mice. The results of immunofluorescence staining suggested that CEP70 was normally expressed in the acrosome and flagellum of control sperm but was hardly detected in the sperm of patient carrying CEP70 variation. We also explored the particular expression pattern of CEP70 during spermatogenesis in humans and mice. Conclusions: Biallelic mutations of CEP70 might be a novel genetic cause of human male infertility, which could potentially serve as a basis for genetic counseling and diagnosis of male infertility.

Association between low ambient temperature during pregnancy and adverse birth outcomes: A systematic review and meta-analysis.

BACKGROUND: Extreme temperature events, including extreme cold, are becoming more frequent worldwide, which might be harmful to pregnant women and cause adverse birth outcomes. We aimed to investigate the association between exposure to low ambient temperature in pregnant women and adverse birth outcomes, such as preterm birth, low birth weight, and stillbirth, and to summarize the evidence herein. METHODS: Relevant studies were searched in PubMed, Cochrane, and Embase electronic databases until November 2021. Studies involving low ambient temperature, preterm birth, birth weight, and stillbirth were included. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses were followed to conduct this study risk of bias and methods for data synthesis. RESULTS: A total of 34 studies were included. First, pregnant women exposed to low ambient temperature had an increased risk of preterm birth (risk ratio [RR] 1.08; 95% confidence interval [CI] 1.04-1.13). Subgroup analyses revealed that exposure during late pregnancy was more likely to induce preterm birth. In addition, only pregnant women exposed to <1st percentile of the mean temperature suffered increased risk of preterm birth. Moreover, pregnant women living in medium or hot areas were more prone to have preterm births than those in cold areas when exposed to low ambient temperatures. Asians and Blacks were more susceptible to low ambient temperatures than Caucasians. Second, pregnant women exposed to low ambient temperature had an increased risk of low birth weight (RR 1.07; 95% CI 1.03-1.12). Third, pregnant women had an increased risk of stillbirth while exposed to low ambient temperature during the entire pregnancy (RR 4.63; 95% CI 3.99-5.38). CONCLUSIONS: Exposure to low ambient temperature during pregnancy increases the risk of adverse birth outcomes. Pregnant women should avoid exposure to extremely low ambient temperature (<1st percentile of the mean temperature), especially in their late pregnancy. This study could provide clues for preventing adverse outcomes from meteorological factors. REGISTRATION: No. CRD42021259776 at PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ).

Diagnostic performance of adenosine deaminase for abdominal tuberculosis: A systematic review and meta-analysis.

Background and aim: Abdominal tuberculosis (TB) is a common type of extrapulmonary TB with an insidious onset and non-specific symptoms. Adenosine deaminase (ADA) levels increase rapidly in the early stages of abdominal TB. However, it remains unclear whether ADA serves as a diagnostic marker for abdominal TB. Methods: We performed a systematic literature search for relevant articles published in PubMed, Web of Science, Cochrane Library, and Embase up to April 2022. First, we used the Quality Assessment of Diagnostic Accuracy Studies tool-2 (QUADAS-2), to evaluate the quality of the included articles. Bivariate and hierarchical summary receiver operating characteristic (HSROC) models were then utilized to analyze pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC). In addition, we explored a subgroup analysis for potential heterogeneity and publication bias among the included literature. Results: Twenty-four articles (3,044 participants, 3,044 samples) which met the eligibility criteria were included in this study. The pooled sensitivity and specificity of ADA for abdominal TB detection were 93% [95% confidence interval (CI): 0.89-0.95] and 95% (95% CI: 0.93-0.96), respectively. PLR and NLR were 18.6 (95% CI: 14.0-24.6) and 0.08 (95% CI: 0.05-0.12), respectively. DOR and AUROC were 236 (95% CI: 134-415) and 0.98 (95% CI: 0.96-0.99), respectively. Furthermore, no heterogeneity or publication bias was found. Conclusions: Our meta-analysis found ADA to be of excellent diagnostic value for abdominal TB and could be used as an auxiliary diagnostic tool. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022297931.

Critical Roles of the Circadian Transcription Factor BMAL1 in Reproductive Endocrinology and Fertility.

Brain and muscle aryl-hydrocarbon receptor nuclear translocator like protein1 (BMAL1), a core component of circadian oscillation, is involved in many physiological activities. Increasing evidence has demonstrated the essential role of BMAL1 in reproductive physiology. For instance, BMAL1-knockout (KO) mice were infertile, with impaired reproductive organs and gametes. Additionally, in BMAL1-KO mice, hormone secretion and signaling of hypothalamus-pituitary-gonadal (H-P-G) hormones were also disrupted, indicating that H-P-G axis was impaired in BMAL1-KO mice. Moreover, both BMAL1-KO mice and BMAL1-knockdown by small interfering RNA (siRNA) in vitro cultured steroidogenic cells showed that BMAL1 was associated with gonadal steroidogenesis and expression of related genes. Importantly, BMAL1 also participates in pathogenesis of human reproductive diseases. In this review, we elaborate on the impaired reproduction of BMAL1-KO mice including the reproductive organs, reproductive endocrine hormones, and reproductive processes, highlighting the vital role of BMAL1 in fertility and reproductive endocrinology.