Peptidomic profile of human milk as influenced by fortification with different protein sources: An in vitro dynamic digestion simulation.

Fortification of human milk (HM) is often necessary to meet the nutritional requirements of preterm infants. The present experiment aimed to establish whether the supplementation of HM with either an experimental donkey milk-derived fortifier containing whole donkey milk proteins, or with a commercial bovine milk-derived fortifier containing hydrolyzed bovine whey proteins, affects peptide release differently during digestion. The experiment was conducted using an in vitro dynamic system designed to simulate the preterm infant's digestion followed by digesta analysis by means of LC-MS-MS. The different fortifiers did not appear to influence the cumulative intensity of HM peptides. Fortification had a differential impact on the release of either donkey or bovine bioactive peptides. Donkey milk peptides showed antioxidant/ACE inhibitory activities, while bovine peptides showed opioid, dipeptil- and propyl endo- peptidase inhibitory and antimicrobial activity. A slight delay in peptide release from human lactoferrin and α-lactalbumin was observed when HM was supplemented with donkey milk-derived fortifier.

Exposición a temperaturas extremas y su efecto en la gestación en un departamento de Colombia / Exposure to extreme temperatures and its effect on pregnancy in a department of Colombia

Introducción: Diversas investigaciones han establecido la relación entre temperatura y duración del embarazo, la exposición a temperaturas altas durante el embarazo plantea interrogantes en especial el papel que esta juega frente a los partos prematuros y partos de bajo peso, es indispensable determinar si las temperaturas altas o bajas tienen un comportamiento protector o de riesgo sobre el feto durante la gestación en regiones tropicales. Objetivo: describir la relación entre la exposición a temperaturas altas y bajas durante el embarazo y su efecto en la edad gestacional y peso al momento del parto en los recién nacidos del departamento del Guaviare-Colombia. Metodología: Estudio tipo observacional, analítico, retrospectivo de corte transversal que busco determinar la relación entre exposición a temperaturas altas y bajas durante el embarazo y su efecto en la edad gestacional y peso al momento del parto en los recién nacidos, el universo estuvo conformado por 10.137 nacidos vivos, de los cuales 9.932 cumplieron los criterios de inclusión. Se determinó Odds Ratio para estimar la asociación entre las variables. Resultados: Dentro de la semana de retraso 3 el estar expuesto a temperaturas máximas percentil 90 es un factor protector para la ganancia ponderal de peso OR < 1, la exposición a temperaturas mínimas percentil 10 se asoció como factor protector para el parto prematuro en la semana de retraso 1 y 2 OR < 1.Conclusión: A pesar del beneficio de las altas y bajas temperaturas durante el embarazo en la ganancia ponderal de peso y disminución del parto prematuro, es recomendable prevenir la exposición a temperaturas extremas durante el periodo de gestación[AU]

Introduction: Various investigations have established the relationship between temperature and duration of pregnancy. Exposure to high temperatures during pregnancy raises questions, especially the role it plays in premature births and low-weight births. It is essential to determine whether high temperatures or low have a protective or risky behavior on the fetus during pregnancy in tropical regions.Objective: to describe the relationship between exposure to high and low temperatures during pregnancy and its effect on gestational age and weight at the time of delivery in newborns in the department of Guaviare-Colombia.Methodology:Observational, analytical, retrospective cross-sectional study that sought to determine the relationship between exposure to high and low temperatures during pregnancy and its effect on gestational age and weight at the time of delivery in newborns. The universe was made up of 10,137 births. alive, of which 9,932 met the inclusion criteria. Odds Ratio was determined to estimate the association between the variables.Results:Within the 3rd week of delay, being exposed to maximum temperatures at the 90th percentile is a protective factor for weight gain OR < 1, exposure to minimum temperatures at the 10th percentile was associated as a protective factor for premature birth in the week. of delay 1 and 2 OR < 1. Conclusion: Despite the benefit of high and low temperatures during pregnancy in weight gain and reduction in premature birth, it is advisable to prevent exposure to extreme temperatures during the gestation period[AU]

Introdução: Várias investigações estabeleceram a relação entre temperatura e duração da gravidez. A exposição a altas temperaturas durante a gravidez levanta questões, especialmente o papel que desempenha nos partos prematuros e nos nascimentos de baixo peso. É essencial determinar se as temperaturas altas ou baixas têm um comportamento protetor ou de risco para o feto durante a gravidez em regiões tropicais. Objetivo:descrever a relação entre a exposição a altas e baixas temperaturas durante a gravidez e seu efeito na idade gestacional e no peso no momento do parto em recém-nascidos no departamento de Guaviare-Colômbia. Metodologia: Estudo observacional, analítico, retrospectivo e transversal que buscou determinar a relação entre a exposição a altas e baixas temperaturas durante a gravidez e seu efeito na idade gestacional e no peso no momento do parto em recém-nascidos. O universo foi composto por 10.137 nascimentos. vivos, dos quais 9.932 preencheram os critérios de inclusão. O Odds Ratio foi determinado para estimar a associação entre as variáveis. Resultados:Na 3ª semana de atraso, a exposição a temperaturas máximas no percentil 90 é fator de proteção para ganho de peso OR < 1, a exposição a temperaturas mínimas no percentil 10 foi associada como fator de proteção para parto prematuro na semana. de atraso 1 e 2 OR < 1.Conclusão:Apesar do benefício das altas e baixas temperaturas durante a gravidez no ganho de peso e redução do parto prematuro, é aconselhável evitar a exposição a temperaturas extremas durante o período de gestação[AU]

Pacing-facilitated Short-long-short Sequences Leading to Ventricular Tachyarrhythmias: A Brief Report.

Pacing-induced recurrent short-long-short sequences constitute an important yet overlooked mechanism for triggering ventricular tachyarrhythmias in patients with cardiovascular implantable electric devices. A careful and thorough retrospective analysis of patients' electrograms allows for a timely diagnosis with appropriate management.

EVALUATION OF OXIDATIVE STRESS MARKERS IN GIRLS WITH PREMATURE THELARCHE AND PRECOCIOUS PUBERTY.

Context: Oxidative products take part in various physiological processes and overproduction of oxidative products is involved in the etiology of many diseases. Objectives: We aimed to evaluate thiol-disulfide homeostasis (TDH); one of the oxidative stress parameters, in girls with premature thelarche (PT) and precocious puberty (PP). Design: This case-control study was conducted between January 2022 and July 2022. Subjects and Methods: TDH parameters, involving native thiol (NT), disulfide, and total thiol (TT), were evaluated in 39 girls with PT, 41 girls with PP and 46 healthy prepubertal girls. The correlations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) levels with the TDH parameters were determined and ROC curve analysis was performed. Results: NT, TT and NT/TT ratio were higher in the PT and PP groups compared to the control group (p<0.01). Disulfide/NT ratio and disulfide/TT ratio were lower in the PT and PP groups compared to the control group (p<0.05). All the TDH values did not statistically differ between the PP and PT group (p>0.05). There was a positive correlation between LH level, FSH level, and NT level, TT level, NT/TT ratio. The best parameter to discriminate PT or PT and control groups were NT and TT (p<0.01). Conclusion: TDH is altered in girls with PT and PP. NT and TT levels can be useful to discriminate prepubertal girls with lipomastia and girls with PP and PT in clinical practice. Further studies on larger cohorts of patients are required to clarify our results.

Analysis of zinc and copper levels in very low birth weight infants using human milk additives: phase 1 trial findings.

OBJECTIVE: The aim of this study was to assess whether the micronutrients zinc and copper, provided by human milk additives, are sufficient for very low birth weight preterm infants. METHOD: A phase 1 randomized double-blind controlled trial was conducted with very low birth weight preterm infants. This is a secondary analysis of copper and zinc. Sixty-six newborns were part of the initial sample, with forty participating and reaching the final stage of the study. Inclusion criteria were: gestational age less than 37 weeks, birth weight greater than or equal to 750 g and less than or equal to 1500 g, small or appropriate for gestational age, exclusively receiving human milk at a volume greater than or equal to 100 mL per kilogram per day, and hemodynamically stable. Participants were randomly assigned to two groups: intervention, Lioneo(received human milk with additive based on lyophilized human milk), n = 20, and control, HMCA (received human milk with commercial additive based on cow's milk protein), n = 20, and their serum levels of zinc and copper were measured on the first and twenty-second days. RESULTS: There was a reduction in intragroup zinc serum levels from the first to the twenty-second day of the study (p < 0.01). There was no intergroup difference. No difference was found in serum copper levels. CONCLUSION: Human milk additives were not sufficient to maintain adequate zinc serum levels in very low birth weight newborns. It was not possible to affirm whether human milk additives were sufficient to maintain adequate serum copper levels in the studied sample. UTN: U1111-1220-0550.

Burden of biliary tract carcinoma in China (1990-2021): Findings from the 2021 Global Burden of Disease Study.

Biliary tract carcinoma (BTC) is a group of malignant tumors that originate in the digestive system and occurs with a high incidence in China. Few consistent and comparable assessments of BTC disease burden have been conducted at national or subnational levels, and little is known about the demographic, temporal, and geographic patterns of epidemiological characteristics and disease burden of BTC in China. The incidence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs) due to premature death and years lived with disability (YLDs) of BTC were comprehensively examined by age, sex, and calendar year in the Chinese population, using the methodological framework and analytical strategies used for the 2021 Global Burden of Disease study. All-age incidence increased from 17,077 to 51,720 between 1990 and 2021, and the age-standardized incidence rate rose by 13.62%; all-age deaths increased from 17,251 to 37,833, but the age-standardized mortality rate fell by nearly one-fifth. The DALYs rose by 89.57% while the age-standardized DALY rate fell by 23.24%. Variations of the tendencies in BTC burden were found between sexes and age groups. Data for each provincial region indicate that coastal eastern provincial regions have higher incidence and YLD levels, whereas northern provincial regions have higher mortality, DALY, and YLL levels. The proportions of DALYs attributable to high body mass index (BMI) illustrate the growing attribution obesity has made, and high BMI usually puts more burden on northern provincial regions. These results provide evidence to support precise, targeted, and customed public health strategies aimed at enhancing biliary tract health among the Chinese population.

Chronic kidney disease associated with extremely premature birth and extremely low birth weight may progress through the burden of growth.

Chronic kidney disease associated with low birth weight and/or premature birth (L/P-CKD) in infants may result from a decreased number of nephrons at birth. These infants may develop acute kidney injury due to exposure to nephrotoxic substances or other events during nephrogenesis in early infancy. Nonetheless, L/P-CKD progression remains unclear. We present three cases of L/P-CKD diagnosed after neonatal intensive care unit (NICU) discharge. Three patients were born extremely prematurely (gestational age, 24-26 weeks) with extremely low birth weight (606-906 g). They were admitted to the NICU (117-311 days) anad received several nephrotoxic medications during the early postnatal period. They showed elevated serum creatinine levels at 4 weeks after birth, which decreased to normal levels at NICU discharge. Proteinuria was first detected during adolescence (10-15 years) on annual school urine screening, with a remarkable increase in their height (18 - 50.8 cm), without known episodes of urinary tract infection, dehydration, lifestyle-related issues, such as excessive salt/protein intake, and extreme lack of exercise that might have caused kidney damage. Their kidneys were smaller than normal on renal ultrasonography. Open renal biopsy findings indicated glomerulomegaly and perihilar glomerulosclerosis in two of the three patients, suggesting glomerular hypertension. The remarkable differences between the body height before CKD and the timing of diagnosis of CKD could contribute to the progress of CKD. Long-term follow-up of low birth weight and extremely premature infants, from NICU discharge until adulthood, should be established.

Probiotics vs. Placebo: Preventing Necrotizing Enterocolitis in a Premature Infant.

BACKGROUND: Necrotizing enterocolitis (NEC) is a severe gastrointestinal condition primarily affecting preterm newborns, leading to significant morbidity and mortality. OBJECTIVE: This prospective cohort study aimed to evaluate the effectiveness of probiotics in preventing NEC in premature infants. Secondary objectives included assessing the impact on mortality, late-onset sepsis, duration of hospital stay, and weight gain. METHODS: The study was conducted at Lady Reading Hospital Medical Teaching Institute, Peshawar, from April 1, 2023, to March 31, 2024, involving 102 preterm infants. Participants were randomly assigned to receive daily oral probiotics (Lactobacillus and Bifidobacterium species) or a placebo. RESULTS: The incidence of NEC was significantly lower in the probiotic group (7.8%) compared to the placebo group (21.6%; p = 0.04). The probiotic group also showed significant reductions in late-onset sepsis (13.7% vs. 29.4%; p = 0.03), shorter hospital stays (42.5 vs. 48.1 days; p = 0.02), and greater weight gain (15.3 vs. 13.4 grams/day; p = 0.01). CONCLUSION: These findings support the integration of probiotics into neonatal care, particularly in resource-limited settings.

Premature Graying of Hair: A Comprehensive Review and Recent Insights.

Background: Hair symbolizes well-being and self-expression, with graying occurring naturally among different racial groups at varying ages. Premature graying has psychological and societal impacts, influencing self-esteem and quality of life. Gray hair usually advances gradually and is permanent, with occasional reports of natural repigmentation. Premature graying of hair (PMGH) results from a complex interplay of genetic, environmental, and cellular factors. Materials and Methods: Studies exploring links between gray hair and conditions such as osteopenia, hearing loss, smoking, obesity, dyslipidemia, and cardiovascular disease have yielded mixed results. Despite continuous research into the causes of gray hair, effective, evidence-based treatments are lacking and still need to be improved. Conclusion: Herein, we reviewed the causes, mechanisms, risk factors, psychosocial effects, and emerging therapies for PMGH.

Cognitive and motor improvement by tummy time practice in preemies from low-income settings: a randomized clinical trial.

Introduction: Early intervention and parental education for preemies are limited in some low-income countries. Thus, this study aimed to assess whether daily tummy time (TT) associated with usual care (UC) enhances motor and cognitive development in preemies from low-income countries. The main and secondary aim was to assess prone head elevation (PHE) and motor and cognitive functions, respectively. Methods: Thirty-one preemies with a mean gestational age at birth of 33.3 ± 1.6 weeks and weighing <2,500 g were included and 18 completed all assessments. Parents from the TT group were asked to perform TT with their preemies for at least 20 min during daily activities and playtime. Motor and cognitive functions were assessed by a blinded examiner using the motor and cognitive composite scores of Bayley-III after two and four months of corrected age. PHE was given by the angle from the tragus of the ear to the supporting surface of the infant; measurements were obtained using the Kinovea® software at baseline, after two, three, and four months of corrected age. Results: The Bayley-III motor composite score of the TT group was higher than the UC group after two and four months of corrected age. The PHE angle increased over time but did not differ between groups. Discussion: Nevertheless, TT expanded the perspective of preemies to explore their bodies and environment, favoring the stimuli for motor and cognitive patterns. The loss of participants (31%) was one of the limitations of the study, illustrating the challenge of providing continued early interventions to preemies from low-income countries. In this sense, TT practice is a home intervention that may improve motor and cognitive function of preemies immediately after hospital discharge.

Dofetilide for the treatment of premature ventricular complexes and ventricular tachycardia in patients with structural heart disease.

BACKGROUND: Dofetilide is a class III antiarrhythmic agent approved for the treatment of atrial fibrillation and atrial flutter. Given the efficacy of other class III agents, it has been used off-label for the treatment of premature ventricular complexes (PVCs) and ventricular tachycardias (VTs). OBJECTIVE: The purpose of this study was to determine the efficacy and safety of dofetilide for ventricular arrythmias (VAs). METHODS: In this retrospective cohort study, 81 patients (59 men; age = 60 ± 14 years; LVEF = 0.34 ± 0.16) were admitted for dofetilide initiation to treat PVCs (29), VTs (42) or both (10). A ≥ 80% decrease in PVC burden was defined as a satisfactory response. An ICD was present in 72 patients (89%). Another antiarrhythmic was previously used in 50 patients (62%). Prior catheter ablation had been performed in 33 patients (41%). RESULTS: During intitiation, dofetilide was discontinued in 12 patients (15%) due to QT prolongation (8) and inefficacy to suppress VAs (4). Among the 32 patients with PVCs who successfully started dofetilide, the mean PVC burden decreased from 20 ± 10% to 8 ± 8% at a median follow-up of 2.6 months (p < .001). PVC burden was reduced by ≥80% in only 11/32 patients (34%). During 7 ± 1 years of follow-up, 41/69 patients (59%) continued to have VAs and received appropriate ICD therapies for monomorphic VTs (35) and polymorphic VT/VF (6) at a median of 8.0 (IQR 2.6-33.2) months. Dofetilide had to be discontinued in 50/69 patients (72%) due to inefficacy or intolerance. The composite outcome of VT/VF recurrence, heart transplantation, or death occurred in 6/12 patients (50%) without dofetilide and 49/69 patients (71%) with dofetilide. The event free survival was similar between patients treated with and without dofetilide (log-rank p = .55). CONCLUSIONS: Treatment with dofetilide was associated with a decrease in PVCs, however clinically significant suppression occurred in a minority of patients. Dofetilide failed to suppress the occurrence of VTs in a majority of patients.

Patent ductus arteriosus closure in small infants weighing less than 1500 g using KA micro plug: steps and tips.

BACKGROUND: Transcatheter patent ductus arteriosus closure in premature infants is gaining attention with rapidly growing experience. The KA micro plug device poses many favourable features for ductus arteriosus closure in premature infants. The study aimed to describe the technique and outcomes of a KA micro plug in closing the ductus arteriosus in premature infants weighing less than 1500 g. METHODS: This is a single-centre retrospective study in premature infants with patent ductus arteriosus weighing less than 1500 g who underwent off-label use of a KA micro plug at the Stead Family Children's Hospital from February 2022 to December 2023. RESULTS: Eighteen premature infants weighing less than 1500 g underwent attempted transcatheter ductus arteriosus closure using a KA micro plug device. Median weight, age, and corrected gestational age at the procedure were 943 g (682-1225), 26 days (9-79), and 28.5 weeks (25.6-32), respectively. The procedure was successful with complete closure achieved in all patients. No major haemodynamic instabilities were encountered. No catheterization-related complications were encountered. On a median follow-up of 10.9 months (0.1-19), all patients are alive with the device in a good position without residual shunt or abnormal findings. CONCLUSION: KA micro plug device for patent ductus arteriosus in infants weighing less than 1500 g is feasible, safe, and effective. We recommend that manufacturers of devices used to close the ductus arteriosus in small infants enhance both the devices and their delivery systems to simplify the procedure and mitigate the risk of haemodynamic instability.

Reproductive outcomes after antenatal corticosteroids: Secondary analysis of 50-year follow-up of the Auckland steroid randomized trial.

INTRODUCTION: Antenatal corticosteroids are widely used to prevent morbidity and mortality after preterm birth, but there are ongoing concerns about the possible risk of long-term adverse effects, including perturbation of endocrine systems, with potential implications for reproduction. A small number of animal studies have suggested possible adverse effects on reproduction after antenatal exposure to corticosteroids, but there is a paucity of human data. MATERIAL AND METHODS: This is a secondary cohort analysis of the 50-year follow-up of the Auckland Steroid Trial (1969-1974) comparing antenatal exposure to corticosteroids or placebo. Participants whose mothers took part in the placebo-controlled randomized trial of antenatal corticosteroids completed a questionnaire reporting reproductive outcomes at 50 years of age. The main outcome was at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks. Additional outcomes included a number of pregnancies or fathered pregnancies ≥20 weeks, outcomes relating to female reproductive lifespan (including age at menarche and menopause), and outcomes relating to their offspring (including birthweight and gestation). RESULTS: Of 917 eligible participants, 415 (45% of eligible) completed the questionnaire at a mean (SD) age of 49.3 (1.0) years. The proportion of participants who had experienced at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks was similar in betamethasone and placebo-exposed groups (163/217 [75%] vs. 136/190 [72%]; RR 1.08, (95% CI 0.95 to 1.22); p = 0.23). Participants exposed to betamethasone had a slightly higher number of pregnancies or fathered pregnancies ≥20 weeks compared to those exposed to placebo (mean 1.89 vs. 1.60; marginal mean difference 0.20, (95% CI 0.03-0.37); p = 0.03). Other outcomes, including female reproductive lifespan and offspring-related outcomes, were similar in both randomized groups. There were also no differences in any outcomes between those born preterm and those born at term. CONCLUSIONS: Antenatal exposure to corticosteroids appears to have no clinically important effect on reproductive outcomes to 50 years.

Exploring the impact of sexual positions on ejaculation: Insights from a survey study by the Andrology Working Group of the Society of Urological Surgery in Turkey.

BACKGROUND: Sexual position is one of the several aspects that affects ejaculation control, which is essential for sexual pleasure. Still little is known, nevertheless, about the connection between sexual positions and ejaculation duration. OBJECTIVE: To investigate the impact of various sexual positions on the duration of ejaculation and gain a deeper understanding of the elements that influence the ability to control ejaculation. METHOD: An online survey was carried out on a sample of 1904 heterosexual men between the ages of 18-65 years. Premature ejaculation (PE) diagnostic tool was used to define PE. Demographic, behavioral, and physiological traits that are linked to PE and non-PE groups were collected. The participants listed their preferred sexual positions and the ones they changed to during ejaculating. Also, analyses were performed between male/female active or deep/shallow thrust positions and PE status. RESULTS: Although there were no appreciable variations in age or circumcision between PE and non-PE groups, the age of first sexual experience was associated with PE status. Groups also varied in the number of weekly ejaculations, the duration of the favored ejaculations, and the characteristics of the erection. The most preferred sexual posture was the doggy style regardless of the group. When the non-PE group felt to ejaculate, they preferred to change the position significantly more than the PE group (74% vs 67.2%; p < 0.05). However, when participants felt ejaculate, non-PE participants tended to switch to shallow thrusting positions significantly more than PE participants, who preferred deeper positions (27.1% vs. 18%; p < 0.05). CONCLUSION: This study underlines the relevance of considering sexual positions in controlling PE. Modifying positions during sexual intercourse may offer a non-pharmacological therapeutic alternative for improving ejaculation control. Future studies in this field might help to create tailored PE treatment strategies.

MED23 depletion induces premature senescence in NSCLC cells by interacting with BCLAF1 and then suppressing NUPR1 expression.

Lung cancer is the leading cause of cancer death worldwide. 85 % of lung cancers are categorized by their histological types as a non-small cell lung cancer (NSCLC) subtype. While the MED23 subunit of the mediator complex has been implicated in lung cancer development, the precise underlying mechanism remains unclear. Our research indicates that elevated MED23 expression is linked to reduced overall survival rates in NSCLC. Depletion of MED23 triggers premature senescence in NSCLC cells. Furthermore, through co-IP and mass spectrometry analyses, we have identified BCLAF1 as a binding partner of MED23, with subsequent confirmation via PLA assays. Subsequently, NUPR1, a transcriptional cofactor known to induce premature senescence in lung cancer cells by disrupting autophagic processes, was validated as a downstream target of the MED23/BCLAF1 complex through RNA-seq and ChIP assays. Thus, the interaction between MED23 and BCLAF1 regulates NUPR1 expression, impacting autophagic flux and leading to premature senescence in NSCLC cells.

Nuclear sorting of short RNA polymerase II transcripts.

Mammalian genomes produce an abundance of short RNA. This is, to a large extent, due to the genome-wide and spurious activity of RNA polymerase II (RNAPII). However, it is also because the vast majority of initiating RNAPII, regardless of the transcribed DNA unit, terminates within a ∼3-kb early "pausing zone." Given that the resultant RNAs constitute both functional and non-functional species, their proper sorting is critical. One way to think about such quality control (QC) is that transcripts, from their first emergence, are relentlessly targeted by decay factors, which may only be avoided by engaging protective processing pathways. In a molecular materialization of this concept, recent progress has found that both "destructive" and "productive" RNA effectors assemble at the 5' end of capped RNA, orchestrated by the essential arsenite resistance protein 2 (ARS2) protein. Based on this principle, we here discuss early QC mechanisms and how these might sort short RNAs to their final fates.

Glutamine Attenuates Inflammation and Stimulates Amniotic Cell Proliferation in Premature Rupture of Membranes-related in vitro Models.

Premature rupture of membranes (PROM), with a prevalence of 15.3% in China, frequently results in adverse pregnancy outcomes. In this study, we aimed to identify amino acid metabolites that were differentially expressed in PROM versus healthy controls (HC) using targeted metabolomics and further explored their mechanisms of action with in vitro models.Inclusion and exclusion criteria were established to recruit 50 PROM and 50 HC cases for targeted metabolomics analysis. Twenty-three amino acid metabolites were quantified in the secretions of the posterior vaginal fornix of pregnant women between 31 and 36 weeks of gestation. Glutamine (0.0216 vs. 0.037 µg/mg, P = 0.003, AUC = 72.1%) was identified as the most differentially expressed amino acid metabolite between PROM and HC groups, and had a negative correlation with the abundance of Gardnerella (r=-0.3868, P = 0.0055), Megasphaera (r=-0.3130, P = 0.0269), and Prevotella (r=-0.2944, P = 0.0380), respectively.In amniotic epithelial cell and macrophage co-culture model, Glutamine reduced inflammatory cytokines and chemokines expression and suppressed macrophage chemotaxis. In LPS stimulated RAW 264.7 inflammation model, Glutamine inhibited the expression of inflammatory proteins iNOS and COX-2, down-regulated mRNA transcription of TNF, IL-6, and IL-1ß, and reduced the production of reactive oxygen species through inhibiting NF-κB signaling pathway, and therefore demonstrated its anti-inflammatory effect. Furthermore, Glutamine protected amniotic epithelial cell from autophagy and stimulated its proliferation, therefore may intensify fetal membrane and prevent PROM in vivo.Our results suggested that low Glutamine level in vaginal secretion can be used as an indicator for PROM, and local Glutamine supplementation is a potential intervention and prevention strategy for PROM.

Network pharmacological analysis and experimental verification of Zisheng Tongmai decoction in the treatment of premature ovarian failure.

Premature ovarian failure (POF) is a disease that seriously jeopardizes women's physical and mental health worldwide. Zisheng Tongmai decoction (ZSTMD), a famous Traditional Chinese Medicine (TCM) formula, has a marked effect on the clinical treatment of POF. This study investigated the potential mechanism of ZSTMD to improve POF through network pharmacology and experimental validation. The active components, key targets and potential mechanisms of ZSTMD against POF were predicted by network pharmacology and molecular docking. The POF model was induced in rats by cyclophosphamide (CTX) and subsequently gavaged with different doses of ZSTMD. KGN cells were treated with different concentrations of quercetin and CTX. Histopathological were observed via hematoxylin and eosin (H&E) staining and immunofluorescence staining. Serum estrogen levels were detected via ELISA. Protein expression was detected via Western blot. We identified quercetin as the main active ingredients targeting VEGFA. Molecular docking showed that VEGFA interacted well with the main active components of ZSTMD. In vivo experiments, ZSTMD significantly increased body weight and the ovarian index, significantly increased E2 and AMH, and decreased FSH and LH in POF rats. Histologic results showed that ZSTMD increased the number of follicles and vascular density in the ovary. It also increased VEGFA and CD31 protein expression. In vitro experiments, quercetin suppressed CTX-induced apoptosis in KGN cells and increased VEGFA protein expression. Our study demonstrated that ZSTMD improves POF by promoting angiogenesis through VEGFA target.

Risk Factors for PVC Induced Cardiomyopathy and Post-Ablation Left Ventricular Systolic Dysfunction Reversibility: A Systematic Review and Meta-Analysis of Observational Studies.

Background: Premature ventricular complex (PVC) induced cardiomyopathy (PVC-CMP) and exacerbated left ventricular systolic dysfunction (LVSD) are common in clinical scenarios. However, their precise risk factors are currently unclear. Methods: We performed a systematic review of PubMed, EMBASE, Web of Science, and Chinese-based literature database (CBM) to identify observational studies describing the factors associated with PVC-CMP and post-ablation LVSD reversibility. A total of 25 and 12 studies, involving 4863 and 884 subjects, respectively, were eligible. We calculated pooled multifactorial odds ratios (OR) and 95% confidence intervals (CI) for each parameter using random-effects and fixed-effects models. Results: The results showed that 3 independent risk factors were associated with PVC-CMP: being asymptomatic (OR and 95% CI: 3.04 [2.13, 4.34]), interpolation (OR and 95% CI: 2.47 [1.25, 4.92]), and epicardial origin (epi-origin) (OR and 95% CI: 3.04 [2.13, 4.34]). Additionally, 2 factors were significantly correlated with post-ablation LVSD reversibility: sinus QRS wave duration (QRSd) (OR and 95% CI: 0.95 [0.93, 0.97]) and PVC burden (OR and 95% CI: 1.09 [0.97, 1.23]). Conclusions: the relatively consistent independent risk factors for PVC-CMP and post-ablation LVSD reversibility are asymptomatic status, interpolation, epicardial origin, PVC burden, and sinus QRS duration, respectively.