BackgroundHerein, we aimed to analyse the effects of body mass index (BMI) on the treatment outcomes of in vitro fertilisation (IVF) in a cohort of women undergoing their first IVF cycle.MethodsA total of 2311 cycles from 986 women undergoing their first IVF/intracytoplasmic sperm injection cycle with fresh/frozen embryo transfer between January 2018 and December 2021 at the Center of Reproductive Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, were considered in this retrospective cohort study. First, the included patients were classified into four groups based on their BMI: underweight (BMI < 18.5 kg/m2, 78 patients), normal weight (18.5 ≤ BMI < 24 kg/m2, 721patients), overweight (24 ≤ BMI < 28 kg/m2, 147 patients), and obese (BMI ≥ 28 kg/m2, 40 patients). The IVF outcomes included the Gn medication days; Gn dosage; number of retrieved oocytes, mature oocytes, fertilized oocytes, cleavages, and available embryos and high-quality embryos; implantation rate; clinical pregnancy rate and live birth rate. Next, all the obtained data were segregated into three different subgroups according to the patient age: < 30 years, 30–38 years and > 38 years; the IVF pregnancy outcomes were compared among the groups.ResultsCompared with the other three groups, the underweight group had a higher number of fertilized oocytes, cleavage and available embryos and a smaller Gn medication days and required a lower Gn dosage. There was no difference in the number of retrieved oocytes and mature oocytes among the groups. Moreover, compared with the women aged 30–38 years in the overweight group, those in the normal weight group had a significantly higher implantation rate, clinical pregnancy rate and live birth rate (p = 0.013 OR 1.75, p = 0.033 OR 1.735, p = 0.020 OR 1.252 respectively). The clinical pregnancy rate was also significantly higher in those aged 30–38 years in the normal weight group than in the obese group (p = 0.036 OR 4.236).ConclusionsAlthough the BMI can greatly affect the pregnancy outcomes of women aged 30–38 years, it has almost no effects on the outcomes of younger or older women.

BackgroundRenal ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Dysfunction of E74-like ETS transcription factor 4 (ELF4) leads to inflammation. This research intended to look into the function and mechanisms of ELF4 in I/R and oxygen–glucose deprivation/reperfusion (OGD/R) model.ResultsIn I/R and OGD/R model, ELF4 expression was downregulated. ELF4 knockout aggravated I/R-induced kidney injury, oxidative stress (OS), endoplasmic reticulum stress (ERS), apoptosis, inflammation, and pyroptosis in mice. In HK-2 cells treated with OGD/R, suppression of ELF4 expression inhibited cell proliferation and promoted cell apoptosis, OS, ERS, inflammation, and pyroptosis. Moreover, ELF4 overexpression led to the opposite results.ConclusionELF4 deficiency aggravated I/R induced AKI, which was involved in apoptosis, OS, ERS, inflammation, and pyroptosis. Targeting ELF4 may be a promising new therapeutic strategy for preventing inflammation after IR-AKI.

BackgroundThe increasing elderly population and wide use of magnetic capsule endoscopy (MCE) have led to more attention to elderly patients.AimThe aim of this study was to assess the performance (including transit time, cleanliness score, positive findings and safety) of MCE in aging patients (≥ 60 years), especially patients over 80 years old.MethodsConsecutive patients of ≥ 60 years undergoing MCE at our center from August 2017 to August 2022 were classified into the oldest (≥ 80 years) and the older (60–79 years) groups. Esophageal transit time (ETT), gastric examination time (GET), small bowel transit time (SITT), and the quality of gastric preparation were compared. Information on examination indications, subjective discomforts, adverse events, and MCE outcomes were compared.ResultsOf 293 enrolled patients, 128 patients were in the oldest group and 165 patients were in the older group. ETT and GET were longer in the oldest group, whereas SITT was slightly longer in the oldest patients. Visualization scores were significantly lower in the body and antrum in the oldest patients. The total visualization score was lower in the older group compared with the oldest group; however, the difference was not significant. Cleanliness scores at the fundus and antrum and total cleanliness scores were lower in the oldest patients compared with the older patients. Positive findings and ulcers and erosions in the small intestine were more common in the oldest group. One patient had nausea during the gastric examination. Capsule retention in the cecum occurred in one case.ConclusionMCE was feasible and safe for aging patients. ETT and GET were markedly longer and gastric cleanliness and visualization were worse, while overall small intestine-positive findings were higher in the oldest patients compared with the older patients.

Pseudorabies virus (PRV) can infect multiple hosts and lead to fatal encephalitis. There is a significant increase in the number of microglia in the brain of animals infected with PRV. However, whether and how microglia contribute to central nervous system damage in PRV infection remain unknown. In the present study, we elucidated that PRV infection can cause more severe inflammatory cell infiltration, thicker and more numerous vessel sleeve walls, and more severe inflammatory responses in the brains of natural hosts (pigs) than in those of nonnatural hosts (mice). In a mice infection model, activated microglia restricted viral replication in the early stage of infection. Acute neuroinflammation caused by microglia hyperactivation at late-stage of infection. Furthermore, in vitro experiments revealed that microglia restricted viral replication and decreased viral infectivity. This may be associated with the phagocytic ability of microglia because we observed a significant increase in the expression of the membrane receptor TREM2 in microglia, which is closely related to phagocytosis, we observed that depletion of microglia exacerbated neurological symptoms, blood–brain barrier breakdown, and peripheral lymphocyte infiltration. Taken together, we revealed the dual role of microglia in protecting the host and neurons from PRV infection.

BackgroundPhosphoglycerate mutase 5 (PGAM5), a phosphatase involved in mitochondrial homeostasis, is reported to be closely related to the metabolic stress induced by high-fat diet (HFD) or cold. In this study, we aimed to investigate the effects of PGAM5 on hepatic steatosis, inflammation and fibrosis in nonalcoholic steatohepatitis (NASH).Methods and resultsWe generated PGAM5 global knockout (GKO) mice and their wildtype (WT) littermates using CRISPR/CAS9. The mice were fed with a high fat high fructose (HFHF) diet for 12 weeks or a methionine choline-deficient (MCD) diet (methionine choline supplemented (MCS) as control) for 6 weeks. Hepatic PGAM5 expression was up-regulated in humans with NASH and WT mice fed with HFHF and MCS, and reduced in WT mice fed with MCD diet. In HFHF-fed mice, GKO had reduced body weight, hepatic triglyceride (TG) content and serum transaminase along with decreased hepatic pro-inflammatory and pro-fibrotic responses compared with their WT control. GKO had increased expression of antioxidative gene glutathione peroxidase-6 (GPX6) and activation of mammalian target of rapamycin (mTOR). In mice fed with MCS diet, GKO significantly increased serum TNF-α and IL-6 and decreased hepatic GPX6 mRNA expression. There was no difference in hepatic steatosis, inflammation or fibrosis between GKO and WT mice fed with MCD diet. We investigated the role of PGAM5 deficiency in a variety of cell types. In differentiated THP-1 cells, PGAM5 silencing significantly increased pro-inflammatory cytokine secretion and decreased antioxidative proteins, including nuclear factor erythroid 2- related factors (NRF2), heme oxygenase-1 (HO-1) and GPX6 without affecting mTOR activity. In HepG2 cells with steatosis, PGAM5 knockdown reduced insulin sensitivity, increased mTOR phosphorylation and reduced the expression of NRF2, catalase (CAT), HO-1 and GPX6. Conversely, PGAM5 knockdown reduced TG accumulation, increased insulin sensitivity, and increased antioxidative genes in 3T3-L1 cells, despite the up-regulation in mTOR phosphorylation.ConclusionsPGAM5-KO relieved hepatic steatosis and inflammation in HFHF model, promoted inflammation in MCS-fed mice and had no effects on the MCD-fed model. The distinct effects may be owing to the different effects of PGAM5-KO on anti-oxidative pathways in energy-dependent, possible involves mTOR, and/or cell type-dependent manner. Our findings suggest that PGAM5 can be a potential therapeutic target for NASH.

BackgroundEvidence shows that genetic factors play important roles in the severity of coronavirus disease 2019 (COVID-19). Sulfatase modifying factor 1 (SUMF1) gene is involved in alveolar damage and systemic inflammatory response. Therefore, we speculate that it may play a key role in COVID-19.ResultsWe found that rs794185 was significantly associated with COVID-19 severity in Chinese population, under the additive model after adjusting for gender and age (for C allele = 0.62, 95% CI = 0.44–0.88, P = 0.0073, logistic regression). And this association was consistent with this in European population Genetics Of Mortality In Critical Care (GenOMICC: OR for C allele = 0.94, 95% CI = 0.90–0.98, P = 0.0037). Additionally, we also revealed a remarkable association between rs794185 and the prothrombin activity (PTA) in subjects (P = 0.015, Generalized Linear Model).ConclusionsIn conclusion, our study for the first time identified that rs794185 in SUMF1 gene was associated with the severity of COVID-19.