The sirtuin-associated human senescence program converges on the activation of placenta-specific gene PAPPA.

Sirtuins are pro-longevity genes with chromatin modulation potential, but how these properties are connected is not well understood. Here, we generated a panel of isogeneic human stem cell lines with SIRT1-SIRT7 knockouts and found that any sirtuin deficiency leads to accelerated cellular senescence. Through large-scale epigenomic analyses, we show how sirtuin deficiency alters genome organization and that genomic regions sensitive to sirtuin deficiency are preferentially enriched in active enhancers, thereby promoting interactions within topologically associated domains and the formation of de novo enhancer-promoter loops. In all sirtuin-deficient human stem cell lines, we found that chromatin contacts are rewired to promote aberrant activation of the placenta-specific gene PAPPA, which controls the pro-senescence effects associated with sirtuin deficiency and serves as a potential aging biomarker. Based on our survey of the 3D chromatin architecture, we established connections between sirtuins and potential target genes, thereby informing the development of strategies for aging interventions.

Transcriptome-wide 1-methyladenosine functional profiling of messenger RNA and long non-coding RNA in bladder cancer.

Introduction: Post-transcriptional RNA modifications are crucial regulators of tumor development and progression. In many biological processes, N1-methyladenosine (m1A) plays a key role. However, little is known about the links between chemical modifications of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) and their function in bladder cancer (BLCA). Methods: Methylated RNA immunoprecipitation sequencing and RNA sequencing were performed to profile mRNA and lncRNA m1A methylation and expression in BLCA cells, with or without stable knockdown of the m1A methyltransferase tRNA methyltransferase 61A (TRMT61A). Results: The analysis of differentially methylated gene sites identified 16,941 peaks, 6,698 mRNAs, and 10,243 lncRNAs in the two groups. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the differentially methylated and expressed transcripts showed that m1A-regulated transcripts were mainly related to protein binding and signaling pathways in cancer. In addition, the differentially genes were identified that were also differentially m1A-modified and identified 14 mRNAs and 19 lncRNAs. Next, these mRNAs and lncRNAs were used to construct a lncRNA-microRNA-mRNA competing endogenous RNA network, which included 118 miRNAs, 15 lncRNAs, and 8 mRNAs. Finally, the m1A-modified transcripts, SCN2B and ENST00000536140, which are highly expressed in BLCA tissues, were associated with decreased overall patient survival. Discussion: This study revealed substantially different amounts and distributions of m1A in BLCA after TRMT61A knockdown and predicted cellular functions in which m1A may be involved, providing evidence that implicates m1A mRNA and lncRNA epitranscriptomic regulation in BLCA tumorigenesis and progression.

Gastrodin ameliorates depressive-like behaviors via modulating gut microbiota in CUMS-induced mice.

PURPOSE: Depression is a psychiatric disorder and the treatment of depression is an urgent problem that need to be solved. Gastrodin (GAS) is a Traditional Chinese Medicine from an orchid and is used for neurological diseases, including depressive disorders. METHODS: To assess the effect of GAS on gut microbiota of depressive mice, we established a chronic unpredictable mild stress (CUMS)-induced mouse model, and GAS was administered to one group of the mice. Animal behavior experiments were used to detect depressive-like behaviors, and 16 S rRNA gene analysis was applied to detect the gut microbiota of each group. All raw sequences were deposited in the NCBI Sequence Read Archive under accession number SRP491061. RESULTS: GAS treatment significantly improved depressive-like behaviors as well as the diversity and abundance of the gut microbiota. The depressive-like behaviors of the CUMS-GAS group were improved in different degrees compared with the CUMS group. The linear discriminant analysis (LDA) of the gut microbiota showed that the makeup of the gut microbiota in mice changed dramatically in the CUMS-GAS group, compared with the CUMS group, Bacteroides (LDA = 3.94, P < 0.05) were enriched in the CUMS-GAS group at the genus level. In comparison to the CUMS group, the CUMS-GAS group had a greater concentration numbers of Lactobacillus, Corynebacterium, Staphylococcus, Bacteroides, Psychrobacter, and Alistipes. CONCLUSION: Our results suggested that GAS improved depressive-like behaviors in mice and impacted the microbial composition of the gut. Our research indicated that dysbiosis of the gut microbiota may be affected by GAS treatment, which improved depressive-like behaviors in the CUMS-induced mouse model of depression.

Clinical characteristics and pregnancy outcome analysis of 20 cases of acute pancreatitis during pregnancy.

OBJECTIVE: This study investigated the clinical characteristics and pregnancy outcomes of acute pancreatitis during pregnancy (APIP). METHODS: A retrospective analysis was conducted on 20 cases of APIP admitted to Hubei Maternal and Child Health Hospital from January 2017 to September 2021. The etiology, clinical manifestations, and perinatal outcomes of APIP were analyzed using descriptive statistical analysis of the collected data. RESULTS: The incidence of APIP in our hospital was 20 (0.02%) cases, all of which occurred in the late stage of pregnancy. Hypertriglyceridemic acute pancreatitis (HTG-AP) was the primary cause of APIP in 10 (50.0%) patients. A total of 11 (55.0%), seven (35.0%) and two (10.0%) patients had mild acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), respectively. Pregnant women with HTG-AP had significantly elevated serum triglyceride levels, had higher prepregnancy body mass indices, were more prone to developing diabetes and were more likely to progress to SAP. With a multidisciplinary approach and individualized treatment plans, there were no maternal deaths, and fetal death only occurred in one (5.0%) case. CONCLUSION: HTG-AP is prone to advancing to more severe states, and it is becoming more common every year. Therefore, blood lipid management during pregnancy should be emphasized. Pregnant women with digestive symptoms or severe hyperlipidaemia should be screened for APIP in a timely manner and receive clinical intervention to improve maternal and fetal outcomes during the perinatal period.

Health economic analysis and medical cost analysis of children with severe hepatitis B in China: A retrospective study from 2016 to 2022.

BACKGROUND: Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China. METHODS: Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran's I  analysis. RESULTS: The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603,) of total cases and cirrhosis cases accounted for 11.23% (180/1603,). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (GDP, Moran's I <0) and percentage of urban population (Moran's I <0), and positively correlated with the number of pediatric beds per million population (Moran's I >0). CONCLUSION: The number of severe hepatitis B cases is low in areas with high GDP levels and high urban population ratios, and health care costs have been declining over the years.

A comprehensive review on asphalt fume suppression and energy saving technologies in asphalt pavement industry.

Based on the environmental issues of high energy consumption and high emissions of asphalt fumes that are associated with hot mixing asphalt pavement construction, especially with modified asphalt mixtures such as waste rubber modified asphalt (WRMA) mixtures, significant environmentally-friendly new technologies have been successfully applied in the field of asphalt pavement materials. These include fume purification equipment, fume suppression or flame-retarding asphalt mixture, and warm mixing or cold mixing asphalt mixture. This paper provides a comprehensive review of the latest technology in this area regarding both asphalt fume suppression and energy conservation within the last six years. Firstly, asphalt fume suppression technologies in production, laying, and combustion scenarios of an asphalt mixture are identified, and asphalt fume purification equipment utilized in the production process is thoroughly examined. The impacts and mechanisms of various fume suppressants and flame retardants of asphalt fumes regarding their influence on the performance of asphalt pavement are discussed. Secondly, from the perspective of reducing asphalt mixture temperature, different mixing techniques such as cold mixing asphalt (CMA), warm mixing asphalt (WMA), and warm mixing based retarding viscosity asphalt (WM-RVA) are introduced and evaluated utilizing energy consumption and carbon emission evaluation models. These results show that the combination of advanced oxidation and traditional purification methods is critical for promoting the green production of asphalt mixtures. In-depth research on nanomaterials and composite-type asphalt fume suppression materials, WM-RVA, and effective combinations of high-performance modification, recycled materials, fume suppression functional materials, and WMA or CMA hold great promise for future development in this field.

A Healthy, Low-Carbohydrate Diet During Pregnancy Is Associated With a Reduced Risk of Gestational Diabetes Mellitus.

CONTEXT: Evidence on the associations of low-carbohydrate diet (LCD) during pregnancy with gestational diabetes mellitus (GDM) has been limited and inconsistent. OBJECTIVE: We aimed to prospectively evaluate the risk of GDM associated with the LCD considering the quality of macronutrients. METHODS: All participants were from a prospective cohort in Wuhan, China. The overall, healthy LCD (emphasizing low-quality carbohydrates, plant protein, and unsaturated fat), and unhealthy LCD (emphasizing high-quality carbohydrates, animal protein, and saturated fat) scores were calculated according to the percentage of energy intake from carbohydrates, protein, and fat. GDM was screened by a 75-g oral glucose tolerance test between 24 and 28 weeks. Poisson regression models were used to calculate relative risks (RRs) and 95% CIs. RESULTS: Of 2337 pregnant women, 257 (11.0%) were diagnosed with GDM. Overall LCD score was not associated with risk of GDM, but the healthy and unhealthy LCD scores were associated with the risk of GDM. The multivariable-adjusted RRs (95% CI) were 0.68 (0.49-0.94) and 1.52 (1.11-2.08) for healthy and unhealthy LCD scores comparing the highest with the lowest quartile. Substituting high-quality carbohydrates for low-quality carbohydrates and animal protein, and substituting unsaturated fat for saturated fat, were associated with a 13% to 29% lower risk of GDM. CONCLUSION: A healthy LCD during pregnancy characterized by high-quality carbohydrates, plant protein, and unsaturated fat was associated with a lower risk of GDM, whereas an unhealthy LCD consisting of low-quality carbohydrates, animal protein, and saturated fat was associated with a higher risk of GDM.

Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling.

The synovium, a thin layer of tissue that adjacent to the joints and secretes synovial fluid, undergoes changes in aging that contribute to intense shoulder pain and other joint diseases. However, the mechanism underlying human synovial aging remains poorly characterized. Here, we generated a comprehensive profile of synovial cell types present in subacromial synovium from young and aged individuals. By delineating aging-related transcriptomic changes across cell types and their associated regulatory networks, we identified two subsets of mesenchymal stromal cell (MSC) in human synovium, which are lining and sublining MSCs, and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated during aging. Moreover, the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling, including vascular hyperplasia and tissue fibrosis. In particular, we identified Forkhead box O1 (FOXO1) as one of the major regulons for aging DEGs of synovium MSCs, and validated its downregulation in both lining and sublining MSC populations of the aged synovium. In human FOXO1-depleted MSCs derived from human embryonic stem cells, we recapitulated the senescent phenotype observed in the subacromial synovium of aged donors. These data indicate the important role for FOXO1 in the regulation of human synovial aging. Overall, our study improves upon our understanding of synovial aging during joint degeneration, thereby informing development of new treatments aimed at rejuvenating the aged joint.

Multidimensional dynamic prediction model for hospitalized patients with the omicron variant in China.

Purpose: To establish dynamic prediction models by machine learning using daily multidimensional data for coronavirus disease 2019 (COVID-19) patients. Methods: Hospitalized COVID-19 patients at Peking Union Medical College Hospital from Nov 2nd, 2022, to Jan 13th, 2023, were enrolled in this study. The outcome was defined as deterioration or recovery of the patient's condition. Demographics, comorbidities, laboratory test results, vital signs, and treatments were used to train the model. To predict the following days, a separate XGBoost model was trained and validated. The Shapley additive explanations method was used to analyze feature importance. Results: A total of 995 patients were enrolled, generating 7228 and 3170 observations for each prediction model. In the deterioration prediction model, the minimum area under the receiver operating characteristic curve (AUROC) for the following 7 days was 0.786 (95% CI 0.721-0.851), while the AUROC on the next day was 0.872 (0.831-0.913). In the recovery prediction model, the minimum AUROC for the following 3 days was 0.675 (0.583-0.767), while the AUROC on the next day was 0.823 (0.770-0.876). The top 5 features for deterioration prediction on the 7th day were disease course, length of hospital stay, hypertension, and diastolic blood pressure. Those for recovery prediction on the 3rd day were age, D-dimer levels, disease course, creatinine levels and corticosteroid therapy. Conclusion: The models could accurately predict the dynamics of Omicron patients' conditions using daily multidimensional variables, revealing important features including comorbidities (e.g., hyperlipidemia), age, disease course, vital signs, D-dimer levels, corticosteroid therapy and oxygen therapy.

CHSY1 promotes CD8+ T cell exhaustion through activation of succinate metabolism pathway leading to colorectal cancer liver metastasis based on CRISPR/Cas9 screening.

BACKGROUND: The most common site of metastasis in colorectal cancer (CRC) is the liver and liver metastases occur in more than 50% of patients during diagnosis or treatment. The occurrence of metastasis depends on a series of events known as the invasive-metastasis cascade. Currently, the underlying genes and pathways regulating metastasis initiation in the liver microenvironment are unknown. METHODS: We performed systematic CRISPR/Cas9 screening using an in vivo mouse model of CRC liver metastasis to identify key regulators of CRC metastasis. We present the full results of this screen,which included a list of genes that promote or repress CRC liver colonization. By silencing these genes individually, we found that chondroitin sulfate synthase 1 (CHSY1) may be involved in CRC metastasis. We verified the function of CHSY1 and its involvement in liver metastasis of CRC through in vivo and in vitro experiments. RESULT: The results of TCGA and CRISPR/Cas9 showed that CHSY1 was overexpressed in CRC primary and liver metastasis tissues and indicated a worse clinical prognosis. In vitro and in vivo experiments confirmed that CHSY1 facilitated the liver metastasis of CRC and CHSY1 induced CD8+ T cell exhaustion and upregulated PD-L1 expression. The metabolomic analysis indicated that CHSY1 promoted CD8+ T cell exhaustion by activating the succinate metabolism pathway leading to liver metastasis of CRC. Artemisinin as a CHSY1 inhibitor reduced liver metastasis and enhanced the effect of anti-PD1 in CRC. PLGA-loaded Artemisinin and ICG probe reduced liver metastasis and increased the efficiency of anti-PD1 treatment in CRC. CONCLUSION: CHSY1 could promote CD8+ T cell exhaustion through activation of the succinate metabolic and PI3K/AKT/HIF1A pathway, leading to CRC liver metastasis. The combination of CHSY1 knockdown and anti-PD1 contributes to synergistic resistance to CRC liver metastasis. Artemisinin significantly inhibits CHSY1 activity and in combination with anti-PD1 could synergistically treat CRC liver metastases. This study provides new targets and specific strategies for the treatment of CRC liver metastases, bringing new hope and benefits to patients.

Developing Hypoimmunogenic Human iPSC-Derived Oligodendrocyte Progenitor Cells as an Off-The-Shelf Cell Therapy for Myelin Disorders.

Demyelinating disorders are among the most common and debilitating diseases in neurology. Canavan disease (CD) is a lethal demyelinating disease caused by mutation of the aspartoacylase (ASPA) gene, which leads to the accumulation of its substrate N-acetyl-l-aspartate (NAA), and consequently demyelination and vacuolation in the brain. In this study, hypoimmunogenic human induced pluripotent stem cell (iPSC)-derived oligodendrocyte progenitor cells (OPC) are developed from a healthy donor as an "off-the-shelf" cell therapy. Hypoimmunogenic iPSCs are generated through CRISPR/Cas9 editing of the human leukocyte antigen (HLA) molecules in healthy donor-derived iPSCs and differentiated into OPCs. The OPCs are engrafted into the brains of CD (nur7) mice and exhibit widespread distribution in the brain. The engrafted OPCs mature into oligodendrocytes that express the endogenous wildtype ASPA gene. Consequently, the transplanted mice exhibit elevated human ASPA expression and enzymatic activity and reduced NAA level in the brain. The transplanted OPCs are able to rescue major pathological features of CD, including defective myelination, extensive vacuolation, and motor function deficits. Moreover, the hypoimmunogenic OPCs exhibit low immunogenicity both in vitro and in vivo. The hypoimmunogenic OPCs can be used as "off-the-shelf" universal donor cells to treat various CD patients and many other demyelinating disorders, especially autoimmune demyelinating diseases, such as multiple sclerosis.

Comparison of the 2009 Institute of Medicine and 2021 Chinese guidelines for gestational weight gain: A retrospective population-based cohort study.

OBJECTIVE: To analyze the associations between gestational weight gain (GWG) and perinatal outcomes based on the GWG guidelines of the Chinese Nutrition Society (CNS) and the Institute of Medicine (IOM). METHODS: This was a retrospective study with 9075 low-risk singleton pregnant women. Logistic regression model was used to analyze associations between GWG categories and perinatal outcomes. Sensitivity analyses were performed based on pre-pregnancy body mass index (calculated as weight in kilograms divided by the square of height in meters). RESULTS: Excessive GWG as defined by the two guidelines was associated with a higher risk of adverse perinatal outcomes. Inadequate GWG was associated with higher risks of small for gestational age (adjusted odds ratio [aOR] 1.34, 95% confidence interval [CI] 1.10-1.64) and preterm birth (aOR 1.70, 95% CI 1.22-2.36), but a lower risk of large for gestational age (LGA) (aOR 0.77, 95% CI 0.63-0.95) according to the IOM guidelines. When using the CNS guidelines, inadequate GWG was associated with only a lower risk of preterm birth (aOR 1.80, 95% CI 1.19-2.70). Sensitivity analyses suggested that excessive GWG was associated with a higher risk of LGA in underweight women. CONCLUSIONS: Both guidelines could demonstrate the relationship between GWG and adverse perinatal outcomes. The CNS guidelines were more suitable for the Chinese population with underweight or normal weight before pregnancy, whereas IOM was more suitable for pregnant women with inadequate GWG.

The value of lipid metabolites 9,10-DOA and 11,12-EET in prenatal diagnosis of fetal heart defects.

AIMS: To explore the maternal metabolic changes of fetal congenital heart disease (FCHD), and screen metabolic markers to establish a practical diagnostic model. METHODS: Maternal peripheral serum from 17 FCHD and 63 non-FCHD pregnant were analyzed by Ultra High-performance Liquid Chromatography-Mass/Mass (UPLC-MS/MS). RESULTS: In the FCHD and the non-FCHD, 132 metabolites were identified, including 35 differential metabolites enriched in the purine, caffeine, primary bile acid, and arachidonic acid metabolism pathway. Finally, the screened (+/-)9,10-dihydroxy-12Z-octadecenoic acid (AUC = 0.888) and 11,12-epoxy-(5Z,8Z,11Z)-icosatrienoic acid (AUC = 0.995) were incorporated into the logistic regression model. The AUC value of the two-metabolite model was 1.0, superior to proline (AUC = 0.867), uric acid (AUC = 0.789), glutamine (AUC = 0.705), and taurine (AUC = 0.923) previously reported. The clinical decision curve analysis (DCA) showed the highest clinical net benefit of the model, and internal validation by bootstrap shows the robustness of the model (Brier Score = 0.005). CONCLUSION: For the prenatal diagnosis of CHD, our findings are of great clinical significance. As an additional screening procedure, the identification model might be used to detect.

Evaluation of ICUs and weight of quality control indicators: an exploratory study based on Chinese ICU quality data from 2015 to 2020.

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.

Association between glycolipids and risk of obstructive sleep apnea: A population-based study.

Background: This study aimed to investigate the associations between multiple glycolipid biomarkers and the risk of obstructive sleep apnea (OSA). Methods: Participants (10,286) aged from 35 to 74 years old were included in this cross-sectional study from the baseline survey of the Guangzhou Heart Study. OSA was ascertained using both Berlin Questionnaire and STOP-BANG Questionnaire. Fasting blood samples were collected from each participant; fasting blood glucose (FBG) and serum concentrations of high-density lipoprotein cholesterol (HDL-CH), low-density lipoprotein cholesterol (LDL-CH), total cholesterol (TC), and triglyceride (TG) were determined. Odds ratio (OR) with 95% confidence interval (CI) was calculated using the multivariate logistic regression model after adjustment for covariates. Results: Of the participants included, 15.56% were categorized into the pre-OSA group, and 8.22% into the OSA group. When comparing the highest with the lowest quartiles, HDL-HC was associated with a 22% (OR: 0.78, 95% CI: 0.65-0.94) and 41% (OR: 0.59, 95% CI: 0.45-0.78) reduced risk of pre-OSA and OSA, triglyceride was associated with a 32% (OR 1.32, 95% CI 1.08-1.60) and a 56% (OR 1.56, 95% CI 1.18-2.07) increased risk of pre-OSA and OSA, and FBG was associated with a 1.37-fold (95% CI 1.13-1.67) risk of pre-OSA and 1.38-fold (95% CI 1.03-1.85) risk of OSA. A significant exposure-response trend was observed for HDL-HC, TG, and FBG with both OSA and Pre-OSA (all p < 0.05). No significant association of LDL-CH and TC with the risk of both pre-OSA and OSA was observed. Conclusion: The findings suggest that serum HDL-CH was inversely associated with OSA risk, while elevated serum TG and FBG could increase the risk of OSA. Healthy glycolipid metabolism warrants more attention in the field of OSA prevention.

Exploring the Potential Molecular Mechanism of Sijunzi Decoction in the Treatment of Non-Segmental Vitiligo Based on Network Pharmacology and Molecular Docking.

Background: Non-segmental vitiligo is a common decolorized skin disease. The purpose of this study was to reveal the active components of Sijunzi decoction (SJZD) and the target genes for the treatment of non-segmental vitiligo. Methods: Based on TCMSP and GEO databases, effective components and targets of SJZD in the treatment of non-segmental vitiligo were revealed by network pharmacology. GO and KEGG were used to analyze the biological functions of SJZD targets. The Cytoscape-cytoHubba plugin was used to identify hub target genes. SsGSEA method was used to analyze the infiltration level of immune cells in non-segmental vitiligo. Molecular docking was performed to predict the interaction between active compounds and hub target genes. Finally, real-time PCR detection was also performed. Results: It was found that 104 active compounds may be effective ingredients in the treatment of non-segmental vitiligo. These 104 compounds acted on 42 differentially expressed target genes. KEGG analysis showed that target genes were significantly enriched in immune-related pathways such as MAPK and TNF signaling pathways. A total of 6 hub target genes (AKT1, CASP3, PPARG, SIRT1, TNF and TP53) were identified using the Cytoscape-cytoHubba plugin. Molecular docking showed that active compounds quercetin, kaempferol, formononetin and naringenin had good binding to hub target genes. We also found that Type 2 T helper cells, CD56bright natural killer cell and CD56dim natural killer cell infiltration levels were abnormal in non-segmental vitiligo and correlated with AKT1. Conclusion: The results of this study indicate that quercetin, kaempferol, formononetin and naringenin in SJZD may play an important role in the treatment of non-segmental vitiligo by acting on AKT1, CASP3, PPARG, SIRT1, TNF and TP53 to regulate immune cell infiltration and multiple signaling pathways.

Performance of Bakri balloon tamponade in controlling postpartum hemorrhage.

OBJECTIVE: Bakri balloon tamponade (BBT) is currently being used worldwide. This study aimed to explore the real-world performance of BBT for the treatment of postpartum hemorrhage (PPH). METHODS: A total of 279 women with PPH who failed to respond to first-line conservative management and received BBT were consecutively recruited, reflecting authentic settings. The maternal baseline clinical data, PPH management, and perinatal outcome were recorded. In addition, the perinatal outcomes of women with pre-BBT blood loss <1000 mL were compared to those with ≥1000 mL. Finally, the factors related to pre-BBT blood loss ≥1000 mL were analyzed by logistic regression. RESULTS: The mean gestational age of all recruited women was 39.03±1.98 weeks, with a primipara proportion of 68.82%, a vaginal delivery rate of 60.93%, a uterine atony rate of 74.91%, and placenta accreta rate of 53.05%. Perinatal outcomes showed a hemostasis success rate of 88.89%, a transvaginal BBT placement rate of 80.29%, and a blood transfusion rate of 65.95%. Compared to women with blood loss <1000 mL (33.33%), women with blood loss ≥1000 mL (66.67%) showed a lower proportion of gestational hypertension (P=0.026), cesarean section (P=0.024), a shorter time from delivery to insertion (P=0.037), and greater pre-BBT blood loss and blood transfusion (both P<0.001). Notably, there were no significant differences in hemostasis success rate (P=0.346) or post-BBT blood loss (P=0.907). Delivery mode and uterine atony were closely correlated with pre-BBT blood loss. CONCLUSIONS: BBT is effective in stopping PPH among women with massive blood loss in documented settings.

Patterns of maternal gestational weight gain in association with allergic diseases in offspring: A prospective cohort study.

OBJECTIVE: To evaluate the association between patterns of gestational weight gain (GWG) and allergic diseases in offspring. DESIGN: Prospective cohort study. SETTING: Prenatal clinics in Wuhan, China. POPULATION: A cohort of 2546 mother and offspring pairs were enrolled before 16 weeks of gestation and followed up to 24 months postpartum. METHODS: Maternal body weights were measured regularly during pregnancy, and their GWG patterns were estimated using the growth mixture model. Robust Poisson models were used to evaluate relative risk (RR) and 95% CI after multivariable adjustment. MAIN OUTCOME MEASURES: Offspring atopic allergy and allergic contact dermatitis were defined according to a physician's diagnosis reported by the mother, and food allergy was reported by the mother. RESULTS: Three GWG patterns were identified: 18.1% (461) of the women were described as pattern 1, characterised by rapid GWG earlier in pregnancy; 56.6% (1442) of the women were described as pattern 2, with steady GWG throughout pregnancy; and 25.3% (643) of the women was described as pattern 3, with rapid GWG later in pregnancy. By the age of 24 months, 360 (14.1%), 109 (4.3%) and 757 (29.7%) offspring had atopic allergy, allergic contact dermatitis or food allergy, respectively. Compared with women in GWG pattern 2, the RRs (95% CIs) among women in pattern 1 were 0.74 (0.55-0.99) for atopic allergy, 0.64 (0.36-1.15) for allergic contact dermatitis and 0.95 (0.81-1.12) for food allergy. CONCLUSIONS: Maternal GWG pattern characterised by rapid GWG earlier in pregnancy was associated with a lower risk of atopic allergy in offspring.

Single-cell transcriptomic atlas of mouse cochlear aging.

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.

Ambient air pollutants in the first trimester of pregnancy and birth defects: an observational study.

OBJECTIVES: As current studies on the relationships between air pollutants exposure during the first trimester and birth defects were not fully elucidated, this study aimed to assess the association between selected air pollutants and birth defects. DESIGN: An observational study. PARTICIPANTS: We obtained 70 854 singletons with gestational age <20 weeks who were delivered at a large maternal and child healthcare centre in Wuhan, China. OUTCOME MEASURES: Birth defects data and daily average concentration of ambient particulate matter ≤10 µm diameter (PM10), PM ≤2.5 µm diameter (PM2.5), sulfur dioxide (SO2) and nitrogen dioxide (NO2) were obtained. Logistic regression analysis was applied to assess the association between maternal air pollutants exposure during first trimester and total birth defects, congenital heart defects (CHDs), limb defects and orofacial clefts with adjustments of potential covariates. RESULTS: There were a total of 1352 birth defect cases included in this study, with a prevalence of 19.08‰. Maternal exposed to high concentrations of PM10, PM2.5, NO2 and SO2 in the first trimester were significantly associated with elevated ORs of birth defects (ORs ranged from 1.13 to 1.23). Additionally, for male fetuses, maternal exposed to high PM2.5 concentration was associated with an elevated odd of CHDs (OR 1.27, 95% CI 1.06 to 1.52). In the cold season, the ORs of birth defects were significantly increased among women exposed to PM2.5 (OR 1.64, 95% CI 1.41 to 1.91), NO2 (OR 1.22, 95% CI 1.08 to 1.38) and SO2 (OR 1.26, 95% CI 1.07 to 1.47). CONCLUSIONS: This study showed unfavourable effects of air pollutants exposure during the first trimester on birth defects. Especially, the association between maternal PM2.5 exposure and CHDs was only observed among male fetuses, and stronger effects of PM2.5, NO2 and SO2 exposure on birth defects were observed in the cold season.