RATIONALE:Primary ciliary dyskinesia (PCD), an underdiagnosed genetic disorder characterised by dysfunctional cilia, is a known cause of bronchiectasis. OBJECTIVES:To prospectively identify PCD among patients with bronchiectasis using nasal nitric oxide (nNO) and clinical features, and to characterize genetic features. METHODS:This cross-sectional study enrolled adolescent and adult patients with bronchiectasis from the BE-China registry at Shanghai Pulmonary Hospital. Individuals with either strong clinical suspicion or nNO ≤77 nl·min-1 received a structured diagnostic work-up, including transmission electron microscopy and whole exome sequencing. Diagnoses followed the 2025 ERS/ATS PCD diagnostic guidelines. RESULTS:Among 373 patients with bronchiectasis, 27 (7.4%) were in the PCD group (14 "Confirmed PCD" and 13 "PCD Highly Likely"). nNO showed high screening accuracy (sensitivity 84.8%, specificity 97.1%). Patients with PCD were younger and had earlier bronchiectasis onset. Age-adjusted regression analysis showed independent associations between PCD and lower BMI (regression coefficient [RC] -1.5; 95% CI -2.9 to -0.1), FEV1 % predicted (RC -18.4; 95% CI -28.3 to -8.6), FVC % predicted (RC -11.3; 95% CI -19.5 to -3.0), and FEV1/FVC (RC -10.3; 95% CI -16.9 to -3.8). Strong associations were observed with rhinosinusitis (OR 25.3; 95% CI 8.8 to 92.1) and P.aeruginosa infection (OR 8.5; 95% CI 3.2 to 25.7). Situs inversus occurred in 25.9% of patients with PCD. DNAH11 was the most common pathogenic gene. CONCLUSIONS:Patients with PCD had more severe disease, reinforcing the need for structured screening in patients with bronchiectasis. nNO combined with clinical features is an effective and reliable screening strategy for PCD in bronchiectasis.

INTRODUCTION:This study assessed the effects of the synthesized ACE inhibitory peptide LAP (Leu-Arg-Pro-Val-Ala-Ala) on cognitive impairment in hypertensive rats. METHODS:Rho-associated coiled-coil containing protein kinase (ROCK) activity in peripheral blood mononuclear cells (PBMCs) was initially measured in elderly patients with hypertension and cognitive impairment using western blot analysis. The effect of LAP on the ROCK pathway was studied in a human cell line with ROCK1. Sixteenweek- old male spontaneously hypertensive rats (SHR) received intragastric LAP (500 μg/week) for eight weeks. Cognitive function was assessed using the Morris water maze test, and thoracic aorta remodeling was evaluated by determining the media/lumen ratio through immunohistochemistry. Amyloid beta (Aβ), phosphorylated tau (p-tau), and apoptotic neurons in the hippocampus were examined by western blot analysis and immunohistochemistry. Protein expression and activation related to the ROCK pathway, including moesin, myosin light chain (MLC), and myosin phosphatase target subunit (MYPT), were analyzed in the aorta and hippocampus using western blot and immunohistochemistry. RESULTS:Hypertensive patients with cognitive impairment showed increased phosphorylated/total myosin-binding subunit ratios in PBMCs, indicating higher ROCK pathway activity. In vitro, LAP reduced p-moesin levels, confirming ROCK inhibition. In vivo, oral LAP lowered blood pressure and heart rate in SHR models and improved cognitive function. LAP also reduced aortic remodeling, decreased hippocampal Aβ and p-tau deposition, reduced neuronal apoptosis, and increased neuronal survival. Mechanistically, LAP inhibited ROCK pathway activation in the aorta and hippocampus, similar to the ROCK inhibitor fasudil. DISCUSSION:Hypertension contributes to neurodegenerative changes through the activation of the ROCK signaling pathway. The study found that the ACE inhibitory peptide LAP not only sustainably lowered blood pressure, but also inhibited the ROCK pathway, reducing hippocampal Aβ and p-tau deposition, thereby offering a dual therapeutic approach for hypertension-related cognitive impairment. CONCLUSION:LAP alleviated hypertension-related cognitive impairment in SHR by inhibiting the hippocampal ROCK pathway, showing therapeutic potential.

Background Peak inspiratory flow (PIF) is critical for selecting inhalation devices in COPD and asthma. This study evaluated PIF distribution, identified disease-specific correlates, and developed assessment tools using routine clinical indicators. Methods This real-world, cross-sectional study measured PIF in 149 patients (COPD and asthma) using a respiratory trainer and analysis software. Hierarchical multivariable linear regression was used to identify PIF-associated factors, and LASSO regression was employed for variable selection of the assessment tools. Results PIF was significantly higher in asthma than COPD patients (73.8 vs. 65.4 L/min, p = 0.007). In COPD (62.32% sufficient PIF), height, BMI, and tidal volume (VT) were positively associated with PIF, while CK-MB was negatively associated. The COPD assessment tool (including height, CK-MB, and VT) achieved an area under the curve (AUC) of 0.821. In asthma (83.75% sufficient PIF), age was negatively associated, while height and vital capacity (VC) were positively associated. The asthma assessment tool (including education level, asthma stage, and VC) achieved an AUC of 0.840. Conclusion PIF distribution and its associated factors are disease-specific. The assessment tools based on routine clinical and pulmonary indicators demonstrate good diagnostic performance, providing a practical auxiliary tool for rapid clinical assessment of inspiratory capacity to guide individualized inhaler selection.

Background Given the need to translate basic research into human therapies, the development and refinement of clinically relevant animal models for bronchiectasis are critically important. To date, there are no well-established animal models for bronchiectasis. Thus, our aim was to develop a novel animal model that accurately recapitulates bronchiectasis-like pathologies. Methods To address this question, clinical strains of chronic Pseudomonas aeruginosa (CPA) were embedded in agar beads in vitro; then CPA-loaded agar beads and papain were repeatedly instilled intratracheally in female C57BL/6 J mice. Experimental assessments included micro-computed tomography (micro-CT) imaging, histological analysis, immune cell infiltration, cytokines, and lung function parameter measurements to evaluate structural damage, immune responses, and lung function impairments in the mouse model. Results In this mouse model, we observed that lung micro-CT imaging revealed significant bronchiectasis, with visible airways in the periphery, cylindrical airway expansion, and an airway-to-artery ratio > 1. Histopathology highlighted immune cell infiltration around the trachea, including lymphocytes, neutrophils, and monocytes, along with Periodic acid-Schiff staining-positive hypermucinous secretion. Compared to controls, the bronchiectasis group exhibited elevated pro-inflammatory cytokines in bronchoalveolar lavage fluid and worse lung function. Conclusion Our study presented a novel mouse model that better replicated the bronchiectasis-like phenotype than the CPA airway infection model, showing the advantages of the "CPA-loaded agar beads and papain"-driven approach in optimizing the disease models. The model mimicked the progression of bronchiectasis closely and could be used for studies on disease pathogenesis as well as the evaluation of novel therapies in the near future.

To compare the clinical efficacy and safety of small-bore (≤ 14 Fr) versus large-bore (> 14 Fr) chest tubes in the treatment of pneumothorax. A retrospective analysis was conducted. Patients were categorized into small-bore and large-bore groups based on the initial drainage tube size. Outcomes, including treatment efficacy, drainage duration, lung re-expansion time, hospital stay, complication rates, and analgesic use, were compared between groups. Subgroup analyses were performed based on pneumothorax type as primary and secondary spontaneous pneumothorax. In the overall population of 95 patients (55 large-bore, 40 small-bore), no statistically significant differences were found between the two groups regarding treatment efficacy (90.9

Baloxavir marboxil (baloxavir) shows satisfactory efficacy and safety for treating influenza, particularly influenza A. However, real-world evidence for influenza B in Chinese populations is scarce. This study aimed to explore the efficacy and safety of baloxavir vs. oseltamivir in Chinese outpatients with influenza B. This real-world cohort study included 811 outpatients with influenza B between November 2023 and January 2024, comprising 394 patients in the baloxavir group and 417 patients in the oseltamivir group. Inverse probability of treatment weighting (IPTW) was applied to minimize potential confounding and achieve covariate balance. In both unweighted and IPTW-weighted cohorts, time to fever resolution was shorter in the baloxavir group (median: 24.0 h) compared with the oseltamivir group (median: 48.0 h) (both P < 0.001). In both cohorts, the baloxavir group (median: 120.0 h) had a shorter time to symptom resolution than the oseltamivir group (median: 168.0 h) (both P < 0.001). Due to residual imbalance, time from symptom onset to antiviral initiation was adjusted for in the multivariable Cox model. After adjustment, the baloxavir group remained associated with faster fever resolution and symptom resolution (all P < 0.001). The incidence of any adverse events was lower in the baloxavir group than in the oseltamivir group (3.6

RATIONALE:The host immune determinants that distinguish protective from life-threatening responses to influenza are poorly understood. Identifying drivers of immunopathology in the human lung is critical for developing potential therapies. OBJECTIVES:To define the cellular and molecular immune landscape of the lung in mild vs severe influenza and to identify key cellular states and pathways associated with disease severity. METHODS:We generated a large-scale single-cell atlas by sequencing more than 520 000 cells from the bronchoalveolar lavage fluid of 88 nonimmunocompromised adult individuals with mild or severe influenza A and healthy controls. Key findings were validated by flow cytometry and protein quantification, and machine-learning models were used to identify predictive signatures. MAIN RESULTS:Severe influenza was characterized by profound pulmonary lymphopenia and a massive influx of functionally dysregulated neutrophils. The infiltrating neutrophils were primed for extracellular trap formation, driving a cytokine storm via the S100A8/A9/A12-TLR4 and CXCL8-CXCR1/2 axes. This pathology coincided with the depletion and functional impairment of resident alveolar macrophages and an expansion of pro-inflammatory, monocyte-derived macrophages that amplified neutrophil recruitment. Lymphopenia in severe disease arose from synergistic cell-death programs, while remaining lymphocytes exhibited a dysfunctional state of concurrent exhaustion and hypercytotoxicity. Mild influenza featured a coordinated adaptive immune response, distinguished by an enrichment of T follicular helper cells and plasma cells. Machine-learning models identified robust cellular and transcriptional signatures predictive of disease severity. CONCLUSIONS:Our atlas defines the divergent immune trajectories in influenza, revealing specific cellular states and pathways that drive immunopathology and provide novel targets for host-directed therapies.

BACKGROUND:Bronchiectasis and diabetes commonly coexist and are associated with immune dysfunction and increased susceptibility to infection. Although diabetes is associated with worse prognosis in cystic fibrosis-related bronchiectasis, data are scarce for its impact on non-cystic fibrosis bronchiectasis. This study aimed to characterise the impact of diabetes on clinical outcomes and microbial and inflammatory profiles in patients with bronchiectasis. METHODS:This analysis comprised data from the European Bronchiectasis Registry (EMBARC), Respiratory Research Network of India (EMBARC-India), Chinese Bronchiectasis Registry (BE-China), and Australian Bronchiectasis Registry (ABR); 30 263 patients with CT-confirmed bronchiectasis in 33 countries were included in the analysis: 16 963 from EMBARC (Jan 12, 2015, to April 12, 2022), 2361 from EMBARC-India plus additional Asian countries (June 1, 2015, to Sept 1, 2017), 10 324 from BE-China (Jan 10, 2020, to March 31, 2024), and 615 from the ABR (March 7, 2016, to Sept 11, 2018). Clinical data were compared between patients with and without diabetes. Long-term outcome data were available in EMBARC and EMBARC-India. Microbiome and inflammatory profiles were characterised in a sub-cohort of EMBARC patients by sputum 16S rRNA sequencing (n=433) and serum Olink (n=479). FINDINGS:2487 (8·2%) of 30 263 patients with bronchiectasis had diabetes. Patients with diabetes had a higher prevalence of comorbidities than those without diabetes, including cardiovascular disorders (53·5% vs 21·8%, p<0·0001), asthma (27·5% vs 21·0%, p<0·0001), and chronic obstructive pulmonary disease (34·3% vs 19·0%, p<0·0001). Patients with diabetes had more severe disease than those without diabetes, with higher Bronchiectasis Severity Index scores (8 [IQR 5-12] vs 7 [4-10], p<0·0001) and UK Medical Research Council (MRC) dyspnoea scores (p<0·0001) and more hospital admissions in the previous year (p<0·0001). After adjustment for confounders, outcomes were significantly worse in patients with diabetes than in those without diabetes, including more frequent exacerbations (incidence rate ratio [IRR] 1·18 [95% CI 1·09-1·28], p<0·0001), hospital admissions (IRR 1·57 [1·40-1·76], p<0·0001), and higher 5-year mortality (hazard ratio 1·80 [1·53-2·12], p<0·0001). The sputum microbiome was significantly altered in patients with diabetes compared to those without diabetes, with increased isolation of Enterobacteriaceae (p<0·0001), Moraxella catarrhalis (p=0·0035), and Haemophilus influenzae (p=0·046). In serum, Gal-4 and GDF-15, established biomarkers of disease severity and cardiovascular risk in diabetes, were significantly increased in patients with diabetes (Gal-4, p<0·0001; GDF-15, p=0·0019). INTERPRETATION:Patients with diabetes and bronchiectasis are a high-risk population with more severe disease, worse outcomes, increased comorbidities, and increased risk of infections compared with patients without diabetes. These findings support inclusion of diabetes as a risk factor in individualised risk assessments for bronchiectasis. FUNDING:European Respiratory Society, Armata, AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GSK, Grifols, Insmed, Janssen, Lifearc, Roche, Verona Pharma, Zambon, National Natural Science Foundation of China, Innovation Program of the Shanghai Municipal Education Commission, Program of the Shanghai Municipal Science and Technology Commission, Program of the Shanghai Shenkang Development Center, EU/European Federation of Pharmaceutical Industries and Associations, Innovative Medicines Initiative, and Inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium.

Background:Airway clearance techniques (ACTs) are guideline-recommended in bronchiectasis, while contemporary patterns and determinants of ACTs adoption remain unclear in China. Methods:A multicentre cross-sectional study was conducted using data from the BE-China cohort between 10 Jan 2020 and 31 Mar 2024. Clinical characteristics and prespecified ACT modalities were collected across 92 hospitals. Multivariable logistic regression identified important associations of ACTs utilization. Findings:Among 9647 patients, 12.2% (1177) used regular ACTs at baseline, and regional heterogeneity in ACTs utilization was observed. Moreover, ACTs users exhibited prolonged disease duration, a higher proportion of severe disease, greater comorbidity, heavier cough and sputum burden, and more frequent pharmacological and ventilatory interventions. Variables associated with increased ACTs utilization included comorbid burden (OR 1.47, 1.28-1.70; p < 0.0001), daily sputum (OR 1.68, 1.33-2.10; p < 0.0001), expectorants usage (OR 3.19, 2.74-3.71; p < 0.0001), inhaled antibiotics (OR 2.04, 1.35-3.07; p = 0.00065), macrolide therapy (OR 2.31, 1.78-2.99; p < 0.0001), other long-term oral antibiotics (OR 1.37, 1.13-1.66; p = 0.0013), noninvasive ventilation requirement (OR 4.11, 3.14-5.39; p < 0.0001), and disease duration (per SD increase, OR 1.08, 1.01-1.15; p = 0.027). Both BE-China and the similar European Bronchiectasis Registry (EMBARC) cohorts showed distinct etiological and comorbidity profiles, yet consistently revealed a higher medication burden among ACTs users. Interpretation:In China, ACTs utilization is primarily concentrated among patients with bronchiectasis who have a heavier symptom burden and greater treatment intensity. Clinicians may leverage the identified associations to optimize adherence and guide phenotype-targeted ACTs implementation strategies, and these findings may serve as a reference for future research. Funding:Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, Innovation Program of Shanghai Municipal Education Commission, Program of Shanghai Municipal Science and Technology Commission, Major Project of Guangzhou National Laboratory.

INTRODUCTION:The present study aimed to investigate macrophage polarization imbalance and its association with sustained NF-κB/NLRP3 signaling under chronic inflammatory stimulation using both in vivo and in vitro COPD-related models. METHODS:This experimental preclinical study was conducted between March and September 2023, at Shanghai Tenth People's Hospital. A chronic obstructive pulmonary disease (COPD)-like inflammatory model was established in C57BL/6J mice (n=5 per group) through combined chronic cigarette smoke (CS) exposure (4 hours/day, 5 days/week for 15 weeks) and intranasal lipopolysaccharide (LPS) administration (7.5 μg on days 1 and 14), together with an in vitro cigarette smoke extract (CSE)-induced RAW264.7 macrophage model (10% CSE for 24 hours). Macrophage M1/M2 polarization and inflammatory responses were assessed using ELISA, qRT-PCR, immunohistochemistry, Western blotting, and flow cytometry. RESULTS:Airflow limitation was observed in CS-exposed model mice, with significant reductions in FEV0.05/FVC (21.70 ± 0.96 vs 27.50 ± 0.94%, p<0.0001) and FEV0.1/FVC (77.39 ± 2.62 vs 87.21 ± 1.95%, p<0.001), along with increased lung resistance (RL: 1.22 ± 0.13 vs 0.97 ± 0.02 cmH2O/(mL/s), p<0.01). Histological examination revealed thickened bronchial walls, disrupted alveolar structure, and inflammatory cell infiltration. TNF-α (BALF: 290.6 ± 7.58 vs 125.6 ± 5.30 pg/mL, p<0.0001), IL-6 (BALF: 67.92 ± 3.02 vs 44.42 ± 2.62 pg/mL, p<0.001), and IL-1β (BALF: 120.3 ± 8.24 vs 87.52 ± 3.40 pg/mL, p<0.01) levels increased dramatically in both CS-exposed mice and CSE-induced RAW264.7 cells, whereas IL-10 levels decreased (BALF: 46.12 ± 1.71 vs 77.19 ± 3.96 pg/mL, p<0.001). CONCLUSIONS:CS and CSE exposure induced M1 macrophage polarization in mice, as well as 10% CSE-induced RAW 264.7 cells, which may be related to the activation of the NF-κB/NLRP3 signaling pathway.

The prognostic nutritional index (PNI), an indicator of nutritional status, has been linked to various diabetic complications. However, its relationship with diabetic peripheral neuropathy (DPN) remains unclear. This study aimed to explore the association between PNI and DPN using machine learning (ML) approaches. A total of 625 patients with type 2 diabetes (T2D) were enrolled, with 282 diagnosed with DPN. PNI was calculated based on serum albumin and lymphocyte count. Random forest (RF) and eXtreme Gradient Boosting (XGBoost) models were developed to predict DPN using clinical and biochemical data. SHapley Additive exPlanations (SHAP) were applied to determine feature importance. Multivariate logistic regression was used to evaluate the relationship between PNI quartile and DPN risks. Both RF and XGBoost models exhibited strong performance. The RF model achieved a recall of 78.4

BACKGROUND:Induction of labor (IOL) with mechanical methods or pharmacological agents is used in about 20% to 30% of all pregnant women. We specialized in comparing the effectiveness and safety of dinoprostone vs transcervical Foley catheter for IOL in term pregnant women with an unfavorable cervix with adequate samples. OBJECTIVE:To compare the effectiveness and safety of dinoprostone vs transcervical Foley catheter for IOL in term pregnant women with an unfavorable cervix. STUDY DESIGN:This is a parallel, open-label randomized controlled trial in two maternal centers in Shanghai, China between October 2019 and July 2022. Women with a singleton pregnancy in cephalic presentation at term and an unfavorable cervix (Bishop score <6) scheduled for IOL were eligible. A total of 1860 women were randomly allocated to cervical ripening with either a dinoprostone vaginal insert (10 mg) or a 60 cc Foley catheter for up to 24 hours. The primary outcomes were vaginal delivery rate and time to vaginal delivery. Secondary outcomes included time to delivery and maternal and neonatal morbidity. Analysis was done from an intention-to-treat perspective. The trial was registered with the China trial registry (CTR2000038435). RESULTS:The vaginal birth rates were 72.8% (677/930) vs 69.9% (650/930) in vaginal dinoprostone and Foley catheter, respectively (aRR 1.04, 95% confidence interval [CI] 0.98-1.10, risk difference: 0.03). Time to vaginal delivery was not significantly different between the two groups (sub-distribution hazard ratio 1.11, 95% CI 0.99-1.24). Vaginal dinoprostone was more likely complicated with hyperstimulation with fetal heart rate changes (5.8% vs 2.8%, aRR 2.09, 95% CI 1.32-3.31) and placenta abruption (0.9% vs 0.1%, aRR: 8.04, 95% CI 1.01-64.15), while Foley catheter was more likely complicated with suspected intrapartum infection (5.1% vs 8.2%, aRR: 0.62, 95% CI 0.44-0.88) and postpartum infection (1.4% vs 3.7%, aRR: 0.38, 95% CI 0.20-0.72). The composite of poor neonatal outcomes was not significantly different between the two groups (4.5% vs 3.8%, aRR 1.21, 95% CI 0.78-1.88), while more neonatal asphyxia occurred in the dinoprostone group (1.2% vs 0.2%, aRR 5.39, 95% CI 1.22-23.92). In a subgroup analysis, vaginal dinoprostone decreased vaginal birth rate slightly in multiparous women (90.6% vs 97.0%, aRR 0.93, 95% CI 0.88-0.99). CONCLUSIONS:In term pregnant women with an unfavorable cervix, IOL with vaginal dinoprostone or Foley catheter has similar effectiveness. Foley catheter leads to better safety for neonates, while it may result in a higher risk of maternal infection. Furthermore, Foley catheter should be preferred in multiparous women.

AbstractBackgroundTo explore the role of heparin-binding proteins released from glycocalyx and neutrophils in the mechanism of Sepsis-induced coagulopathy development. The therapeutic mechanism of Heparin in septic coagulation caused by Hparin-binding Protein and glycocalyx was studied by comparing the changes of Hparin-binding Protein and glycocalyx metabolites before and after heparin administration.MethodsPatients diagnosed with sepsis from November 2021 to November 2022 were selected and prospectively studied. Basic clinical data were collected and main indicators were detected for enrolled patients. Hparin-binding Protein and glycocalyx metabolites(HA、HS、SDC-1) were determined by ELISA kit. The main observation indexes were the changes of Hparin-binding Protein and glycocalyx metabolites in two groups before and after heparin administration.ResultsA total of 148 subjects were screened, and 80 met inclusion and exclusion criteria. Of these, 24 were in the SIC( Sepsis-induced coagulopathy) group and 56 were in the non-SIC group. The levels of HBP(Hparin-binding Protein) and glycocalyx metabolites in SIC group were higher than those in non-SIC group. After heparin treatment, the levels of HBP in SIC and non-sic groups were increased, and the levels of glycocalyx metabolites were decreased. Compared with the non-SIC group, patients in the SCI group had more significant increase in HBP level and decrease in glycocalyx metabolites.ConclusionPlasma HBP may affect blood coagulation and endothelial function on glycocalyx. Heparin may indirectly protects the glycocalyx by replacing the HBP that binds to the glycocalyx.

Background & Aims: Acetaminophen (APAP) is the most common cause of drug-induced liver injury (DILI); however, treatment options are limited. Mas is a G protein-coupled receptor whose role in APAP-induced hepatotoxicity has not yet been examined. Methods: Intrahepatic Mas expression was determined in both human and mouse DILI models. Mas1(-/-), AlbcreMas1(f/f), Ppara(-/-), Mas1(-/-)Ppara(-/-) and wild-type mice were challenged with APAP for the in vivo analyses of Mas-AKT-FOXO1 axis-dependent lipophagy and fatty acid oxidation (FAO), using pharmacological compounds and genetic tools. Liver samples were collected for RNA-sequencing, proteomics, metabolomics, lipidomics, and metabolic flux analysis. Live-imaging of liver and histological, biochemical, and molecular studies were performed to evaluate APAP-induced hepatotoxicity in mice. Primary hepatocytes and hepatic cell lines were exposed to APAP for in vitro analysis. Results: Intrahepatic Mas expression was significantly upregulated in human and mouse DILI models. Mice with systemic, liver-specific, or hepatocyte-specific Mas1 deficiency were vulnerable to APAP-induced hepatotoxicity. They exhibited substantially impaired lipophagy and downstream FAO, which was accompanied by the activation of AKT and suppression of FOXO1. In addition, the prophylactic activation of Mas conferred strong protection against APAP challenge in mice, with remarkably enhanced lipophagy and FAO dependent on the AKT-FOXO1 axis. Moreover, the protective effects of AVE0991 were substantially diminished by the inhibition of either lipophagy or FAO. Conclusions: The activation of Mas on hepatocytes enhanced AKT-FOXO1-dependent lipophagy and downstream FAO, protecting mice from APAP-induced hepatotoxicity and indicating that hepatocyte-specific Mas might be a novel therapeutic target for DILI. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

PurposeThe study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves.MethodsA retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. ResultsA total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p < 0.001), and had higher rates of symptoms (p = 0.003) or shared living room (p < 0.001). Risk factors analysis showed that the 2019-nCov antigen positive (OR = 1.86, 95%CI 1.40–2.48, p < 0.001), symptoms development (OR = 1.86, 95%CI 1.34–2.58, p < 0.001), direct contact exposure (OR = 1.47, 95%CI 1.09–1.96, p = 0.010) were independent risk factors for the cohabitant transmission of COVID-19, and a separate room with a separate toilet could reduce the risk of family transmission (OR = 0.62, 95%CI 0.41–0.92, p = 0.018).ConclusionPatients showing negative 2019-nCov antigen tests, being asymptomatic, living in a separate room with a separate toilet, or actively avoiding direct contact with cohabitants were at low risk of family transmission, and the study recommended that avoiding direct contact and residential disinfection could reduce the risk of all cohabitants within the same house being infected with COVID-19.

Previous research has demonstrated significant differences in intestinal flora between pregnant women with intrahepatic cholestasis of pregnancy (ICP) and healthy pregnant women. The objective of our study is to identify the key bacteria involved in ICP rats and explore the underlying mechanism. We established an ICP rat model and collected rat feces for metagenomic sequencing and found that Roseburia intestinalis (R.I) is the key bacteria in ICP. Transplantation of R.I improved phenotypes associated with ICP through the bile acid/farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) signaling pathway. We used the FXR antagonist Z-Guggulsterone (Z-Gu) to verify the key role of FXR in ICP and found that Z-Gu reversed the benefits of R.I on ICP rats. Our research highlights the important role of intestinal flora in the pathogenesis of ICP and provides a novel approach for its treatment.