An adult with hemorrhagic varicella co-infects with cytomegalovirus: a case report.

BACKGROUND: Hemorrhagic varicella (HV) is a particular form of chicken pox.,with high mortality in adults. This form of the disease is rare, to date, approximately 4 cases have been reported. Occasional cases of HV have been documented in adults with hematologic disorders or other diseases. While there is one reported case of simultaneous reactivation of cytomegalovirus in an adult with chickenpox, there is a lack of information regarding changes in liver function indicators for such patients. This is unfortunate, as CMV reactivation can further exacerbate liver failure and increase mortality. In this report, we present a case of hemorrhagic varicella reactivation with cytomegalovirus and provide some relevant discussions. CASE PRESENTATION: We present the case of a 25-year-old male with HV, who had a history of nephrotic syndrome generally controlled with orally administered prednisone at a dosage of 50 mg per day for two months. The patient arrived at the emergency room with complaints of abdominal pain and the presence of hemorrhagic vesicles on his body for the past 3 days. Despite medical evaluation, a clear diagnosis was not immediately determined. Upon admission, the leukocyte count was recorded as 20.96 × 109/L on the first day, leading to the initiation of broad-spectrum antibiotic treatment. Despite the general interpretation that a positive IgG and a negative IgM indicate a previous infection, the patient's extraordinarily elevated IgG levels, coupled with a markedly increased CMV DNA quantification, prompted us to suspect a reactivation of the CMV virus. In light of these findings, we opted for the intravenous administration of ganciclovir as part of the treatment strategy. Unfortunately,,the patient succumbed to rapidly worsening symptoms and passed away. Within one week of the patient's demise, chickenpox gradually developed in the medical staff who had been in contact with him. In such instances, we speculate that the patient's diagnosis should be classified as a rare case of hemorrhagic varicella. CONCLUSION: Swift identification and timely administration of suitable treatment for adult HV are imperative to enhance prognosis.

Predicting overall survival and prophylactic cranial irradiation benefit in small-cell lung cancer with CT-based deep learning: A retrospective multicenter study.

BACKGROUND AND PURPOSE: To develop a computed tomography (CT)-based deep learning model to predict overall survival (OS) among small-cell lung cancer (SCLC) patients and identify patients who could benefit from prophylactic cranial irradiation (PCI) based on OS signature risk stratification. MATERIALS AND METHODS: This study retrospectively included 556 SCLC patients from three medical centers. The training, internal validation, and external validation cohorts comprised 309, 133, and 114 patients, respectively. The OS signature was built using a unified fully connected neural network. A deep learning model was developed based on the OS signature. Clinical and combined models were developed and compared with a deep learning model. Additionally, the benefits of PCI were evaluated after stratification using an OS signature. RESULTS: Within the internal and external validation cohorts, the deep learning model (concordance index [C-index] 0.745, 0.733) was far superior to the clinical model (C-index: 0.635, 0.630) in predicting OS, but slightly worse than the combined model (C-index: 0.771, 0.770). Additionally, the deep learning model had excellent calibration, clinical usefulness, and improved accuracy in classifying survival outcomes. Remarkably, patients at high risk had a survival benefit from PCI in both the limited and extensive stages (all P < 0.05), whereas no significant association was observed in patients at low risk. CONCLUSIONS: The CT-based deep learning model exhibited promising performance in predicting the OS of SCLC patients. The OS signature may aid in individualized treatment planning to select patients who may benefit from PCI.

Evaluation of Mucosal Healing in Crohn's Disease: Radiomics Models of Intestinal Wall and Mesenteric Fat Based on Dual-Energy CT.

This study aims to assess the effectiveness of radiomics signatures obtained from dual-energy computed tomography enterography (DECTE) in the evaluation of mucosal healing (MH) in patients diagnosed with Crohn's disease (CD). In this study, 106 CD patients with a total of 221 diseased intestinal segments (79 with MH and 142 non-MH) from two medical centers were included and randomly divided into training and testing cohorts at a ratio of 7:3. Radiomics features were extracted from the enteric phase iodine maps and 40-kev and 70-kev virtual monoenergetic images (VMIs) of the diseased intestinal segments, as well as from mesenteric fat. Feature selection was performed using the least absolute shrinkage and selection operator (LASSO) logistic regression. Radiomics models were subsequently established, and the accuracy of these models in identifying MH in CD was assessed by calculating the area under the receiver operating characteristic curve (AUC). The combined-iodine model formulated by integrating the intestinal and mesenteric fat radiomics features of iodine maps exhibited the most favorable performance in evaluating MH, with AUCs of 0.989 (95% confidence interval (CI) 0.977-1.000) in the training cohort and 0.947 (95% CI 0.884-1.000) in the testing cohort. Patients categorized as high risk by the combined-iodine model displayed a greater probability of experiencing disease progression when contrasted with low-risk patients. The combined-iodine radiomics model, which is built upon iodine maps of diseased intestinal segments and mesenteric fat, has demonstrated promising performance in evaluating MH in CD patients.

Inactivation of antibiotic resistant bacteria by Fe3O4 @MoS2 activated persulfate and control of antibiotic resistance dissemination risk.

Antibiotic resistance poses a global environmental challenge that jeopardizes human health and ecosystem stability. Antibiotic resistant bacteria (ARB) significantly promote the spreading and diffusion of antibiotic resistance. This study investigated the efficiency and mechanism of inactivating tetracycline-resistant Escherichia coli (TR E. coli) using Fe3O4 @MoS2 activated persulfate (Fe3O4 @MoS2/PS). Under optimized conditions (200 mg/L Fe3O4 @MoS2, 4 mM PS, 35 °C), TR E. coli (∼7.5 log CFU/mL) could be fully inactivated within 20 min. The primary reactive oxygen species (ROS) responsible for TR E. coli inactivation in the Fe3O4 @MoS2/PS system were hydroxyl radicals (•OH) and superoxide radicals (•O2-). Remarkably, the efflux pump protein was targeted and damaged by the generated ROS during the inactivation process, resulting in cell membrane rupture and efflux of cell content. Additionally, the horizontal transmission ability of residual antibiotic resistance genes (ARGs) harboring in the TR E. coli was also reduced after the inactivation treatment. This study offers an efficient approach for TR E. coli inactivation and substantial mitigation of antibiotic resistance dissemination risk.

Automatic Segmentation and Radiomics for Identification and Activity Assessment of CTE Lesions in Crohn's Disease.

BACKGROUND: The purpose of this article is to develop a deep learning automatic segmentation model for the segmentation of Crohn's disease (CD) lesions in computed tomography enterography (CTE) images. Additionally, the radiomics features extracted from the segmented CD lesions will be analyzed and multiple machine learning classifiers will be built to distinguish CD activity. METHODS: This was a retrospective study with 2 sets of CTE image data. Segmentation datasets were used to establish nnU-Net neural network's automatic segmentation model. The classification dataset was processed using the automatic segmentation model to obtain segmentation results and extract radiomics features. The most optimal features were then selected to build 5 machine learning classifiers to distinguish CD activity. The performance of the automatic segmentation model was evaluated using the Dice similarity coefficient, while the performance of the machine learning classifier was evaluated using the area under the curve, sensitivity, specificity, and accuracy. RESULTS: The segmentation dataset had 84 CTE examinations of CD patients (mean age 31 ±â€…13 years , 60 males), and the classification dataset had 193 (mean age 31 ±â€…12 years , 136 males). The deep learning segmentation model achieved a Dice similarity coefficient of 0.824 on the testing set. The logistic regression model showed the best performance among the 5 classifiers in the testing set, with an area under the curve, sensitivity, specificity, and accuracy of 0.862, 0.697, 0.840, and 0.759, respectively. CONCLUSION: The automated segmentation model accurately segments CD lesions, and machine learning classifier distinguishes CD activity well. This method can assist radiologists in promptly and precisely evaluating CD activity.

The automatic segmentation and radiomics of computed tomography enterography images can assist radiologists in accurately and quickly identifying Crohn's disease lesions and evaluating Crohn's disease activity.

Photocatalytic Degradation of Acetaminophen in Aqueous Environments: A Mini Review.

Over the past few decades, acetaminophen (ACT), a typical nonsteroidal anti-inflammatory drug (NSAID), has gained global usage, positioning itself as one of the most extensively consumed medications. However, the incomplete metabolism of ACT leads to a substantial discharge into the environment, classifying it as an environmental contaminant with detrimental effects on non-target organisms. Various wastewater treatment technologies have been developed for ACT removal to mitigate its potential environmental risk. Particularly, photocatalytic technology has garnered significant attention as it exhibits high efficiency in oxidizing and degrading a wide range of organic pollutants. This comprehensive review aims to systematically examine and discuss the application of photocatalytic technology for the removal of ACT from aqueous environments. Additionally, the study provides a detailed overview of the limitations associated with the photocatalytic degradation of ACT in practical applications, along with effective strategies to address these challenges.

In vitro corrosion resistance and dual antibacterial ability of curcumin loaded composite coatings on AZ31 alloy: Effect of amorphous calcium carbonate.

Rapid corrosion and bacterial infection are obstacles to put into use biodegradable magnesium (Mg) alloy as biomedical materials. In this research, an amorphous calcium carbonate (ACC)@curcumin (Cur) loaded poly-methyltrimethoxysilane (PMTMS) coating prepared by self-assembly method on micro-arc oxidation (MAO) coated Mg alloy has been proposed. Scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy are adopted to analyze the morphology and composition of the obtained coatings. The corrosion behaviour of the coatings is estimated by hydrogen evolution and electrochemical tests. The spread plate method without or with 808 nm near-infrared irradiation is applied to evaluate the antimicrobial and photothermal antimicrobial ability of the coatings. Cytotoxicity of the samples is tested by 3-(4,5)-dimethylthiahiazo(-z-y1)-2,5-di- phenytetrazoliumromide (MTT) and live/dead assay culturing with MC3T3-E1 cells. Results show that the MAO/ACC@Cur-PMTMS coating exhibited favourable corrosion resistance, dual antibacterial ability, and good biocompatibility. Cur was employed as an antibacterial agent and photosensitizer for photothermal therapy. The core of ACC significantly improved the loading of Cur and the deposition of hydroxyapatite corrosion products during degradation, which greatly promoted the long-term corrosion resistance and antibacterial activity of Mg alloys as biomedical materials.

Risk factors associated with indoor transmission during home quarantine of COVID-19 patients.

Purpose: The 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. Methods: A 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. Results: A 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). Conclusion: Patients 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.

CTE-Based Radiomics Models Can Identify Mucosal Healing in Patients with Crohn's Disease.

RATIONALE AND OBJECTIVES: To develop computed tomography enterography (CTE)-based radiomics models to assess mucosal healing (MH) in patients with Crohn's disease (CD). MATERIALS AND METHODS: CTE images were retrospectively collected from 92 confirmed cases of CD at the post-treatment review. Patients were randomly divided into developing (n = 73) and testing (n = 19) groups. Radiomics features were extracted from the enteric phase images, and the least absolute shrinkage and selection operator (LASSO) logistic regression was applied for feature selection using 5-fold cross-validation on the developing group. The selected features were further identified from the top-ranked features and used to create improved radiomics models. Machine learning models were constructed to compare radiomics models with different radiomics features. The area under the ROC curve (AUC) was calculated to assess the predictive performance for identifying MH in CD. RESULTS: Among the 92 CD patients included in our study, 36 patients achieved MH. The AUC of the radiomics model 1, which was based on the 26 selected radiomics features, was 0.976 for evaluating MH in the testing cohort. The AUCs of radiomics models 2 and 4, based on the top 10 and top 5 positive and negative radiomics features, were 0.974 and 0.952 in the testing cohort, respectively. The AUC of the radiomics model 3, built by removing features with r > 0.5, was 0.956 in the testing cohort. The clinical utility of the clinical radiomics nomogram was confirmed by the decision curve analysis (DCA). CONCLUSION: The CTE-based radiomics models have demonstrated favorable performance in assessing MH in patients with CD. Radiomics features can be used as a promising imaging biomarker for MH.

Mucosal healing assessment in Crohn's disease with normalized iodine concentration from dual-energy CT enterography: comparison with endoscopy.

OBJECTIVES: Mucosal healing (MH) is an important goal in the treatment of patients with Crohn's disease (CD). Noninvasive assessment of MH with normalized iodine concentration (NIC) is unknown. METHODS: In this retrospective study, 94 patients with diagnosed CD underwent endoscopy and dual-energy CT enterography (DECTE) at the post-infliximab treatment review. Two radiologists reviewed DECTE images by consensus for assessing diseased bowel segments of the colon or terminal ileum, and the NIC was measured. Patients were divided into transmural healing (TH), MH and non-MH groups. The diagnostic performance of the MH and non-MH groups with clinical factors and NIC was assessed utilizing receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 94 patients included in our study, 8 patients achieved TH, 34 patients achieved MH, and 52 patients did not achieve MH at the post-IFX treatment review. The area under the ROC curve (AUC), sensitivity, specificity, and accuracy values were 0.929 (95% confidence interval [CI] 0.883-0.967), 0.853, 0.827, and 0.837, respectively, for differentiating MHs from non-MHs, and the optimal NIC threshold was 0.448. The AUC of the combined model for distinguishing MHs from non-MHs in CD patients, which was based on the NIC and calprotectin, was 0.964 (95% CI 0.935-0.987). CONCLUSIONS: The normalized iodine concentration measurement in DECTE has good performance in assessment MH in patients with CD. Iodine concentration from DECTE can be used as a radiologic marker for MH.

Visible-light-driven photocatalytic degradation of tetracycline hydrochloride by Z-scheme Ag3PO4/1T@2H-MoS2 heterojunction: Degradation mechanism, toxicity assessment, and potential applications.

Residual antibiotics in wastewater threaten living organisms and the ecosystem, while the photocatalytic process is recognized as one of the most eco-friendly and promising technologies for the treatment of antibiotic wastewater. In this study, a novel Z-scheme Ag3PO4/1T@2H-MoS2 heterojunction was synthesized, characterized, and used for the visible-light-driven photocatalytic degradation of tetracycline hydrochloride (TCH). It was found that Ag3PO4/1T@2H-MoS2 dosage and coexisting anions had significant effects on the degradation efficiency, which could reach up to 98.9 % within 10 min under the optimal condition. Combing experiments and theoretical calculations, the degradation pathway and mechanism were thoroughly investigated. The excellent photocatalytic property of Ag3PO4/1T@2H-MoS2 was achieved attributed to the Z-scheme heterojunction structure, which remarkably inhibited the recombination of photoinduced electrons and holes. The potential toxicity and mutagenicity for TCH and generated intermediates were evaluated, which revealed the ecological toxicity of antibiotic wastewater was reduced effectively during the photocatalytic degradation process.

Comparison of microstructure, mechanical property, and degradation rate of Mg-1Li-1Ca and Mg-4Li-1Ca alloys.

Mg-1 wt.% Li-1 wt.% Ca (LX11) and Mg-4 wt.% Li-1 wt.% Ca (LX41) alloys share the same hexagonal closed-packed crystalline structure. However, the differences in microstructure, mechanical properties, and degradation rates between the two alloys are not well understood. Hereby, the above three aspects of LX11 and LX41 alloys were studied via optical microscopy, tensile tests, and electrochemical polarization and electrochemical impedance spectroscopy, together with hydrogen evolution. The concentration of the released Mg2+, Ca2+, and Li+ ions was analyzed using a flame atomic absorption spectrophotometer. Results demonstrated that the LX11 alloy was composed of finer α-Mg grains, fewer twins, and smaller volume fractions of the intermetallic phases Mg2Ca than the LX41 alloy. The increasing Li concentration generated a weak decrease in the yield strength of the Mg-Li-Ca alloys, a remarkable increase in elongation to failure, and a stable ultimate tensile strength. The LX11 alloy had better corrosion resistance than the LX41 alloy. The release rate of the cations (Mg2+, Ca2+, and Li+) varied significantly with time. The release rate of metallic ions in Hank's solution cannot reflect the true corrosion rate of Mg-Li-Ca alloys due to the formation of the precipitated corrosion products and their difference in solubility. The dealloying corrosion mechanism of the Mg2Ca phase in Mg-Li-Ca alloys was proposed.

Survival benefits of para-aortic lymphadenectomy in colorectal cancer with clinically suspected para-aortic lymph node metastasis: a meta-analysis and systematic review.

BACKGROUND AND OBJECTIVES: In patients with colorectal cancer and clinically suspected para-aortic lymph node metastasis, the survival benefit of para-aortic lymphadenectomy is unknown. We conducted a meta-analysis and systematic review to investigate it. METHODS: PubMed, Web of Science, and EMBASE were searched until January 2000 to April 2022 to identify studies reporting overall survivals, complication rates, and hazard ratios of prognostic factors in patients with colorectal cancer undergoing para-aortic lymphadenectomy, and those data were pooled. RESULTS: Twenty retrospective studies (1021 patients undergoing para-aortic lymphadenectomy) met the inclusion criteria. Meta-analysis indicates that participants undergoing para-aortic lymphadenectomy were associated with 5-year survival benefit, compared to those not receiving para-aortic lymphadenectomy (odds ratio = 3.73, 95% confidence interval: 2.05-6.78), but there was no significant difference in complication rate (odds ratio = 0.97, 95% confidence interval: 0.46-2.08). Further analysis of para-aortic lymphadenectomy group showed that 5-year survival of the positive group with pathologically para-aortic lymph node metastasis was lower than that of the negative group (odds ratio = 0.19, 95% confidence interval: 0.11-0.31). Moreover, complete resection (odds ratio = 5.26, 95% confidence interval: 2.02-13.69), para-aortic lymph node metastasis (≤4) (hazard ratio = 1.88, 95% confidence interval: 0.97-3.62), and medium-high differentiation (hazard ratio = 2.98, 95% confidence interval: 1.48-5.99) were protective factors for survival. Preoperative extra-retroperitoneal metastasis was associated with poorer relapse-free survival (hazard ratio = 1.85, 95% confidence interval: 1.10-3.10). CONCLUSION: Para-aortic lymphadenectomy had promising clinical efficacy in prolonging survival rather than complication rate in patients with colorectal cancer and clinically diagnostic para-aortic lymph node metastasis. Further prospective studies should be performed. TRIAL REGISTRATION: PROSPERO: CRD42022379276.

Application of immune checkpoint inhibitors in immunotherapy for gastric cancer.

Gastric cancer is the fifth most common cancer worldwide. With the development of immunotherapy, especially the application of immune checkpoint inhibitors (ICIs), the prognosis of advanced gastric cancer has improved. At present, ICIs combined with other therapies or dual ICI strategies in the treatment of advanced gastric cancer have shown clinical effectiveness and controllable safety. In addition, predictive biomarkers facilitate the precise selection of patients. Therefore, it is crucial to explore rational combinations and reliable predictive biomarkers for ICI therapy. This article reviews the recent advances in ICIs and relevant predictive biomarkers in the treatment of gastric cancer.

In recent years, with the application of immunotherapy, clinical efficacy in gastric cancer has been effectively improved. At present, it is encouraging that immunotherapy combined with chemotherapy has become the first choice for the treatment of patients with advanced gastric cancer. However, researchers remain committed to exploring the efficacy of immunotherapy in combination with various therapies. Equally important, the identification of biomarkers can facilitate the selection of patients suitable for immunotherapy. This article summarizes important immunotherapy clinical trials and discusses therapeutic combinations and biomarkers being explored.

Effect of continuing the use of renin-angiotensin system inhibitors on mortality in patients hospitalized for coronavirus disease 2019: a systematic review, meta-analysis, and meta-regression analysis.

BACKGROUND: The effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on mortality was preliminarily explored through the comparison of ACEIs/ARBs with non-ACEIs/ARBs in patients with coronavirus disease 2019 (COVID-19). Reaching a conclusion on whether previous ACEI/ARB treatment should be continued in view of the different ACE2 levels in the comparison groups was not unimpeachable. Therefore, this study aimed to further elucidate the effect of ACEI/ARB continuation on hospital mortality, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) in the same patient population. METHODS: We searched PubMed, the Cochrane Library, Ovid, and Embase for relevant articles published between December 1, 2019 and April 30, 2022. Continuation of ACEI/ARB use after hospitalization due to COVID-19 was considered as an exposure and discontinuation of ACEI/ARB considered as a control. The primary outcome was hospital mortality, and the secondary outcomes included 30-day mortality, rate of ICU admission, IMV, and other clinical outcomes. RESULTS: Seven observational studies and four randomized controlled trials involving 2823 patients were included. The pooled hospital mortality in the continuation group (13.04%, 158/1212) was significantly lower than that (22.15%, 278/1255) in the discontinuation group (risk ratio [RR] = 0.45; 95% confidence interval [CI], 0.28-0.72; P = 0.001). Continuation of ACEI/ARB use was associated with lower rates of ICU admission (10.5% versus 16.2%, RR = 0.63; 95% CI 0.5-0.79; P < 0.0001) and IMV (8.2% versus 12.5%, RR = 0.62; 95% CI 0.46-0.83, P = 0.001). Nevertheless, the effect was mainly demonstrated in the observational study subgroup (P < 0.05). Continuing ACEI/ARB had no significant effect on 30-day mortality (P = 0.34), acute myocardial infarction (P = 0.08), heart failure (P = 0.82), and acute kidney injury after hospitalization (P = 0.98). CONCLUSION: Previous ACEI/ARB treatment could be continued since it was associated with lower hospital deaths, ICU admission, and IMV in patients with COVID-19, although the benefits of continuing use were mainly shown in observational studies. More evidence from multicenter RCTs are still needed to increase the robustness of the data. Trial registration PROSPERO (CRD42022341169). Registered 27 June 2022.

Corrosion resistance and mechanisms of Nd(NO3)3 and polyvinyl alcohol organic-inorganic hybrid material incorporated MAO coatings on AZ31 Mg alloy.

This work reports the design and preparation of novel organic (polyvinyl alcohol, PVA)-inorganic (neodymium nitrate, Nd(NO3)3) hybrid coatings on micro-arc oxidation (MAO) coating for magnesium (Mg) alloy corrosion protection. X-ray diffractometer, X-ray photoelectron spectroscopy, fourier transform infrared spectroscopy, field emission scanning electron microscope, Energy Dispersive X-ray spectrometer and surface roughness were applied to characterize the chemical composition and surface morphology of the coatings. The corrosion resistance of the coatings was evaluated by electrochemical and salt spray tests. The results suggested that the formation of PVA-Nd3+ and PVA-Mg2+ complexes promoted the enrichment of Nd3+ on the surface, and thereby improved the sealing quality and compactness of the coating. Interestingly, when the coating was damaged, the Nd3+ ions were transformed to their carbonates and covered the active sites, and thus exhibiting self-healing function. Further, the corrosion resistance of PVA-Nd3+ modified MAO composite coating on AZ31 Mg alloy was improved.

The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China): Protocol of a prospective multicenter observational study.

BACKGROUND: Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. METHODS: The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at - 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. CONCLUSIONS: Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653.

Acinar ATP8b1/LPC pathway promotes macrophage efferocytosis and clearance of inflammation during chronic pancreatitis development.

Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has not been confirmed to occur in chronic pancreatitis (CP). Here, we investigated whether efferocytosis constitutes a novel regulatory target in CP and its mechanisms. PRSS1 transgenic (PRSS1Tg) mice were treated with caerulein to mimic CP development. Phospholipid metabolite profiling and epigenetic assays were performed with PRSS1Tg CP models. The potential functions of Atp8b1 in CP model were clarified using Atp8b1-overexpressing adeno-associated virus, immunofluorescence, enzyme-linked immunosorbent assay(ELISA), and lipid metabolomic approaches. ATAC-seq combined with RNA-seq was then used to identify transcription factors binding to the Atp8b1 promoter, and ChIP-qPCR and luciferase assays were used to confirm that the identified transcription factor bound to the Atp8b1 promoter, and to identify the specific binding site. Flow cytometry was performed to analyze the proportion of pancreatic macrophages. Decreased efferocytosis with aggravated inflammation was identified in CP. The lysophosphatidylcholine (LPC) pathway was the most obviously dysregulated phospholipid pathway, and LPC and Atp8b1 expression gradually decreased during CP development. H3K27me3 ChIP-seq showed that increased Atp8b1 promoter methylation led to transcriptional inhibition. Atp8b1 complementation substantially increased the LPC concentration and improved CP outcomes. Bhlha15 was identified as a transcription factor that binds to the Atp8b1 promoter and regulates phospholipid metabolism. Our study indicates that the acinar Atp8b1/LPC pathway acts as an important "find-me" signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. Bhlha15, Atp8b1, and LPC could be clinically translated into valuable therapeutic targets to overcome the limitations of current CP therapies.