Altered immune cell in human severe acute pancreatitis revealed by single-cell RNA sequencing.

Background: Severe acute pancreatitis (SAP) is characterized by inflammation, with inflammatory immune cells playing a pivotal role in disease progression. This study aims to understand variations in specific immune cell subtypes in SAP, uncover their mechanisms of action, and identify potential biological markers for predicting Acute Pancreatitis (AP) severity. Methods: We collected peripheral blood from 7 untreated SAP patients and employed single-cell RNA sequencing for the first time to construct a transcriptome atlas of peripheral blood mononuclear cells (PBMCs) in SAP. Integrating SAP transcriptomic data with 6 healthy controls from the GEO database facilitated the analysis of immune cell roles in SAP. We obtained comprehensive transcriptomic datasets from AP samples in the GEO database and identified potential biomarkers associated with AP severity using the "Scissor" tool in single-cell transcriptomic data. Results: This study presents the inaugural construction of a peripheral blood single-cell atlas for SAP patients, identifying 20 cell subtypes. Notably, there was a significant decrease in effector T cell subsets and a noteworthy increase in monocytes compared to healthy controls. Moreover, we identified a novel monocyte subpopulation expressing high levels of PPBP and PF4 which was significantly elevated in SAP. The proportion of monocyte subpopulations with high CCL3 expression was also markedly increased compared to healthy controls, as verified by flow cytometry. Additionally, cell communication analysis revealed insights into immune and inflammation-related signaling pathways in SAP patient monocytes. Finally, our findings suggest that the subpopulation with high CCL3 expression, along with upregulated pro-inflammatory genes such as S100A12, IL1B, and CCL3, holds promise as biomarkers for predicting AP severity. Conclusion: This study reveals monocytes' crucial role in SAP initiation and progression, characterized by distinct pro-inflammatory features intricately linked to AP severity. A monocyte subpopulation with elevated PPBP and CCL3 levels emerges as a potential biomarker and therapeutic target.

Mental health of primary health care physicians and nurses following prolonged infection control rules: a national survey in China.

Introduction: This study examined the prevalence and correlates of probable mental health disorders, including psychological distress, somatization, depression, anxiety, phobic anxiety (PHO), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and insomnia among Chinese primary health care (PHC) physicians and nurses amid the post-pandemic period in 2022. Method: Region-stratified sampling was conducted to recruit a national sample of 4,246 respondents from 31 July 2022 to 12 August 2022. A total of 692 primary healthcare institutions were identified in 30 provincial-level administrative regions of China. An online questionnaire was used for assessing probable mental health disorders using Symptoms Checklist-90-Revised (SCL-90-R) and PTSD Checklist for DSM-5 (PCL-5), and sleeping problems using Insomnia Severity Index (ISI). Data on demographics and work were also collected. Bivariate analysis and multiple logistic regression were conducted to identify significant correlates of probable mental health disorders. Results: A total of 4,246 valid questionnaires were identified. Results showed that relative to the prevalence of probable mental health disorders among health care workers at the early stage of the pandemic in China, there was an overall decreased prevalence except for somatization, PHO, and OCD among the current PHC physicians and nurses. Multiple logistic regressions showed that significant risk factors of common probable mental health disorders, namely psychological distress, SOM, DEP, ANX, PHO, OCD, PTSD, and insomnia, were female gender, multimorbidity, history of psychiatric disorders, quarantine experience, never asking anyone for help, and overtime work. Conclusion: Attention should be given to preexisting psychiatric and multimorbid conditions, social support, and work-related stressors. Regular assessment and psychological interventions are needed to enhance the mental health of PHC professionals even after public health crisis.

Genetic analyses of inflammatory polyneuropathy and chronic inflammatory demyelinating polyradiculoneuropathy identified candidate genes.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare, immune-mediated disorder in which an aberrant immune response causes demyelination and axonal damage of the peripheral nerves. Genetic contribution to CIDP is unclear and no genome-wide association study (GWAS) has been reported so far. In this study, we aimed to identify CIDP-related risk loci, genes, and pathways. We first focused on CIDP, and 516 CIDP cases and 403,545 controls were included in the GWAS analysis. We also investigated genetic risk for inflammatory polyneuropathy (IP), in which we performed a GWAS study using FinnGen data and combined the results with GWAS from the UK Biobank using a fixed-effect meta-analysis. A total of 1,261 IP cases and 823,730 controls were included in the analysis. Stratified analyses by gender were performed. Mendelian randomization (MR), colocalization, and transcriptome-wide association study (TWAS) analyses were performed to identify associated genes. Gene-set analyses were conducted to identify associated pathways. We identified one genome-wide significant locus at 20q13.33 for CIDP risk among women, the top variant located at the intron region of gene CDH4. Sex-combined MR, colocalization, and TWAS analyses identified three candidate pathogenic genes for CIDP and five genes for IP. MAGMA gene-set analyses identified a total of 18 pathways related to IP or CIDP. Sex-stratified analyses identified three genes for IP among males and two genes for IP among females. Our study identified suggestive risk genes and pathways for CIDP and IP. Functional analyses should be conducted to further confirm these associations.

An Adaptive Multi-D-Norm-Driven Sparse Unfolding Deconvolutional Network for Bearing Fault Diagnosis.

Impulsive blind deconvolution (IBD) is a popular method to recover impulsive sources for bearing fault diagnosis. Its underpinnings are in the design of objective functions based on prior knowledge of impulsive sources and a transfer function to describe transmission path influences. However, popular objective functions cannot retain waveform impulsiveness and periodicity cyclostationarity simultaneously, and the single convolution operation of IBD methods is insufficient to describe transmission paths composed of multiple linear and nonlinear units. Inspired by the MaxPooling period modulation intensity (MPMI) and convolutional sparse learning (CSL), an adaptive multi-D-norm-driven sparse unfolding deconvolution network (AMD-SUDN) is proposed in this paper. The core strategy is that one target vector with simultaneous impulsiveness and cyclostationarity is constructed automatically through the MPMI; then, this vector is substituted into the multi D-norm to design objective functions. Moreover, an iterative soft threshold algorithm (ISTA) for the CSL model is derived, and its iterative steps are unfolded into one deconvolution network. The algorithm's performance and the hyperparameter configuration are investigated by a set of numerical simulations. Finally, the proposed AMD-SUDN is applied to detect the impulsive features of bearing faults. All comparative results verify that the proposed AMD-SUDN achieves a better deconvolution accuracy than state-of-the-art IBD methods.

Ischemia-inhibited ferric chelate reductase 1 improves ferroptosis-mediated intestinal ischemia injury via Hippo signaling.

The precise mechanism of ferroptosis as a regulatory cell death in intestinal ischemia injury induced by vascular intestinal obstruction (Vio) remains to be elucidated. Here, we evaluated iron levels, glutathione peroxidase 4 (GPX4) and Acyl-CoA synthetase long-chain family member 4 (ACSL4) changes after intestinal ischemia injury to validate ferroptosis. As an enzyme for Fe3+ reduction to Fe2+, Ferric Chelate Reductase 1 (FRRS1) is involved in the electron transport chain and the tricarboxylic acid (TCA) cycle in mitochondria. However, whether it is involved in ferroptosis and its role in intestinal ischemia injury need to be clarified. In the present study, FRRS1 was overexpressed in vivo and in vitro. The results showed that overexpression of FRRS1 prevented ischemia-induced iron levels, reactive oxygen species (ROS) production, lipid peroxidation, inflammatory responses, and cell death. Meanwhile, FRRS1 overexpression promoted GPX4 expression and suppressed ACSL4 levels. Further studies revealed that FRRS1 overexpression inhibited the activity of large tumor suppressor 1 (LATS1) / Yes-associated protein (YAP) / transcriptional co-activator with PDZ-binding motif (TAZ), a key component of Hippo signaling. In conclusion, this study demonstrates that FRRS1 is intimately involved in the inhibition of ferroptosis and thus protection of the intestine from intestinal ischemia injury, its downstream mechanism was related to Hippo signaling. These data provide new sight for the prevention and treatment of intestinal ischemia injury.

Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia.

BACKGROUND: Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs. METHODS: We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG). RESULTS: In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10-6; rs12322371, OR = 1.14, p = 3.15×10-6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10-6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10-5; rs76959804, OR = 3.57, p = 1.77×10-5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10-6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16). CONCLUSION: The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence.

Genome-wide association study analysis of disease severity in Acne reveals novel biological insights.

Acne vulgaris is a common skin disease that affects >85% of teenage young adults among which >8% develop severe lesions that leaves permanent scars. Genetic heritability studies of acne in twin cohorts have estimated that the heritability for acne is 80%. Previous genome-wide association studies (GWAS) have identified 50 genetic loci associated with increased risk of developing acne when compared to healthy individuals. However only a few studies have investigated genetic association with disease severity. GWAS of disease progression may provide a more effective approach to unveil potential disease modifying therapeutic targets. Here, we performed a multi-ethnic GWAS analysis to capture disease severity in acne patients by using individuals with normal acne as a control. Our cohort consists of a total of 2,956 participants, including 290 severe acne cases and 930 normal acne controls from FinnGen, and 522 cases and 1,214 controls from BioVU. We also performed mendelian randomization (MR), colocalization analyses and transcriptome-wide association study (TWAS) to identify putative causal genes. Lastly, we performed gene-set enrichment analysis using MAGMA to implicate biological pathways that drive disease severity in Acne. We identified two new loci associated with acne severity at the genome-wide significance level, six novel associated genes by MR, colocalization and TWAS analyses, including genes CDC7, SLC7A1, ADAM23, TTLL10, CDK20 and DNAJA4 , and 5 novel pathways by MAGMA analyses. Our study suggests that the etiologies of acne susceptibility and severity have limited overlap, with only 26% of known acne risk loci presenting nominal association with acne severity and none of the novel severity associated genes reported as associated with acne risk in previous GWAS.

Commercial SCR catalyst modified with Cu metal to simultaneously efficiently remove NO and toluene in the fuel gas.

Developing an environmentally friendly selective catalytic reduction (SCR) catalyst to effectively eliminate both nitric oxides (NO) and toluene has garnered significant attention for regulating emissions from automobiles and the combustion of fossil fuels. This study synthesized a series of novel commercial V2O5-WO3/TiO2 catalysts modified with Cu through the wet impregnation method, which was employed to simultaneously remove NO and toluene from the fuel gas. The assessment of catalyst removal performance was conducted at a selective catalytic reduction system, and the experimental results showed a significant increase in the catalytic activity due to the modification of the copper metal. The 10% Cu/SCR catalyst showed a superior activity that the NO and toluene conversion reached 100% and 95.56% at 300 °C, respectively. Subsequently, various characterization techniques were employed to investigate the crystal phase, morphology, physical features, chemical states, and surface acidity properties of the synthesis catalysts. According to the characterization results, the presence of Cu metal did not have a noticeable impact on the physical property. However, the redox performance was enhanced, and the number of surface acidic sites was also increased after adding Cu to the SCR catalyst. Furthermore, the redox cycle of Cu metal and V species was facilitated to produce more active oxygen which helped to improve the NO and toluene conversion. This work offered a novel perspective into the synergistic oxidation of both NO and toluene, which was potentially relevant for improving the selective catalytic reduction process in coal-fired power plants.

The resin-supported iron-copper bimetallic composite as highly active heterogeneous Fenton-like catalysts for degradation of gaseous toluene.

In this study, a resin-supported iron-copper bimetallic heterogeneous Fenton catalyst with excellent removal performance, superior economy and outstanding recoverability was synthesized by an impregnation method and used to remove gaseous toluene. Experiments disclosed that 3-FeCu@LXQ-10 possessed extremely high catalytic capacity. At a temperature of 30 °C, an initial toluene concentration of 200 mg/m3 and H2O2 atomization amount of 3 mmol/h, the toluene removal efficiency of 3-FeCu@LXQ-10 was 97.50%. Experimental tests had revealed that the bimetallic supported catalysts exhibited higher catalytic activity than single metal-supported catalysts, owing to an interaction effect between iron and copper metal ions. Furthermore, electron paramagnetic resonance (EPR) and radical quenching tests were carried out, and the results indicated •OH radicals performed a key role in the Fenton-like process. In addition, the iron-copper bimetallic catalysts exhibited good reusability and stability characteristics during six degradation cycles. This study shows promising potential in using FeCu@LXQ-10 as a heterogeneous catalyst for removing toluene.

Ancestral diversity in lipoprotein(a) studies helps address evidence gaps.

INTRODUCTION: The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations. METHODS: Here, we examined how ancestrally diverse studies could clarify Lp(a)'s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations. RESULTS: Fourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R2=15% in East Asians) to high (R2=50% in Europeans) accuracy. For all populations, PRS showed promise as a 'rule out' for elevated Lp(a) because certainty of assignment to the low-risk threshold was high (88.0%-99.9%) across PRS thresholds (80th-99th percentile). Causal effects of increased Lp(a) with increased glycated haemoglobin were estimated for Europeans (p value =1.4×10-6), although inverse effects in Africans and East Asians suggested the potential for heterogeneous causal effects. Finally, Hispanic/Latinos were the only population in which known associations with coronary atherosclerosis and ischaemic heart disease were identified in external testing of Lp(a) PRS phenotypic effects. CONCLUSIONS: Our results emphasise the merits of prioritising ancestral diversity when addressing Lp(a) evidence gaps.

Expression quantitative trait methylation analysis elucidates gene regulatory effects of DNA methylation: the Framingham Heart Study.

Expression quantitative trait methylation (eQTM) analysis identifies DNA CpG sites at which methylation is associated with gene expression. The present study describes an eQTM resource of CpG-transcript pairs derived from whole blood DNA methylation and RNA sequencing gene expression data in 2115 Framingham Heart Study participants. We identified 70,047 significant cis CpG-transcript pairs at p < 1E-7 where the top most significant eGenes (i.e., gene transcripts associated with a CpG) were enriched in biological pathways related to cell signaling, and for 1208 clinical traits (enrichment false discovery rate [FDR] ≤ 0.05). We also identified 246,667 significant trans CpG-transcript pairs at p < 1E-14 where the top most significant eGenes were enriched in biological pathways related to activation of the immune response, and for 1191 clinical traits (enrichment FDR ≤ 0.05). Independent and external replication of the top 1000 significant cis and trans CpG-transcript pairs was completed in the Women's Health Initiative and Jackson Heart Study cohorts. Using significant cis CpG-transcript pairs, we identified significant mediation of the association between CpG sites and cardiometabolic traits through gene expression and identified shared genetic regulation between CpGs and transcripts associated with cardiometabolic traits. In conclusion, we developed a robust and powerful resource of whole blood eQTM CpG-transcript pairs that can help inform future functional studies that seek to understand the molecular basis of disease.

Performance and mechanisms of iron/copper-doped zirconium-based catalyst containing hydroxyl radicals for enhanced removal of gaseous benzene.

In the present study, novel copper-doped zirconium-based MOF (UIO-66) and copper-doped iron-based UIO-66 catalysts were prepared by hydrothermal synthesis method to improve the removal performance of gaseous benzene. The characteristics of the catalysts were analyzed by means of XRD, SEM, XPS, BET, and EPR. The copper loading catalyst had high crystallinity and irregular globular. The three kinds of catalysts with different Cu/Fe ratios had regular cubic shape. Compared with the catalyst supported with single copper, the bimetal Cu/Fe modification had a certain adjustment effect on the morphology, which specifically reflected in the uniform size and shape of catalyst particles with better dispersibility. The factors of different metal loading, dose of H2O2, and reaction temperature on benzene removal have been studied. It has been observed that in heterogeneous advanced oxidation removal of benzene, 3-Cu@UIO-66 and Cu1.5/Fe1.5@UIO-66 achieved the highest benzene removal efficiency of 81.2% and 94.6%, respectively. EPR results showed that the increase of Cu loading and different Cu/Fe ratios promoted the yield of hydroxyl radicals, thus promoted the benzene removal efficiency. The efficiency of heterogeneous oxidation removal of benzene first increased and then decreased with the increase of temperature due to H2O2 instability. DFT calculations exhibited that the Feoct-Cu-O site was a more effective activation site than the single Feoct-O site. Dissociative adsorption occurred with the O-O bond of H2O2 cracked, and the formed hydroxyls parallel adsorbed on the benzene surface. The combination of benzene and hydroxyls was strong chemisorption with the torsion angle of benzene ring obviously turned. The work was of great importance for identifying the roles of the novel catalyst for the removal of benzene pollutant from waste gases.

Effects of maternal supplementation of fish oil during late gestation and lactation on growth performance, fecal microbiota structure and post-weaning diarrhoea of offspring piglets.

Homeostasis of gut microbiota is a critical contributor to growth and health in weaned piglets. Fish oil is widely reported to benefit health of mammals including preventing intestinal dysfunction, yet its protective effect during suckling-to-weaning transition in piglets remains undetermined. Low (30 g/d) and high (60 g/d) doses of n-3-rich fish oil were supplemented in sows from late gestation to lactation. Serum indicators and gut microbiota were determined to evaluate the effects of maternal fish oil on growth performance, immunity and diarrhea of piglets. DHA and EPA in the colostrum as well as serum of suckling and 1-week post-wean piglets were significantly and linearly increased by maternal supplementation of fish oil (P < 0.05). IGF1 and T3 in nursing and weaned piglets were significantly elevated by maternal fish oil (P < 0.05), and the increase of IGF1 was concerning the dosage of fish oil. Colostrum IgG, plasma IgG, IgM in suckling piglets, IgG, IgM and IgA in weaned piglets were significantly increase as maternal replenishment of fish oil increased (P < 0.05). Additionally, cortisol was significantly reduced in weaned pigs (P < 0.05), regardless of dosage. 16S rRNA sequencing revealed that α-diversity of fecal microbiota in nursery piglets, and fecal Lactobacillus genus, positively correlated with post-weaning IgA, was significantly increased by high dosage. Collectively, maternal fish oil during late pregnancy and lactation significantly promoted growth, enhanced immunity, and reduced post-weaning diarrhea in piglets, therefore facilitated suckling-to-weaning transition in piglets, which may be partially due to the altered gut microbial community.

Exercise training has a protective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model with improved neural and intestinal pathology and modified intestinal flora.

Parkinson's disease (PD) is a common neurodegenerative disease with the exact etiology still unclear, but gut microbial disorders are thought to be related to the initiation and progression of it. Exercise training has a significant effect on the intestinal flora, so to investigate the promotion effect of exercise training on Parkinson's disease, we performed a rotarod walking training (5 times a week at 25 rpm for 20 min for 8 weeks) on a chronic mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and observed the locomotor function of mice, function of dopaminergic neurons, intestinal mucosal barrier condition, intestinal inflammation and the structure and composition of intestinal flora. The results showed in these PD mice, exercise training improved their motility, increased the dopamine (DA) content in the striatum, along with promoted the gene expression of tyrosine hydroxylase and brain-derived neurotrophic factor in the striatum, which suggests this exercise training might protect striatal dopaminergic neurons from MPTP damage; the results also showed exercise training promoted recovery from ileal pathology, reduced the gene expression of intestinal inflammatory factors, and significantly altered the composition and structure of the intestinal flora in these mice.

Overexpression of miR-146a-5p Ameliorates Inflammation and Autophagy in TLCs-Induced AR42J Cell Model of Acute Pancreatitis by Inhibiting IRAK1/TRAF6/NF-κB Pathway.

MicroRNA-146a-5p (miR-146a-5p) has been shown to mediate the inflammatory responses and autophagy in many diseases; however, its role in acute pancreatitis (AP) is not clear. OBJECTIVE: To determine the expression and role of miR-146a-5p in taurolithocholic acid-3-sulphate (TLCs) induced-AR42J cell model of AP. METHODS: Quantitative reverse transcription polymerase chain reaction, western blot, enzyme linked immunosorbent assay (ELISA), miRNA mimics or vectors or small interfering RNAs transfection and dual-luciferase reporter assay were employed in this study. RESULTS: miR-146a-5p was concentration-dependently decreased; while, interleukin-1 receptor associated kinase 1 (IRAK1) and tumor necrosis factor receptor associated factor 6 (TRAF6) were concentration-dependently increased after TLCs treatment. TLCs induced high levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and impaired autophagy characterized as increased of LC3-II/I and decreased expression of p62. Overex-presion of miR-146a-5p and knockdown of IRAK1/TRAF6 inhibited TLCs-induced inflammation and autophagy. Luciferase assay confirmed miR-146a-5p can directly target IRAK1 and TRAF6. The expression of p-NF-κB p65 was increased by TLCs, decreased by miR-146a-5p overexpression and IRAK1/ TRAF6 knockdown but increased after upregulation of IRAK1/TRAF6. CONCLUSIONS: Overexpression of miR-146a-5p ameliorates inflammation and autophagy in TLCs-treated AR42J cells by inhibiting IRAK1/ TRAF6/NF-κB pathway.

Polygenic risk scores for prediction of breast cancer risk in women of African ancestry: a cross-ancestry approach.

Polygenic risk scores (PRSs) are useful for predicting breast cancer risk, but the prediction accuracy of existing PRSs in women of African ancestry (AA) remains relatively low. We aim to develop optimal PRSs for the prediction of overall and estrogen receptor (ER) subtype-specific breast cancer risk in AA women. The AA dataset comprised 9235 cases and 10 184 controls from four genome-wide association study (GWAS) consortia and a GWAS study in Ghana. We randomly divided samples into training and validation sets. We built PRSs using individual-level AA data by a forward stepwise logistic regression and then developed joint PRSs that combined (1) the PRSs built in the AA training dataset and (2) a 313-variant PRS previously developed in women of European ancestry. PRSs were evaluated in the AA validation set. For overall breast cancer, the odds ratio per standard deviation of the joint PRS in the validation set was 1.34 [95% confidence interval (CI): 1.27-1.42] with the area under receiver operating characteristic curve (AUC) of 0.581. Compared with women with average risk (40th-60th PRS percentile), women in the top decile of the PRS had a 1.98-fold increased risk (95% CI: 1.63-2.39). For PRSs of ER-positive and ER-negative breast cancer, the AUCs were 0.608 and 0.576, respectively. Compared with existing methods, the proposed joint PRSs can improve prediction of breast cancer risk in AA women.

Molecular characterization of vascular intestinal obstruction using whole-exome sequencing.

Background: Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. This study aimed to identify several mutations associated with vascular intestinal obstruction. Methods: Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. The mutation genes in each patient and the mutation genes shared by all 9 patients were identified. Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. Copy number variations (CNVs) were identified using the open-source software CNV kit. Results: In total, all 9 patients shared 112 mutation genes. The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. MUC5AC was the protein with the highest degree in the PPI network. After searching the TiGER database, the keratin 18 (KRT18), MUC4, and MUC3A genes were found to be significantly more highly expressed in the colon tissues than the other tissues. Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Conclusions: Our study identified multiple mutations in 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18), and the CYP2W1 deletion. Our findings extend understandings of the potential pathological mechanism of vascular intestinal obstruction.

Tasks of COVID-19 prevention and control management teams at primary health care facilities in mainland China: a nationwide online cross-sectional survey.

BACKGROUND: This research aimed to investigate the tasks performed by Coronavirus Disease 2019(COVID-19) prevention and control management teams at primary healthcare (PHC) facilities during COVID-19 pandemic across the mainland China. METHODS: An online survey was performed and COVID-19 prevention and control management teams at PHC facilities were invited to participate in this research. The top 7 most important tasks in the three different periods of COVID-19 containment were selected and ranked. Participations of tasks were surveyed. RESULTS: A total of 998 valid responses (an effective rate of 99.11%) were collected. The respondents were divided into Group A (≤5 respondents within each PHC facility, n1 = 718) and Group B (> 5 respondents within each PHC facility, n2 = 280). The consensus was selected from top 7 most important tasks including screening at travel centers/intervals and screening at entry centers, at-home/centralized quarantine management, transferring, pre-examination/triage and fever sentinel surveillance clinic/fever clinic. Pre-examination/triage and fever sentinel surveillance clinic/fever clinic works became more significant in the regular prevention and control period. Adjusted analysis found that team members of Group A with a college, undergraduate college and graduate school educational background were less involved in pre-examination/triage works (aOR: 0.28; 95%CI: 0.09-0.86, P = 0.026; aOR: 0.30; 95%CI: 0.10-0.90, P = 0.031; aOR: 0.21; 95%CI: 0.05-0.82, P = 0.024). Those who were over the median age were twice more likely to be engaged in managing fever sentinel surveillance of clinic/fever clinic visitors (aOR: 2.18; 95%CI: 1.16-4.08, P = 0.015). Those being specialized in nursing and other specialties were less likely to participate in fever sentinel surveillance of clinic/fever clinic works (aOR: 0.44; 95%CI: 0.24-0.81, P = 0.009; aOR: 0.30; 95%CI: 0.16-0.58, P < 0.001). Those came from central and western China were less likely to participate in centralized quarantine management (aOR: 0.61; 95%CI: 0.38-0.98, P = 0.042; aOR: 0.64; 95%CI: 0.42-0.97, P = 0.037). Team members came from central and western China were twice less likely to participate in screening at travel centers/intervals (aOR: 1.75; 95%CI: 1.14-2.70, P = 0.011; aOR: 1.63; 95%CI: 1.07-2.48, P = 0.024). CONCLUSION: In mainland China, team members of COVID-19 prevention and control at PHC facilities are mainly responsible for screening, quarantine, transferring and monitoring during the COVID-19 pandemic. Pre-examination/triage and the fever sentinel surveillance clinic/fever clinic were gradually valued. Team members with lower educational background are competent in pre-examination/triage works, but more experienced general practitioners are more likely to be in charge of fever sentinel surveillance clinic/fever clinics work. The necessity of COVID-19 prevention and control management teams to participate in screening at travel centers/intervals is subjected to further discussions.

Vaccination coverage among COVID-19 prevention and control management teams at primary healthcare facilities in China and their attitudes towards COVID-19 vaccine: a cross-sectional online survey.

OBJECTIVE: To investigate the COVID-19 vaccination coverage rate and differences among various COVID-19 prevention primary healthcare (PHC) facilities in China and understand their attitudes towards COVID-19 vaccine. These findings are helpful to provide important suggestions to further improve national COVID-19 vaccination rate. DESIGN: A nationwide cross-sectional online survey was designed and conducted among COVID-19 prevention and control management teams at PHC facilities in mainland China. In the self-designed questionnaires, each subject was asked to evaluate on a 1-10 scale (10=extremely important/acceptable/influential) the COVID-19 vaccination importance, acceptance and factors related to vaccine hesitancy. SETTING: Subjects from 31 provinces and autonomous regions including minorities across mainland China were invited to complete the questionnaire between 22 February 2021 and 2 March 2021. PARTICIPANTS: Were selected by multistage stratified sampling, 998 valid questionnaires (valid rate 99.11%) were collected. The respondents were divided into group A (≤5 respondents within each PHC facility, n1=718) and group B (>5 respondents within each PHC facility, n2=280). OUTCOME MEASURES: Survey on vaccination rate and attitude towards COVID-19 vaccine included the following: (1) if the subjects think the vaccination is important in containment of COVID-19 pandemic (1-10 scale, 10=extremely important), (2) if they would accept COVID-19 vaccine (1-10 scale, 10=extremely acceptable) and (3) their opinions on 7 factors possibly related to vaccine hesitancy (1-10 scale, 10=extremely influential). All the items were designed based on the previous expert interviews. RESULTS: Our results showed vaccination rate was greater in group A (85.93%) than in group B (66.43%) (p<0.001). Detailed analyses revealed that in group A, male members were twice as likely to get vaccinated as compared with female members (adjusted OR (aOR): 2.07; 95% CI: 1.26 to 3.43, p=0.004). In group B, those who were at or under the median age had twice the odds of vaccination coverage compared with those who were over the median age (aOR: 2.29; 95% CI: 1.22 to 4.33, p=0.010). In addition, those who were specialised in traditional Chinese medicine were less likely to get vaccinated against COVID-19 compared with those who were specialised in general medicine, with the aOR: 0.10 (95% CI: 0.01 to 0.83, p=0.033). By analysing the factors that influenced the vaccination attitudes among the 998 respondents, we found no significant difference between the vaccinated and unvaccinated participants. However, further detailed analyses found that team members with undergraduate college education were less likely to score higher in COVID-19 vaccination importance than those with technical secondary school education (aOR: 0.35; 95% CI: 0.13 to 0.93, p=0.035); Furthermore, those with non-medical job titles had nearly twice the odds of giving a higher score for the uncertainty of vaccine efficacy compared with those with junior medical titles (aOR: 1.70; 95% CI: 1.02 to 2.85, p=0.016). Team members with a non-medical title were more likely to give a higher score for advice on social sources compared with those with a junior medical title (aOR: 1.70; 95% CI: 1.02 to 2.85, p=0.042). CONCLUSION: In PHC facilities, although there was a higher COVID-19 vaccination rate among COVID-19 prevention and control teams, some subgroups with different descriptive characters showed negative attitudes towards COVID-19 vaccination. Because primary care workers in China are highly expected to receive the vaccination, and support and educate the public for COVID-19 vaccination. Thus, it is important and necessary to continue to educate them about their vaccination concerns and change their attitudes towards vaccination. Our findings are highly beneficial for designing public vaccination education strategies.

Prevention and control of COVID-19 by primary health care facilities in China: a field-survey-based qualitative study in three typical cities.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) containment, primary health care (PHC) facilities inChina played an important role in providing both healthcare and public care services to community populations. The tasks of COVID-19 containment facilitated by PHC facilities were different among different regions and during different periods of COVID-19 pandemic. We sought to investigate the gaps on task participation, explore existing problems and provide corresponding solutions. METHODS: Semi-structured face-to-face interviews with COVID-19 prevention and control management teams of PHC facilities were conducted. Purposive stratified sampling was used and 32 team members of 22 PHC facilities were selected from Wuhan (as high-risk city), Shanghai (as medium-risk city) and Zunyi (as low-risk city). Framework analysis was employed to analyze the transcribed recordings. RESULTS: The main tasks of PHC facilities during the early period of the pandemic included assisting in contact tracing and epidemiological investigation, screening of populations at high-risk at travel centers/internals, house-by-house, or pre-examination/triage within PHC facilities; at-home/ centralized quarantine management; the work of fever sentinel clinics. Further analyses revealed the existing problems and suggestions for improvement or resolutions. Regular medical supply reserves were recommended because of the medical supply shortage during the pre-outbreak period. Temporarily converted quarantine wards and centralized quarantine centers could be used to deal with pressures on patients' treatment and management of the febrile patients. Only after strict evaluation of nucleic acid testing (NAT) results and housing conditions, decision on quarantine at-home or centralized quarantine centers could be made. Settings of fever sentinel clinics at PHC facilities allowed fever patients with no COVID-19 infection risks for treatment without being transferred to fever clinics of the designed secondary hospitals. Psychological intervention was sometimes in need and really helped in addressing individuals' mental pressures. CONCLUSIONS: During the COVID-19 containment, PHC facilities in China were responsible for different tasks and several problems were encountered in the working process. Accordingly, specific and feasible suggestions were put forward for different problems. Our findings are highly beneficial for healthcare teams and governments in handling similar situations.