Analysis of clinical characteristics and risk factors between elderly patients with severe and nonsevere Omicron variant infection

BACKGROUND Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has led to millions of confirmed cases and deaths worldwide.Elderly patients are at high risk of developing and dying from COVID-19 due to advanced age,decreased immune function,intense inflammatory response,and comorbidities.Shanghai has experienced a wave of infection with Omicron,a new variant of SARS-CoV-2,since March 2022.There is a pressing need to identify clinical features and risk factors for disease progression among elderly patients with Omicron infection to provide solid evidence for clinical policy-makers,public health officials,researchers,and the general public.AIM To investigate clinical characteristic differences and risk factors between elderly patients with severe and nonsevere Omicron SARS-CoV-2 variant infection.METHODS A total of 328 elderly patients with COVID-19 admitted to the Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 2022 to June 2022 were enrolled and divided into a severe group(82 patients)and a nonsevere group(246 patients)according to the diagnosis and treatment protocol of COVID-19(version 7).The clinical data and laboratory results of both groups were collected and compared.A chi-square test,t test,Mann-Whitney U test,hierarchical log-rank test,univariate and multivariate logistic regression,and hierarchical analyses were used to determine significant differences.RESULTS The severe group was older(84 vs 74 years,P<0.001),included more males(57.3%vs 43.9%,P=0.037),had a lower vaccination rate(P<0.001),and had a higher proportion of comorbidities,including chronic respiratory disease(P=0.001),cerebral infarction(P<0.001),chronic kidney disease(P=0.002),and neurodegenerative disease(P<0.001),than the nonsevere group.In addition,severe disease patients had a higher inflammatory index(P<0.001),greater need for symptomatic treatment(P<0.001),longer hospital stay(P=0.011),extended viral shedding time(P=0.014),and higher mortality than nonsevere disease patients(P<0.001).No difference was observed in the application of Paxlovid in the severe and nonsevere groups(P=0.817).Oxygen saturation,cerebral infarction,and D-dimer were predictive factors for developing severe disease in patients with COVID-19,with D-dimer having an excellent role(area under the curve:90.1%,95%CI:86.1-94.0%).In addition,D-dimer was a risk factor for developing severe COVID-19 according to multivariate stratified analysis.CONCLUSION The clinical course of severe COVID-19 is complex,with a higher need for symptomatic treatment.D-dimer is a suitable biomarker for identifying patients at risk for developing severe COVID-19.

MicroRNA-15a-cell division cycle 42 signaling pathway in pathogenesis of pediatric inflammatory bowel disease

AIM To determine whether cell division cycle(Cdc)42 is regulated by microRNA(miR)-15 a in the development of pediatric inflammatory bowel disease(IBD).METHODS We cultured 293 T cells, used plasmids and performed dual-luciferase assay to determine whether Cdc42 is a miR-15 a target gene. We cultured Caco-2 cells, and stimulated them with tumor necrosis factor(TNF)-α. We then employed lentiviruses to alter the expression of miR-15 a and Cdc42. We performed quantitative reverse transcription polymerase chain reaction(qRTPCR) and immunofluorescence to determine whether Cdc42 is regulated by miR-15 a in Caco-2 cells. Finally, we collected ileocecal tissue by endoscopy from patients and performed qRT-PCR to examine the expression of miR-15 a and Cdc42 in pediatric IBD patients.RESULTS Target Scan and dual-luciferase assay revealed thatCdc42 was a miR-15 a target gene. MiR-15 a expression increased(P = 0.0038) and Cdc42 expression decreased(P = 0.0013) in cells stimulated with TNF-α, and the expression of the epithelial junction proteins zona occludens(ZO)-1(P < 0.05) and E-cadherin(P < 0.001) decreased. Cdc42 levels decreased in miR-15 a-mimic cells(P < 0.001) and increased in miR-15 a inhibitor cells(P < 0.05). ZO-1 and E-cadherin decreased in mi R-15 a-mimic cells(P < 0.001) but not in the miR-15 a inhibitor + TNF-α cells. In Lv-Cdc42 + TNF-α cells, ZO-1 and E-cadherin expression increased compared to the Lv-Cdc42-NC + TNF-α(P < 0.05) or miR-15 a-mimic cells(P < 0.05). Fifty-four pediatric IBD patients were included in this study, 21 in the control group, 19 in the Crohn's disease(CD) active(AC) group, seven in the CD remission(RE) group, and seven in the ulcerative colitis(UC) group. MiR-15 a increased and Cdc42 decreased in the CD AC group compared to the control group(P < 0.05). miR-15 a decreased and Cdc42 increased in the CD RE group compared to the CD AC group(P < 0.05). miR-15 a was positively correlated with the Pediatric Crohn's disease Activity Index(PCDAI)(P = 0.006), while Cdc42 was negatively correlated with PCDAI(P = 0.0008). Finally, miR-15 a expression negatively correlated with Cdc42 in pediatric IBD patients(P = 0.0045).CONCLUSION Mi R-15 a negatively regulates epithelial junctions through Cdc42 in Caco-2 cells and pediatric IBD patients.

Intestinal dysbiosis in pediatric Crohn's disease patients with IL10RA mutations

BACKGROUND Several studies have employed animal models to explore the association between microbiota and interleukin(IL) 10 signaling;however,limited information is available about the human microbiome.AIM To characterize the microbiome in patients with IL10 RA mutations and to explore the association between gut dysbiosis and disease severity.METHODS Fecal samples were collected from patients who were diagnosed with loss-offunction mutations in the IL10 RA gene between January 2017 and July 2018 at the Children’s Hospital of Fudan University.Age-matched volunteer children were recruited as healthy controls.Patients with Crohn’s disease(CD) were used as disease controls to standardize the antibiotic exposure.Microbial DNA was extracted from the fecal samples.All analyses were based on the 16 S rRNA gene sequencing data.RESULTS Seventeen patients with IL10 RA mutations(IL10 RA group),17 patients with pediatric CD, and 26 healthy children were included.Both patients with IL10 RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability.The relative abundance of Firmicutes was substantially increased in the IL10 RA group(P=0.02).On further comparison of the relative abundance of taxa between patients with IL10 RA mutations and healthy children,13 taxa showed significant differences.The IL10 RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD.CONCLUSION In patients with IL10 RA mutations and early onset inflammatory bowel disease,gut dysbiosis shows a moderate association with disease severity.

Antistatic Structural Color and Photoluminescent Membranes from Co-assembling Cellulose Nanocrystals and Carbon Nanomaterials for Anti-counterfeiting

Static charges on optical ant-counterfeiting membranes may lead to materials structural changes,dust stain aggravation,and misreading of optical information.Incorporating conductive particles is a common way to transfer accumulative charges,but the key issue is how to achieve high dispersion and effective distribution of particles.According to the strategy of assembly-induced structural colors,cellulose nanocrystals(CNCS)were employed as a solid emulsifier to stabilize hydrophobic carbon nanoparticles(CNPs)in aqueous media;subsequently.by solvent evaporation-modulated co-assembly under a condition of 30°C and 20 RH%,the binary suspensions containing 2wt% CNC and CNPs with the equivalent concentration relative to CNC ranged from 1:40 to 1:10 were used to prepare antistatic composite membranes.Surface chemistry regulation of CNCs was applied to optimize the dispersiblity of CNPs and the orientation of assembled CNC arrays,and the hydrophilic CNCS were more favorable for dispersion and assembly of binary suspension systems.Meanwhile,one dimension carbon nanotube(CNT)and zero-dimension carbon black(CB)were found to show better dispersibility than two dimension graphene,which was verified by a semi-quantitative theoretical study.Moreover,the stable binary systems of CNT/CNC and CB/CNC were chosen for co-assembly as membranes,and the uniaxial orientation could be optimized as the fll-width of 9.8°at half maximum deviation angle while the surface resistivity could also drop down to 3.42 × 102 Qcmcm-1.The structural color character of such paper homology and antistatic integrated membranes contributes to optical information hiding and-reading,and shows great potential as optical mark recognition materials for electrostatic discharge protective packaging and anti.counterfeiting applications.