Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective:To explore and analyze the clinical features and prognostic factors of secondary intestinal diffuse large B-cell lymphoma(SI-DLBCL),in order to provide reference for the basic research and clinical diagnosis and treatment of secondary lymphoma of rare sites in the field of hematology.Methods:The clinical data of 138 patients with SI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were collected and sorted,the clinical and pathological features,diagnosis,treatment and prognosis were analyzed.Cox regression risk model was used to conduct univariate and multivariate analysis on the prognostic risk factors.Results:Among the 138 patients with SI-DLBCL included in this study,85(61.59％)were male,53(38.41％)were female,the median age of onset was 59.5(16-84)years,the clinical manifestations lacked specificity,the first-line treatment regimen was mainly chemotherapy(67.39％),94 cases(68.12％)received chemotherapy alone,40 cases(28.98％)were treated with chemotherapy combined with surgery,and 4 cases(2.90％)were treated with surgery alone.The median follow-up time was 72(1-148)months.Among the 138 patients with SI-DLBCL,79(57.25％)survived,34(24.64％)died,25 cases(18.12％)lost to follow-up,the PFS rates of 1-year,3-year and 5-year were 57.97％,49.28％and 32.61％,and the OS rates of 1-year,3-year and 5-year were 60.14％,54.35％and 34.06％,respectively.The results of univariate Cox regression analysis showed that age,Lugano stage and IPI score were the influencing factors of OS in SI-DLBCL patients,and age,Lugano stage and IPI score were the influencing factors of PFS in SI-DLBCL patients.The results of multivariate Cox analysis showed that Lugano stage was an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.Conclusion:Patients with SI-DLBCL are more common in middle-aged and elderly men,and the early clinical manifestations lack specificity,and the first-line treatment regimen is mainly R-CHOP chemotherapy,and Lugano stage is an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.

Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.

Helicobacter pylori is a common gram-negative bacterium, which is associated with a variety of gastroenteric diseases, such as gastritis, duodenal ulcer and gastric cancer. Recent studies suggested a potential role of Helicobacter pylori in the pathogenesis of common ocular diseases, such as central serous chorioretinopathy, glaucoma, anterior uveitis and ocular adnexal lymphoma. Helicobacter pylori might affect the pathophysiological process of ocular diseases through oxidative damage, circulatory disorders and immune injury. Some studies also suggested that eradication of Helicobacter pylori had certain effects on some ocular diseases. This review aims to summarize current evidence of the Helicobacter pylori in the pathogenesis of common ocular diseases, so as to encourage innovative approaches in the prevention and treatment of these ocular diseases.

Humans ; Child ; Lymphoma, Large B-Cell, Diffuse/pathology*

OBJECTIVE: To explore the coincidence rate of G-banding karyotype analysis and fluorescence in situ hybridization (FISH) for the diagnosis of children with sex chromosome mosaicisms. METHODS: A retrospective analysis was carried out for 157 children with suspected sex chromosome abnormalities who had presented at Shenzhen Children's Hospital from April 2021 to May 2022. Interphase sex chromosome FISH and G-banding karyotyping results were collected. The coincidence rate of the two methods in children with sex chromosome mosaicisms was compared. RESULTS: The detection rates of G-banding karyotype analysis and FISH were 26.1% (41/157) and 22.9% (36/157) , respectively (P > 0.05). The results of G-banding karyotype analysis showed that 141 cases (89.8%) were in the sex chromosome homogeneity group, of which only 5 cases (3.5%) were inconsistent with the results of FISH. There were 16 cases (10.2%) in the sex chromosome mosaicism group, of which 11 cases (68.8%) were inconsistent with the results of FISH. There was a statistical difference between the two groups in the coincidence rate of the results of the two methods (P < 0.05). CONCLUSION No significant difference was found between G-banding karyotype analysis and FISH in the detection rate of chromosome abnormalities. The coincidence rate in the mosaicism group was lower than that in the homogeneity group, and the difference was statistically significant. The two methods should be combined for clinical diagnosis.
Humans ; Mosaicism ; In Situ Hybridization, Fluorescence/methods* ; Retrospective Studies ; Karyotyping ; Chromosome Aberrations ; Sex Chromosome Aberrations ; Karyotype ; Chromosome Banding ; Sex Chromosomes

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by diffuse alveolar injury primarily caused by an excessive inflammatory response. Regrettably, the lack of effective pharmacotherapy currently available contributes to the high mortality rate in patients with this condition. Xuebijing (XBJ), a traditional Chinese medicine recognized for its potent anti-inflammatory properties, exhibits promise as a potential therapeutic agent for ALI/ARDS. This study aimed to explore the preventive effects of XBJ on ALI and its underlying mechanism. To this end, we established an LPS-induced ALI model and treated ALI mice with XBJ. Our results demonstrated that pre-treatment with XBJ significantly alleviated lung inflammation and increased the survival rate of ALI mice by 37.5%. Moreover, XBJ substantially suppressed the production of TNF-α, IL-6, and IL-1β in the lung tissue. Subsequently, we performed a network pharmacology analysis and identified identified 109 potential target genes of XBJ that were mainly involved in multiple signaling pathways related to programmed cell death and anti-inflammatory responses. Furthermore, we found that XBJ exerted its inhibitory effect on gasdermin-E-mediated pyroptosis of lung cells by suppressing TNF-α production. Therefore, this study not only establishes the preventive efficacy of XBJ in ALI but also reveals its role in protecting alveolar epithelial cells against gasdermin-E-mediated pyroptosis by reducing TNF-α release.
Animals ; Mice ; Alveolar Epithelial Cells ; Pyroptosis ; Gasdermins ; Lipopolysaccharides/adverse effects* ; Tumor Necrosis Factor-alpha ; Acute Lung Injury/drug therapy* ; Respiratory Distress Syndrome