Objective:Distribution and antibiotic resistance of pathogen isolated from children with intra-abdominal infection (IAI) associated sepsis in the intensive care unit (ICU) were analyzed to provide a reference for the empirical anti-infective treatment of IAI in children.Methods:We retrospectively analyzed the data of 116 children with culture-positive IAI-associated sepsis admitted to Children's Hospital of Zhejiang University School of Medicine from January 2019 to December 2021. Clinical isolation and drug resistance analysis were conducted based on different years of onset, locations of onset, and primary diseases.Results:A total of 186 strains of pathogens causing children with IAI-associated sepsis in ICU were collected. The distribution and antibiotic resistance of pathogen were as follows: the percentages of gram-positive bacteria, gram-negative bacteria, and fungi were 53.2%, 40.9%, and 5.9%, respectively; the top four strains were Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis, accounting for 57.0% of all isolates; Enterococcus faecium(19.9%) and Enterococcus faecalis (10.2%) were the dominating gram-positive bacteria; Escherichia coli (13.4%) and Klebsiella pneumoniae (13.4%) were more common gram-negative bacteria; Fungi were dominated by Candida albicans (3.8%).Fifty-seven strains of gram-positive bacteria were detected in 61 children with infectious diseases, mainly Enterococcus faecium (28 strains). There were 53 gram-negative strains, mainly Klebsiella pneumoniae (21 strains). Thirty-two strains of gram-positive bacteria were detected in 40 children with digestive tract malformation, and Enterococcus faecalis (six strains) were the most common. There were 14 gram-negative strains, mainly Escherichia coli (six strains). In 13 children with malignant tumors of digestive system, nine strains of gram-positive bacteria were cultured, and Enterococcus faecium (four strains) was the most common. There were eight gram-negative strains, mainly Escherichia coli (four strains).In the 46 community-acquired IAI patients,30 gram-positive isolates were cultured,mainly including Enterococcus faecium (12 strains), Staphylococcus epidermidis (seven strains), and Viridans streptococci (six strains); Forty gram-negative isolates mainly contained Escherichia coli (16 strains), Klebsiella pneumoniae (14 strains), and Enterobacter cloacae (five strains). In the 70 hospital-associated IAI patients, 69 gram-positive isolates such as Enterococcus faecium (25 strains), Enterococcus faecalis (17 strains), Enterococcus gallinarum (eight strains), and Staphylococcus aureus (seven strains) were cultured;Tirty-six gram-negative isolates were dominated by Klebsiella pneumoniae (11 strains), Escherichia coli (nine strains), Pseudomonas aeruginosa (four strains), and Acinetobacter baumannii (four strains). The mixed infection rate of clinical pathogens was up to 46.6%, and the overall resistance rate was 43.4%, in which gram-negative bacteria had high sensitivity to piperacillin/tazobactam, cefoperazone/sulbactam, imipenem, and tigecycline.The detection rates of Klebsiella pneumoniae and Escherichia coli producing extended-spectrum β-lactamases were 36.0% and 24.6%, respectively, with 100% sensitivity to tigecycline. Gram-positive bacteria showed 100% sensitivity to vancomycin, linezolid, and tigecycline. Conclusion:Pathogen isolated from children with IAI-associated sepsis in ICU were dominated by Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis,respectively. Before confirmation of pathogenic bacteria, antibacterial agents can be selected according to the infection type. It is important to note that a single broad-spectrum antibacterial agent or combination medication can be considered the initial empirical choice due to the large variety of pathogens, high rates of mixed infections, and high overall resistance.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

School-age children are in a specific development stage corresponding to juvenility, when the white matter of the brain experiences ongoing maturation. Diffusion-weighted magnetic resonance imaging (DWI), especially diffusion tensor imaging (DTI), is extensively used to characterize the maturation by assessing white matter properties in vivo. In the analysis of DWI data, spatial normalization is crucial for conducting inter-subject analyses or linking the individual space with the reference space. Using tensor-based registration with an appropriate diffusion tensor template presents high accuracy regarding spatial normalization. However, there is a lack of a standardized diffusion tensor template dedicated to school-age children with ongoing brain development. Here, we established the school-age children diffusion tensor (SACT) template by optimizing tensor reorientation on high-quality DTI data from a large sample of cognitively normal participants aged 6-12 years. With an age-balanced design, the SACT template represented the entire age range well by showing high similarity to the age-specific templates. Compared with the tensor template of adults, the SACT template revealed significantly higher spatial normalization accuracy and inter-subject coherence upon evaluation of subjects in two different datasets of school-age children. A practical application regarding the age associations with the normalized DTI-derived data was conducted to further compare the SACT template and the adult template. Although similar spatial patterns were found, the SACT template showed significant effects on the distributions of the statistical results, which may be related to the performance of spatial normalization. Looking forward, the SACT template could contribute to future studies of white matter development in both healthy and clinical populations. The SACT template is publicly available now ( https://figshare.com/articles/dataset/SACT_template/14071283 ).

The construction of high-quality public hospitals is the key to the construction of high-quality and efficient medical service system. The authors introduced the implementation of " 1+ 5″ engine-driven high-quality transformation development strategy in Zhejiang Provincial People′s Hospital, that is, adhering to the party building to lead the development of the hospital, and formulating measures to build a high-quality hospital from the five aspects of quality and safety, operational efficiency, brand influence, innovation driven and sustainable development, so as to provide some reference for other hospitals′ high-quality development.

Objective:To analyze the dynamic characteristics of rodents population density distribution in plague foci of Yinchuan City, Ningxia, and to provide reference for early warning of the plague.Methods:The plague surveillance results and epidemic reports of Yinchuan City from 2015 to 2018 were collected retrospectively, and the data were obtained from the database of Yinchuan City Center for Disease Control and Prevention. Descriptive method was used to analyze the species, number, density, fleas, vector index, etiology and serology results of rodents in the plague foci.Results:From 2015 to 2018, 4 families, 8 genera, 13 species, and 8 843 rodents were captured in the plague foci of Yinchuan City, and Meriones unguiculatus (4 557 rodents) was the dominant species. The survey area of host animal density was 1 459 hm 2, 3 805 rodents were captured, and the average density was 2.61/hm 2, of which the Meriones unguiculatus density was 1.98/hm 2. A total of 41 488 traps of nocturnal rodents were investigated, and 2 660 rodents were captured, with an average capture rate of 6.41%. A total of 6 952 fleas were obtained, belonging to 4 families, 7 genera, and 8 species; Xenopsylla conformis conformis (4 597 fleas) and Nosopsyllus laeviceps kuzenkovi (1 761 fleas) were the dominant species. Among them, there were 2 286 flea-infected rodents, the body flea-infected rate was 25.85% (2 286/8 843), and the body flea-infected index was 0.76. A total of 220 gerbils nests were investigated, and the nest flea-infected rate was 34.55% (76/220), and the nest flea-infected index was 0.98. No plague bacterium was isolated by pathogen detection of rodents and fleas. The results of indirect hemagglutination test were all negative. Conclusion:The Meriones unguiculatus is the dominant species in the plague foci of Yinchuan City, the average density is still high, attention should be paid to the occurrence of plague outbreaks.

Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies (GWAS) of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients (survival GWAS) and gene expression (expression quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also provides the associations between 8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb.
Aged ; Asian Continental Ancestry Group ; genetics ; China ; epidemiology ; Databases, Genetic ; Esophageal Squamous Cell Carcinoma ; genetics ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Genome-Wide Association Study ; Humans ; Internet ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; User-Computer Interface

ABSTRACT:Objective To assess the effect of prolonged laparoscopic surgery on peritoneal mesothelial cells and fibrinolysis in humans.Methods We examined prospectively 1 6 consecutive patients who underwent laparoscopic surgery (LAP)and 2 1 patients who underwent conventional open surgery (OP)for high-medium rectal cancer with curative intent.During the procedure,biopsy of the parietal peritoneum was made before operation and at 45 min,90 min,and 120 min after operation.The tissue-type plasminogen activator (tPA)and plasminogen activator inhibitor-1 (PAI-1 )were determined by enzyme-linked immunosorbent assay in peritoneal tissues.The cellular injury was detected by LDH assay.The proliferation was quantified by MTT assay.Results PAI-1 activity in the peritoneal tissue was significantly lower in LAP group than in the OP group.tPA activity decreased after 45min of open surgery,but there was no significant change in the LAP group.With time extension,the LDH activity increased and the proliferation of the mesothelial cells decreased.Conclusion Preservation of a prolonged hypofibrinolytic state by inhibition of PAI-1 up-regulation during LAP may predispose patients to less postoperative peritoneal adhesion. The cellular injury becomes apparent and the proliferation is inhibited during prolonged laparoscopic surgery.

Objective Cryptococcosis is a potential life-threatening systemic mycosis with a heterogeneous susceptible popu-lation which is classified into three groups according to the current guidelines, including AIDS patients, organ transplantation recipients ( OTR) , and non-HIV-infected and non-transplant hosts ( NHNT) .This study aimed to discuss the influence of basic diseases on the clinical features and prognosis of NHNT cryptococcosis patients. Methods Using a retrospective cohort study design, we retrieved the clinical data about 73 NHNT cryptococcosis patients treated in Jinling Hospital.Based on the presence or absence of immunodefi-ciency or infection-increasing complications, we divided the patients into a basic disease group ( n=35) and a non-basic disease group ( n=38) and analyzed their clinical characteristics, chest radiographic features, laboratory results, and clinical outcomes. Results Compared with the non-basic disease group, the basic disease group showed a significantly higher incidence rate of disseminated disea-ses (62.9%vs 21.1%, P<0.01), more cases of patchy consolidation (47.4%vs 16.7%, P<0.05) and mixed lesion (31.6%vs 3.3%, P<0.05) in chest radiography, and a higher mortality (30.0%vs 5.3%, P=0.016). Conclusion Basic diseases have a great impact on the clinical features and prognosis of NHNT cryptococcosis.NHNT patients with basic diseases are susceptible to dis-seminated diseases with severer clinical symptoms and a higher mortality.

Objective Vaccination is a most effective method for the prevention of severe diseases caused by pandemic influenza and microRNA ( miRNA) mediated gene silencing has offered a novel approach to the construction of new vaccines.Our study aimed to construct a recombinant influenza A ( H1 N1 ) virus with the PB1 gene that carries the target fragment of miRNA Let-7b. Methods After comparing the sequence of the A/Nanjing/108/2009 H1N1 viral fragments with that of Let-7b, we selected PB1 as the optimal gene sequence, inserted the Let-7b binding target gene into PB1, ligated the modified fragments with pDP 2000, and named the recombinant plasmids pDP-mu-PB1 and pDP-sclb-PB1, respectively.We co-transfected the MDCK and 293T cells with the recombinant and other seven plasmids and injected the supernatant into the allantoic cavity of the chickenembryo for virus propagation, followed by detection of the virus by hemagglutination ( HA) assay and measurement of the viral titer by TCID50 .We amplified the viral cRNA by RT-PCR and identified the viruses by agarose gel electrophoresis and nucleotide sequence analysis. Results PB1 was the optimal sequence ( 83 bp -107bp) for the attenuation of viruses.The HA-titers of miRT-H1N1 and scbl-H1N1 were 1∶32 and 1∶64, and their viral loads were 4.68 ×105 and 7.94 ×104 TCID50/mL, respectively.Nucleotide sequence analysis showed the expected fragment in the rescued virus. Conclusion A recombinant strain vaccine was successfully constructed, which has laid the foundation for fur-ther assessment of virulence.

Objective Dendritic cell-associatedC-type lectin-1 ( Dectin-1) is one of the most important receptors in antifungal innate immune response.This study was to construct a recombinant adenovirus vector expressing themurine Dectin-1gene and acquire a high-concentration adenovirus by amplification and purification. Methods The PCR amplification product CLEC7A-pIRES2-EGFP was cloned into the intermediate vector pDONR221, and then recom-bined with the backbone vector pAD/CMV/V5-DEST to produce a re-combinant plasmid pAD-CLEC7A-pIRE2S -EGFP.The recombinant plasmid was linearized with Pac I and transfected into human embryon-ic kidney ( HEK293) cells to produce recombinant adenovirus pAD-CLEC7Ap-IRES 2-EGFP. The adenovirus was propagated in the HEK293 cells and purified by filtering through the cellulose acetate membrane and concentrating column.Fluorescence microscopy and re-al-time PCR were used to determine the expression of the Dectin-1 gene. Results PCR identification, enzyme digestion, and sequen-cing results manifested theDectin-1 gene in the vector, with the final adenovirus titer of 5×1011 IU/mL.Fluorescence microscopy revealed green fluorescence and real-time PCR assay confirmed that the expression of Dectin-1 was improved by 8677.25 times. Conclusion A relatively high-titer adenovirus expressing Dectin-1 was acquired,which may help to further study the high expression of Dectin-1 in anti-fungal innate immunity in vitro and in vivo.