Objective To investigate the temporal changes in pathological damage and macrophage polarization in liver and spleen tissues of mice infected with Angiostrongylus cantonensis, and to preliminarily unravel the peripheral immune responses during the early stage of A. cantonensis infection. Methods Forty female BALB/c mice at ages of 6 to 8 weeks were randomly divided into four groups, including the control group and 7-, 14-, and 21-day infection groups, with 10 mice in each group. Each mouse in the infection groups was inoculated with 30 third-stage (L3) larvae of A. cantonensis by oral gavage, and five mice were randomly selected from each infection group on days 7, 14, and 21 post-infection, while mice in the control group were given the same volume of physiological saline and five mice were randomly selected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled. The histopathological changes of mouse liver and spleen tissues were observed using hematoxylin and eosin (HE) staining, and the percentage of positive staining area and the co-localization positive rates of the macrophage surface antigens F4/80, CD86, and CD206 were quantified in mouse liver and spleen tissues using immunohistochemical and immunofluorescence staining. In addition, five mice were collected from each infection group on days 7, 14, and 21 post-infection, and five mice were collected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled for detection of macrophage markers CD86 and CD206 and macrophage phenotyping using flow cytometry, and the expression of M1 macrophage markers, including inducible nitric oxide synthase (Nos2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and M2 markers, including arginase 1 (Arg1), mannose receptor C-type 1 (Mrc1) and chitinase-like protein 3 (Chil3) was quantified in mouse liver and spleen tissues using real-time quantitative PCR (RT-qPCR) assay. Results Proliferative lesions of the hepatocyte were observed in mouse liver tissues and the follicular structures of the mouse spleen white pulp were disrupted 21 days post-infection with A. cantonensis. Immunohistochemical staining showed that there were significant differences in the percentages of F4/80, CD86 and CD206 positive staining areas in the liver and spleen tissues among the four groups of mice (F = 242.40, 197.14, 183.19, 157.65, 242.35 and 146.24; all P values < 0.001), and the percentages of positive staining in the liver and spleen tissues of mice in the 14-day infection group [(4.45 ± 0.51)%, (3.74 ± 0.67)%, (8.32 ± 0.72)%, (16.56 ± 1.14)%, (11.62 ± 0.52)%, and (8.29 ± 0.72)%, respectively] and the 21-day infection group [(3.70 ± 0.11)%, (3.22 ± 0.43)%, (11.53 ± 1.03)%, (12.59 ± 1.05)%, (9.02 ± 0.83)%, and (11.67 ± 1.10)%, respectively] were higher than in the control group [(0.35 ± 0.16)%, (0.40 ± 0.02)%, (0.93 ± 0.05)%, (2.78 ± 0.26)%, (2.33 ± 0.20)%, and (1.85 ± 0.20)%, respectively] (all P values < 0.05). Immunofluorescence staining showed significant differences in the positive rates of F4/80 co-localization with CD86 and CD206 in mouse liver and spleen tissues among the four groups (F = 24.42, 25.28, 54.51 and 130.55; all P values < 0.001). Flow cytometry detected significant differences in the proportions of CD86⁺ and CD206⁺ macrophages in mouse liver and spleen tissues among the four groups (F = 67.98, 18.41, 29.77, 172.80; all P values < 0.001), and the proportions of CD206⁺ macrophages in the liver and spleen of the 21-day infection group were significantly higher than those in the control group [(9.25 ± 2.55)% vs (3.83 ± 0.72)%, and (4.22 ± 0.56)% vs (0.47 ± 0.18)%, respectively] (both P values < 0.05). In addition, RT-qPCR assay quantified significant differences in the relative mRNA expression of M1 macrophage markers (IL-1β, TNF-α and Nos2) and M2 macrophage markers (Arg1, Chil3 and Mrc1) in mouse liver and spleen tissues among the four groups (F = 41.30, 31.82, 199.33, 19.96, 62.01, 119.76, 23.67, 95.90, 72.27, 82.59, 123.41 and 29.75; all P values < 0.05). Conclusions A. cantonensis infection may cause progressive pathological damage in mouse liver and spleen tissues, accompanied by dynamic temporal changes in macrophage polarization. M1 macrophage polarization predominates at the early stage of A. cantonensis infection and shifts towards M2 polarization at the later stages, suggesting that M2 polarization may participate in immune regulation at late stages of A. cantonensis infection by suppressing excessive inflammatory responses and promoting tissue repair.

Objective:To investigate the effect of deubiquitinating enzymes(DUBs) USP2 on depressive-like behavior and hippocampal NF-κB expression in mice.Methods:(1) USP2 silencing experiment: Two USP2 silencing interference sequences with the highest knockdown efficiency were screened and cloned into a lentivirus vector. Mice were microinjected with lentivirus vector into both sides of hippocampus to silence the USP2 gene, and depressive behavior and USP2 protein expression in hippocampal tissue were observed. (2) Venlafaxine intervention experiment: total 32 healthy male C57BL/6 mice were randomly divided into virus control group, Venlafaxine group, USP2 silencing group, and USP2 silencing+ Venlafaxine group according to the random number table method, with 8 mice in each group. Mice were injected with lentivirus into both side of the hippocampus, and 7 days later, they were given intraperitoneal injection of Venlafaxine (5 mg/kg, once a day, for a total of 14 days). After the administration, the depressive behavior of mice was detected by forced swimming test(FST) and tail suspension test(TST), and the expression levels of USP2, p-IκBα, IκBα, p-NF-κB p65, and NF-κB p65 in the hippocampus of mice were detected by Western blot.SPSS 25.0 and GraphPad Prism 8.0 were used for data processing and chart drawing.The t-test was used for comparison between two groups, One-way ANOVA was used for comparison among multiple groups, and Tukey HSD or LSD- t was used for post hoc pairwise comparison when there was homogeneity of variance. Results:(1)The results of the USP2 silencing experiment showed that both screened USP2 silencing sequences had good gene knockout effects. The expression levels of USP2 protein in the hippocampus of mice injected with USP2 silencing virus were lower than those of the negative control virus groups (both P<0.05). The immobility time of mice in the FST and TST was higher than that of the negative control virus group (both P<0.05). (2)Venlafaxine intervention experiment: There were statistically significant differences in immobility time among the four groups of mice in the FST and TST ( F=8.90, 4.41, both P<0.05). The immobility time of FST and the immobility time of TST in the USP2 silencing+ Venlafaxine group ((48.13±12.76) s, (77.38±12.35) s) were lower than those in the USP2 silencing group((129.88±11.67)s, (148.29±15.31)s) (both P<0.05). There were statistically significant differences in the expression levels of USP2, p-IκBα, and p-NF-κB p65 proteins in the hippocampal tissues of the four groups of mice ( F=8.39, 5.78, 21.32, all P<0.05).The expression level of USP2 protein in the USP2 silencing group(0.49±0.07) was lower than that in the USP2 silencing+ Venlafaxine group(0.79±0.08) and virus control group(1.00±0.07)(both P<0.05), while the expression levels of p-IκBα, p-NF-κB p65 protein (1.63±0.18, 2.14±0.24) were higher than those in the virus control group (1.00±0.06, 1.00±0.04) and the USP2 silencing+ Venlafaxine group (0.70±0.23, 0.68±0.09) (both P<0.05). Conclusion:USP2 scilencing can induce depressive-like behaviors in mice. Venlafaxine ameliorates USP2 silencing-induced depressive-like behaviors, which may be associated with the hippocampal NF-κB signaling pathway.

This review has introduced the Coronary Artery Tree description and Lesion EvaluaTion(CatLet or Hexu)angiographic scoring system,which,based solely on coronary angiography results,has characterized 6 types of right coronary artery,3 types of left descending artery,and 3 types of diagonal size,together resulting in 54 types of coronary circulation pattern.This novel angiographic scoring system can be utilized to account for coronary anatomy in its diversity,severity and complexity of diseased coronary arteries,and their subtended myocardial territories in jeopardy.The CatLet angiographic scoring system is unique in that the importance of a coronary artery is weighted according to its subtended myocardial segments,by which the variability of coronary artery has been accounted for and measured.Researchers at home and abroad have increasingly paid attention to its clinical utilities,which warrant further validation in the context of large sample size,prospective,and randomized controlled trials.The CatLet angiographic scoring system is accessible at www.catletscore.com.

Objective:To investigate the effect of deubiquitinating enzymes(DUBs) USP2 on depressive-like behavior and hippocampal NF-κB expression in mice.Methods:(1) USP2 silencing experiment: Two USP2 silencing interference sequences with the highest knockdown efficiency were screened and cloned into a lentivirus vector. Mice were microinjected with lentivirus vector into both sides of hippocampus to silence the USP2 gene, and depressive behavior and USP2 protein expression in hippocampal tissue were observed. (2) Venlafaxine intervention experiment: total 32 healthy male C57BL/6 mice were randomly divided into virus control group, Venlafaxine group, USP2 silencing group, and USP2 silencing+ Venlafaxine group according to the random number table method, with 8 mice in each group. Mice were injected with lentivirus into both side of the hippocampus, and 7 days later, they were given intraperitoneal injection of Venlafaxine (5 mg/kg, once a day, for a total of 14 days). After the administration, the depressive behavior of mice was detected by forced swimming test(FST) and tail suspension test(TST), and the expression levels of USP2, p-IκBα, IκBα, p-NF-κB p65, and NF-κB p65 in the hippocampus of mice were detected by Western blot.SPSS 25.0 and GraphPad Prism 8.0 were used for data processing and chart drawing.The t-test was used for comparison between two groups, One-way ANOVA was used for comparison among multiple groups, and Tukey HSD or LSD- t was used for post hoc pairwise comparison when there was homogeneity of variance. Results:(1)The results of the USP2 silencing experiment showed that both screened USP2 silencing sequences had good gene knockout effects. The expression levels of USP2 protein in the hippocampus of mice injected with USP2 silencing virus were lower than those of the negative control virus groups (both P<0.05). The immobility time of mice in the FST and TST was higher than that of the negative control virus group (both P<0.05). (2)Venlafaxine intervention experiment: There were statistically significant differences in immobility time among the four groups of mice in the FST and TST ( F=8.90, 4.41, both P<0.05). The immobility time of FST and the immobility time of TST in the USP2 silencing+ Venlafaxine group ((48.13±12.76) s, (77.38±12.35) s) were lower than those in the USP2 silencing group((129.88±11.67)s, (148.29±15.31)s) (both P<0.05). There were statistically significant differences in the expression levels of USP2, p-IκBα, and p-NF-κB p65 proteins in the hippocampal tissues of the four groups of mice ( F=8.39, 5.78, 21.32, all P<0.05).The expression level of USP2 protein in the USP2 silencing group(0.49±0.07) was lower than that in the USP2 silencing+ Venlafaxine group(0.79±0.08) and virus control group(1.00±0.07)(both P<0.05), while the expression levels of p-IκBα, p-NF-κB p65 protein (1.63±0.18, 2.14±0.24) were higher than those in the virus control group (1.00±0.06, 1.00±0.04) and the USP2 silencing+ Venlafaxine group (0.70±0.23, 0.68±0.09) (both P<0.05). Conclusion:USP2 scilencing can induce depressive-like behaviors in mice. Venlafaxine ameliorates USP2 silencing-induced depressive-like behaviors, which may be associated with the hippocampal NF-κB signaling pathway.

To promote the primary Traditional Chinese Medicine(TCM)service capacity,promote the high development of TCM in County Medical Communities,it takes Jinjiang as the subject to explore the construction path of TCM service system in County Medical Communities based on"healthcare,medical insurance and medicine"linkage reform.A tertiary TCM service network of"city-town-village"is constructed through implementing"three projects"and"six enhancements".The mode significantly improved the service accessibility of TCM,and formed the innovation mechanism,including differentiation appraisal system and"pharmacy sharing online",etc.It explores the practical challenges of human resources weakness and insufficient information exchange,promotes the improvement strategies of enhancing talent group construction and promoting information platform,so as to provide practical references for contructing the TCM service system of County Medical Communities in China.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To characterize the epidemiology, antimicrobial susceptibility, and molecular mechanisms of carbapenem-resistant Enterobacterales (CRE) carrying multiple carbapenemase genes in China, and to provide evidence for infection control and antibiotic stewardship.Methods:From 2016 to 2023, 115 CRE isolates harboring at least two carbapenemase genes were collected from 41 hospitals in 18 provinces across China. Species identification, antimicrobial susceptibility testing, and whole-genome sequencing were performed. Multilocus sequence typing (MLST) and capsular typing were conducted using Kleborate, plasmid replicon types were identified with PlasmidFinder, and a core genome phylogenetic tree was constructed.Results:The majority of isolates belonged to Klebsiella spp. (80.0%, 92/115), followed by E. cloacae (8.7%, 10/115) and E. coli (6.1%, 7/115). The isolates were mainly from Hebei, Beijing, Shandong, and Hunan (60.9%, 70/115), and sputum was the predominant specimen (43.5%, 50/115). The most common genotype was bla KPC+bla NDM (73.0%, 84/115), primarily in Klebsiella spp. (79.8%, 67/84), followed by bla NDM+bla IMP (15.7%, 18/115). The prevalent plasmid replicon types were IncFII (77.5%, 86/111), IncFIB (68.5%, 76/111), IncR (51.4%, 57/111), and IncX3 (20.7%, 23/111). Notably, 88.6% (31/35) of ST11-KL64 K. pneumoniae strains co-harbored IncFII, IncFIB, and IncR plasmids simultaneously. Between 2016 and 2022, the dominant subtype among Klebsiella spp. isolates was bla KPC-2+bla NDM-1 (56.2%, 36/64). In 2023, the bla KPC-2+bla NDM-13 subtype (29.5%, 19/64) emerged and exhibited clonal transmission (single nucleotide polymorphism 2?74 bp) in Hebei, Beijing, and Jilin. Susceptibility testing showed widespread resistance to β-lactams (90.2%-100%). Aztreonam-avibactam, tigecycline, and colistin retained high activity, with susceptibility rates of 90.16%-98.36%. Conclusions:In China, the majority of clinical Enterobacteriaceae strains that harbor multiple carbapenemases are Klebsiella spp. co-producing KPC and NDM enzymes. Dissemination is driven by both clonal expansion of ST11-KL64 and horizontal transfer of IncFII, IncFIB, and IncR plasmids. The recent emergence and regional clonal spread of the bla KPC-2+bla NDM-13 genotype underscore the urgent need for strengthened surveillance and containment measures.

Objective:It aims to explore the advantages,disadvantages,opportunities and challenges of Chinese medicine practitioners participating in the"three-division co-management"service model in diabetes management,analyze its performance in policy support,resource matching and patient satisfaction,and put forward optimization strategies to enhance the role of Chinese medicine practitioners in chronic disease management.Methods:Through literature analysis,questionnaire survey and semi-structured interview,the data of six pilot units of"three divisions co-management"in Jinjiang were collected,and the internal and external environment of Chinese medicine practitioners participating in the"three divisions co-management"model was systematically evaluated by the Strengths,Weaknesses,Opportunities,Threats(SWOT)and the Politics,Economic,Society,Technology(PEST).Results:Chinese medicine practitioners' participation in the"three-division co-management"model has obvious advantages in policy support,resource matching and patient satisfaction,but it also faces key obstacles such as lack of incentive mechanism,shortage of Chinese medicine practitioners' resources and limitation of medical insurance reimbursement.The survey shows that 99.7％of the respondents are willing to choose this mode again,and 96.43％of the respondents said that the medical experience has improved significantly.However,43.92％of the subjects think that the professional knowledge and skills of doctors need to be improved,and 32.2％of the subjects think that the effect of Chinese medicine treatment on reducing the dependence and side effects of western medicine is limited.Conclusion:It is feasible and practical for Chinese medicine practitioners to participate in the"three divisions co-management"model,but it is necessary to further improve its service effect and sustainability by improving the performance appraisal mechanism,expanding the scope of medical insurance reimbursement,and strengthening the training for Chinese medicine practitioners' resources.

Objective To analyze the correlation between lesion volume,lesion mass,and maximum lesion diameter in the assessment of advanced hepatocarcinoma with lung metastasis,and to evaluate the application value of total volume response and total mass response of lung metastatic lesions in efficacy assessment.Methods A retrospective analysis was conducted on the CT imaging data of 20 patients clinically confirmed with hepatocarcinoma and lung metastases,followed by subsequent follow-up to monitor their survival outcomes.Volume measurement software was used to measure the volume of lesions before and after treatment.We recored lesion diameter,volume measurements and CT values,calculated the mass of the lesions.The correlation between lesion volume,mass and diameter was analyzed,as well as the correlation between the change rates of volume,mass and lesion diameter.Additionally,the total volume and total mass of all lesions were calculated.The correlation between the change rates of total volume/total mass and the change rate of pulmonary lesion diameter under the RECIST 1.1 criteria,as well as the correlation with changes in patients'tumor markers,were analyzed.Furthermore,the overall volume response and overall mass response of lesions were evaluated based on changes in total volume and total mass,and their consistencies with the RECIST 1.1 criteria for efficacy evaluation were analyzed.Finally,univariate Cox regression analysis was performed to explore the association between these variables and patient survival outcomes.Results There was strong correlation between lesion volume,mass and tumor diameter(r=0.771,0.775),between the rate of change in mass and the rate of change in lesion diameter(r=0.846),and between the rates of change in total volume/total mass and the rate of change in pulmonary lesion diameter under the RECIST 1.1 criteria(r=0.800,0.896).The correlation between the rates of change in total volume/total mass and patients'tumor markers was not statistically significant.There was moderate correlation between the rate of change in volume and the rate of change in lesion diameter(r=0.692).The evaluation results of total volume response and total mass response for pulmonary lesions in advanced hepatocarcinoma with lung metastasis were generally consistent with the RECIST 1.1 criteria(Kappa=0.486,0.426).Univariate Cox regression analysis revealed that total lesion volume(P=0.047)and total lesion mass(P=0.049)were independent prognostic factors for survival outcomes.Conclusion Lesion volume,mass,and diameter,as well as their respective change rates,were found to be interrelated.Furthermore,total lesion volume and total lesion mass were identified as independent prognostic factors for survival outcomes.The total volume response and total mass response are promising evaluation methods in evaluating the efficacy of lung metastasis of hepatocarcinoma,which are different from the RECIST 1.1 evaluation criteria.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.