To investigate the genetic relatedness between carbapenem-resistant Klebsiella pneumoniae(CRKP) strains isolated from intestinal colonization and subsequent bloodstream infections.

Objective To investigate the effectiveness of applying the CIPP(Context,Input,Process,and Product)model in the training of general workers in a disinfection supply center.Methods From January to March 2023,a total of 24 general workers in our hospital's disinfection supply center underwent traditional training as the pre-management phase.Subse-quently,from July to September 2023,a training system centered on the CIPP model was implemented as the post-management phase.After the training,the examination results and training evaluations were analyzed using SPSS 13.0 statistical software.Results The technical training of the general workers resulted in improved learning outcomes compared to before the training.Conclusion By applying the CIPP model in the training of general workers in a disinfection supply center,their grasp of basic knowledge and professional skills can be enhanced.This can reduce technical errors during operations,improve the quality of sterile items,and reduce the risk of nosocomial infections,thereby ensuring patient safety.

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.

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4⁺ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8⁺ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.

Objective To investigate the effect of sirtuin 3(SIRT3)on the oxidative stress response and hypoxia inducible factor-1α(HIF-1α)expression in lung cancer cells through reactive oxygen species(ROS)under hypoxic conditions and its mechanism.Methods Human non-small cell lung cancer A549 cells were exposed to hypoxia for 0 h,12 h,24 h and 48 h.The mRNA and protein expressions of HIF-1α and SIRT3 were detected by RT-PCR and Western blot to determine the optimal time of hypoxia induction.A549 cells were divided into 5 groups:control group,hypoxia group,hypoxia+ROS inhibitor n-acetylcysteine(NAC)group,hypoxia+(SIRT3 overexpression)SIRT3-OE group and hypoxia+SIRT3-OE+NAC group.Cell proliferation was detected by MTT assay.Cell apop-tosis was detected by flow cytometry.The mRNA and protein expressions of HIF-1 α and SIRT3 in each group were detected by RT-PCR and Western blot.ROS content in each group was detected by flow cytometry.The contents of malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in the cells of each group were detected by biochemical kits.Results The optimal induction time of hypoxia was 24 h.Compared with the control group,the apoptosis rate,SIRT3 mRNA and protein levels,SOD and GSH contents in the hypoxia group signifi-cantly decreased(P＜0.01),the cell proliferation ability,HIF-1 α mRNA and protein levels,ROS and MDA con-tent in cells significantly increased(P＜0.01).Compared with the hypoxia group,the apoptosis rate,SIRT3 mR-NA and protein levels,SOD and GSH contents in the hypoxia+NAC and hypoxia+SIRT3-OE groups increased(P＜0.05),the cell proliferation ability,HIF-1 α mRNA and protein levels,ROS and MDA content in cells de-creased(P＜0.05).Compared with the hypoxia+NAC group,the apoptosis rate,SIRT3 mRNA and protein lev-els,SOD and GSH contents in the hypoxia+SIRT3-OE+NAC group significantly increased(P＜0.01),the cell proliferation ability,HIF-1 α mRNA and protein levels,ROS and MDA content in cells significantly decreased(P＜0.01).Conclusion Under hypoxic conditions,SIRT3 can promote cell apoptosis and inhibit lung cancer pro-gression by mediating ROS to inhibit oxidative stress response and HIF-1 α expression in lung cancer cells.

Objective:To conduct meta analysis to compare the effect of complete resection with or without postoperative radiotherapy (PORT) on survival in stage Ⅲ(N 2) non-small cell lung cancer (NSCLC). Methods:Relevant studies of the efficacy of PORT for stage Ⅲ(N 2) NSCLC were searched from Wanfang Data, PubMed, and Cochrane Library from January 2006 to January 2022. Literature screening, extraction of information and assessment of the risk of bias of the included literature was carried out by two independent researchers. Meta analysis was performed using R4.0.3 software. Results:A total of 12 publications consisting of 2992 patients were included, 1479 cases in the PORT group and 1513 cases in the control group. PORT improved the overall survival (OS) and disease free survival (DFS) compared to the control group. Fixed-effects model meta analysis of 6 randomized controlled trials showed that PORT did not significantly reduce the risk of death ( HR=0.98, 95% CI: 0.80-1.20). Fixed-effects model meta analysis of 6 retrospective studies showed that PORT improved prognosis ( HR=0.68, 95% CI: 0.59-0.79). PORT could improve OS of patients with multiple (station) metastasis of ipsilateral mediastinum and / or submandibular lymph nodes ( HR=0.89, 95% CI: 0.80-0.99). Conclusions:PORT could improve OS and DFS in stage Ⅲ(N 2) NSCLC. A trend towards benefit can be observed in the subgroup with multiple/multi-station N2 metastasis.

The continuing challenges that limit effectiveness of tumor therapeutic vaccines were high heterogeneity of tumor immunogenicity, low bioactivity of antigens, as well as insufficient lymph nodes (LNs) drainage of antigens and adjuvants. Transportation of in situ neoantigens and adjuvants to LNs may be an effective approach to solve the abovementioned problems. Therefore, an FA-TSL/AuNCs/SV nanoplatform was constructed by integrating simvastatin (SV) adjuvant loaded Au nanocages (AuNCs) as cores (AuNCs/SV) and folic acid modified thermal-sensitive liposomes (FA-TSL) as shells to enhance de novo antitumor immunity. After accumulation in tumor guided by FA, AuNCs mediated photothermal therapy (PTT) induced the release of tumor-derived protein antigens (TDPAs) and the shedding of FA-TSL. Exposed AuNCs/SV soon captured TDPAs to form in situ recombinant vaccine (AuNCs/SV/TDPAs). Subsequently, AuNCs/SV/TDPAs could efficiently transport to draining LNs owing to the hyperthermia induced vasodilation effect and small particle size, achieving co-delivery of antigens and adjuvant for initiation of specific T cell response. In melanoma bearing mice, FA-TSL/AuNCs/SV and laser irradiation effectively ablated primary tumor, against metastatic tumors and induced immunological memory. This approach served a hyperthermia enhanced platform drainage to enable robust personalized cancer vaccination.

ObjectiveTo explore the relationship between occupational stress， psychological capital and insomnia among nurses， and to test the mediating effect of psychological capital on the relationship between nurses' occupational stress and insomnia. MethodsStratified random sampling method was utilized in selecting 810 nurses from a tertiary A-level hospital from March to May 2021. The Effort-Reward Imbalance questionnaire （ERI）， Psychological Capital Questionnaire （PCQ） and Athens Insomnia Scale （AIS） were used to evaluate the occupational stress， psychological capital and insomnia of nurses， respectively. Then the mediation effect of psychological capital on the relationship between occupational stress and insomnia in nurses was tested by PROCESS macro program. ResultsA total of 658 （81.23%） questionnaires were effectively collected. Analysis found that nurses' effort-reward ratio was positively correlated with AIS score （r=0.379， P<0.01）， and negatively correlated with PCQ score （r=-0.275， P<0.01）. Nurses' PCQ score was negatively correlated with AIS score （r=-0.402， P<0.01）. Nurses' occupational stress could negatively predict psychological capital （β=-11.024， t=-7.324， P<0.01）， and positively predict insomnia （β=4.117， t=10.478， P<0.01）. Psychological capital could negatively predict insomnia （β=-0.087， t=-9.083， P<0.01）. The predictive effect of occupational stress on insomnia was statistically significant with psychological capital introduced as a mediating variable （β=3.158， t=8.185， P<0.01）. ConclusionPsychological capital plays a partial mediating role in the relationship between occupational stress and insomnia in nurses.

Purpose: C5α receptor 1 (C5ΑR1) is associated with the development of various human cancers. However, whether it is involved in the development of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) is poorly understood. We explored the expression, biological role, and associated mechanisms of C5AR1 in HBV-related hepatoma cells. Materials and Methods: The expression of C5ΑR1 mediated by HBV and HBV core protein (HBc) was detected in hepatoma cells. The function of nuclear factor кB (NF-κB) pathway in HBc-induced C5AR1 expression was assessed. The roles of C5ΑR1 in the activation of intracellular signal pathways, the upregulation of inflammatory cytokines, and the growth and migration of hepatoma cells mediated by HBc, were investigated. The effect of C5α in the development of HCC mediated by C5AR1 was also measured. Results: C5ΑR1 expression was increased in HBV-positive hepatoma cells. Dependent on HBc, HBV enhanced the expression of C5ΑR1 at the mRNA and protein levels. Besides, HBc could promote C5ΑR1 expression via the NF-κB pathway. Based on the C5ΑR1, HBc facilitated the activation of JNK and ERK pathways and the expression and secretion of interleukin-6 in hepatoma cells. Furthermore, C5ΑR1 was responsible for enhancing the growth and migration of hepatoma cells mediated by HBc. Except these, C5α could promote the malignant development of HBc-positive HCC via C5AR1. Conclusion We provide new insight into the mechanisms of hepatocarcinogenesis mediated by HBc. C5ΑR1 has a significant role in the functional abnormality of hepatoma cells mediated by HBc, and might be utilized as a potential therapeutic target for HBV-related HCC.

Purpose: C5α receptor 1 (C5ΑR1) is associated with the development of various human cancers. However, whether it is involved in the development of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) is poorly understood. We explored the expression, biological role, and associated mechanisms of C5AR1 in HBV-related hepatoma cells. Materials and Methods: The expression of C5ΑR1 mediated by HBV and HBV core protein (HBc) was detected in hepatoma cells. The function of nuclear factor кB (NF-κB) pathway in HBc-induced C5AR1 expression was assessed. The roles of C5ΑR1 in the activation of intracellular signal pathways, the upregulation of inflammatory cytokines, and the growth and migration of hepatoma cells mediated by HBc, were investigated. The effect of C5α in the development of HCC mediated by C5AR1 was also measured. Results: C5ΑR1 expression was increased in HBV-positive hepatoma cells. Dependent on HBc, HBV enhanced the expression of C5ΑR1 at the mRNA and protein levels. Besides, HBc could promote C5ΑR1 expression via the NF-κB pathway. Based on the C5ΑR1, HBc facilitated the activation of JNK and ERK pathways and the expression and secretion of interleukin-6 in hepatoma cells. Furthermore, C5ΑR1 was responsible for enhancing the growth and migration of hepatoma cells mediated by HBc. Except these, C5α could promote the malignant development of HBc-positive HCC via C5AR1. Conclusion We provide new insight into the mechanisms of hepatocarcinogenesis mediated by HBc. C5ΑR1 has a significant role in the functional abnormality of hepatoma cells mediated by HBc, and might be utilized as a potential therapeutic target for HBV-related HCC.