ObjectiveTo explore the clinical characteristics and risk factors for 30-day mortality in hospitalized patients with bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MethodsData were obtained retrospectively from the electronic medical records of inpatients at a tertiary A-grade hospital in Shanghai from January 2016 to December 2023. The collected variables included age, gender, department, surgical treatment, empirical antibiotic therapy, Pitt Bacteremia score (PBS), Charlson comorbidity index (CCI), INCREMENT-CPE score (ICS), length of hospital stay, the time from CRKP-BSI to discharge and, etc. The follow-up period ended upon discharge, with the follow-up outcomes defined as in-hospital mortality or discharge. The endpoint was defined as death within 30 days (including day 30) caused by CRKP-BSI or infection-related complications. Patients who survived within 30 days after CRKP-BSI were classified into the survival group, while those who died within 30 days were classified into the death group. Independent risk factors for 30-day mortality in patients with CRKP-BSI were analyzed using univariate and multivariate Cox regression analysis. ResultsA total of 71 hospitalized patients with CRKP-BSI, comprising 51 males and 20 females, with an average age of (65.12±18.25) years, were included during the study period. The M (P₂₅, P₇₅) of hospital stay were 37.00 (24.00, 56.00) days, and M (P₂₅, P₇₅) of the duration from CRKP-BSI to discharge or death were 18.00 (7.00, 35.00) days. There were 20 deaths (28.17%) in the death group and 51 survivors (71.83%) in the survival group. The results of multivariate Cox regression analysis showed that the ICS as an independent risk factor for 30-day mortality in CRKP-BSI patients (HR=1.379, 95%CI: 1.137‒1.671, P=0.001). Each 1-point increase in the ICS was associated with a 37.9% increase in the risk of mortality. ConclusionThe ICS is found to be a risk factor for 30-day mortality in patients with CRKP-BSI, which may facilitate the prediction for the risk of 30-day mortality and thereby support clinical decision-making for patients with CRKP-BSI.

Objective The occurrence of chickenpox in rapidly developing areas poses substantial seasonal risk to children.However,certain factors influencing local chickenpox outbreaks have not been studied.Here,we examined the relationship between spatial clustering,heterogeneity of chickenpox outbreaks,and socioeconomic factors in Southern China. Methods We assessed chickenpox outbreak data from Southern China between 2006 and 2021,comprising both relatively fast-growing parts and slower sub-regions,and provides a representative sample of many developing regions.We analyzed the spatial clustering attributes associated with chickenpox outbreaks using Moran's I and local indicators of spatial association and quantified their socioeconomic determinants using Geodetector q statistics. Results There were significant spatial heterogeneity in the risk of chickenpox outbreaks,with strong correlations between chickenpox risk and various factors,particularly demographics and living environment.Furthermore,interactive effects among specific are factors,such as population density and per capita residential building area,percentage of households with toilets,percentage of rental housing,exhibited q statistics of 0.28,0.25,and 0.24,respectively. Conclusion This study provides valuable insights into the spatial dynamics of chickenpox outbreaks in rapidly developing regions,revealing the socioeconomic factors affecting disease transmission.These implications extend the formulation of effective public health strategies and interventions to prevent and control chickenpox outbreaks in similar global contexts.

Objective To evaluate the ability of average nucleotide identity(ANI)and 16S rDNA technology on the identification of Salmonella.Methods The genomes and corresponding serovars of global Salmonella were downloaded in batch from the GenBank database.The classical strains of Salmonella were used as typing strains.The ANI analysis was conducted by the fastANI software according to the silent parameters.The species and serovars of Salmonella were identified by their 16S rDNA using the online software SpeciesFinder.Results Among the downloaded 2 306 genomes,1 767 strains of Salmonella had 178 serovars,with 323 strains(18.3%)of Salmonella Typhimurium and 300 strains(17.0%)of Salmonella Enteritidis being the most common.The ANI analysis showed that with a 95%threshold,only 30 strains(1.3%)of Salmonella were assigned to a specific subspecies,while the remaining 2 276 strains(98.7%)of Salmonella could be assigned to 2-5 subspecies.When the threshold was 97%,all 2 306 strains(100%)of Salmonella could be assigned to a specific subspecies.Based on the analysis of 16S rDNA,only 1 072 strains(46.5%)of Salmonella were identified,of which 95.2%(1 021/1 072)of Salmonella subspecies were completely consistent with the results of ANI(≥97%)analysis.Only 2.4%(19/784)of Salmonella strains showed consistent results with known serovars.Conclusion ANI is more suitable for the identification of Salmonella species and subspecies,and ANI≥97%can be used as the identification standard for Salmonella subspecies.The sensitivity of 16S rDNA for the identification of Salmonella still needs to be improved.

Abstract: Objective　To study severe fever with thrombocytopenia syndrome virus (SFTSV) in tick samples from different species and genera in Suizhou City, Hubei Province, China, and to explore the phylogenetic relationship between ticks and patients sources of viruses at the molecular evolutionary level. Methods In 2016 and 2017, over a continuous two-year period, 1 158 ticks were collected from Suizhou, Hubei, and their species and genera were identified. Meanwhile, 86 serum samples were collected to detect SFTSV RNA by real-time quantitative reverse transcription-PCR. All viral RNA-positive supernatants of tick homogenates were inoculated into Vero cells for viral isolation, and full genome sequencing of isolated strains was conducted. Phylogenetic tree research on SFTSV strains from ticks and cases was performed using the bootstrapped maximum-likelihood (1 000 iterations) method with Molecular Evolutionary Genetics Analysis (MEGA) software, ver. 11.0 to provide confidence estimates. Results Haemaphysalis longicornis, Ixodes sinensis, and Rhipicephalus microplus were the dominant species (95.34%) in Suizhou City, Hubei Province, China. Tick samples were pooled according to their species and developmental stage, yielding 832 pools, of which 4 were positive for SFTSV by qRT-PCR. The overall minimum infection rate (MIR) in the region was 0.35%. One SFTSV strain named HB 2016-P35, was successfully isolated from Haemaphysalis longicornis and demonstrated high homology to 16 previously reported patient-derived viruses in Hubei Province, especially to the human strain HB 2017-49 from the same region, with a genome similarity of 99.9%. In addition, the molecular phylogenetic analysis revealed five distinct SFTSV genotypes in Hubei, covering almost all currently known SFTSV genotypes. Conclusions Some areas of Suizhou City, Hubei Province, demonstrate a relatively low level of SFTSV carrying and transmission by ticks. The new SFTSV strain isolated from ticks exhibits similar genotype characteristics and high sequence homology with viruses carried by cases in surrounding cases. The study suggests that tick-to-human transmission is most likely the pathway for human infection with SFTSV, highlighting the need for continual and long-term monitoring of tick carriage of SFTSV in endemic areas.

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8⁺ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

OBJECTIVE: To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout. METHODS: The Sidt2 knockout (Sidt2^-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed. RESULTS: Sidt2^-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 μmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2^-/- HL7702 cells. CONCLUSION Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.
Humans ; Lysosome-Associated Membrane Glycoproteins/metabolism* ; Autophagy ; Apoptosis ; Hepatocytes ; Lysosomes/metabolism* ; Chloroquine/pharmacology* ; Nucleotide Transport Proteins/metabolism*

Objective:To investigate the prevalence of pretreatment drug resistance and the genetic polymorphism of CRF08_BC strains among HIV-1 patients in China.Methods:This cross-sectional survey involved the plasma samples of HIV patients in a national pretreatment HIV drug resistance survey conducted in 2018. RNA was extracted from the samples. The fragments containing protease and partial reverse transcriptase (PR/RT) regions were obtained and sequenced. Drug resistance was analyzed using Stanford HIVdb Program. Differences in polymorphic mutations between drug-resistant and non-drug-resistant HIV-1 strains were analyzed by Chi-square test or Fisher′s exact test. The association between drug-resistant and polymorphic mutations was evaluated using CorMut R package. Molecular transmission networks were constructed using HIV-TRACE software. Results:Totally 465 partial pol sequences were obtained from individuals with CRF08_BC infection in 25 provinces and cities. The total pretreatment drug resistance rate was 17.8% (83/465). The pretreatment drug resistance rates to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) were 16.6% (77/465), 1.1% (5/465) and 0.9% (4/465), respectively. The resistance rate to rilpivirine (RPV) was the highest (15.7%, 73/465). The most common mutation was E138A (11.6%, 54/465). There were six polymorphic mutations (S162C, K102Q, T200A, V179E, I202V, T200M) that co-variated with E138A. The molecular transmission network showed that patients infected with CRF08_BC strains carrying the resistant mutations at position E138 mainly gathered in clusters in Yunnan and Sichuan, and the highest degree of connection was in Lincang, Yunnan. Conclusions:In China, HIV-1 CRF08_BC-infected patients showed a high rate of pretreatment resistance to one of the second-generation NNRTIs, namely RPV. Further researches were warranted to evaluate the impacts of co-mutations of the E138A mutation and polymorphic sites on HIV resistance and replicative capacity.