Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Objective Exploring the mechanism of mitophagy-mediated efferocytosis in myocardial fibrosis progression based on transcriptomics and bioinformatics,with potential chinese herbal medicine prediction and experimental validation.Methods A rat model of myocardial fibrosis was constructed by injecting angiotensin Ⅱ subcutaneously.RNA extraction and high-throughput sequencing were performed on myocardial tissue of rats,and differentially expressed genes(DEGs)were detected.Efferocytosis-related genes(ERGs)were obtained from the GeneCards database,and the intersection of DEGs and ERGs was mapped using the"venneuler"package in R 4.2.0 software.Differentially expressed efferocytosis-related genes(DEERGs)were obtained,and KEGG and GO enrichment analyses were performed for DEERGs.The network analysis of protein-to-protein interactions(PPI)and identification of key genes of DEERGs and mitochondrial autophagy(PINK1,P62)were conducted.The key genes were imported into Coremine database for chinese herbal medicine prediction.Combined with the Traditional Chinese Medicine pathogenesis of myocardial fibrosis and the previous research progress,the highest frequency of Astragali Radix,Carthami Flos and Lepidii Semen was selected for animal experiments.Masson staining was used to analyze the degree of fibrosis.Mitochondrial swelling assay and mitochondrial membrane potential detection were performed to evaluate the extent of mitochondrial dysfunction.RT-PCR and Western blot were employed to measure the mRNA and protein expression of mitophagy-related genes to assess mitophagy levels.Cardiac-resident macrophages were isolated,treated with AngⅡ,and subsequently assessed for their efferocytosis of apoptotic endothelial cells.Results There were 428 DEGs between in the control group and model group,including 165 up-regulated and 263 down-regulated DEGs.250 ERGs were identified from GeneCards database,and 12 DEERGs were obtained by drawing the intersection of DEGs and ERGs.KEGG and GO enrichment analysis of DEERGs showed that the process involved cellular burial,mitochondrial autophagy and endothelial cell regulation.PPI network analysis and identification of key genes of DEERGs and mitochondrial autophagy(PINK1,P62)were performed.The top 10 key genes were HIF1A,PINK1,GABARAP,ARG1,PPARG,UCP2,SQSTM1,CD36,SIRT1 and RAB7A.The key genes were imported into Coremine database to search for corresponding chinese herbal medicine.The most frequent ones were Astragali Radix,Carthami Flos and Lepidii Semen.Experimental validation demonstrated that the Astragali Radix,Carthami Flos and Lepidii Semen formulation inhibited AngⅡ-induced myocardial fibrosis and improved cardiac function in rats.Notably,it significantly enhanced the efferocytosis of apoptotic endothelial cells by AngⅡ-treated resident macrophages,with the high-dose group showing the most pronounced effect(P<0.05).Mechanistic studies using the high-dose Astragali Radix,Carthami Flos and Lepidii Semen formulation group revealed that,compared to control and model groups,the treatment group exhibited reduced mitophagy and ameliorated mitochondrial dysfunction(P<0.05).Conclusion The Astragali Radix,Carthami Flos and Lepidii Semen formulation may inhibit excessive mitophagy by regulating the expression of PINK1 and P62,promote macrophage efferocytosis,and thereby suppress the formation of myocardial fibrosis.

OBJECTIVE: To investigate the clinical characteristics and prognostic of venetoclax (VEN) combined targeted therapy in acute leukemia (AL) patients with PICALM∷MLLT10 fusion gene positivity. METHODS: A retrospective analysis was conducted on 16 PICALM∷MLLT10-positive AL patients treated at the First Affiliated Hospital of Soochow University from January 2021 to August 2024. These patients were diagnosed by targeted RNA sequencing (RNA-seq) or reverse transcription multiplex PCR, including newly diagnosed and relapsed/refractory (R/R) cases. The immunophenotypes, genetic features, gene mutations, and the efficacy of VEN combination targeted therapy of patients were evaluated. RESULTS: Among the 16 cases, 3 were confirmed by reverse transcription multiplex PCR, and 13 were detected through targeted RNA-seq among 528 AL patients, with a detection rate of 2.46%. The averge age of patients was (28.0±8.58) years. Patients exhibited diverse immunophenotypes, including 7 cases of acute myeloid leukemia, 5 of acute T-lymphoblastic leukemia, 1 of acute B-lymphoblastic leukemia, 1 of acute undifferentiated leukemia, and 2 of mixed-phenotype acute leukemia. Among them, 11 had extramedullary disease (EMD), 14 expressed CD7, and 12 expressed CD33. Major co-occurring mutations included PHF6 (6 cases), NOTCH1 (5 cases), and 7 cases with complex karyotypes. Of the 12 patients who received standard induction therapy, 7 did not achieve remission (PR+NR). All 4 patients treated with VEN combination therapy achieved complete remission (CR). Among the 7 induction failure cases, 4 achieved CR upon re-induction with VEN, while the remaining 3 re-induced with standard therapy, did not achieve CR. Thirteen patients received allogeneic hematopoietic stem cell transplantation, including 6 who received maintenance therapy with hypomethylating agents (HMA) alone or in combination with VEN, and seven were followed up. Survival analysis showed that the overall survival was better in the maintenance therapy group (P =0.044). CONCLUSION PICALM∷MLLT10-positive AL involves multiple lineages and demonstrates poor response to conventional chemotherapy. VEN combination therapy shows promising efficacy in both newly diagnosed and R/R patients. Post-transplant maintenance therapy with HMA alone or combined with VEN may extend survival; however, further clinical validation is required.
Humans ; Sulfonamides/therapeutic use* ; Retrospective Studies ; Prognosis ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Adult ; Male ; Female ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Objective:To analyze the temporal distribution of other infectious diarrhea (OID) in Shenzhen and provide evidence for the prevention and control of OID.Methods:The incidence data of OID in Shenzhen from 2011 to 2023 were collected. The seasonal and trend decomposition using loess (STL), seasonal index method, concentration degree and circular distribution method were used to analyze the incidence trend and temporal distribution of OID.Results:A total of 477 611 cases of OID were reported in Shenzhen from 2011 to 2023, with an average annual incidence rate of 260.19/100 000 showing a fluctuating upward trend. The seasonal index method indicated that October-January was period with high incidence of OID in Shenzhen and the seasonal intensity began to decrease in 2020. STL revealed an obvious incidence peak in winter. The concentration method showed that OID had a certain seasonality before 2018 except 2016, but the seasonality was not obvious after 2018. The circular distribution results showed that r was 0.05, mean angle ā was 1.92° and angular standard deviation s was 141.93° ( Z=1 033.37, P<0.001), with the peak on January 1 st and the high incidence period from August 11 th to May 25 th. Conclusions:OID had a certain degree of seasonality in Shenzhen, with an obvious incidence peak in winter. Since the seasonal intensity of OID decreased after 2018, the surveillance, early warning and risk assessment of OID should be continued, and prevention and control measures should be adjusted timely according to the change in the characteristics of the epidemic.

Objective To analyze the monitoring of healthcare-associated infection(HAI)in the intensive care unit(ICU)over the past 12 years based on Joinpoint regression model,and evaluate the trend changes and relevant fac-tors of HAI incidence.Methods ICU patients in a tertiary first-class hospital from January 2012 to December 2023 were selected and performed prospective monitoring.Trend changes of HAI incidence and the correlation with con-sumption of hand hygiene products as well as HAI management measures were analyzed.Results From 2012 to 2023,6 929 ICU patients were included in the monitoring,543 patients had 655 episodes of HAI,with incidence and case incidence of HAI being 7.84％ and 9.45％,respectively.The average severity of the disease was 3.62,and the adjusted HAI incidence was 2.17％.The daily incidence of ventilator-associated pneumonia(VAP),cathe-ter-associated urinary tract infection(CAUTI),and central line-associated bloodstream infection(CLABSI)were 6.19‰,3.45‰,and 1.23‰,respectively.The consumption of hand hygiene products was 122.98 mL/bed-day.The compliance rate and correct rate of hand hygiene were 90.63％and 90.46％,respectively.From 2012 to 2023,incidence of HAI(51.29％vs 4.39％),case incidence of HAI(72.41％vs 4.94％),the adjusted incidence of HAI(15.98％vs 1.04％),daily incidence of VAP(22.50‰ vs 4.33‰),daily incidence of CAUTI(14.23‰ vs 1.64‰),and daily incidence of CLABSI(10.60‰ vs 0.20‰)all decreased significantly(all P＜0.05).Both con-sumption of hand hygiene products(75.16 mL/bed-day vs 147.35 mL/bed-day)and correct rate of hand hygiene(85.00％vs 90.28％)increased significantly(both P＜0.05).A total of 1 946 pathogens were detected,with an increase in the proportion of Staphylococcus aureus(1.30％ vs 9.57％)and a decrease in the proportion of fungi(11.04％vs 1.74％).The daily consumption of hand hygiene products negatively correlated with the incidence of HAI,the case incidence of HAI,as well as the daily incidence of CAUTI and CLABSI(all P＜0.05).Incorpora-ting HAI real-time monitoring system and HAI management into performance assessment could decrease HAI-rela-ted incidence(P＜0.05).Conclusion HAI-related incidence presents a downward trend.Scientific and comprehen-sive HAI prevention and control management measures such as healthcare workers'hand hygiene management,on-line HAI real-time monitoring system,and incorporating HAI management into performance assessment can de-crease HAI-related incidence and promote the improvement of medical quality.

Aging is comprehensively influenced by multiple fac-tors such as internal genes,cellular metabolism,external envi-ronment,and lifestyle habits.Among them,epigenetic regula-tion plays a core role.Epigenetic modifications,including DNA methylation,histone modification,heterochromatin remodeling,and non-coding RNA regulation,act in concert with the three-di-mensional genome architecture to precisely regulate gene expres-sion.This review elaborates on the factors influencing epigenetic regulation,as well as the mechanisms of how epigenetics affects the occurrence of organismal aging and the corresponding inter-vention strategies,providing relevant insights for uncovering the mechanisms of aging and preventing/treating aging-related disea-ses.

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*