Fungal infections have emerged as a critical public health issue endangering human health. However, the existing arsenal of antifungal agents is limited in diversity and is commonly plagued by drawbacks including narrow antimicrobial spectrums and the frequent emergence of drug resistance, which severely compromises the efficacy of clinical treatments. Pathogenic fungi can develop extensive adaptability to currently available drugs through multiple mechanisms, which are mainly manifested in three aspects: drug resistance, tolerance and persistence. The molecular mechanisms and regulatory pathways underlying drug resistance, tolerance and persistence in pathogenic fungi were systematically summarized in this review, and the counteractive strategies such as combination therapy and the development of novel antifungal agents were further discussed, which aimed to provide theoretical basis and practical reference for the precision treatment of fungal infections.

Objective To evaluate the radiation impact of a self-developed digital miniature CT on the human body and the environment under simulated scanning conditions, and verify its safety and regulatory compliance. Methods Under typical head scanning conditions with the digital miniature CT (70 kV/10 mA), the equivalent doses received at the body surface sites corresponding to the thyroid, breast, stomach, liver, kidney, and gonads of the phantom were measured without protection and with 0.5 mmPb equivalent protection using LiF (Mg, Cu, P) thermoluminescent dosimeters. The ambient dose equivalent rates at the bed level inside the CT room at different directions and distances from the scanning center were measured using a model AT1121 X/γ dosimeter. The equivalent doses of organs on both sides of the phantom and the ambient equivalent dose rates on the left and right sides of the longitudinal axis of the bed in the CT room were compared. The Mann-Whitney test was used at a significance level of P < 0.05. Results During a single scan of the head with the digital miniature CT, the equivalent doses at the body surface sites corresponding to the thyroid, breast, stomach, liver, kidney, and gonads without protection were 1.04, 0.95, 0.55, 0.57, 0.40, and 0.12 mSv, respectively, which were only 0.84% to 8.24% of the doses inside the irradiation field. With 0.5 mm Pb equivalent protection, the equivalent dose of the thyroid decreased from 8.24 mSv to 3.27 mSv with a reduction of 60.3%, and the doses of the other organs were reduced to 1.5-11.5 μSv with the maximum reduction of 14 times. In the longitudinal axis direction of the CT bed, the ambient dose equivalent rate at a distance of 2 m from the scanning center was reduced to 0.066 mSv/h, which was only 9.6% of the ambient equivalent dose rate at a distance of 50 cm from the scanning center. Conclusion The digital miniature CT has advantages in ensuring patient safety, optimizing imaging quality, and promoting technological development, demonstrating promising application potential. However, the radiation protection of personal and CT room should not be ignored.

Primary aldosteronism(PA) is the most common endocrine cause of secondary hypertension and is characterized by hypertension, hypokalemia, suppressed renin, and inappropriately elevated aldosterone. Increasing evidence indicates disturbances in calcium homeostasis among patients with PA. The calcium-regulatory system encompasses calcium and phosphate, parathyroid hormone(PTH), and vitamin D. Patients with PA frequently exhibit hypocalcemia, hypophosphatemia, elevated PTH, and reduced vitamin D levels. Clarifying the contribution of calcium dysregulation to PA pathogenesis is clinically relevant for mitigating target-organ damage. This review summarizes: (1) the role of aberrant calcium signaling in the development of PA; (2) characteristic features of calcium homeostasis in PA; and (3) the interactions between the renin-angiotensin-aldosterone system(RAAS) and calcium-regulatory pathways. Overall, abnormalities in calcium signaling appear integral to the pathogenesis of PA, and disrupted calcium homeostasis may aggravate target-organ injury in affected patients.

Primary aldosteronism(PA) is the most common endocrine cause of secondary hypertension and is characterized by hypertension, hypokalemia, suppressed renin, and inappropriately elevated aldosterone. Increasing evidence indicates disturbances in calcium homeostasis among patients with PA. The calcium-regulatory system encompasses calcium and phosphate, parathyroid hormone(PTH), and vitamin D. Patients with PA frequently exhibit hypocalcemia, hypophosphatemia, elevated PTH, and reduced vitamin D levels. Clarifying the contribution of calcium dysregulation to PA pathogenesis is clinically relevant for mitigating target-organ damage. This review summarizes: (1) the role of aberrant calcium signaling in the development of PA; (2) characteristic features of calcium homeostasis in PA; and (3) the interactions between the renin-angiotensin-aldosterone system(RAAS) and calcium-regulatory pathways. Overall, abnormalities in calcium signaling appear integral to the pathogenesis of PA, and disrupted calcium homeostasis may aggravate target-organ injury in affected patients.

Objectives:This study aimed to analyze the clinical and molecular characteristics of carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) in patients with hematological diseases and to explore prognostic risk factors.Methods:This retrospective study included patients with hematologic diseases with CRE BSI at the Institute of Hematology and Blood Diseases Hospital from January 2015 to December 2022. The clinical features, carbapenemase test results, antimicrobial treatments, and outcomes were analyzed.Results:A total of 120 patients developed CRE BSI. Escherichia coli (58/120, 48.3%) was the most prevalent Enterobacteriaceae, followed by Klebsiella pneumoniae (52/120, 43.3%). A total of 93 CRE strains were tested for carbapenemase, of which 75 strains produced carbapenemase (metalloenzyme: 51 strains; serine enzyme: 24 strains). The 30-day mortality rate after BSI was 24.2% (29/120). Univariate analysis revealed significantly lower mortality in patients treated with the ceftazidime-avibactam-containing regimen than in those treated with other antibiotics (7.8% vs 36.2%, P<0.001). Moreover, initiating active therapy within 24 h of BSI onset significantly reduced mortality (15.0% vs 33.3%, P=0.019). The proportion of patients with CRE colonization receiving active therapy within 12 and 24 h was significantly higher compared with patients without colonization (12 h: 14.5% vs 34.1%, P=0.012; 24 h: 40.8% vs 65.9%, P=0.008). Multivariate analysis revealed that septic shock ( HR=24.436, 95% CI 4.148 - 143.966, P<0.001) and pulmonary infection ( HR=9.346, 95% CI 2.718-32.140, P<0.001) were independent risk factors for death within 30 days. Appropriate therapy was initiated within 24 h ( HR=0.225, 95% CI 0.059 - 0.851, P=0.028), and treatment with the ceftazidime-avibactam-containing regimen ( HR=0.082, 95% CI 0.018-0.362, P=0.001) significantly reduced mortality. Conclusion:The prognosis of CRE BSI in patients with hematological diseases is poor. Timely, appropriate therapy and receipt of a ceftazidime-avibactam-containing regimen can improve survival and prognosis.

Objectives:This study aimed to analyze the clinical and molecular characteristics of carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) in patients with hematological diseases and to explore prognostic risk factors.Methods:This retrospective study included patients with hematologic diseases with CRE BSI at the Institute of Hematology and Blood Diseases Hospital from January 2015 to December 2022. The clinical features, carbapenemase test results, antimicrobial treatments, and outcomes were analyzed.Results:A total of 120 patients developed CRE BSI. Escherichia coli (58/120, 48.3%) was the most prevalent Enterobacteriaceae, followed by Klebsiella pneumoniae (52/120, 43.3%). A total of 93 CRE strains were tested for carbapenemase, of which 75 strains produced carbapenemase (metalloenzyme: 51 strains; serine enzyme: 24 strains). The 30-day mortality rate after BSI was 24.2% (29/120). Univariate analysis revealed significantly lower mortality in patients treated with the ceftazidime-avibactam-containing regimen than in those treated with other antibiotics (7.8% vs 36.2%, P<0.001). Moreover, initiating active therapy within 24 h of BSI onset significantly reduced mortality (15.0% vs 33.3%, P=0.019). The proportion of patients with CRE colonization receiving active therapy within 12 and 24 h was significantly higher compared with patients without colonization (12 h: 14.5% vs 34.1%, P=0.012; 24 h: 40.8% vs 65.9%, P=0.008). Multivariate analysis revealed that septic shock ( HR=24.436, 95% CI 4.148 - 143.966, P<0.001) and pulmonary infection ( HR=9.346, 95% CI 2.718-32.140, P<0.001) were independent risk factors for death within 30 days. Appropriate therapy was initiated within 24 h ( HR=0.225, 95% CI 0.059 - 0.851, P=0.028), and treatment with the ceftazidime-avibactam-containing regimen ( HR=0.082, 95% CI 0.018-0.362, P=0.001) significantly reduced mortality. Conclusion:The prognosis of CRE BSI in patients with hematological diseases is poor. Timely, appropriate therapy and receipt of a ceftazidime-avibactam-containing regimen can improve survival and prognosis.

Objective:To evaluate the relationship between hippocampal macrophage polarization and perioperative neurocognitive disorders in mice with tibial fractures.Methods:Forty-five clean-grade healthy male C57/BL6 mice, aged 5-7 months, were divided into 3 groups ( n=15 each) using the random number table method: control group (group C), anesthesia group (group A) and anesthesia surgery group (group AS). Group C received no treatment. Group A was anesthetized with isoflurane inhaled for 15 min. In AS group, intramedullary nail fixation of tibial fracture was performed under anesthesia through inhalation of 2% isoflurane. Morris water maze test and open field test were performed before anesthesia/on 1 day before surgery and after anesthesia/on 1, 3 and 7 days after operation. Five mice were randomly selected after the behavioral experiments were completed at each time point, and hippocampal tissues were taken after the animals were sacrificed for determination of the expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, chemokine (c-c motif) ligand 12 (CCL2), CCL5, CCL8, iNOS and Arg-1 mRNA (by quantitative real-time polymerase chain reaction), expression of iNOS and Arg-1 proteins (by Western blot), and percentage of CD11b, CD45, CD86 and CD206 cells in hippcampal area (by immunofluorescence staining). Results:Compared with group C, the escape latency was significantly prolonged after operation, the number of crossing the platform was reduced after operation, the expression of TNF-ɑ, IL-6, CCL5 and CCL8 mRNA and iNOS protein and mRNA was up-regulated, the expression of Arg-1 protein and mRNA was down-regulated, the percentages of CD11b + CD45 + cells and CD11b + CD86 + cells in the hippocampus were increased, and the percentages of CD11b + CD206 + cells were decreased in AS group ( P<0.05), and no significant change was found in the parameters mentioned above in group A ( P>0.05). Compared with group A, the escape latency was significantly prolonged after surgery, the frequency of crossing the platform was reduced after surgery, the expression of iNOS mRNA was up-regulated, the percentages of CD11b + CD45 + cells and CD11b + CD86 + cells were increased, and the percentages of CD11b + CD206 + cells were decreased in AS group ( P<0.05). Conclusions:The occurrence of PND may be related to increased polarization to M1 macrophages in the hippocampus and decreased polarization to M2 macrophages in mice with tibial fracture, which further leads to central inflammatory responses.

Objective:To establish a set of scientific and reasonable indicator system of common prosperity in the field of health, so as to promote the construction and evaluation of the demonstration area of common prosperity with high quality of health.Methods:According to the requirements of promoting common prosperity demonstration area with high quality of health in Zhejiang province, the initial indicator pool was established through literature research and theoretical analysis in July 2021, and experts were convened to carry out expert brainstorming to determine indicator system in the form of meetings. Delphi method was used to conduct two rounds of expert consultation on the indicator system.Finally, the analytic hierarchy process and percentage weight method were used to calculate the indicator weight value.Results:The final indicator system included 4 first-level indicators and 30 second-level indicators. Among the first-level indicators, the weight values of the development, equilibrium, inclusiveness, and sustainability were 0.326 4, 0.242 8, 0.245 8, and 0.185 0. There were 8 second-level indicators in developmental indicator dimension, of which the indicator with the highest weight was the per capita health expectancy. The balance indicator dimension included 6 second-level indicators, of which the indicator with the highest weight was the per capita financing difference of basic medical insurance between the urban workers with the urban-rural residents. The inclusive indicator dimension included 6 second-level indicators, and the proportion of personal health expenditure to total health expenditure had the highest weight. The sustainability indicator dimension included 10 second-level indicators, and the proportion of government health expenditure in fiscal expenditure had the highest weight.Conclusions:The indicator system constructed in this research could provide certain guidance and reference for promoting the construction of common prosperity in health, and provide some reference for follow-up research in this field.

OBJECTIVES: Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality. METHODS: The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality. RESULTS: A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801). CONCLUSIONS PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis* ; Antibodies, Antineutrophil Cytoplasmic/analysis* ; China/epidemiology* ; Humans ; Kidney Failure, Chronic/complications* ; Lymphocytes ; Peroxidase ; Retrospective Studies

Objective:To explore the expression and clinical significance of immunosuppressive receptor T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) on the peripheral blood mononuclear cells (PBMC) in silicosis patients with Mycobacterium tuberculosis infection. Methods:August 2018, a total of 78 patients with silicosis (all were quarry workers in Sanmen County, Zhejiang Province) were enrolled and divided into silicosis combined with active pulmonary tuberculosis group (APTB group), silicosis combined with latent tuberculosis infection group (LTBI group), and simple silicosis with non-tuberculosis infection group (non-TB group). Flow cytometry was used to analyze the expressions of TIGIT, programmed death-1 (PD-1) and transcription factor T-bet on PBMC from patients. Mann-Whitney U test and Pearson correlations analysis were used for statistical analysis. Results:Among the 78 patients, eight were in the APTB group, 24 in the LTBI group, and 46 in the non-TB group. The expressions of PD-1 and TIGIT on CD8 + T cells in the APTB group (29.45%(16.78%) and 65.40%(12.12%), respectively) were significantly higher than those in the LTBI group (17.40%(11.17%) and 48.30%(28.75%), respectively; U=23.500 and 43.500, respectively, P=0.000 8 and 0.020 5, respectively) and non-TB group (15.95%(12.46%) and 45.30%(19.75%), respectively; U=64.000 and 69.000, respectively, P=0.002 3 and 0.003 8, respectively), and the differences were all statistically significant. The expression of TIGIT was positively correlated with PD-1 on CD8 + T cells in silicosis patients ( r=0.434 3, P<0.01). The proportion of PD-1 + TIGIT + CD8 + T cells in the APTB group (19.90%(22.67%)) was significantly higher than those in the non-TB group (11.55%(11.29%), U=76.500, P=0.007 1) and LTBI group (11.55%(10.53%), U=41.000, P=0.015 4), while the proportion of PD-1 -TIGIT -CD8 + T cells in the APTB group (30.60%(12.90%)) was significantly lower than non-TB group (48.90%(18.98%), U=58.000, P=0.001 3) and LTBI group (47.20%(24.59%), U=41.000, P=0.015 4). The differences were all statistically significant. The expression of T-bet on the peripheral blood CD8 + T cells in the APTB group (29.45%(16.78%)) was higher than that in the non-TB group (15.95%(12.46%)) and the LTBI group (17.40%(11.17%)), and the differences were both statistically significant ( U=46.500 and 46.000, respectively, P=0.000 3 and 0.028 3, respectively). The expression of T-bet on CD8 + T cells was positively correlated with TIGIT on CD8 + T cells ( r=0.456 7, P<0.01). The expression of T-bet on PD-1 + TIGIT + CD8 + T cells in the APTB group (65.40%(12.12%)) was higher than those in the LTBI group (48.30%(28.75%), U=23.500, P=0.000 8) and non-TB group (45.30%(19.75%), U=65.000, P=0.002 6), and the differences were both statistically significant. Conclusion:The immunosuppressive receptor PD-1 and TIGIT are highly expressed on CD8 + T cells in silicosis patients with active pulmonary tuberculosis, which indicates CD8 + T cells exhaustion in these population, while the highly co-expression of T-bet suggests the exhausted subsets may have reversed potentiality.