Objective: To evaluate the equity of human resource allocation in centers for disease control and prevention (CDCs) in China, so as to provide insights into optimizing human resource and promoting the high-quality development of CDCs. Methods: The number, age, educational level and professional title of CDCs personnel from 2017 to 2021 were collected from China Health Statistics Yearbook and China Statistical Yearbook. General information of human resource in CDCs across different provinces (autonomous regions, municipalities) was described, and the equity of human resource allocation was assessed using agglomeration degree. Results: The number of personnel in CDCs was 190 730 in 2017, and it began to increase from 2020, reaching 209 550 in 2021, with an average annual growth rate of 2.47%. The staffing gap decreased from 52 534 to 37 655. The proportion of personnel aged 55 years and older increased from 10.74% to 16.69%, the proportion of personnel with a bachelor's degree or above increased from 36.50% to 47.80%, the proportion of personnel with senior professional titles increased from 9.75% to 13.31%, and the number of personnel per 10 000 permanent residents increased from 1.36 to 1.48. Agglomeration degree analysis indicated that the equity of human resource allocation in terms of both geography and population was relatively good among the CDCs of 12 provinces (autonomous regions, municipalities) including Beijing, Tianjin and Liaoning; the equity of human resource allocation was relatively good in terms of geography and was relatively poor in terms of population among 11 provinces (autonomous regions, municipalities) including Shanghai, Jiangsu and Zhejiang; the equity of human resource allocation was relatively poor in terms of geography and was relatively good in terms of population among the CDCs of 8 provinces (autonomous regions, municipalities) including Inner Mongolia, Heilongjiang and Hainan. Conclusions Although there was an increase in the number of personnel in CDCs from 2017 to 2021, the growth rate was low. There were differences in the equity of human resource allocation among provinces (autonomous regions, municipalities), with a relative shortage of human resource in CDCs in the east area.

Objective: To analyze the disease burden of chronic obstructive pulmonary disease (COPD) and changes in its risk factors among residents in Zhejiang Province from 1990 to 2021, so as to identify key priorities for COPD prevention and control. Methods: Data on COPD mortality and disability-adjusted life years (DALY) for residents in Zhejiang Province from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Standardized mortality and standardized DALY rate were calculated using the GBD 2021 world population standard structure. Premature mortality was computed via the life table method. The average annual percent change (AAPC) was applied to analyze trends in COPD mortality, DALY rate, and premature mortality. Changes in deaths of COPD risk factors were evaluated using population attributable fraction (PAF). Results: From 1990 to 2021, the standardized COPD mortality in Zhejiang Province decreased from 272.40/100 000 to 70.56/100 000 (AAPC=-4.395%), and the standardized DALY rate declined from 4 167.37/100 000 to 1 071.89/100 000 (AAPC=-4.396%). Similar downward trends were observed in both males (AAPC=-3.933%, -4.173%) and females (AAPC=-4.785%, -4.480%), all P<0.05. Crude mortality and DALY rates increased with age, and the crude mortality and DALY rates of various age groups in Zhejiang Province showed decreasing trends from 1990 to 2021 (all P<0.05). The premature mortality declined from 4.37% to 0.60% from 1990 to 2021 (AAPC=- 6.206%), with consistent trends across males and females (AAPC=- 6.144%, - 6.379%, all P<0.05). From 1990 to 2021, particulate matter pollution showed the largest reduction in PAF (- 56.76%), while ambient ozone pollution had the largest increase (103.07%) in Zhejiang Province. By 2021, smoking became the leading risk factor for deaths of COPD (PAF=43.32%). Conclusions The standardized mortality, standardized DALY rate, and premature mortality for COPD show consistent declining trends in Zhejiang Province from 1990 to 2021. However, risk factors such as smoking and ambient ozone pollution require intensified focus to further reduce disease burden of COPD.

Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

OBJECTIVES: To investigate the correlation of PRELID1 with gastric cancer (GC) progression, prognosis, and epithelial-mesenchymal transition (EMT) and the underlying mechanisms. METHODS: We analyzed the data of 115 patients undergoing radical gastrectomy for GC in our hospital between February, 2018 and March, 2023 to explore the correlation of PRELID1 expression level in GC tissues with tumor progression and patient prognosis. In cultured GC cells, the effects of lentivirus-mediated overexpression or interference of PRELID1 were observed on cell migration, invasion and EMT. RESULTS: Immunohistochemical staining revealed significantly higher PRELID1 expression in GC tissues (P<0.001), whose expression level was positively correlated with CEA ≥5 ng/mL (P=0.007), CA199 ≥37 U/mL (P=0.007), G_3-4 stages (P=0.001), T_3-4 stages (P=0.001), and N_2-3 stages (P=0.020). Univariate and Cox multifactorial analysis showed that high PRELID1 level was an independent risk factor affecting 5-year survival of GC patients (P=0.001). In cultured GC cells, PRELID1 overexpression obviously promoted cell proliferation, migration, invasion, and the expressions of MMP2 and MMP9, and interference of PRELID1 produced the opposite changes. PRELID1 overexpression also increased the expressions of N-cadherin and vimentin and reduced the expression of E-cadherin. Mechanistic analyses showed that up-regulation of PRELID1 increased the expression of p-PI3K, p-AKT, and p-mTOR in GC cells, whereas its interference caused the opposite changes; the application of 740 Y-P, a PI3K/AKT pathway activator, significantly enhanced the migration, invasion, and EMT of GC cells with PRELID1 knockdown. CONCLUSIONS PRELID1 is highly expressed in GC and affects prognosis of the patients, and its high expression promotes migration, invasion and epithelial mesenchymal transition of GC cells possibly by activating the PI3K/AKT/mTOR pathway.
Humans ; Stomach Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Prognosis ; Cell Movement ; Cell Line, Tumor ; Male ; Female ; Middle Aged ; Signal Transduction ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism*

Objective To evaluate the predictive value of triglyceride-glucose body mass index(TyG-BMI),atherogenic index of plasma(AIP),and postprandial glucose excursion(PPGE)for sarcopenia in patients with type 2 diabetes mellitus(T2DM).Methods An observational cohort trial was conducted on 590 hospitalized T2DM patients(322 males and 268 females)admitted to Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University between January 2023 and December 2024.General demographic data and key metabolic indicators,including fasting plasma glucose(FPG),postprandial 2-hour plasma glucose(PPG),triglyceride(TG)were collected,and then TyG-BMI,AIP,and PPGE were calculated.Based on the Asian Working Group for Sarcopenia(AWGS)2019 criteria,they were divided into a sarcopenia group(n=140)and a non-sarcopenia group(n=450).After 1∶1 propensity score matching(PSM),102 patients with sarcopenia were matched with 102 without.Differences in metabolic indicators FPG,PPG,TyG-BMI,AIP and PPGE were compared between the 2 groups.Spearman correlation analysis was conducted to assess correlations of these indicators with sarcopenia.Conditional logistic regression analysis was performed to identify independent risk factors,and receiver operating characteristic(ROC)curves were plotted to assess predictive performance.An external validation cohort consisting of 192 T2DM patients from Department of Endocrinology of Jiangbei Branch of First Affiliated Hospital of Army Medical University between January 2023 and December 2024 was included to validate the prediction model.Results After PSM,the baseline data of the 2 groups was balanced(P>0.05).The sarcopenia group showed higher levels of PPG,AIP,and PPGE,but lower TyG-BMI value than the non-sarcopenia group(all P=0.001).Spearman correlation analysis revealed that the TyG-BMI was negatively correlated(r=-0.404,P=0.001),whereas AIP and PPGE were positively correlated with concomitant sarcopenia(r=0.280,P=0.001;r=0.372,P=0.001)in the T2DM patients.Conditional logistic regression analysis identified AIP(OR=14.367)and PPGE(OR=1.245)as independent risk factors,while TyG-BMI(OR=0.966)as independent protective factors.ROC curve analysis revealed that the area under the curve(AUC)of the combined model of TyG-BMI,AIP and PPGE in predicting sarcopenia was 0.918,and the AUC value was 0.954 in external validation,with good sensitivity and specificity.Conclusion TyG-BMI,AIP,and PPGE are important metabolic predictors in T2DM patients with sarcopenia.Their combination has good screening value for sarcopenia,and can be applied in external prediction for T2DM patients.

OBJECTIVE To optimize the rivaroxaban dosing regimen for anticoagulation in patients with different renal function levels. METHODS The administration regimen was determined based on the drug instructions for rivaroxaban and the actual medication situation of the patient. The target concentration range and the subsection interval were established using rivaroxaban blood minimum concentration for patients from Hebei General Hospital and reference range of rivaroxaban laboratory monitoring concentration recommended by International Council for Standardization in Hematology. The probability of different dosing regimens in each target concentration range was investigated with Monte Carlo simulation using Oracle Crystal Ball software （V11.1.2.4）. RESULTS A total of 97 patients with non-valvular atrial fibrillation were enrolled and the minimum concentration of rivaroxaban was tested 125 times with a median trough concentration of 32.2 ng/mL； a total of 121 patients with venous thrombosis were enrolled and the minimum concentration was tested 159 times with a median minimum concentration of 31.0 ng/mL. The reference range for steady-state minimum concentration in patients with non-valvular atrial fibrillation was 12-137 and 3-153 ng/mL， while the reference range for steady-state minimum concentration in patients with venous thrombosis was 6-239 and 3-224 ng/mL. Monte Carlo simulation results showed that in patients with non-valvular atrial fibrillation， the optimal rivaroxaban dosing regimen for patients with glomerular filtration rate （eGFR） 0-30 mL/min was 5 mg once daily； for patients with eGFR＞30-60 mL/min， the optimal dosing regimen was 10-20 mg once daily or 5 mg twice daily； for patients with eGFR＞60-90 mL/min， the optimal dosing regimen was 15-30 mg once daily or 5-10 mg twice daily； for patients with eGFR＞90-120 mL/min， the optimal dosing regimen was 25-30 mg once daily or 5-15 mg twice daily. For patients with venous thrombosis， it is not recommended to use rivaroxaban more than 5 mg once daily for patients with eGFR 0-30 mL/min； the optimal dosing regimens of rivaroxaban were 5 mg once daily for patients with eGFR＞30-60 mL/min， 25- 30 mg once daily or 5-15 mg twice daily for patients with eGFR＞60-90 mL/min， 10-15 mg twice daily for patients with eGFR＞ 90-120 mL/min. CONCLUSIONS Rivaroxaban should be selected carefully as the anticoagulants for patients with severe renal function impairment. Rivaroxaban possesses a wide reference range in the minimum concentration and considerable individual variability. The dosage and frequency of rivaroxaban can be personalized through the Monte Carlo simulation method， taking into account patients’ renal function.

OBJECTIVE To explore the independent risk factors of voriconazole （VCZ）-related liver injury in elderly patients with hypoproteinemia. METHODS Elderly patients with invasive fungal infection and hypoproteinemia who were hospitalized in the respiratory intensive care unit of our hospital and treated with VCZ from August 2020 to July 2023 were selected. They were divided into group A （liver injury group） and group B （non-liver injury group） based on whether the liver injury occurred after using VCZ. Pearson correlation analysis was used to analyze the correlation between minimum concentration （cmin） of VCZ and inflammatory factor[C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）]， as well as liver function [alanine transaminase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， total bilirubin （TBIL）]； univariate analysis was performed by using χ 2 test； Logistic regression analysis was used to analyze the independent risk factors affecting the occurrence of liver injury. RESULTS A total of 320 patients were included in the study， of whom 56 developed liver injury， with an incidence of 17.50%. The VCZ cmin in group A was significantly higher than group B （P＝ 0.021）. CRP， PCT， IL-6， and TBIL were correlated with VCZ cmin （P＜0.05）. CRP， PCT， IL-6， and TBIL had a significant impact on VCZ cmin （P＜0.05）. VCZ cmin， PCT， and TBIL were independent risk factors for liver injury （P＜0.05）. The patients with VCZ cmin≥3.76 mg/L had a significantly increased risk of liver injury. CONCLUSIONS VCZ cmin， PCT， and TBIL are independent risk factors for the occurrence of liver injury in elderly patients with hypoproteinemia. For patients with high PCT and TBIL， VCZ cmin and liver function should be closely monitored during VCZ treatment to reduce the risk of liver injury.

Objective: To analyze the disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019, so as to provide the basis for prevention and control of colorectal cancer. Methods: Based on data of 2019 Global Burden of Disease (GDB 2019), disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019 was assessed using years of life lost (YLL), years lived with disability (YLD), disability-adjusted life years (DALY). Results: In 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province were 496.15/105, 31.81/105 and 527.96/105, respectively. From 1990 to 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province increased by 114.90%, 482.60% and 123.38%, respectively, showing increasing trends (average annual percent change values were =2.663, 6.283 and 2.800, respectively,all P<0.05). From 1990 to 2019, the YLL rate, YLD rate and DALY rate in the age groups of 15 to 49 years, 50 to 69 years and 70 years and older showed increasing trends (all P<0.05). In 1990, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in calcium, diet low in milk, diet low in whole grains, smoking, alcohol use, low physical activity, high fasting plasma glucose, diet high in red meat, diet low in fiber and high body mass index. In 2019, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in milk, diet low in whole grains, diet low in calcium, alcohol use, diet high in red meat, high body mass index, high fasting plasma glucose, low physical activity, diet low in fiber and diet high in processed meat. Conclusions The disease burden of colorectal cancer in Zhejiang Province showed an upward trend from 1990 to 2019. The top ten risk factors for colorectal cancer remained between 1990 and 2019, while there was a slight change in ranking.

Spontaneous abortion is one of the most common complications of pregnancy， and two or more spontaneous abortions in a row are defined as recurrent spontaneous abortion （RSA）， of which about half of patients have unknown etiology. However， the pathogenesis of unexplained RSA （URSA） has not been elucidated， and the lack of effective treatment has made it one of the key and difficult points in the field of obstetrics and gynecology. This article conducts a literature review of recent research on URSA and finds that the pathogenesis of URSA is related to the imbalance of immune tolerance at the maternal-fetal interface， apoptosis of trophoblast cells， inhibition of angiogenesis， and activation of immune responses. Immunotherapy （including cell therapy， cytokine therapy， and immunosuppressive intervention）， hormone drugs， anticoagulant regimens， and traditional Chinese medicine therapies are commonly used in clinical practice to intervene in URSA， but the safety and effectiveness of some therapies are still controversial.