Adenosine, a critical molecule regulating cellular function both inside and outside cells, is controlled by two human adenosine deaminases: ADA1 and ADA2. While ADA1 primarily resides in the cytoplasm, ADA2 can be transported to lysosomes within cells or secreted outside the cell. Patients with ADA2 deficiency (DADA2) often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood. Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages. Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages, and its intracellular concentration decreases in cells secreting TNF-α. This suggests that ADA2 may function as a lysosomal adenosine deaminase, regulating TNF-α expression by the cells. Interestingly, pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage (BAL), correlating with elevated pro-inflammatory cytokine levels. Conversely, cord blood has low ADA2 levels, creating a more immunosuppressive environment. Additionally, secreted ADA2 can bind to apoptotic cells, activating immune cells by reducing extracellular adenosine levels. These findings imply that ADA2 release from monocytes during inflammation, triggered by growth factors, may be crucial for cell activation. Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.
Humans ; Adenosine Deaminase/deficiency* ; Monocytes/cytology* ; Cell Differentiation ; Intercellular Signaling Peptides and Proteins/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Biomarkers/metabolism* ; Macrophages/metabolism* ; Pneumonia/metabolism*

Objective:To explore the correlation between serum nidogen-2 (NID-2) and thoracic aortic calcification in patients with chronic kidney disease (CKD), and construct a risk prediction model based on NID-2 to evaluate its value in predicting the risk of the severe thoracic aortic calcification and cardiovascular and cerebrovascular events in CKD patients.Methods:It was a prospective cohort study. Patients with CKD at stage 3 to 5D in the Zhongda Hospital Affiliated to Southeast University from January 2022 to January 2023 were enrolled. Syngo.via software was used to evaluate the volume of thoracic aortic calcification, and enzyme-linked immunosorbent assay was employed to determine the level of serum NID-2. According to the volume of thoracic aortic calcification, the patients were divided into three groups: no calcification group, mild calcification group and severe calcification group. The top 25% of the patients were defined as no or mild calcification group, and the latter 75% were defined as severe calcification group. The follow-up period was one year. During the follow-up period, cardiovascular and cerebrovascular events, as well as all-cause death among the enrolled patients were recorded. Logistic regression analysis was used to screen the influencing factors of thoracic aortic calcification. Based on the results of logistic regression analysis, a nomogram prediction model was constructed. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve were employed to evaluate the discrimination, calibration and clinical practicality of the nomogram model.Results:A total of 132 patients were included, with 91 males (68.94%) and age of (56.51±16.37) years. There were 60 CKD 3-5 stage patients (non-dialysis, 45.45%) and 72 CKD 5D patients (dialysis, 54.55%). Serum ND-2 levels differed significantly among healthy individuals, dialysis patients and non-dialysis patients ( H=70.651, P<0.001). There was no statistically significant difference in serum NID-2 level between the no or mild calcification group and the severe calcification group in dialysis patients ( Z=350.00, P=0.426). The serum NID-2 level in the severe calcification group was significantly higher than that in the no or mild calcification group in non-dialysis patients ( Z=242.00, P=0.019). In non-dialysis patients, there was a statistically significant correlation between serum NID-2 level and volume of thoracic aortic calcification ( r=0.40, P<0.001). In dialysis patients, there was no statistically significant correlation between serum NID-2 level and volume of each segment of thoracic aortic calcification (all P>0.05). The univariate logistic regression analysis showed that, age, hemoglobin, serum albumin, estimated glomerular filtration rate, NID-2, hypertension, type 2 diabetes mellitus and cerebral infarction were correlated factors of thoracic aortic calcification in non-dialysis patients (all P<0.05). Multivariate logistic regression analysis showed that age ( OR=1.22, 95% CI 1.08-1.50, P=0.010) was an independent correlated factor of thoracic aortic calcification in non-dialysis patients. The above related variables of univariate logistic regression analysis were incorporated into a nomogram to construct a predictive model for severe vascular calcification in non-dialysis patients, yielding an AUC of 0.94 (95% CI 0.89-0.99) in ROC curve, with a sensitivity of 83% and a specificity of 95%. A nomogram model based on above variables for predicting cardiovascular and cerebrovascular events in non-dialysis patients demonstrated an AUC of 0.95 (95% CI 0.90-1.00) in ROC curve, with a sensitivity of 95% and a specificity of 87%. Conclusions:In non-dialysis patients, serum NID-2 level in the severe calcification group is significantly higher than that in the no or mild calcification group. The serum NID-2 is a related factor of thoracic aortic calcification and cardiovascular and cerebrovascular events in non-dialysis patients. The nomogram prediction model constructed by combining NID-2 with age, hemoglobin, serum albumin, estimated glomerular filtration rate, hypertension, type 2 diabetes mellitus and cerebral infarction has a high predictive value for the risk of thoracic aortic calcification as well as cardiovascular and cerebrovascular events in non-dialysis patients.

Against the backdrop of the global acceleration of cervical cancer elimination, China has been promoting pilot programs offering free or subsidized HPV vaccination for eligible girls. In 2022, Zhejiang Province initiated a free bivalent HPV vaccination program for eligible girls, expanding from pilot areas to the whole province. Through key measures such as effective multi-sectoral collaboration, full financial support, comprehensive health education and high-quality vaccination services, the program was successfully implemented. However, challenges were encountered during the implementation of the program, including difficulties in target population definition and HPV vaccine selection, as well as significant gap between vaccination intention and behavior. This article systematically analyzes the practices and challenges faced by Zhejiang Province, and proposes corresponding strategies and suggestions based on the best practices both domestically and internationally. It aims to provide references for the implementation of similar programs in other regions or even integrating HPV vaccine into the immunization program.

Since the introduction of human papillomavirus (HPV) vaccines, countries around the world have actively promoted large-scale vaccination with HPV vaccines to improve their coverage for target populations. This study conducts a multidimensional analysis to quantify the policies, implementation models and evaluation outcomes of the free HPV vaccination program across countries at high, upper-middle and lower-middle income levels. The results reveal distinct patterns in implementation and evaluation among these countries. The results also suggest that China can learn from successful international experiences to explore more effective vaccination strategies to increase coverage. In parallel, it is essential to develop a scientifically grounded evaluation framework and conduct systematic evaluations to effectively support the continuous implementation of the free HPV vaccination program for target populations in China. Furthermore, China may consider incorporating appropriate HPV vaccines into the National Immunization Program and dynamically adjusting vaccine types as needed to accelerate the elimination of cervical cancer.

Objective:To analyze the epidemiological characteristics of herpes zoster (HZ) in Zhoushan and Shaoxing cities of Zhejiang Province from 2022 to 2024.Methods:The HZ data were obtained from the Zhejiang Regional Health Information Platform. Specifically, information was sourced from 42 public hospitals and 149 primary healthcare institutions in Zhoushan and Shaoxing, covering both outpatient and inpatient records (e.g., name, sex, date of birth, ID number, visit date, diagnosis code, admission/discharge dates, and medical expenses). Additionally, vaccination records were matched by ID number from the Zhejiang Immunization Planning Smart Service Information System, including vaccination date, dose, and manufacturer. Permanent resident population data for both cities were collected and stratified by age, sex, and district/county. Based on these data, the epidemiological characteristics of HZ, such as incidence rate, hospitalization rate, and recurrence rate, as well as the occurrence of complications and vaccination, were analyzed.Results:From 2022 to 2024, a total of 45 280 initial HZ cases were identified. The mean age of patients was 57.82 years, with 52.69% being female patients and 95.01% being outpatient cases. Notably, the overall incidence rate of HZ was 3.18‰, showing a significant upward trend ( P<0.001). HZ occurred throughout the year without marked seasonality. The incidence rate increased with age ( P<0.001). The incidence rate was higher in females than males (3.46‰ vs. 2.91‰, P<0.001) and also higher in Shaoxing than Zhoushan (3.38‰ vs. 1.87‰, P<0.001). Regarding complications, these occurred in 44.51% (20 157/45 280) of patients, with the most common complication being postherpetic neuralgia. The incidence rate of HZ with complications was lower than that without complications (1.41‰ vs. 1.76‰, P<0.001), but both hospitalization (0.14‰ vs. 0.03‰, P<0.001) and recurrence rates (27.43‰ vs. 6.69‰, P<0.001) were higher for cases with complications. Additionally, among individuals aged ≥40 years, the overall HZ vaccination rate was 1.42‰. Conclusion:Herpes zoster imposes a substantial disease burden in Zhejiang Province, while the vaccination rate remains low.

Against the backdrop of the global acceleration of cervical cancer elimination, China has been promoting pilot programs offering free or subsidized HPV vaccination for eligible girls. In 2022, Zhejiang Province initiated a free bivalent HPV vaccination program for eligible girls, expanding from pilot areas to the whole province. Through key measures such as effective multi-sectoral collaboration, full financial support, comprehensive health education and high-quality vaccination services, the program was successfully implemented. However, challenges were encountered during the implementation of the program, including difficulties in target population definition and HPV vaccine selection, as well as significant gap between vaccination intention and behavior. This article systematically analyzes the practices and challenges faced by Zhejiang Province, and proposes corresponding strategies and suggestions based on the best practices both domestically and internationally. It aims to provide references for the implementation of similar programs in other regions or even integrating HPV vaccine into the immunization program.

Since the introduction of human papillomavirus (HPV) vaccines, countries around the world have actively promoted large-scale vaccination with HPV vaccines to improve their coverage for target populations. This study conducts a multidimensional analysis to quantify the policies, implementation models and evaluation outcomes of the free HPV vaccination program across countries at high, upper-middle and lower-middle income levels. The results reveal distinct patterns in implementation and evaluation among these countries. The results also suggest that China can learn from successful international experiences to explore more effective vaccination strategies to increase coverage. In parallel, it is essential to develop a scientifically grounded evaluation framework and conduct systematic evaluations to effectively support the continuous implementation of the free HPV vaccination program for target populations in China. Furthermore, China may consider incorporating appropriate HPV vaccines into the National Immunization Program and dynamically adjusting vaccine types as needed to accelerate the elimination of cervical cancer.

Objective:To analyze the epidemiological characteristics of herpes zoster (HZ) in Zhoushan and Shaoxing cities of Zhejiang Province from 2022 to 2024.Methods:The HZ data were obtained from the Zhejiang Regional Health Information Platform. Specifically, information was sourced from 42 public hospitals and 149 primary healthcare institutions in Zhoushan and Shaoxing, covering both outpatient and inpatient records (e.g., name, sex, date of birth, ID number, visit date, diagnosis code, admission/discharge dates, and medical expenses). Additionally, vaccination records were matched by ID number from the Zhejiang Immunization Planning Smart Service Information System, including vaccination date, dose, and manufacturer. Permanent resident population data for both cities were collected and stratified by age, sex, and district/county. Based on these data, the epidemiological characteristics of HZ, such as incidence rate, hospitalization rate, and recurrence rate, as well as the occurrence of complications and vaccination, were analyzed.Results:From 2022 to 2024, a total of 45 280 initial HZ cases were identified. The mean age of patients was 57.82 years, with 52.69% being female patients and 95.01% being outpatient cases. Notably, the overall incidence rate of HZ was 3.18‰, showing a significant upward trend ( P<0.001). HZ occurred throughout the year without marked seasonality. The incidence rate increased with age ( P<0.001). The incidence rate was higher in females than males (3.46‰ vs. 2.91‰, P<0.001) and also higher in Shaoxing than Zhoushan (3.38‰ vs. 1.87‰, P<0.001). Regarding complications, these occurred in 44.51% (20 157/45 280) of patients, with the most common complication being postherpetic neuralgia. The incidence rate of HZ with complications was lower than that without complications (1.41‰ vs. 1.76‰, P<0.001), but both hospitalization (0.14‰ vs. 0.03‰, P<0.001) and recurrence rates (27.43‰ vs. 6.69‰, P<0.001) were higher for cases with complications. Additionally, among individuals aged ≥40 years, the overall HZ vaccination rate was 1.42‰. Conclusion:Herpes zoster imposes a substantial disease burden in Zhejiang Province, while the vaccination rate remains low.

Objective:To explore the correlation between serum nidogen-2 (NID-2) and thoracic aortic calcification in patients with chronic kidney disease (CKD), and construct a risk prediction model based on NID-2 to evaluate its value in predicting the risk of the severe thoracic aortic calcification and cardiovascular and cerebrovascular events in CKD patients.Methods:It was a prospective cohort study. Patients with CKD at stage 3 to 5D in the Zhongda Hospital Affiliated to Southeast University from January 2022 to January 2023 were enrolled. Syngo.via software was used to evaluate the volume of thoracic aortic calcification, and enzyme-linked immunosorbent assay was employed to determine the level of serum NID-2. According to the volume of thoracic aortic calcification, the patients were divided into three groups: no calcification group, mild calcification group and severe calcification group. The top 25% of the patients were defined as no or mild calcification group, and the latter 75% were defined as severe calcification group. The follow-up period was one year. During the follow-up period, cardiovascular and cerebrovascular events, as well as all-cause death among the enrolled patients were recorded. Logistic regression analysis was used to screen the influencing factors of thoracic aortic calcification. Based on the results of logistic regression analysis, a nomogram prediction model was constructed. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve were employed to evaluate the discrimination, calibration and clinical practicality of the nomogram model.Results:A total of 132 patients were included, with 91 males (68.94%) and age of (56.51±16.37) years. There were 60 CKD 3-5 stage patients (non-dialysis, 45.45%) and 72 CKD 5D patients (dialysis, 54.55%). Serum ND-2 levels differed significantly among healthy individuals, dialysis patients and non-dialysis patients ( H=70.651, P<0.001). There was no statistically significant difference in serum NID-2 level between the no or mild calcification group and the severe calcification group in dialysis patients ( Z=350.00, P=0.426). The serum NID-2 level in the severe calcification group was significantly higher than that in the no or mild calcification group in non-dialysis patients ( Z=242.00, P=0.019). In non-dialysis patients, there was a statistically significant correlation between serum NID-2 level and volume of thoracic aortic calcification ( r=0.40, P<0.001). In dialysis patients, there was no statistically significant correlation between serum NID-2 level and volume of each segment of thoracic aortic calcification (all P>0.05). The univariate logistic regression analysis showed that, age, hemoglobin, serum albumin, estimated glomerular filtration rate, NID-2, hypertension, type 2 diabetes mellitus and cerebral infarction were correlated factors of thoracic aortic calcification in non-dialysis patients (all P<0.05). Multivariate logistic regression analysis showed that age ( OR=1.22, 95% CI 1.08-1.50, P=0.010) was an independent correlated factor of thoracic aortic calcification in non-dialysis patients. The above related variables of univariate logistic regression analysis were incorporated into a nomogram to construct a predictive model for severe vascular calcification in non-dialysis patients, yielding an AUC of 0.94 (95% CI 0.89-0.99) in ROC curve, with a sensitivity of 83% and a specificity of 95%. A nomogram model based on above variables for predicting cardiovascular and cerebrovascular events in non-dialysis patients demonstrated an AUC of 0.95 (95% CI 0.90-1.00) in ROC curve, with a sensitivity of 95% and a specificity of 87%. Conclusions:In non-dialysis patients, serum NID-2 level in the severe calcification group is significantly higher than that in the no or mild calcification group. The serum NID-2 is a related factor of thoracic aortic calcification and cardiovascular and cerebrovascular events in non-dialysis patients. The nomogram prediction model constructed by combining NID-2 with age, hemoglobin, serum albumin, estimated glomerular filtration rate, hypertension, type 2 diabetes mellitus and cerebral infarction has a high predictive value for the risk of thoracic aortic calcification as well as cardiovascular and cerebrovascular events in non-dialysis patients.

Alzheimer's disease(AD), the most common neurodegenerative disease, has shown an increasing incidence among younger people. With the onset of disease, most patients' cognitive function will show a progressive decline, bringing a heavy burden to the society and the family. Studies have shown that fibroblast growth factor (FGF) may be involved in the pathogenesis of AD through multiple mechanisms. This article reviews the mechanism of FGF in AD, with the hope of providing new ideas for elucidating the pathogenesis and early diagnosis of AD.