The study aims to examine the effects and potential mechanisms of disulfiram (DSF) on cardiac hypertrophic injury, focusing on the role of transforming growth factor-β-activated kinase 1 (TAK1)-mediated pan-apoptosis (PANoptosis). H9C2 cardiomyocytes were treated with angiotensin II (Ang II, 1 µmol/L) to establish an in vitro model of myocardial hypertrophy. DSF (40 µmol/L) was used to treat cardiomyocyte hypertrophic injury models, either along or in combination with the TAK1 inhibitor, 5z-7-oxozeaenol (5z-7, 0.1 µmol/L). We assessed cell damage using propidium iodide (PI) staining, measured cell viability with CCK8 assay, quantified inflammatory factor levels in cell culture media via ELISA, detected TAK1 and RIPK1 binding rates using immunoprecipitation, and analyzed the protein expression levels of key proteins in the TAK1-mediated PANoptosis pathway using Western blot. In addition, the surface area of cardiomyocytes was measured with Phalloidin staining. The results showed that Ang II significantly reduced the cellular viability of H9C2 cardiomyocytes and the binding rate of TAK1 and RIPK1, significantly increased the surface area of H9C2 cardiomyocytes, PI staining positive rate, levels of inflammatory factors [interleukin-1β (IL-1β), IL-18, and tumor necrosis factor α (TNF-α)] in cell culture media and p-TAK1/TAK1 ratio, and significantly up-regulated key proteins in the PANoptosis pathway [pyroptosis-related proteins NLRP3, Caspase-1 (p20), and GSDMD-N (p30), apoptosis-related proteins Caspase-3 (p17), Caspase-7 (p20), and Caspase-8 (p18), as well as necroptosis-related proteins p-MLKL, RIPK1, and RIPK3]. DSF significantly reversed the above changes induced by Ang II. Both 5z-7 and exogenous IL-1β weakened these cardioprotective effects of DSF. These results suggest that DSF may alleviate cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Animals ; MAP Kinase Kinase Kinases/physiology* ; Rats ; Myocytes, Cardiac/pathology* ; Disulfiram/pharmacology* ; Cardiomegaly ; Apoptosis/drug effects* ; Cell Line ; Angiotensin II ; Necroptosis/drug effects* ; Interleukin-1beta/metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Lactones ; Resorcinols ; Zearalenone/administration & dosage*

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective: To analyze the strengths, weaknesses, opportunities and threats of the construction on intelligent vaccination clinics in Zhejiang Province, so as to provide countermeasures for promoting the construction of intelligent vaccination clinics in Zhejiang Province. Methods: By reviewing the annual reports of Zhejiang immunization planning, survey data from Zhejiang Centers for Disease Control and Prevention and Immunization Intelligent Service System, data of human resources of immunization planning, vaccine procurement, construction progress of intelligent vaccination clinics and vaccination were collected. The relevant literature was searched to gather information on the construction standards and norms of intelligent vaccination clinics. The analysis of the strengths, weaknesses, opportunities and threats (SWOT) of the construction of intelligent vaccination clinics was conducted, and corresponding countermeasures and suggestions were proposed. Results: The National Immunization Program reported vaccine rate in Zhejiang Province is more than 99%, and standardized vaccination clinics have been popularized throughout the province. The vaccination staff are professional, and a province-wide intelligent immunization service information system has been established, providing the resources and conditions for the construction of intelligent vaccination clinics. However, there are problems such as low data quality and matching efficiency in vaccination, insufficient data interoperability and sharing, unbalanced regional capabilities in intelligent transformation, and uneven distribution of talent and resources. It is crucial to seize the opportunities presented by the development of big data and artificial intelligence, rely on the regional development of the Internet and health industry, seize the opportunity of rapid growth in demand for intelligent vaccination services and high public acceptance, accelerate the construction of intelligent vaccination clinics, and establish intelligent vaccination service standards as soon as possible. Conclusion We should seize the opportunities presented by the digital reform and development, fully utilize the existing vaccination resources and strengths, address the shortcomings, and accelerate the construction of intelligent vaccination clinics in Zhejiang Province.

Objective:To evaluate the epidemiological characteristics and explore the associated factors of breakthrough cases (BC) from Public Health Emergency Events (PHEEs) of varicella in Zhejiang Province from 2019 to 2022.Methods:Data on cases were obtained from the China Information System for Disease Control and Prevention and the PHEEs Reporting Information Database of Varicella in Zhejiang Province. History records were matched through the Zhejiang Provincial Immunization Information System. Descriptive analysis and multiple logistic regression model with a bidirectional stepwise selection method were performed to explore associated factors for BC during 2019-2022.Results:A total of 144 276 varicella cases were reported from 2019 to 2022, with the annual reported incidence of 47.35-82.80 cases per 100 000 population. Among these cases, 109 172 were non-breakthrough cases (NBC, accounting for 75.67%), 34 517 were BC (23.92%), and the rest 587 cases had unclear vaccination history on varicella (0.41%). A total of 214 PHEEs of varicella were reported, of which 99.07% occurred in school settings. The proportion of PHEEs that occurred in high school increased significantly as time went on ( χ2trend=5.742, P=0.017). Multiple logistic regression model which focused on "BC vs. NBC (as the reference)" indicated that the year of onset ( OR=1.585, 95% CI:1.343-1.878), the month of onset (taking January as the reference, OR=2.311-15.652), city (taking Hangzhou as the reference, Jiaxing OR=2.370, Jinhua OR=2.197, Lishui OR=0.134), age ( OR=0.887, 95% CI: 0.826-0.944), PHEEs setting (taking "primary school and below" as the reference, "high school and above" OR=0.516, 95% CI: 0.305-0.897), and the number of rashes ( OR=0.569, 95% CI: 0.458-0.703) were associated factors. Multiple logistic regression model which focused on "two-dose BC vs. one-dose BC (as the reference)" showed that the age of initial vaccination ( OR=0.045, 95% CI: 0.014-0.107), the time interval from onset to the last dose ( OR=0.037, 95% CI: 0.011-0.087) and the age of onset ( OR=20.724, 95% CI: 8.383-72.485) were associated factors. Conclusion:During 2019-2022, the reported high-risk group of varicella in Zhejiang Province has shifted to adolescents and young adults. Although vaccination could not completely prevent the onset of VZV, it could relieve clinical symptoms and delay the age of onset.

Objective:To evaluate the epidemiological characteristics and explore the associated factors of breakthrough cases (BC) from Public Health Emergency Events (PHEEs) of varicella in Zhejiang Province from 2019 to 2022.Methods:Data on cases were obtained from the China Information System for Disease Control and Prevention and the PHEEs Reporting Information Database of Varicella in Zhejiang Province. History records were matched through the Zhejiang Provincial Immunization Information System. Descriptive analysis and multiple logistic regression model with a bidirectional stepwise selection method were performed to explore associated factors for BC during 2019-2022.Results:A total of 144 276 varicella cases were reported from 2019 to 2022, with the annual reported incidence of 47.35-82.80 cases per 100 000 population. Among these cases, 109 172 were non-breakthrough cases (NBC, accounting for 75.67%), 34 517 were BC (23.92%), and the rest 587 cases had unclear vaccination history on varicella (0.41%). A total of 214 PHEEs of varicella were reported, of which 99.07% occurred in school settings. The proportion of PHEEs that occurred in high school increased significantly as time went on ( χ2trend=5.742, P=0.017). Multiple logistic regression model which focused on "BC vs. NBC (as the reference)" indicated that the year of onset ( OR=1.585, 95% CI:1.343-1.878), the month of onset (taking January as the reference, OR=2.311-15.652), city (taking Hangzhou as the reference, Jiaxing OR=2.370, Jinhua OR=2.197, Lishui OR=0.134), age ( OR=0.887, 95% CI: 0.826-0.944), PHEEs setting (taking "primary school and below" as the reference, "high school and above" OR=0.516, 95% CI: 0.305-0.897), and the number of rashes ( OR=0.569, 95% CI: 0.458-0.703) were associated factors. Multiple logistic regression model which focused on "two-dose BC vs. one-dose BC (as the reference)" showed that the age of initial vaccination ( OR=0.045, 95% CI: 0.014-0.107), the time interval from onset to the last dose ( OR=0.037, 95% CI: 0.011-0.087) and the age of onset ( OR=20.724, 95% CI: 8.383-72.485) were associated factors. Conclusion:During 2019-2022, the reported high-risk group of varicella in Zhejiang Province has shifted to adolescents and young adults. Although vaccination could not completely prevent the onset of VZV, it could relieve clinical symptoms and delay the age of onset.

This study aims to investigate the protective effect of resveratrol against liver injury in hindlimb unloading rats. Thirty 2-month-old male SD rats were randomly divided into normal group (Control), hindlimb unloading model group (Model), and hindlimb unloading+resveratrol administration group (Model+Res). The Model + Res group was injected intraperitoneally with 30 mg/kg of resveratrol, and the Control and Model groups were injected intraperitoneally with an equal volume of 0.9% NaCl. Liver tissues were collected after 28 days and analyzed for oxidative stress, inflammatory factors, energy metabolism indices, Na ⁺-K ⁺-ATPase and Ca ²⁺-Mg ²⁺-ATPase activity, and morphological changes were observed by hematoxylin-eosin staining. The protein expression levels of Bax, Bcl-2, p-PI3K, PI3K, p-AKT, and AKT were detected by Western blotting. Compared with the Control group, hepatocytes in the Model group showed swelling, abnormal morphology, nuclear consolidation, and cell membrane disruption. Oxidative stress, inflammatory factor levels, hepatic glycogen accumulation, and energy metabolism were increased in the liver tissues of the Model group, while resveratrol treatment significantly reversed these changes. The results of Western blotting showed that resveratrol significantly reduced the expression of Bax and increased the expression levels of Bcl-2, and the proteins of p-PI3K/PI3K and p-AKT/AKT expression levels. It is suggested that 28 days of hindlimb unloading treatment could lead to liver tissue injury in rats, which is manifested as oxidative stress, inflammatory response, energy metabolism disorder and increased apoptosis level, and resveratrol has a certain mitigating effect on this.
Animals ; Resveratrol ; Male ; Liver/pathology* ; Rats, Sprague-Dawley ; Rats ; Hindlimb Suspension ; Oxidative Stress/drug effects* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Stilbenes/pharmacology* ; bcl-2-Associated X Protein/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Apoptosis/drug effects*

OBJECTIVE: To provide evidence for further reducing the incidence of central line-associated bloodstream infection (CLABSI) according to investigation of the prevention and control of CLABSI in intensive care unit (ICU) in Shandong Province. METHODS: The questionnaire was developed by experts from Shandong Critical Care Medical Quality Control Center, combining domestic and foreign guidelines, consensus and research. A convenient sampling method was used to recruit survey subjects online from October 11 to 31, 2023 in the province to investigate the management status of central venous catheter (CVC) in ICU units of secondary and above hospitals. RESULTS: A total of 201 valid data were collected, involving 186 hospitals in the province, with a total of 201 ICU units, mainly comprehensive ICU (91%). The beds in ICU units were mainly single rooms (89%) and triple rooms (79%), and the ratio of doctors to total beds was 0.54 : 1. The training on the knowledge and operation of intravascular catheter-associated bloodstream infection in each ICU unit was mainly irregular (49%), and 96% of the catheter operators were authorized by the hospital. In terms of CVC selection, 89% of ICU units used dual-chamber CVC, and 86% of ICU units used catheters without antibiotic coating. When selecting the placement site, for conventional CVC catheterization, 65% preferred subclavian vein. Femoral vein was preferred in 87% of ICU units undergoing continuous renal replacement therapy. 95% of ICU units had established standardized operation procedure (SOP) for CVC placement. 86% of ICU units were capable of ultrasound positioning or guided puncture at the time of catheterization. During catheterization, 88% of ICU units met the sterile dress code. Before and after catheterzation, 81% and 77% of ICU units standardized hand hygiene. Only 31% of ICU units were covered from head to toe by aseptic wipes. For the choice of skin disinfectant, the majority of ICU units (72%) only used iodophor. After tube placement, 54% of ICU units chose sterile transparent dressing and 25% chose sterile gauze dressing. 98% of ICU units were sutured to secure the catheter. Regarding catheter replacement and removal, 45% of ICU units could not be removed or replaced within 2 days in emergency situations where the principle of sterility was not guaranteed. When CLABSI was suspected, 55% of ICU units were able to obtain the catheter tip, transcatheter blood culture, and contralateral peripheral vein blood culture at the same time. For CVC replacement frequency, most ICU units (75%) would not be replaced regularly, and some ICU units would be replaced regularly, but the frequency of replacement was different. For CLABSI prevention and control, 82% of ICU units developed a verification form or supervision form. When analyzing the sources of CLABSI data, most of them were filled in by themselves (60%). As for the frequency of data analysis, 57% were once a month. CONCLUSIONS All ICU units in Shandong Province are standardized in terms of the authorization of operators, the formulation of SOP, the formulation and implementation of verification form and supervision form, ultrasound-guided puncture, and hand hygiene before and after catheterization. However, there are still deficiencies in the training on knowledge and operation of intravascular catheter-associated bloodstream infections, maximum aseptic coverage, catheter replacement and removal, and the reporting sources of CLABSI data, which need to be strengthened in the follow-up work. At present, the selection of CVC, the selection of catheterization site, the selection of skin disinfectant and the selection of dressings after catheterization still need further research.
Intensive Care Units ; Humans ; Surveys and Questionnaires ; China/epidemiology* ; Cross-Sectional Studies ; Catheter-Related Infections/epidemiology* ; Catheterization, Central Venous/methods* ; Cross Infection/epidemiology* ; Central Venous Catheters/adverse effects* ; Infection Control/methods*

Objective:To study whether male was the risk factor for prognosis of patients with differentiated thyroid cancer (DTC) after 131I treatment based on propensity score matching (PSM) method. Methods:From April 2016 to January 2021, 1 677 patients (age: 11-84 (43.9±12.5) years) with DTC who underwent total thyroidectomy and received 131I treatment in Tianjin Medical University General Hospital were retrospectively enrolled and patients were divided into male group ( n=546) and female group ( n=1 131). The evaluation results of patients were divided into excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR) and structural incomplete response (SIR). Among them, ER and IDR were divided into good prognosis group, and BIR and SIR were divided into poor prognosis group. The PSM method was adopted to process all data to reduce the influence of data bias and confounding variables. χ2 test was used for data analysis. Multivariate logistic regression was used to analyze the risk factors affecting prognosis, and ROC curve was used to analyze the relationship between stimulated thyroglobulin (sTg) level and poor prognosis. Results:Before PSM, the proportion of male patients with poor prognosis was significantly higher than that of female patients (21.2%(116/546) vs 14.0%(158/1 131); χ2=17.53, P=0.001). After PSM, there was no difference in the proportion of poor prognosis between male and female groups (19.9%(107/537) vs 15.6%(84/537); χ2=5.43, P=0.143). Multivariate logistic regression analysis showed that male (odds radio ( OR)=1.439 (95% CI: 1.016-2.038), P=0.040), high T stage(T3+ T4 stage)( OR=1.816 (95% CI: 1.273-2.590), P=0.001), N1b stage ( OR=1.766 (95% CI: 1.233-2.530), P=0.002), M1 stage ( OR=9.833 (95% CI: 3.190-30.309), P<0.001) and sTg level ( OR=1.035 (95% CI: 1.029-1.042), P<0.001) were risk factors for poor prognosis before PSM, while high T stage (T3+ T4 stage)( OR=1.870 (95% CI: 1.212-2.886), P=0.005), M1 stage ( OR=8.993 (95% CI: 2.434-33.225), P=0.001), sTg level ( OR=1.040 (95% CI: 1.030-1.049), P<0.001) were still risk factors, and N1b stage ( OR=1.459 (95% CI: 0.938-2.270), P=0.094), male ( OR=1.383 (95% CI: 0.912-2.096), P=0.127) were no longer risk factors for poor prognosis after PSM. ROC curve analysis showed that the cut-off value of sTg was 10.25 μg/L, with the sensitivity of 81.0%(222/274) and the specificity of 84.2%(1 181/1 403). Conclusions:After reduction of selection bias by PSM, male is no longer a risk factor for prognosis after 131I treatment of DTC. In addition, high T stage(T3+ T4 stage), M1 stage and sTg≥10.25 μg/L were risk factors for poor prognosis.

OBJECTIVE To study of the dynamic evolution process of the themes of off-label drug use from a macroscopic perspective, perspective is needed to reveal the overall development vein of the field, and discover research hot spots and development trends of the field. METHODS A total of 3 876 literatures published in Web of Science from 2012 to 2022 on the topic of off-label drug use were used to obtain three visual maps of overlapping map, systematic evolution map and strategic map by using SciMAT analysis, and these maps of each period were analyzed. RESULTS Over the past ten years, there had been an increasing in the number of publications, themes, and keywords on the off-label drug use, with research themes from the former period having a large impact on the latter period, with complex evolutionary pathways and increasing evolutionary themes. Roughly, 14 evolutionary paths were formed in 4 research directions:adolescents and children, treatment, off label use, and drug RCT. CONCLUSION The content and scope of research in the field of off-label drug use will be diversified and developed, with greater focus on pediatric drug use, psychiatric drug use, COVID-19, and guidelines will be paid more attention.