ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

Ferroptosis， a new form of programmed cell death different from apoptosis， necrosis， and autophagy， is closely associated with a variety of physiological and pathological processes. Iron-mediated accumulation of reactive oxygen species is the main inducement of ferroptosis， the mechanism of which is related to intracellular lipid metabolism， iron metabolism， and antioxidant defense pathways. Multiple signaling axes and regulators jointly regulate the occurrence and disruption of ferroptosis. Studies have demonstrated that ferroptosis regulates the growth and proliferation of tumor cells. Inducing ferroptosis in tumor cells can control the growth， metastasis， and multi-drug resistance of tumors. Therefore， the effect and mechanism of ferroptosis on tumor cells have become a hot topic in anti-cancer research. As the research advances， a variety of ferroptosis inducers has been used in the clinical chemotherapy for cancers and demonstrate significant efficacy. Accordingly， the development of ferroptosis-inducing anticancer drugs has become a new research direction for tumor treatment. Some active ingredients such as lycorine， oleanolic acid， dihydroartemisinin， pseudolaric acid B， and ophiopogonin B of Chinese medicines can induce ferroptosis in tumor cells via lipid metabolism， iron metabolism， system X_c^-， and GPX4/GSH to regulate the development of tumors， demonstrating a promising prospect in clinical treatment. Based on the theory of the mechanism of ferroptosis， this paper reviews the research progress in ferroptosis induced by active ingredients of Chinese medicines in tumor cells and describes the metabolic regulatory network of ferroptosis from signaling pathways and regulatory factors， providing new strategies for applying active ingredients of Chinese medicines in the treatment of tumors.

Objective To explore the relationship between serum leucine 2-rich glycoprotein 1(LRG1),lactate dehydrogenase(LDH)with periodontal indicators and periodontal lesions degree in patients with type 2 diabetes mellitus(T2DM)and chronic periodontitis(CP).Methods 112 patients with T2DM combined with CP admitted to our hospital from July 2022 to July 2023(T2DM combined with CP group)were selected and catego-rized into mild,moderate,and severe groups according to the degree of periodontal pathology;112 patients with CP alone(CP group)were selected from our hospital during the same period,and then 112 patients with T2DM alone(T2DM group)were selected;and LRG1,LDH,and periodontal indexes were measured;Pearson method was applied to analyze the correlation between serum LRG1,LDH,and periodontal indicators.The influencing factors of severe T2DM combined with CP were analyzed using multivariate logistic regression.ROC curve was plotted to analyze the diagnostic value of serum LRG1 and LDH for severe T2DM combined with CP.Results The levels of LRG1 and LDH in the CP group,T2DM group,and T2DM combined with CP group increased sequentially(P＜0.05).The levels of serum LRG1,LDH,AL,PD,and BI increased sequentially in the mild,moderate,and severe groups(P＜0.05).According to Pearson correlation analysis,serum LRG1 was positively correlated with LDH(P＜0.05).Serum LRG1 and LDH were positively correlated with AL,PD,and BI(P＜0.05).According to logistic regression analysis,LRG1,LDH,AL,PD,and BI were all factors for severe T2DM combined with CP(P＜0.05).According to the ROC curve,the AUC for the combined diagnosis of serum LRG1 and LDH in severe T2DM with CP was 0.910,and the combination of the two was better than their individual diagnosis(Z combination vs LRG1=2.659,Z combination vs LDH=2.627,P＜0.05).Conclusion LRG1 and LDH are greatly elevated in the serum of patients with T2DM combined with CP,and they are related to periodontal indicators and the periodontal lesions degree.

Talaromycosis marneffei has been increasing in recent years. Our understanding of this disease has gradually deepened through extensive basic and clinical research, but there are still many limitations. In this article, by incorporating the latest research advancements, we discuss important issues in managing Talaromycosis marneffei trends, aiming to guide effective prevention and control of the disease, improving public health, and reducing the healthcare burden.

Abstract OBJECTIVE To study the mechanism of NLRP3 gene’s regulation on inflammatory response in non-alcoholic fatty liver disease(NAFLD) mice induced by high-fat and high-fructose diet using NLRP3 gene knockout mice. METHODS Use male homozygous(NLRP3-/-) mice, and the high-fat and high-fructose diet was used to establish NAFLD model in NLRP3 knockout(KO) mice and wild-type(WT) mice, divided into KO high-fat and high-fructose diet(KO-HFD) group and WT high-fat and high-fructose diet(WT-HFD) group, while the WT and KO groups were also established. The body weight of mice in each group were observed. The changes of ALT, AST, TG, TC, MDA, SOD, lipidosis, apoptosis rate, IL-1β, IL-18, TNF-α, NF-κB, NLRP3, Caspase-1 and ASC in serum and tissue samples were tested to study the mechanism of the NLRP3 gene regulating the inflammatory response in NAFLD mice. RESULTS As time goes on, the mice weight of each group increased gradually, but the KO-HFD group increased less than the WT-HFD group. Each group’s level of ALT, AST, TG, TC in serum increased gradually, but the KO-HFD group increased less than the WT-HFD group. The level of MDA in liver tissues of each group was gradually increased and the level of SOD was gradually decreased, but the change range of KO-HFD group was smaller than that of WT-HFD group. The results of oil red O staining and Tunel section showed that the degree of lipid deposition and apoptosis in hepatocytes increased gradually in all groups, but the changes in KO-HFD group were less than that in WT-HFD group. The levels of serum and liver inflammatory factors IL-1β, IL-18, TNF-α and NF-κB increased in all groups, but the changes of KO-HFD group 20 weeks were less than those of WT-HFD group 20 weeks, and the difference was statistically significant. The expression levels of NLRP3 inflammasomes and related inflammatory cytokines NLRP3, Caspase-1, ASC, IL-1β and IL-18 in liver tissues of WT-HFD group were higher than those of KO-HFD group. The mRNA transcription levels of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in WT-HFD group were gradually increased, while there was no change in KO-HFD group. CONCLUSION The NLRP3 gene may be activated in NAFLD mice model, resulting in increased expression of NLRP3 inflammasome-associated protein, promoting the synthesis and secretion of downstream inflammatory factors, resulting in significant inflammatory response and liver damage, and promoting the progression of NAFLD disease.

Greenspace may bring benefits to human health. Evidence on greenness and health has accumulated in western countries, and several reviews have summarized such evidence. Researchers have also conducted some studies on greenspace and human health in Chinese population, but no prior review has pooled or summarized them. To provide more comprehensive evidence on this topic, we searched and summarized studies on greenspace and health that were conducted specifically in Chinese population. We found that a certain number of studies have been conducted in China, and the evidence indicates that greenspace exposure may reduce the odds of cardiovascular diseases, mental health disorders, adverse birth outcomes as well as mortality. However, most of the current reported studies were of cross-sectional design or randomized controlled trails targeting short-term effects, and prospective cohort studies were scarce. Moreover, greenness exposure was mainly assessed using greenness index like normalized difference vegetative index (NDVI), which were static and cannot distinguish construction and species of greenspaces. Future prospective studies with more precise greenness exposure assessment are warranted to evaluate the prior findings.

Background The prevalence rate of work-related musculoskeletal disorders (WMSDs) among manufacturing workers is relatively high and has been widely concerned. However, research on the prevalence and risk factors of multi-site WMSDs is still insufficient. Objective To explore the prevalence and risk factors of multi-site WMSDs of assembly workers in four manufacturing enterprises. Methods The "Chinese Musculoskeletal Questionnaire" was used to conduct a cross-sectional survey among 1401 assembly workers selected by convenient sampling in four manufacturing enterprises, and their demographic characteristics, the prevalence of WMSDs in various body parts, and the information about biomechanical factors, work organizations, work environment, and psychosocial factor exposure were collected. The prevalence of WMSDs and multi-site WMSDs were estimated, Pearson χ² test was used for univariate analysis of multi-site WMSDs risk factors, and logistic regression was used for multi-factor analysis. Results The total prevalence rate of WMSDs was 54.9% (769/1 401). The top three affected sites were neck (41.4%), shoulders (30.7%), and wrist/hand (25.1%). The prevalence rate of multi-site WMSDs was 41.9% (587/1 401). The prevalence rates of multi-site WMSDs in railway vehicle assembly and riveting workers were higher than those in electronic parts processing and glass manufacturing workers (P<0.001). The results of logistic regression analysis showed that individual factors such as female (OR=2.09, 95%CI: 1.48−2.97) and drinking (OR=1.52, 95%CI: 1.05−2.18), biomechanics factors such as keeping head down for a long time (OR=1.37, 95%CI: 1.22–1.53), keeping bending frequently (OR=1.18, 95%CI: 1.03–1.34), and keeping arms up for a long time (OR=1.25, 95%CI: 1.10–1.41), work organizational factors such as electronic parts processing, railway vehicle assembly, and riveting (OR values were 3.23, 5.70, and 13.83, respectively), environmental factors such as temperature a little cold (OR=4.84, 95%CI: 1.90–12.37), noise seriously affecting work (OR=2.25, 95%CI: 1.23–4.11), and psychosocial factors such as high job demands (OR=1.47, 95%CI: 1.04–2.08), fatigue after work (OR=1.92−2.61) were risk factors of multi-site WMSDs. Conclusion The prevalence rate of multi-site WMSDs in assembly workers is high, and the main influencing factors include individual factors, awkward work postures, environmental factors, and psychosocial factors.

Background China's manufacturing industry is still labor-intensive, and assembly employees in manufacturing industry are facing a great risk of work-related musculoskeletal disorders (WMSDs). Objective To investigate and analyze the prevalence and distribution of WMSDs among assembly workers in manufacturing enterprises and explore the relationship between WMSDs and ergonomic exposure factors such as posture load and mental load. Methods From July to September 2017, by convenient sampling, a cross-sectional survey was conducted to select 670 workers engaged in electronic accessories assembly and railway vehicle manufacturing in three manufacturing enterprises in two cities in northern China as the research participants. The posture load assessment was based on the Chinese Musculoskeletal Questionnaire independently developed by our research group. The mental load assessment was based on a revised Chinese version of the Subjective Workload Assessment Technique. An unconditional logistic regression model was used to explore the relationship between ergonomic exposure and WMSDs. Results The overall prevalence rate of WMSDs was 39.6% (265/670) with 43.8% in males and 25.2% in females; the highest prevalence rate was 47.7% in the group aged 40 years and over. The prevalence rate of WMSDs in the electronic accessories assembly workers was 16.9%, that in the railway vehicle manufacturing workers was 57.3%, and the difference was statistically significant (\begin{document}$ {\chi ^2} $\end{document}=112.63, P<0.001). The mental load score [median (first quartile, third quartile)] was 55.6 (51.9, 83.3) points, and the posture load score was 27.1 (16.0, 41.5) points. The results of unconditional logistic regression model showed that women (OR=3.152, 95%CI: 1.458-6.813), drinkers (OR=1.934, 95%CI: 1.124-3.326), and railway vehicle manufacturing worker (OR=3.416, 95%CI: 1.756-6.644) had a higher risk of reporting WMSDs; The higher the mental load (OR=1.019, 95%CI: 1.007-1.031) and posture load (OR=1.034, 95%CI: 1.019-1.050), the higher the risk of reporting WMSDs. The hierarchical analysis results showed that the risk of reporting WMSDs was higher among the electronic accessories assembly workers who were older (compared with those aged <30 years, OR_30-39=2.526 and OR_≥40=12.263, respectively) and with higher posture load (OR=1.025, 95%CI: 1.002-1.049), as well as among the railway vehicle manufacturing workers who were drinking (OR=2.035, 95%CI: 1.155-3.583), obese (OR=3.094, 95%CI: 1.185-8.078), with higher mental load (OR=1.013, 95%CI: 1.001-1.025) and posture load (OR=1.033, 95%CI: 1.018-1.049). Conclusion There is a significant correlation between reporting WMSDs and ergonomic exposures such as posture load and mental load, and drinking is also a risk factor of WMSDs. The risk of reporting WMSDs in female workers in assembly manufacturing industry is higher than that in male workers. The overall prevalence rate of WMSDs in railway vehicle manufacturing workers is higher than that in electronic accessories assembly workers.