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.

Objective:To evaluate the risk of developing pulmonary tuberculosis (PTB) among individuals with latent tuberculosis infection (LTBI) in schools and the protective effect of tuberculosis preventive treatment (TPT).Methods:A retrospective cohort study was conducted to collect data on 15 school outbreaks that occurred in Guangdong Province from 2017 to 2021. Baseline information on tuberculin skin test (TST) or interferon-gamma release test (IGRA) was obtained during contact surveys, as well as baseline information such as TPT. The incidence of PTB between 2017 and 2022 was queried using the Chinese Center for Disease Control and Prevention Information System. Poisson regression analysis was used to compare the incidence risk of PTB in the LTBI population under different TST states at baseline. Current cases, new cases and all cases (the sum of the two) were used as dependent variables. Cox regression models were used to analyze various risk factors affecting the risk of PTB in the LTBI population and evaluate the protective effect of TPT.Results:A total of 6 550 contacts were included in this study, of which 409 received TPT. Within 0-3 months after baseline survey, 119 cases were diagnosed as current cases [19.4‰, 119/(6 550-409)]. A total of 17 221.65 person-years of follow-up were conducted, during which 71 new cases were diagnosed (4.1/1 000 person-years, 71/17 221.65). The incidence density of PTB was 47.7/1 000 person-years, 6.6/1 000 person-years, 1.4/1 000 person-years, and 0.9/1 000 person-years, respectively, in TST strong/IGRA positive, TST moderate positive, TST generally positive, and TST and IGRA negative populations. The difference in PTB incidence density was statistically significant [likelihood ratio test LRT=153.16, P<0.001]. TPT was performed for individuals with strong TST or IGRA positivity, and the protection rate could reach 93% ( HR=0.07, 95% CI: 0.02-0.23). Conclusion:After the outbreak of the school epidemic, individuals with strong TST/IGRA positivity have a higher risk of developing PTB in the future. Targeted implementation of TPT can achieve better protection effects. In addition, the risk of developing PTB in individuals with moderate TST positivity is also worth noting.

Objective:To evaluate the risk of developing pulmonary tuberculosis (PTB) among individuals with latent tuberculosis infection (LTBI) in schools and the protective effect of tuberculosis preventive treatment (TPT).Methods:A retrospective cohort study was conducted to collect data on 15 school outbreaks that occurred in Guangdong Province from 2017 to 2021. Baseline information on tuberculin skin test (TST) or interferon-gamma release test (IGRA) was obtained during contact surveys, as well as baseline information such as TPT. The incidence of PTB between 2017 and 2022 was queried using the Chinese Center for Disease Control and Prevention Information System. Poisson regression analysis was used to compare the incidence risk of PTB in the LTBI population under different TST states at baseline. Current cases, new cases and all cases (the sum of the two) were used as dependent variables. Cox regression models were used to analyze various risk factors affecting the risk of PTB in the LTBI population and evaluate the protective effect of TPT.Results:A total of 6 550 contacts were included in this study, of which 409 received TPT. Within 0-3 months after baseline survey, 119 cases were diagnosed as current cases [19.4‰, 119/(6 550-409)]. A total of 17 221.65 person-years of follow-up were conducted, during which 71 new cases were diagnosed (4.1/1 000 person-years, 71/17 221.65). The incidence density of PTB was 47.7/1 000 person-years, 6.6/1 000 person-years, 1.4/1 000 person-years, and 0.9/1 000 person-years, respectively, in TST strong/IGRA positive, TST moderate positive, TST generally positive, and TST and IGRA negative populations. The difference in PTB incidence density was statistically significant [likelihood ratio test LRT=153.16, P<0.001]. TPT was performed for individuals with strong TST or IGRA positivity, and the protection rate could reach 93% ( HR=0.07, 95% CI: 0.02-0.23). Conclusion:After the outbreak of the school epidemic, individuals with strong TST/IGRA positivity have a higher risk of developing PTB in the future. Targeted implementation of TPT can achieve better protection effects. In addition, the risk of developing PTB in individuals with moderate TST positivity is also worth noting.

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 investigate the intrinsic neural mechanism of aggressive behavior in CD 1 mice.Methods CD1 mice with aggressive behavior were screened out by resident intruder test.After the aggressive conditioned pair preference was further verified,the activated brain regions of the whole brain were labeled with c-Fos,and the types of neurons activated by the aggressive behavior were analyzed by double immunofluorescence labeling.Finally,the effects of activity of these neurons regulated by optogenetics on aggressive behavior were observed.Results The c-Fos screening revealed that about 82％of the CD1 mice showed aggressive behavior.After the occurrence of aggressive behavior,the main activation occured in the medial prefrontal cortex(mPFC),and the results of immunofluorescence double labeling showed that the c-Fos positive neurons in the mPFC were mainly glutamatergic neurons.Finally,glutamatergic neurons in the mPFC could be activated by optogenetics,and the activation inhibited the aggressive behavior of CD1 mice.In contrast,optogenetics could inhibit glutamatergic neurons in the mPFC and then promote the aggressive behavior of CD1 mice.Conclusion Glutamatergic neurons in the mPFC are an important component in the regulation of aggressive behavior in CD1 mice.

OBJECTIVE: We aimed to understand the willingness and barriers to the acceptance of tuberculosis (TB) preventive treatment (TPT) among people with latent TB infection (LTBI) in China. METHODS: A multicenter cross-sectional study was conducted from May 18, 2023 to December 31, 2023 across 10 counties in China. According to a national technical guide, we included healthcare workers, students, teachers, and others occupations aged 15-65 years as our research participants. RESULTS: Overall, 17.0% (183/1,077) of participants accepted TPT. There were statistically significant differences in the acceptance rate of TPT among different sexes, ages, educational levels, and occupations ( P < 0.05). The main barriers to TPT acceptance were misconceptions that it had uncertain effects on prevention (57.8%, 517/894), and concerns about side effects (32.7%, 292/894). CONCLUSION An enhanced and comprehensive understanding of LTBI and TPT among people with LTBI is vital to further expand TPT in China. Moreover, targeted policies need to be developed to address barriers faced by different groups of people.
Humans ; China/epidemiology* ; Adult ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Young Adult ; Adolescent ; Aged ; Latent Tuberculosis/prevention & control* ; Patient Acceptance of Health Care ; Tuberculosis/prevention & control* ; Antitubercular Agents/therapeutic use* ; Health Knowledge, Attitudes, Practice

Objective:To investigate the correlation between hyponatremia and the severity of coronavirus disease 2019 (COVID-19).Methods:Clinical data of 12 patients with COVID-19 admitted to Shantou Central Hospital from January 23 to February 5 in 2020 were retrospectively analyzed, including gender, age, symptoms, lab test and clinical outcomes, to analyze the change trend of blood Na + level in the patients with COVID-19. Results:Among the 12 patients with COVID-19, there were 8 males and 4 females with the mean age of (38.0±16.3) years old, most of them were admitted to the hospital with cough and/or fever. All patients had a positive nucleic acid test for 2019 novel coronavirus (2019-nCoV), and were discharged after clinical treatment with oxygen therapy, antiviral, antibacterial, anti-inflammatory, and nutritional support. All patients were of ordinary type when they were admitted to the hospital. Among them, 1 patient turned into a severe case during the course of the disease, and 1 patient showed a tendency to become severe case. It was found that 10 patients without severe conversion had an average blood Na + of (138.3±1.3) mmol/L at admission, and the lowest blood Na + during the course of disease was (135.9±3.1) mmol/L. However, 2 patients who became severe and had a tendency to become severe disease (Na + levels at admission were 140.0 mmol/L and 138.0 mmol/L, respectively) experienced hyponatremia during the course of the disease (the lowest blood Na + levels were 129.0 mmol/L and 122.0 mmol/L). Further analysis showed that the lower serum Na + level, the higher level of white blood cell count (WBC) and C-reactive protein (CRP), but serum Na + level was consistent with the change trend of lymphocytes, suggesting that hyponatremia was closely correlated with severe inflammation reaction. Conclusions:Serum Na + showed decreasing tendency during the development of COVID-19, and hyponatremia was closely related to the severity of COVID-19. It was necessary to pay great attention to the change trend of blood Na + level. However, further research was needed to obtain more reliable conclusions and explorer the pathophysiological mechanisms.

Objective: To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression. Methods: HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed. Results: Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation (P values: 0.009, 0.001, <0.01 and <0.01, respectively). Different HER2 expression status was observed between primary and recurrent tumors in 7.6% (48/635) cases. The rates of HER2 positivity ranged from 2% to 10% among different institutions. The rates of HER2 FISH amplification were dramatically different among the 23 hospitals (0-100%) with an average rate of 10% (810/8 156) in patients with HER2 IHC 2+ . Conclusions HER2 expression is associated with clinicopathologic characteristics. HER2 re-assessment of tumor tissue and use of in situ hybridization techniques increase HER2 positivity. The current retrospective study should reflect the HER2 status in gastric adenocarcinoma of Chinese patients.

Objective To investigate the relationship between Pin1 and CyclinD1 expression and the development of gastrointestinal stromal tu?mor(GIST). Methods The protein and mRNA expression of Pin1 and CyclinD1 in 85 samples of GIST and adjacent non?cancerous tissues were detected by immunohistochemistry and real?time quantitative polymerase chain reaction. Results The expression rate of Pin1 protein in GIST tis?sues(64.7%;55/85)was higher than that in adjacent non?cancerous tissues(26.7%;4/15). Similarly,the expression rate of CyclinD1 protein in GIST tissues(42.3%;36/85)was higher than that in adjacent non?cancerous tissues(6.7%;1/15). The expression of Pin1 and CyclinD1 mRNA in GIST tissues was 7.03 and 5.53 times that in adjacent non?cancerous tissues ,respectively. There was no obvious correlation between the expres?sion of Pin1 and clinicopathological parameters. The expression of CyclinD1 was positively correlated with the grade of NIH and tumor diameter (P<0.05). There was a significant correlation between the expression of Pin1 and CyclinD1 in GIST tissues. Conclusion The expression of both Pin1 and CyclinD1 was up?regulated in GIST tissues. The significant correlation between the expression of Pin1 and CyclinD1 in GIST tissues sug?gests that their synergistic effect promotes carcinogenesis and the development of GIST.