Background China is a major coal producer and consumer country in the world. Coal workers' pneumoconiosis (CWP) is a primary factor endangering the occupational health of coal miners. Research on the disease burden of CWP and its changing trend is significant for disease prevention & control and associated policies. Objective To analyze the disease burden of CWP in China from 1990 to 2021 and its changing trend, and predict the disease burden from 2022 to 2035. Methods Using the Global Burden of Disease Study (GBD) database of 2021, numbers ofincident cases, prevalent cases, deaths, and disability-adjusted life years (DALYs) as well as crude and age-standardized rates of CWP in China were retrieved. Linear regression model was used to calculate the estimated annual percentage change (EAPC) of the age-standardized rates. Joinpoint regression model was used to analyze the temporal trend of disease burden and the disease burden of different sexes and age groups, and Bayesian age-period-cohort (BAPC) model was used to forecast the trend of CWP disease burden. Results In 1990, the incident, prevalent, and deaths cases of CWP in China were 3266, 18872, and 1561, respectively, and the DALYs of CWP were 44614.718 person-years. In 2021, the incident, prevalent, and deaths cases of CWP were 3446, 23975, and 1229, respectively, and the DALYs of CWP were 29610.754 person-years. From 1990 to 2021, the age-standardized incidence, prevalence, mortality, and DALYs rates of CWP in China all showed a downward trend, with the EAPCs of −3.121%, −2.532%, −4.018%, and −4.268%, respectively. The disease burden of CWP in China was mainly concentrated in the male population. The annual average percent change analysis indicated that each standardized rate showed a fluctuating downward trend in different periods. The BAPC model showed that from 2022 to 2035, the age-standardized rates of CWP in China would continue to decline steadily. In 2035, the age-standardized incidence, prevalence, mortality, and DALYs rates of CWP would be reduced to 0.10 per 100000, 0.74 per 100000, 0.03 per 100000, and 0.74 per 100000, respectively. Conclusion The disease burden contributed by CWP in China generally show a downward trend from 1990 to 2021, and it is expected that the age-standardized rates will continue to decline steadily from 2022 to 2035.

The αPD-L1 antibody-based immune checkpoint blockade therapy is still limited by the poor clinical response rate as it is mainly utilized to block surface PD-L1 on tumor cells while ignoring abundant PD-L1 exosomes secreted in the environment, causing tumor immune evasion. Here, we proposed an exosome biogenesis inhibition strategy to suppress tumor exosomes secretion from the source, reducing the inhibitory effect on T cells and enhancing chemo-immunotherapy efficacy. We developed sulfafurazole homodimers (SAS) with disulfide linkages, effectively releasing the drug in response to glutathione (GSH) and inhibiting 4T1 tumor-derived exosomes secretion. Subsequently, gemcitabine (Gem) was encapsulated to induce immunogenic cell death (ICD). Consequently, Gem@SAS inhibited the secretion of tumor exosomes by more than 70%, increased proliferation and granzyme B secretion ability of T cells by more than 2 times, and showed superior efficacy in breast cancer treatment as well as lung metastasis of breast cancer.

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

Objective:To investigate the feasibility and safety of intracardiac echocardiography(ICE)combined with total three-dimensional(T3D)technique in zero-fluoroscopy individualized transseptal puncture.Methods:A total of 112 patients with atrial fibrillation who underwent radiofrequency ablation in Yongchuan Hospital Affiliated to Chongqing Medical University from April 2021 to March 2024 were enrolled,and according to the method for transseptal puncture,they were randomly divided into ICE+T3D group with 56 patients and ICE group with 56 patients.The two groups were analyzed in terms of baseline data,time to atrial reconstruc-tion,time to coronary sinus electrode placement,frequency of ICE probe adjustment during transseptal puncture,duration of transsep-tal puncture,pretreatment time before ablation,incidence rate of complications,and the duration and dosage of X-ray exposure.Results:There were no significant differences in baseline data between the two groups.Compared with the ICE group,the ICE+T3D group had a significantly lower frequency of ICE probe adjustment during transseptal puncture(1.70±0.63 vs.5.34±1.71,P<0.001)and the duration of transseptal puncture(3.66±1.09 min vs.4.90±1.92 min,P<0.001).Compared with the ICE group,the ICE+T3D group had significantly longer time to atrial reconstruction(22.44±3.13 min vs.12.34±2.12 min,P<0.001)and pretreatment time be-fore ablation(49.41±3.52 min vs.37.65±4.04 min,P<0.001).In the ICE+T3D group,43(76.8%)patients achieved zero radiation during pretreatment before ablation,and 13 patients received X-ray due to the difficulty in catheter placement;compared with the ICE group,the ICE+T3D group had a significantly shorter duration of X-ray exposure(1.68±0.72 min vs.3.14±1.95 min,P=0.010)and a significantly lower dosage of X-ray exposure(6.28±2.78 mGy vs.23.85±21.32 mGy,P=0.004).During the stage of transseptal punc-ture,all patients in the ICE+T3D group achieved zero radiation,while 45 patients(80.4%)in the ICE patients received X-ray.In terms of complications,there were no life-threatening complications such as cardiac tamponade,perforation of the aorta by mistake,and embolization in either group,while there was one case(1.8%)of vascular complications in each group.Conclusions:ICE combined with T3D after integration and improvement is a safe and reliable procedure for zero-fluoroscopy individualized transseptal puncture.

Objective:To investigate the effects of Zhuanggu Zhitong Capsules on JNK signaling molecules and their phosphorylated proteins in postmenopausal osteoporosis model female mice.Methods:The rats were divided into sham-operation group, blank group, model group, positive drug group, and Zhuanggu Zhitong Capsules group according to the random number table method, with 10 rats in each group. The model group, the positive drug group and the Zhuanggu Zhitong Capsules group were prepared by bilateral ovarian detomy to prepare a female mouse model of postmenopausal osteoporosis. The positive drug group was given 0.9 mg/kg of alendronate sodium, the Zhuanggu Zhitong Capsules group was given was Zhuanggu Zhitong Capsules 1.944 g/kg for gavage, and the blank group, sham-operation group, and model group were given the same volume of normal saline for gavage, once a day for a total of 13 weeks. Rat vaginal exfoliated cells were stained with Wright's staining; serum Omentin-1 and 25(OH)D 3 levels were determined by ELISA; renal tissue and femoral structure were observed by HE staining; JNK and p-JNK protein expressions were detected by immunohistochemical staining; JNK mRNA levels were detected by PCR. Results:Compared with the model group, the serum levels of 25(OH)D3 and Omentin-1 in the Zhuanggu Zhitong Capsules group and the positive drug group increased ( P<0.01), the mean gray values of JNK and p-JNK protein in bone and kidney tissues decreased ( P<0.01), and the mRNA levels of JNK in bone and kidney tissues decreased ( P<0.01). Conclusion:Zhuanggu Zhitong Capsules can effectively improve the bone microstructure of postmenopausal osteoporotic rats, and its mechanism may be related to the regulation of JNK signaling pathway.

Objective To conduct a retrospective cohort study on the influencing factors of poor prognosis of young and middle-aged patients with pulmonary tuberculosis. Methods Selecting 426 young and middle-aged patients who were diagnosed with pulmonary tuberculosis in our hospital from January to December 2018 as the research subjects. Collecting the social demography information of all patients and the information of potential factors affecting the prognosis (allergy history, smoking history, drinking history, BMI level, disease information, treatment information, etc.) and discussing the factors affecting the prognosis of young and middle-aged pulmonary tuberculosis patients and their effects. Results The average age of 426 patients was (41.93±5.17) years old, the average BMI of them was (21.97±3.15) kg/m2, and an average course of disease of them was (2.76±0.99) years. There was no significant difference in the basic sexual information between men and women. In this study, a total of 128 patients with poor prognosis were retrospectively followed up, including 90 males and 38 females. The detection rate of males was significantly higher than that of females (χ²=16.976, P<0.05). The detection rate of poor prognosis was lower in patients with lower BMI levels (F=12.774, P<0.001) and longer disease course (F=3.704, P<0.001). In addition, the proportion of patients with poor prognosis who had a history of smoking (χ²=18.850, P<0.001) and had comorbidities was higher (χ²=38.924, P<0.001), and the proportion of patients with ≥ 3 lung field lesions (χ²=127.207, P<0.001) and those with pulmonary cavities (χ²=32.566, P<0.001) were also higher, with statistically significant differences compared to those with good prognosis. Among those with poor prognosis, the proportion of regular treatment was lower (χ²=16.715, P<0.001), and the proportion of adverse reactions was higher (χ²=17.315, P<0.001). At the same time, a total of 128 cases with poor prognosis were retrospectively followed up in this study, and the incidence of poor prognosis was higher in males than in females (χ²=16.976，P<0.05) . At the same time , research has shown that the detection rate of poor prognosis has a potential positive correlation with lower BMI, longer disease duration, smoking history, comorbidities, ≥ 3 lung field lesions, and the presence of pulmonary cavities, while there is a potential negative correlation with regular treatment, both P<0.05. In the study, univariate regression equations were used to discuss the impact of potential factors on adverse prognosis. It can be seen that male, emaciated body type, disease course ≥ 5 years, smoking history, number of lung field lesions ≥ 3, pulmonary cavities, and comorbidities are potential risk factors, with HR>1 and P<0.05; Regular treatment suggests a potential protective factor, with an HR of 0.341 and P<0.05. Multivariate regression analysis further suggests that male, emaciated body type, smoking history, pulmonary cavities, and comorbidities are potential risk factors, with HR>1 and P<0.05; Regular treatment still showed potential protective factors, with an HR of 0.408, P<0.05. Conclusion: Male, emaciated body type, disease course ≥ 5 years, smoking history, number of lung field lesions ≥ 3, presence of pulmonary cavities and comorbidities are potential risk factors, while regular treatment suggests potential protective factors. Conclusion More targeted disease control and management should be implemented for middle-aged and young patients with pulmonary tuberculosis based on the aforementioned influencing factors to improve their prognosis.

Objective:To investigate the clinicopathological, immunohistochemical, and molecular genetic characteristics of microsecretory adenocarcinoma (MSA) of the salivary gland, and to improve the understanding of this rare tumor.Methods:Cases originally diagnosed as MSA at the Department of Oral Pathology, the Ninth People′s Hospital of Shanghai Jiao Tong University School of Medicine were retrospectively collected. The cases of polymorphous adenocarcinoma and adenocarcinoma, not otherwise specified from January 2000 to January 2020 were reviewed to identify potential misdiagnosed MSA cases. Clinicopathological analysis and follow-up of all confirmed MSA cases were performed, and relevant literature was reviewed.Results:A total of 4 MSA cases were identified, including 2 screened from the polymorphous adenocarcinoma cohort. Of the 4 MSA patients, 3 were male and 1 was female, with an average age of 53 years (range, 37-67 years). Three cases occurred in the palate, and one in the buccal region. The clinical manifestation was usually a slow-growing painless mass. Tumors were generally small, with a maximum diameter ranging from 0.7 to 1.8 cm (average, 1.2 cm). Microscopically, the tumor was unencapsulated and showed an infiltrative growth pattern. The tumor cells appeared small in size and showed bland, cubic and flattened cytological features, forming microcystic lumens and glandular tubes. Significant basophilic secretions were seen in the lumens. Between the tumor nests there was fibro-myxoid stroma. Immunohistochemistry showed diffusely or partially positive staining for cytokeratin 7, S-100, SOX-10, p63 and vimentin and negative staining for p40, mammaglobin, and calponin. The proliferation index of Ki-67 was relatively low (1%-3%). Four MSA cases all harbored SS18 gene rearrangement as shown by fluorescence in situ hybridization (FISH), including 2 cases with MEF2C::SS18 fusion gene through RNA-targeted next generation sequencing. All 4 patients underwent surgical resection without any adjuvant treatments. Three patients were followed up for a period of 2 to 203 months. No tumor recurrence, metastasis, or disease-related death was found.Conclusions:Salivary gland MSA is a novel and rare low-grade carcinoma with unique and consistent histological morphology, immunophenotype, and molecular changes. Immunohistochemical staining and SS18 break apart FISH are useful for the diagnosis of the tumor with atypical morphology and high-grade transformation.

Purpose/Significance To investigate and analyze the current status and influencing factors of digital health literacy(DHL)of the elderly,and to provide references for relevant departments.Method/Process The eHEALS scale is used to investigate the DHL status of 419 elderly people aged 60 and above in Shanghai through convenience sampling,and the influencing factors are explored through binary logistic regression analysis.Result/Conclusion Low education,smoking,and health anxiety are risk factors,while regular physical exami-nation is protective factor.Relevant departments should focus on the elderly people with lower education,and strengthen research and edu-cation on health examinations,smoking hazards,and the alleviation of anxiety.

Objective:To evaluate the effect of stratified management of cardiovascular diseases risk in community population based on China-PAR.Methods:It was a single arm study. Beijing Jiaotong University faculty and staff who participated in annual health check-up from 2019 to 2021 and met the inclusion/exclusion criteria were enrolled in the study. The general data, physical examination and laboratory test results, including age, residence region, waist circumference, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C),blood pressure (BP), taking antihypertensive drugs,diabetes, family history of cardiovascular diseases,were collected. Participants were stratified according to China-PAR assessment model and then stratified management was carried out. For low-risk populations, family doctors provided online guidance or outpatient follow-up if necessary after their first interview. For middle and high-risk groups, outpatient and telephone follow-up were arranged in addition to online guidance. Relevant examinations were completed and drug treatment or adjustment were given by doctors when necessary. Frequency of outpatient follow-up for middle and high-risk groups was different and patients in these two groups were scored again at the end of 2-year follow-up.Results:A total 284 participants were enrolled,197 participants (69.4%) were males with a age of (46.9±8.8) years. Among them, 205 participants (72.2%) were in low-risk group, including 136 males (66.3%), and their 10-year risk of cardiovascular diseases was (2.5±0.1)%; 59 participants (20.8%) were in middle-risk group, including 43 males (72.9%), and their 10-year risk of cardiovascular diseases was (7.1±0.2)%;20 participants (7.0%) were in high-risk group,including 18 males (90.0%) and their 10-year risk of cardiovascular diseases was (14.0±1.1)%. After 2 years follow-up, the proportion of dietary imbalances and alcohol drinking, waist circumference, blood pressure, fasting glucose levels and risk score decreased significantly in high risk group ( P<0.05). The proportion of dietary imbalances, waist circumference, blood pressure, total cholesterol, and LDL-C levels decreased significantly in medium risk group ( P<0.05). In high-risk group, 2 participants (10.0%) converted to low-risk, 8 participants (40.0%) converted to middle-risk. In middle-risk group, 5 participants (8.5%) converted to low-risk and 7 participants (11.9%) converted to high-risk. Conclusion:The risk factors and risk stratification of cardiovascular disease in community population can be improved by stratified management based on China-PAR risk assessment model.

Objective:To investigated the prevalence of anxiety and depression symptoms in patients with colorectal polyps in part of Xinjiang area and to explore the associated influencing factors related to psychological status, and to provide evidence and clues to promote the diagnosis and treatment of psychosomatic diseases in digestive system.Methods:From December 2021 to June 2022, at the First Affiliated Hospital of Shihezi University, the Fourth Division Hospital of Xinjiang Production and Construction Corps, the Third Division Hospital of Xinjiang Production and Construction Corps (Kashgar Hospital), the Thirteenth Division Red Star Hospital of Xinjiang Production and Construction Corps, the Tenth Division Beitun Hospital of Xinjiang Production and Construction Corps, the Seventh Division Hospital of Xinjiang Production and Construction Corps, the Fifth Division Hospital of Xinjiang Production and Construction Corps, patients who underwent colonoscopy and colorectal polyps detected were enrolled. The generalized anxiety disorder scale-7 (GAD-7) was used to screen anxiety symptoms, and the patient health questionaire-8 (PHQ-8) was performed to screen depression symptoms, and the general situation questionnaire was used to collect clinical information of patients. The questionnairs were completed via the Questionnaire Star platform or paper questionnaire, and a database was established. The patients were divided into groups according to whether with anxiety and depression symptoms. Multivariable logistic regression models was performed to analyze the factors related to anxiety and depression.Results:A total of 516 questionnaires were distributed and collected, among which 9 questionnaires were incomplete and 507 questionnaires were valid, the effective rate of questionnaires was 98.26%. The detection rates of anxiety and depression symptoms in 507 patients with colorectal polyps were 21.50%(109/507) and 19.33%(98/507), respectively. The results of multivariable logistic analysis revealed that female ( OR=3.87, 95% confidence interval (95% CI) 2.30 to 6.51, P<0.001), maximum diameter of polyp ( OR=1.74, 95% CI 1.14 to 2.67, P=0.011), perception of polyps as cancer ( OR=13.96, 95% CI 1.48 to 132.07, P=0.022), and the occurrence of gastrointestinal symptoms after polyp detection ( OR=5.43, 95% CI 1.74 to 16.92, P=0.004) were independent risk factors of anxiety in patients with colorectal polyps. Female ( OR=2.42, 95% CI 1.47 to 4.00, P=0.001), the number of polyps ( OR=1.07, 95% CI 1.01 to 1.13, P=0.028) and the count of gastrointestinal symptoms ( OR=2.04, 95% CI 1.34 to 3.10, P=0.001) were independent risk factors of depression in patients with colorectal polyps. Conclusion:Gender, polyp size, number of polyps, disease perception, and concomitant gastrointestinal symptoms are associated with anxiety and depression in patients with colorectal polyps.