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 establish an optimal limiting dose for dose limiting rings placed in the anterior and posterior regions of the neck for reducing head and neck lymphedema under intensity-modulated radiation therapy(IMRT)for early nasopharyngeal carcinoma(NPC)from a dosimetric perspective.Method Fifteen newly diagnosed early-stage nasopharyngeal carcinoma patients who underwent CT localization for radiotherapy at the Cancer Hospital of Guangzhou Medical University from January to September 2022 were included in the study.Each case was designed with five sets of radiotherapy plans.Plan A consisted of conventional unlimited-field plans,while Plans B-E consisted of limited-field plans with dose constraints set at 20,18,16,and 14 Gy,respectively,with the remaining parameters consistent with Plan A.The impact on target coverage and organ-at-risk constraints was evaluated through variance analysis and pairwise multiple comparisons using a randomized block design to determine the optimal dose limits.Results The gradient of 16Gy was determined as the optimal dose limiting cutoff point for achieving the balance between target coverage and organ limiting dose.Compared with the conventional plan,The plans with the placement of a cervical anterior and posterior dose limiting ring(16Gy)did not change the target dose coverage(P>0.05),but only yielded a slight change in the homogeneity index(P<0.05).It did not cause any changes of the dosage in the inner ear,mandible,and brainstem(all P>0.05),but lead to statisti-cally significant reductions in the oral cavity,throat,and thyroid(all P<0.05).It caused a slight increase of the dose in the parotid gland and spinal cord(both P<0.05),but the increased dose was anyhow within the tolerance range.Conclusion The dosimetric investigation determines an optimal dose limit cutoff point for the cervical ante-rior and posterior dose limiting rings.It is expected to provide a design method for IMRT plans to reduce head and neck lymphedema after radiotherapy for early NPC.

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.

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 explore the influencing factors for compliance to colonoscopy screening for colorectal cancer in outpatients.Methods:Patients aged 40-74 years who visited the outpatient gastroenterology department of 7 tertiary hospitals in 7 regions of Xinjiang from January 2022 to June 2022 were enrolled. Recommendations for colonoscopy screening were made according to the patient's medical conditions, and the questionnaire was used to collect information. The Chi-square test was used to compare the differences of compliant and non-compliant patients. Multivariate logistic regression was used to analyze the influencing factors of compliance to colonoscopy screening.Results:A total of 463 valid questionnaires were obtained from 7 centers, in which, 427 outpatients (92.2%) followed the recommendation for colonoscopy screening, and 36 (7.8%) did not. Chi-square test results showed that there were statistically significant differences between the two groups in gender, age, education, subjective cognition of intestinal polyps, personal history of colorectal polyps, family history of colorectal cancer, family history of colorectal polyps, abdominal pain or distension, and defecation habit or stool changes ( P<0.05). The results of multivariate regression analysis showed that the screening compliance of patients aged 40-49 years ( P=0.005, OR=0.141, 95% CI: 0.036-0.549) and 50-59 years ( P=0.039, OR=0.257, 95% CI: 0.071-0.932) was lower than that of patients aged 60-74 years. The screening compliance of patients with high school education ( P=0.011, OR=3.121, 95% CI: 1.304-7.473) and college education or above ( P=0.016, OR=3.544, 95% CI: 1.270-9.890) was higher than those with primary school education and below. Patients with personal history of colorectal polyps ( P=0.015, OR=12.288, 95% CI: 1.629-92.719), family history of colorectal cancer ( P=0.038, OR=8.506, 95% CI: 1.124-64.351) and changes in defecation habit or stool trait ( P=0.039, OR=4.794, 95% CI: 1.085-21.192) also had higher compliance. Conclusion:Age, educational level, personal history of colorectal polyps, and family history of colorectal cancer are related to colonoscopy screening compliance in outpatients of 7 tertiary hospitals in 7 regions of Xinjiang. The independent risk factors affecting compliance to colorectal cancer screening in outpatients are age of 40-59 years, lower educational level, no previous history of polyps or family history of colorectal cancer, and no defecation habit or stool changes.

Celastrol is extracted from the traditional Chinese medicine Tripterygium wilfordii Hook.f..It is a kind of traditional Chinese medicine monomer with extensive pharmacological activity and has anti-tumor,anti-inflammation,anti-oxidation and neuroprotective effects.Studies have found that celastrol is not only closely related to obesity,tumor and cardiovascular diseases,but also plays a neuroprotective role in the cerebrovascular system by regulating various signaling pathways.At present,effective drugs for stroke are still limited,but with the deepening of the research on celastrol,its therapeutic potential in stroke has received more and more attention,especially in ischemic and hemorrhagic stroke,which has shown good therapeutic effects.Therefore,this is the first time to systematically summarize the therapeutic effects of celastrol on stroke and the underlying mechanisms involved,in order to provide further directions and references for the neuroprotective effects of celastrol.

Objective:To construct a systematic quality control management model for insulin pump and analyze its clinical application effect.Methods:To construct a systematic quality control management model for insulin pumps,that is,to manage the whole process of insulin pump equipment installation process,fault detection and pipeline replacement,comprehensively monitor the patient'daily medication and physical condition,timely detect and deal with faults,so that insulin pumps can better serve patients to effectively control blood sugar.32 insulin pumps configured by Shanghai Sixth People's Hospital were selected.120 patients with type 2 diabetes who used insulin pumps and equipment in conventional management mode from July 2022 to October 2022 were included in the control group,and 120 patients with type 2 diabetes who used insulin pumps and equipment in systematic quality control management mode from October 2022 to July 2023 were included in the observation group.The common faults of the two groups,the treatment effect of the equipment,and the patient compliance before and after the use of the equipment were compared.Results:The incidence of common faults such as redness rate at implantation site,tube blockage rate,tube dislocation rate and instrument damage rate in the observation group were lower than those in the control group,with significant differences(x2=6.737,6.664,9.955,6.793,P<0.05).The installation time,fault discovery time and tube replacement time of the observation group,with significant differences(t=6.078,5.428,5.786,P<0.05).The scores of diet control,exercise,blood sugar monitoring and medication compliance in the observation group were higher than those in the control group,with significant differences(t=6.816,12.627,20.169,15.317,P<0.05).Conclusion:Applying the systematic quality control management model to insulin pump management can reduce the incidence of insulin pump failures,shorten installation time,and enable insulin pumps to better serve patients to effectively control blood sugar and protect their health.

Systemic lupus erythematosus (SLE) shows a significant gender difference. In addition to X chromosome inactivation (XCI) abnormalities, which may lead to the gender difference in SLE, studies have found that estrogen plays a key role in regulating Th17/Treg immune balance in SLE. Estrogen indirectly affects the quantity and function of Th17 and Treg cells by acting on B cells. In this process, the mutual influence and the interaction between B and T cells promote the development of SLE. Recent studies have reported gender differences in intestinal microbiota, which may lead to sex-dependent genetic susceptibility and epigenetic changes in autoimmune diseases represented by SLE. The interaction between estrogen and intestinal microbiota in SLE affects the immune balance of Th17/Treg cells. This paper mainly reviews the way estrogen works, and the mechanisms by which estrogen regulates Th17/Treg immune balance and the interaction between B and T cells in SLE, hoping to provide new targets for new therapeutic strategies such as selective estrogen receptor modulators.