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.

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

Porcine reproductive and respiratory syndrome(PRRS),an infectious disease,poses a significant threat to the swine industry.The causative agent of the disease is porcine reproductive and respiratory syndrome virus(PRRSV),which primarily infects porcine alveolar macrophages and destroys the immune system.In the absence of specific antiviral drugs targeting PRRSV,vacci-nation is of paramount importance for the prevention and control of this disease.Currently,there are numerous types of PRRS vaccines,such as attenuated live vaccines,inactivated vaccines,sub-unit vaccines,DNA vaccines,vector vaccines,and so forth.However,only attenuated live virus and inactivated virus vaccines are widely employed for the prevention and control of PRRS.Live vac-cines offer relatively better protection effects,but they have weak cross-protection and pose safety concerns.Inactivated vaccines are safe but have poor immunogenicity.This article conducts a com-prehensive review of the advantages,disadvantages,and applicability of PRRS vaccines,including attenuated live vaccines,inactivated vaccines,subunit vaccines,vector vaccines,DNA vaccines,mR-NA vaccines,virus-like particle vaccines,etc.,aiming to provide a theoretical basis for the research and development of the next generation of PRRS vaccines.

Objective:To analyze the characteristics of CD4 + T cell subsets and cytokines in patients with mixed connective tissue disease (MCTD) and the correlation of MCTD disease activity, laboratory data, and clinical symptoms with cytokines. Methods:A total of 48 MCTD patients (including 24 newly diagnosed patients and 24 treated patients) were enrolled from the Department of Rheumatology and Immunology, the Second Hospital of Shanxi Medical University from 2018 to 2021. Meanwhile, 49 healthy subjects who underwent physical examination were recruited (healthy control group). The absolute counts of CD4 + T cell subsets in peripheral blood samples were analyzed by flow cytometry. The levels of serum cytokines were detected by flow bead array. Analysis of variance and Mann-Whitney U test were used to compare the differences between groups. Pearson or Spearman correlation analysis was used for correlation analysis. Logistic regression analysis was used to analyze related factors. The receiver operating characteristic curve was used to detect the best cut-off value and effectiveness. Results:The absolute counts of Th1 ( P<0.01), Th2 ( P<0.01) and Treg cells ( P<0.01) in the newly diagnosed MCTD patients and the treated MCTD patients were lower than those in the healthy subjects. The levels of cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α) in the two MCTD groups were higher than those in the healthy control group ( P<0.01). Further analysis revealed that the cardiac enzymes in MCTD patients included creatine kinase, creatine kinase-MB, aspartate aminotransferase, α-hydroxybutyrate dehydrogenase, and lactate dehydrogenase were positively correlated with cytokines ( P<0.05). In addition, it was found that IL-2 was positively correlated with erythrocyte sedimentation rate ( r=0.477, P<0.001), but it was negatively correlated with complement C3 ( r=-0.546, P=0.002) and complement C4 ( r=-0.422, P=0.02). IL-10 was correlated with the myositis symptoms in MCTD patients and the area under the receiver operator characteristic curve was 0.745 (95% CI: 0.576-0.915, P<0.05). Conclusions:This study provides insights into the unique immunological characteristics of CD4 + T lymphocyte subsets and cytokines in patients with MCTD, and also reveals a close correlation between cytokines and cardiac enzymes in MCTD patients. IL-2 has been shown to be associated with disease activity in MCTD patients. The level of IL-10 may be related to the occurrence of myositis symptoms in MCTD.

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.

Porcine reproductive and respiratory syndrome(PRRS),an infectious disease,poses a significant threat to the swine industry.The causative agent of the disease is porcine reproductive and respiratory syndrome virus(PRRSV),which primarily infects porcine alveolar macrophages and destroys the immune system.In the absence of specific antiviral drugs targeting PRRSV,vacci-nation is of paramount importance for the prevention and control of this disease.Currently,there are numerous types of PRRS vaccines,such as attenuated live vaccines,inactivated vaccines,sub-unit vaccines,DNA vaccines,vector vaccines,and so forth.However,only attenuated live virus and inactivated virus vaccines are widely employed for the prevention and control of PRRS.Live vac-cines offer relatively better protection effects,but they have weak cross-protection and pose safety concerns.Inactivated vaccines are safe but have poor immunogenicity.This article conducts a com-prehensive review of the advantages,disadvantages,and applicability of PRRS vaccines,including attenuated live vaccines,inactivated vaccines,subunit vaccines,vector vaccines,DNA vaccines,mR-NA vaccines,virus-like particle vaccines,etc.,aiming to provide a theoretical basis for the research and development of the next generation of PRRS vaccines.

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.

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.

BACKGROUND:Mn can participate in oxidation-reduction reactions in various organisms.For example,as a metal-assisted group in superoxide dismutase 2,Mn plays a role in helping to remove reactive oxygen species.Therefore,the development of novel anti-oxidative stress materials containing Mn has become a research focus in recent years.OBJECTIVE:To investigate the protective effect of Mn bioceramic powder material on oxidative stress damage to chondrocytes by reducing the reactive oxygen species pathway.METHODS:Bioceramic powders containing Mn were prepared by molten salt method.Primary mouse chondrocytes were isolated and cultured.Bioceramic powder containing 0,0.15,and 0.30 mg/mL of Mn was added into H2O2 solution.The H2O2 clearance rate was detected after incubation without light.The passage 2 to passage 4 chondrocytes were co-cultured with complete media containing Mn-containing bioceramic powder with different mass concentrations(0,0.15,and 0.30 mg/mL).Cell viability was detected by cell live/dead staining.The passage 2-4 chondrocytes(or cartilage tissue)were divided into four groups for intervention:Complete culture medium was added to the blank control group.The H2O2 group was added and cultured with complete medium containing H2O2.H2O2+low mass concentration Mn powder group was cultured by adding H2O2+0.15 mg/mL Mn-containing bioceramic powder.The complete medium containing H2O2+0.30 mg/mL Mn-containing bioceramic powder was added to the H2O2+high mass concentration Mn powder group.Viability of chondrocytes was detected by CCK-8 assay.Generation of reactive oxygen species of chondrocytes was detected by 2,7-dichlorofluorescein diacetate probe.Expression of chondrocyte-related factors was detected by qRT-PCR.The tissue structure and function of cartilage were detected by toluidine blue staining.RESULTS AND CONCLUSION:(1)Both doses of Mn-containing bioceramic powders could significantly remove H2O2 in vitro,and they were concentration dependent.The results of cell live/death staining showed that 0.15 mg/mL bioceramic powder containing Mn had chondrocyte safety,and 0.30 mg/mL bioceramic powder containing Mn had chondrocytotoxicity.(2)The results of CCK-8 assay showed that the two mass concentrations of Mn-containing bioceramic powders could significantly reduce the inhibitory effect of H2O2 on chondrocyte viability,and inhibit the generation of reactive oxygen species induced by H2O2 in chondrocytes in a mass concentration dependent manner.Both kinds of Mn-containing bioceramic powders could reverse the H2O2-induced increase of mRNA expression of a disintegrin and metalloproteinase with thrombospondin motifs-5 and decrease of proteoglycan mRNA expression in chondrocytes.(3)Toluidine blue staining results showed that both concentrations of Mn-containing bioceramic powder could protect the integrity of cartilage tissue structure under oxidative stress,and 0.30 mg/mL of Mn-containing bioceramic powder could also reduce the functional damage of cartilage tissue.(4)The results indicate that the Mn-containing bioceramic powder can protect chondrocytes under oxidative stress by clearing reactive oxygen species,maintaining the extracellular matrix homeostasis.However,0.30 mg/mL Mn-containing bioceramic powder has certain chondrocytotoxicity,so 0.15 mg/mL Mn-containing bioceramic powder is preferred for follow-up studies.

BACKGROUND:Mn can participate in oxidation-reduction reactions in various organisms.For example,as a metal-assisted group in superoxide dismutase 2,Mn plays a role in helping to remove reactive oxygen species.Therefore,the development of novel anti-oxidative stress materials containing Mn has become a research focus in recent years.OBJECTIVE:To investigate the protective effect of Mn bioceramic powder material on oxidative stress damage to chondrocytes by reducing the reactive oxygen species pathway.METHODS:Bioceramic powders containing Mn were prepared by molten salt method.Primary mouse chondrocytes were isolated and cultured.Bioceramic powder containing 0,0.15,and 0.30 mg/mL of Mn was added into H2O2 solution.The H2O2 clearance rate was detected after incubation without light.The passage 2 to passage 4 chondrocytes were co-cultured with complete media containing Mn-containing bioceramic powder with different mass concentrations(0,0.15,and 0.30 mg/mL).Cell viability was detected by cell live/dead staining.The passage 2-4 chondrocytes(or cartilage tissue)were divided into four groups for intervention:Complete culture medium was added to the blank control group.The H2O2 group was added and cultured with complete medium containing H2O2.H2O2+low mass concentration Mn powder group was cultured by adding H2O2+0.15 mg/mL Mn-containing bioceramic powder.The complete medium containing H2O2+0.30 mg/mL Mn-containing bioceramic powder was added to the H2O2+high mass concentration Mn powder group.Viability of chondrocytes was detected by CCK-8 assay.Generation of reactive oxygen species of chondrocytes was detected by 2,7-dichlorofluorescein diacetate probe.Expression of chondrocyte-related factors was detected by qRT-PCR.The tissue structure and function of cartilage were detected by toluidine blue staining.RESULTS AND CONCLUSION:(1)Both doses of Mn-containing bioceramic powders could significantly remove H2O2 in vitro,and they were concentration dependent.The results of cell live/death staining showed that 0.15 mg/mL bioceramic powder containing Mn had chondrocyte safety,and 0.30 mg/mL bioceramic powder containing Mn had chondrocytotoxicity.(2)The results of CCK-8 assay showed that the two mass concentrations of Mn-containing bioceramic powders could significantly reduce the inhibitory effect of H2O2 on chondrocyte viability,and inhibit the generation of reactive oxygen species induced by H2O2 in chondrocytes in a mass concentration dependent manner.Both kinds of Mn-containing bioceramic powders could reverse the H2O2-induced increase of mRNA expression of a disintegrin and metalloproteinase with thrombospondin motifs-5 and decrease of proteoglycan mRNA expression in chondrocytes.(3)Toluidine blue staining results showed that both concentrations of Mn-containing bioceramic powder could protect the integrity of cartilage tissue structure under oxidative stress,and 0.30 mg/mL of Mn-containing bioceramic powder could also reduce the functional damage of cartilage tissue.(4)The results indicate that the Mn-containing bioceramic powder can protect chondrocytes under oxidative stress by clearing reactive oxygen species,maintaining the extracellular matrix homeostasis.However,0.30 mg/mL Mn-containing bioceramic powder has certain chondrocytotoxicity,so 0.15 mg/mL Mn-containing bioceramic powder is preferred for follow-up studies.