Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Objective： To investigate the relationship between the lipid metabolism-related gene sterol carrier protein 2(SCP2) and prostate cancer (PCa) from a multi-omics perspective using single-cell transcriptomes combined with Mendelian randomization. Methods： Single-cell transcriptome data of benign and malignant prostate tissues were obtained from GSE120716, GSE157703 and GSE141445 datasets, respectively. Integration, quality control and annotation were performed on the data to categorize the epithelial cells into high and low SCP2 expression groups, followed by further differential and trajectory analyses. Single nucleotide polymorphism (SNP) data for SCP2 expression quantitative trait loci (eQTL) were subsequently downloaded from Genotype-Tissue Expression (GTEx) and investigated from the PCa Society Cancer-Related Genomic Alteration Panel for the Investigation of Cancer-Related Alterations (PRACTICAL) to obtain PCa outcome data for Mendelian randomization analysis to validate the causal relationship between SCP2 and PCa. Results： High SCP2-expressing epithelial cells had higher energy metabolism and proliferation capacity with low immunotherapy response and metastatic tendency. Trajectory analysis showed that epithelial cells with high SCP2 expression may have a higher degree of malignancy, and SCP2 may be a key marker gene for differentiation of malignant epithelial cells in the prostate. Further Mendelian randomization results showed a significant causal relationship between SCP2 and PCa development (OR=1.045, 95% CI: 1.010 －1.083, P=0.011). Conclusion： By combining single-cell transcriptome and Mendelian randomization, the role of the lipid metabolism-related gene SCP2 in PCa development has been confirmed, and new targets and therapeutic directions for PCa treatment have been provided.
Humans ; Prostatic Neoplasms/genetics* ; Male ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Single-Cell Analysis ; Sequence Analysis, RNA ; Carrier Proteins/genetics* ; Transcriptome ; Lipid Metabolism

Objective:Accurately grasping the disability levels and characteristics of the elderly population in China is of significant importance for responding effectively to the care service needs of this demographic.Methods:Based on multi-wave data(2011-2023)from three nationally representative aging-related surveys CLHLS,CHARLS and CALSS,this study assessed,compared,and predicted the disability levels and characteristics of China's elderly population.Results:Direct estimates from existing survey data showed low reliability.Integrated multi-source projections indicate that the disability rate among China's population aged 65 and older will follow a phased upward trend,ranging approximately between 12.27%and 15.05%from 2025 to 2050,with the disabled elderly population growing continuously from 25.9 million to 58.64 million.Bathing,toileting,and dressing were the three activities with the highest disability rates.Discussion and Suggestions:Future efforts should focus on improving the construction of an elderly capacity assessment system and addressing the shortage of high-quality disability data.Research should emphasize the evaluation process of item-specific disability among older adults.It is essential to grasp the phased characteristics of changes in disability levels and identify critical windows of opportunity for response.Based on the item-specific disability characteristics of older adults,the focus of elderly care services,facilities,and product supply should be accurately targeted.

Aim To investigate the effect of circRNF13 on oxaliplatin resistance in colorectal cancer cells and its related mechanism.Methods Cell transfection was used to overexpress circRNF13 in oxaliplatin-sensi-tive colorectal cancer cells SW620 or to inhibit cir-cRNF13 expression in oxaliplatin-resistant colorectal cancer cells SW620/OXA.Real-time quantitative fluo-rescent PCR(qRT-PCR)was used to detect the ex-pression levels of circRNF13,miR-16-5p,and mir-324-5p.Cell Count Kit 8(CCK-8)was used to meas-ure cell viability.Clonal formation experiments were used to measure clonal formation number.Western blot was used to detect CyclinD1,PCNA,Bax,Bcl-2 and cleaved caspase-3 protein expression level.Flow cy-tometry and in situ end labeling(TUNEL)were used to detect apoptosis.Dual luciferase assay was used to verify the targeting relationship between circRNF13 and miR-16-5p and mir-324-5p.Results The expression level of circRNF13 in SW620/OXA cells was signifi-cantly higher than that in SW620 cells,while the ex-pression levels of miR-16-5p and miR-324-5p were sig-nificantly lower than those in SW620 cells(P＜0.05).Overexpression of circRNF13 significantly in-creased the IC50 of oxaliplatin against SW620 cells,and inhibition of circRNF13 expression significantly decreased the IC50 of oxaliplatin against SW620/OXA cells.Overexpression of circRNF13 significantly in-creased cell viability,clonal formation number,Cy-clinD1,PCNA and Bcl-2 levels of oxaliplatin treated SW620 cells,while significantly decreased apoptosis rate,apoptosis index,Bax and cleaved caspase-3 lev-els(P＜0.05).Inhibition of circRNF13 expression significantly decreased the cell viability,clonal forma-tion number,CyclinD1,PCNA and Bcl-2 levels of ox-aliplatin treated SW620/OXA cells,while significantly increased the apoptosis rate,apoptosis index,Bax and cleaved caspase-3 levels(P＜0.05).circRNF13 tar-geted inhibition of the expression of miR-16-5p and mir-324-5p.Conclusions circRNF13 can increase oxaliplatin resistance in colorectal cancer cells,and the mechanism may be related to the targeted inhibition of circRNF13 on the expression of miR-16-5p,mir-324-5p and other miRNAs.

Objective:Accurately grasping the disability levels and characteristics of the elderly population in China is of significant importance for responding effectively to the care service needs of this demographic.Methods:Based on multi-wave data(2011-2023)from three nationally representative aging-related surveys CLHLS,CHARLS and CALSS,this study assessed,compared,and predicted the disability levels and characteristics of China's elderly population.Results:Direct estimates from existing survey data showed low reliability.Integrated multi-source projections indicate that the disability rate among China's population aged 65 and older will follow a phased upward trend,ranging approximately between 12.27%and 15.05%from 2025 to 2050,with the disabled elderly population growing continuously from 25.9 million to 58.64 million.Bathing,toileting,and dressing were the three activities with the highest disability rates.Discussion and Suggestions:Future efforts should focus on improving the construction of an elderly capacity assessment system and addressing the shortage of high-quality disability data.Research should emphasize the evaluation process of item-specific disability among older adults.It is essential to grasp the phased characteristics of changes in disability levels and identify critical windows of opportunity for response.Based on the item-specific disability characteristics of older adults,the focus of elderly care services,facilities,and product supply should be accurately targeted.

Aim To investigate the effect of circRNF13 on oxaliplatin resistance in colorectal cancer cells and its related mechanism.Methods Cell transfection was used to overexpress circRNF13 in oxaliplatin-sensi-tive colorectal cancer cells SW620 or to inhibit cir-cRNF13 expression in oxaliplatin-resistant colorectal cancer cells SW620/OXA.Real-time quantitative fluo-rescent PCR(qRT-PCR)was used to detect the ex-pression levels of circRNF13,miR-16-5p,and mir-324-5p.Cell Count Kit 8(CCK-8)was used to meas-ure cell viability.Clonal formation experiments were used to measure clonal formation number.Western blot was used to detect CyclinD1,PCNA,Bax,Bcl-2 and cleaved caspase-3 protein expression level.Flow cy-tometry and in situ end labeling(TUNEL)were used to detect apoptosis.Dual luciferase assay was used to verify the targeting relationship between circRNF13 and miR-16-5p and mir-324-5p.Results The expression level of circRNF13 in SW620/OXA cells was signifi-cantly higher than that in SW620 cells,while the ex-pression levels of miR-16-5p and miR-324-5p were sig-nificantly lower than those in SW620 cells(P＜0.05).Overexpression of circRNF13 significantly in-creased the IC50 of oxaliplatin against SW620 cells,and inhibition of circRNF13 expression significantly decreased the IC50 of oxaliplatin against SW620/OXA cells.Overexpression of circRNF13 significantly in-creased cell viability,clonal formation number,Cy-clinD1,PCNA and Bcl-2 levels of oxaliplatin treated SW620 cells,while significantly decreased apoptosis rate,apoptosis index,Bax and cleaved caspase-3 lev-els(P＜0.05).Inhibition of circRNF13 expression significantly decreased the cell viability,clonal forma-tion number,CyclinD1,PCNA and Bcl-2 levels of ox-aliplatin treated SW620/OXA cells,while significantly increased the apoptosis rate,apoptosis index,Bax and cleaved caspase-3 levels(P＜0.05).circRNF13 tar-geted inhibition of the expression of miR-16-5p and mir-324-5p.Conclusions circRNF13 can increase oxaliplatin resistance in colorectal cancer cells,and the mechanism may be related to the targeted inhibition of circRNF13 on the expression of miR-16-5p,mir-324-5p and other miRNAs.

Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I

Objective: To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods: This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results: The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion: LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.
Humans ; Male ; Hyperlipoproteinemia Type II/genetics* ; Lipase/genetics* ; Lipids ; Mutation ; Pedigree ; Phenotype ; Proteins

OBJECTIVE: To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. METHODS: A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. RESULTS: A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (P_trend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. CONCLUSIONS In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

In China, the current standard for cosmetic adverse reactions related skin disease (GB/T 17149.1-1997) was jointly issued by the Ministry of Health and the State Bureau of Technical Supervision in 1997, cosmetic-allergic adverse reactions include allergic contact dermatitis and photo-allergic contact dermatitis according to this standard. The increasing use and changes in cosmetic ingredients or formula lead to a significant increase for the incidence of adverse reactions as the cosmetics industry is developing rapidly in the last 20 years. In the meantime, the clinical manifestations have become more diverse. In recent years, there have been many reports on the special manifestations for cosmetic allergy and allergen test, which provide a reference for the subsequent improvement of the diagnosis and prevention.
Humans ; Patch Tests/adverse effects* ; Dermatitis, Allergic Contact/therapy* ; Cosmetics/adverse effects* ; China ; Incidence ; Allergens/adverse effects*