Objective:To comprehensively understand the disease burden of liver cirrhosis and other chronic liver diseases caused by alcohol use in China from 1990 to 2019, as well as to predict the trends in disease burden from 2020 to 2030.Methods:The analysis utilized data from the Global Burden of Disease study in 2019 (GBD2019). Key indicators such as incidence rate, mortality rate, disability-adjusted life years (DALY), years of life lost due to premature mortality, and years lived with disability were selected to describe the disease burden of alcohol-related liver cirrhosis and other chronic liver diseases in China from 1990 to 2019. The estimated annual percentage change (EAPC) was used to depict the temporal trends in disease burden. Furthermore, a Bayesian age-period-cohort (BAPC) model was constructed using R software to predict the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of alcohol-related liver cirrhosis and other chronic liver diseases in China from 2020 to 2030.Results:From 1990 to 2019, the incidence of alcohol-related liver cirrhosis and other chronic liver diseases in China showed an upward trend, with an EAPC of 0.31% (95% CI: 0.10%-0.52%). However, the DALY declined, with an EAPC of -2.81% (95% CI: -2.92% - -2.70%). The ASMR showed a downward trend, with an EAPC of -2.55% (95% CI: -2.66% - -2.45%). The highest incidence of cirrhosis of liver caused by alcohol and other chronic liver diseases was reported in the age group of 35-49 years, while the ASMR increased gradually with age, with a significant rise after the age of 30. The age-standardized DALY rate peaked between the ages of 55 and 64. The disease burden indicators for males were consistently higher than those for females during the same period. According to the predictions of the BAPC model, from 2020 to 2030, the ASIR for cirrhosis of liver caused by alcohol and other chronic liver diseases in the entire population of China was projected to increase from 3.45/100 000 in 2020 to 3.78/100 000 in 2030, a growth of 9.57%. Conversely, the ASMR was expected to decrease from 1.45/100 000 in 2020 to 1.24/100 000 in 2030, a reduction of 14.48%. Conclusions:The disease burden of cirrhosis of liver caused by alcohol and other chronic liver diseases remained serious in China, especially in men and the middle-aged to elderly population. There is a pressing need to prioritize attention and resources towards these groups. Despite the projected decrease in ASMR, the ASIR continued to rise and is expected to persist in its upward trend until 2030.

Objective To explore the effect and possible pharmacological mechanism of Bufei Tongbi Decoction in the treatment of systemic lupus erythematosus interstitial lung disease (SLE-ILD).Methods The effective components and related targets of Bufei Tongbi Decoction were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Uniprot database. Key genes for SLE-ILD were screened based on DrugBank,DisGeNET,GeneCards,PharmGKB,OMIM,and GEO databases. Using Cytoscape software,a drug active ingredient-target-disease relationship network diagram was constructed to obtain the effective active ingredients and possible mechanisms of action of Bufei Tongbi Decoction in the treatment of SLE-ILD. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal related target genes and pathway functions. Taking C57BL/6 mice as normal group,MRL/lpr mice were injected with bleomycin 5mg/kg in the nasal cavity. According to the random number table method,the mice were divided into model group,Bufei Tongbi Decoction low-dose group (10.4 g/(kg·d)),Bufei Tongbi Decoction medium-dose group (20.8 g/(kg·d)),Bufei Tongbi Decoction high-dose group (41.6 g/(kg·d)) and prednisone group (3 mg/(kg·d)). The intervention lasted for 28 days. Hematein eosin and Masson staining were used to observe the pathological changes of mouse lung tissue,the expressions of transforming growth factor-β1 (TGF-β1) and collagen type Ⅲ (Col-Ⅲ) in lung tissue were detected by immunohistochemistry,and the expressions of interleukin-1β(IL-1β),interleukin-10 (IL-10) and interleukin-17 (IL-17) in serum were detected by ELISA. The mRNA expressions of matrix metallopeptidase 1(MMP-1),hypoxia inducible factor-1α(HIF-1α),retinoid-related orphan receptor γt (RORγt ) and forkhead box P3 (FOXP3) in lung tissue were analyzed by RT-PCR,the protein expressions of HIF-1α and MMP-1 in lung tissue were detected by Western blotting,and the expressions of T helper 17 cells (Th17) and regulatory T cells (Treg cells) in blood were detected by cytometry.Results A total of 163 effective ingredients,259 targets,1729 SLE-ILD disease targets,958 SLE-ILD differential genes and 40 drug-disease interaction targets were obtained by screening. GO functional enrichment and KEGG pathway enrichment showed that IL-17 signaling pathway activated by IL-1β and MMP-1,and Th17 cell differentiation activated by IL-1β and HIF-1α were the main pathways. Animal experiments showed that Bufei Tongbi Decoction could effectively improve the degree of lung interstitial lesion and reduce the expressions of TGF-β1 and Col-Ⅲ in SLE-ILD mice (P<0.01). The expressions of IL-1β,HIF-1α and IL-17 were decreased (P<0.01). Medium and high doses of Bufei Tongbi Decoction decreased the expressions of MMP-1 and RORγt mRNA (P<0.01),and increased the expressions of IL-10 and FOXP3 mRNA (P<0.01). Bufei Tongbi Decoction could reduce the proportion of Th17 cells,increase the proportion of Treg cells,downregulate the balance of Th17/Treg (P<0.05),and improve the immune disorder. Conclusion Bufei Tongbi Decoction has the characteristics of multi-target and multi-pathway in treating SLE-ILD,and its mechanism may be related to the regulation of Th17/Treg cell balance.

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8