Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To explore the effect of miR-296-3p on hepatic fibrosis induced by bile duct ligation(BDL)in rats.Methods 25 SD rats were randomly divided into sham group,model(BDL)group,NC adv group,miR-296-3p adv group and miR-296-3p sponge adv group,with 5 rats in each group.The pathological changes were ob-served in rat liver tissue via HE,Masson and Sirius Red staining;the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin(TBIL)in the serum of rat in each group were detected;the expression levels of miR-296-3p,interleukin(IL)-6,IL-1 β,tumor necrosis factor(TNF)-α and smooth muscle actin(α-SMA),type Ⅰ collagen(Col1A1),and connective tissue growth factor(CTGF)mRNA in rat liver tissue were detected by qRT-PCR;the expression levels of α-SMA,Col1A1 and CTGF proteins were detected by Western blot.Immunohistochemical staining(IHC)was performed to detect the expression of α-SMA in liver tissue.Target genes of miR-296-3p was predicted by bioinformatic analysis using the online database.Zinc finger and BTB do-main-containing protein20(ZBTB20)mRNA and protein expression levels were detected.Results The pathologi-cal staining results showed that compared with sham group,a large number of infiltrated inflammatory cells and col-lagen deposition were observed in the liver tissues of rats in the BDL group and NC adv group.Compared with NC adv group,the inflammatory cells and collagen deposition decreased in the liver tissues of miR-296-3p adv group.However,in miR-296-3p sponge adv group,collagen product and inflammatory reaction increased.Compared with sham group,the contents of ALT,AST and TBIL in serum of rats in BDL group and NC adv group increased,the expression level of miR-296-3p decreased,the mRNA expression levels of IL-6,IL-1β,TNF-α increased,and the mRNA and protein expression levels of α-SMA,Col1A1 and CTGF increased(all P＜0.05).Compared with the NC adv group,the contents of ALT,AST and TBIL in serum of rats in miR-296-3p adv group decreased,the ex-pression level of miR-296-3p increased,the mRNA expression levels of IL-6,IL-1 β and TNF-α,and the mRNA and protein expression levels of α-SMA,Col1A1 and CTGF in liver tissues decreased(all P＜0.05).The results of miR-296-3p sponge adv group were opposite to those of miR-296-3p adv group(all P＜0.05).The bioinformat-ics website predicted that ZBTB20 might be a candidate target gene of miR-296-3p.Compared with sham group,the expression of ZBTB20 mRNA and protein in the liver tissues of BDL group and NC adv group increased(P＜0.05),and the expression of ZBTB20 in the liver tissues of miR-296-3p adv group decreased compared with NC adv group(P＜0.05).However,the expression of ZBTB20 in liver tissues of miR-296-3p sponge adv group in-creased(P＜0.05).Conclusion miR-296-3p expression decreases in BDL-induced hepatic fibrosis in rats,and miR-296-3p may inhibit hepatic fibrosis in BDL rats by targeting ZBTB20.

Objective To investigate the effect of miR-199a-5p on common bile duct ligation(BDL)-induced liver fibrosis in rats by regulating intestinal flora.Methods The 25 SD rats were randomly divided into five groups:the Sham group,the BDL group,the negative control adenovirus(NC adv)group,the miR-199a-5p adv group and the miR-199a-5p sponge adv group.The pathological changes of liver tissue and the degree of liver fibrosis were ob-served by HE,Masson and Sirius Red staining.The levels of aspartate aminotransferase(AST),alanine amin-otransferase(ALT),total bilirubin(TBIL)and direct bilirubin(DBIL)in serum of rats were determined by a fully automatic biochemical analyzer.The mRNA expression level of miR-199a-5p in liver tissue of rats was detec-ted by qRT-PCR.The protein expression levels of α-smooth muscle actin(α-SMA)and collagen type 1 alpha 1(COL1A1)in liver tissue of rats were detected by double immunofluorescence staining and Western blot experi-ment.Rat feces were collected for 16S rRNA high-throughput sequencing.Results The expression of miR-199a-5p was up-regulated in the liver tissue of BDL rats(P＜0.01).Compared with the NC adv group,the degree of liver injury and collagen deposition were relatively serious,the levels of AST,ALT,TBIL and DBIL in serum and the expression levels of α-SMA and COL1A1 in liver tissue increased in the miR-199a-5p adv group(all P＜0.05).However,the results of miR-199a-5p sponge adv intervention were opposite(all P＜0.05).The 16S rRNA sequencing results showed that rats treated with miR-199a-5p adv were characterized by increased diversity and richness of intestinal microbiota,changed composition of intestinal microbiota,while the results of miR-199a-5p sponge adv interfering with the bacterial community were opposite(all P＜0.05).Conclusion miR-199a-5p promotes liver fibrosis of BDL rats,and its mechanism may be related to regulating the diversity and abundance of intestinal microbiota.

Objective To analyze the occupational health status of radiation workers in Guangdong Province. Methods A total of 8 913 radiation workers who underwent occupational medical examination (OME) in Guangdong Province Hospital for Occupational Disease Prevention and Treatment in 2020 were selected as the exposure group, and 2 024 non-radiological workers who underwent health examination in the same hospital in the same period of time were selected as the control group using convenient sampling method. The study analyzed the prevalence of abnormalities in thyroid, eye lens, blood pressure, complete blood count and micronucleus in individuals of the two groups. Results The abnormal rates of eye lens, blood pressure and complete blood count in the radiation workers in the exposure group were higher than those in the control group (23.3% vs 8.0%, 18.6% vs 9.0%, 18.1% vs 8.5%, all P<0.01). However, there was no significant difference in the abnormal rates of thyroid and micronucleus in workers between these two groups (12.8% vs 11.5%, 0.1% vs 0.0%, all P>0.05). The abnormal rates of thyroid, eye lens and blood pressure in radiation workers increased with the exposure period of radiation (all P<0.05). Conclusion Long-term exposure to low-dose ionizing radiation have certain effects on the thyroid, eye lens, and blood pressure of radiation workers, with a time-effect relationship of years of radiation work.

Objective To investigate the effect of CXXC finger protein 4 (CXXC4) on the proliferation and apoptosis of pancreatic cancer PANC-1 cells.Methods The expression level of CXXC4 in pancreatic canc-er tissues and its relationship with prognosis and clinicopathological stage of the patients were analyzed in on-line databases.The qRT-PCR technique was used to detect the mRNA expression level of CXXC4 in human normal pancreatic ductal epithelial cell line (HPNE) and pancreatic cancer cell PANC-1,AsPC-1 and BxPC-3. si-NC,si-CXXC4,pcDNA3.1 and pCDNA3.1-CXXC4 were respectively transfected into PANC-1 cells.West-ern blot was conducted to detect the effectiveness of CXXC4 knockdown and overexpression.CCK-8,colony formation,EdU and immunofluorescence assays were conducted to analyze the effect of CXXC4 knockdown or overexpression on the proliferation and apoptosis of PANC-1 cells.The bioinformatic websites was used to predict the upstream microRNA (miRNA) of CXXC4.The Starbase database was adopted to analyze the cor-relation between miR-450b-5p and CXXC4 expression in pancreatic cancer tissues.Results The TCGA data-base results showed that the expression of CXXC4 in pancreatic cancer tissues was lowly expressed compared with in paracancerous pancreatic tissues (P<0.001),moreover which was associated with the overall survival and poor prognosis in the patients with pancreatic cancer (P<0.05).The GEPIA database analysis results showed that compared with stage Ⅰ pancreatic cancer,the CXXC4 expression in stage Ⅱ pancreatic cancer was decreased (P<0.05).Compared with HPNE cells,the CXXC4 expression in 3 kinds of pancreatic cancer cells was decreased (P<0.05).Compared with the si-NC group,the proliferation and colony formation ability of PANC-1 cells in the si-CXXC4 group were enhanced,the expressions of proliferation markers Ki67 and PC-NA were increased,and the expressions of apoptosis markers Bax,caspase-3 and caspase-9 were decreased;compared with the pcDNA3.1 group,the PANC-1 cells in the pcDNA3.1-CXXC4 group obtained the opposite results (all P<0.05).The bioinformatic websites predicted that miR-450b-5p was the upstream miRNA of CXXC4,CXXC4 in pancreatic cancer tissues was negatively correlated with the miR-450b-5p expression (r=-0.227) and miR-450b-5p in various mammalian species was highly conserved.Conclusion CXXC4 inhibits the proliferation of PANC-1 cells in pancreatic cancer and promotes theirs apoptosis.

Objective:To analyze and explore the clinical characteristics and risk factors related to nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia.Methods:252 hospitalized patients with liver cirrhosis combined with atrial arrhythmia from January 2014 to December 2021 were enrolled, and their clinical characteristics were analyzed. The above-mentioned patients were divided into groups according to their nosocomial mortality rate. Among them, 45 nosocomial mortality cases were classified as the mortality group, and 207 survival cases were classified as the survival group. The differences in clinical data and laboratory data between the two groups were compared. The risk factors for nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia were analyzed. The t-test, or rank-sum test, was used to compare measurement data. The chi-square test, or Fisher's exact probability method, was used to compare enumeration data. Multivariate analysis was performed by the logistic regression method.Results:Among the 252 cases, the male-to-female ratio was the same (male/female ratio: 126/126). The age range was 26 to 89 (66.77±10.46) years. Han ethnicity accounted for 79.5%. The main type of atrial arrhythmia was atrial fibrillation ( P ?

Objective:To explore the application effect of theory of inventive problem solving(TRIZ)in the management of loaner instruments in central sterile supply department(CSSD).Methods:TRIZ management team was set up to analyze problems in cleaning,disinfection and sterilization of loaner instruments.The invention principles of TRIZ were compared to determine targeted solutions to the corresponding problems.A total of 1,000 pieces of loaner instruments received by The Third Affiliated Hospital of Air Force Medical University were selected from January and December 2023 were selected,the 500 pieces received from January to June were managed by routine standard management mode,and the 500 pieces received from July to December were managed by the TRIZ management mode.The qualification rates of instruments cleaning,disinfection,packaging and sterilization,the incidence of adverse events,the satisfaction scores of clinical departments and assessment results of newly hired nurses of CSSD were compared between the two management modes.Results:The qualification rates of instruments cleaning,disinfection,packaging and sterilization of TRIZ management mode were 98.00%(490/500),97.20%(486/500),96.40%(482/500)and 96.00%(480/500),respectively,which were higher than those of routine standard management mode,the difference was statistically significant(x2=12.029,11.685,8.859,8.322,P<0.05).The incidence of adverse events of TRIZ management mode was 0%,the routine standard management mode was 1.20%,the difference was statistically significant(x2=6.036,P<0.05).The average scores of CSSD newly hired nurses in of theoretical knowledge,treatment process,cleaning,disinfection and sterilization and packaging of TRIZ management mode were(89.20±6.69)points,(88.47±3.48)points,(92.47±5.37)points and(92.00±5.83)points,respectively,which were higher than those of routine standard management mode,the difference was statistically significant(t=3.993,4.402,3.926,3.332,P<0.05).The satisfaction scores of clinical department personnel with instruments quality,distribution,handover,information traceability,service attitude and overall satisfaction of TRIZ management mode were(18.65±0.81)points,(18.85±1.04)points,(18.95±1.05)points,(18.40±0.75)points,(18.35±0.93)points and(93.20±1.91)points,respectively,which were higher than those of the routine standard management mode,the difference was statistically significant(t=3.599,5.889,4.851,4.865,2.075,8.723,P<0.05).Conclusion:The application of TRIZ in the management of loaner instruments in CSSD can significantly improve theoretical knowledge and practical skills of newly hired nurses in CSSD,thereby improving the qualification rates of instruments cleaning,disinfection,packaging and sterilization of loaner instruments,reducing the occurrence of instrument-related adverse events and improving satisfaction of department personnel with instruments use.

Objective:To investigate the association and predictive value of serum biomarkers with carotid atherosclerosis(CAS)in the elderly population.Methods:The data used in this study were obtained from the China Hainan Centenarian Cohort Study(CHCCS), a prospective cohort that includes elderly individuals from community populations in Hainan Province.The baseline survey was conducted between 2014 and 2019.A total of 737 elderly individuals aged 80 to 100 were included in the analysis.The study examined various factors including questionnaires, physical examination data, liver and kidney function indicators(albumin, aspartate aminotransferase, alanine aminotransferase, total bilirubin, and glomerular filtration rate), blood cell counts(red blood cells, white blood cells, platelets, neutrophil count, lymphocyte count, and monocyte count), inflammatory markers(high-sensitivity C-reactive protein), and lipid metabolism markers(total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein AI, and apolipoprotein B).The objective was to explore the lipids of serum biomarkers and diagnostic performance of carotid atherosclerosis.Results:The prevalence of CAS in the elderly population was found to be 80.7%.Spearman's correlation analysis and a fully adjusted multivariate logistic regression model were used to examine the relationship between CAS and various factors in elderly patients.Result showed that systolic blood pressure, heart rate, and serum apolipoprotein B levels were significantly correlated with CAS[ OR(95% CI): 1.012(1.004-1.021), 0.998(1.011-1.024); 15.796(4.914-50.772), respectively; all P<0.001].Additionally, ROC curve analysis demonstrated that the combined application of serum apolipoprotein B, systolic blood pressure, and heart rate improved the predictive value of CAS in the elderly(Area under the curve: 0.820, 95% CI: 0.782-0.858; Sensitivity: 78.8%; Specificity: 86.8%; Positive likelihood ratio: 5.97; Negative likelihood ratio: 0.24). Conclusions:Our study discovered that serum apolipoprotein B is an autonomous risk factor for CAS among the elderly.The utilization of a specific set of biomarkers, in conjunction with other risk markers, holds potential as a promising strategy for evaluating CAS in the elderly population.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.