BACKGROUND:To date,the pathogenesis of pulmonary fibrosis is still unknown,and there are limited treatment options available.Numerous studies have found an important role of non-coding RNAs in the development of pulmonary fibrosis. OBJECTIVE:To review the regulatory role of non-coding RNAs in the pathogenesis of pulmonary fibrosis in recent years,in order to provide a more in-depth understanding of the pathogenesis of pulmonary fibrosis. METHODS:The first author searched the literature published from 2000 to 2024 by computer,and searched CNKI,WanFang,VIP,and PubMed databases using the search terms of"non-coding RNA,microRNA,long-chain non-coding RNA,circular RNA,pulmonary fibrosis,review"in Chinese and English.Finally,65 articles were included according to the inclusion criteria. RESULTS AND CONCLUSION:Pulmonary fibrosis,as a chronic and usually fatal lung disease,may arise not only spontaneously but also be as a secondary consequence of other diseases.It is mainly characterized by abnormal proliferation and massive accumulation of extracellular matrix in the interstitium of the lungs.Non-coding RNAs are RNA molecules transcribed from the genomes that are not involved in protein-coding processes and by virtue of their regulatory capabilities,they have become first-line molecular players in a variety of biological phenomena.Non-coding RNAs have been found to play a key role in the pathogenesis of pulmonary fibrosis,and microRNAs,long non-coding RNAs,and circular RNAs can be involved in the development of pulmonary fibrosis by influencing gene expression,post-transcriptional modifications,and intercellular signaling.This provides a new direction for the subsequent exploration of the specific molecular mechanisms of pulmonary fibrosis,and a theoretical basis and new ideas for the development of new targeted drugs for pulmonary fibrosis.

Objective: To investigate the protective effects of morusin on lipopolysaccharide (LPS)-induced acute liver injury in mice and its underlying mechanisms. Methods: Thirty-two male specific pathogen-free (SPF) C57BL/6J mice were randomly divided into four groups (n = 8 per group): control, LPS, low-dose morusin (morusin-L, 10 mg/kg), and high-dose morusin (morusin-H, 20 mg/kg) groups. The mice in each group were administered the corresponding drugs or normal saline via continuous gavage daily for 16 consecutive days. Except for control group, which received an equal volume of normal saline, other groups were intraperitoneally injected with LPS (5 mg/kg) 2 h after the last gavage to establish the acute liver injury model. Serum and liver tissues were collected for subsequent analysis 6 h after LPS injection. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected with biochemical methods. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in serum were measured by enzyme-linked immunosorbent assay (ELISA). Hepatic pathological changes were evaluated by hematoxylin-eosin (HE) staining. The 16S ribosomal RNA (16S rRNA) sequencing was performed to assess the composition of intestinal flora, linear discriminant analysis effect size (LEfSe) was applied for multi-level species discrimination, and Spearman’s correlation analysis was performed. The liver tissues of mice with acute liver injury were analyzed by RNA sequencing (RNA-seq) technology to identify differentially expressed genes (DEGs), and then enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was conducted. The expression levels of selected genes was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), while immunohistochemistry (IHC) was performed to examine the expression levels of IL-6, myeloid differentiation primary response 88 (MYD88), and toll-like receptor 2 (TLR2). Results: Morusin significantly reduced the serum levels of ALT, AST, and inflammatory factors (TNF-α, IL-6, and IL-1β) (P < 0.05, P < 0.01, or P < 0.001), while alleviating the hepatic pathological damage in mice. Based on efficacy comparisons, morusin-H group was selected for subsequent microbiome and transcriptome analyses. Microbiome analysis revealed that morusin-H effectively mitigated LPS-induced gut dysbiosis and restored the Firmicutes/Bacteroidota balance (P < 0.01). At the genus level, morusin-H significantly reduced the abundances of norank_f_Muribaculaceae, Desulfovibrio, Parabacteroides, and Muribaculum (P < 0.05, P < 0.01, or P < 0.001). At the phylum, family, and genus levels, our findings indicated that morusin-H treatment caused a significant decrease in the abundance of Desulfobacterota, Desulfovibrionaceae, and Desulfovibrio (P < 0.01). Importantly, the abundance of Desulfovibrio was positively correlated with the levels of ALT, AST, TNF-α, IL-1β, and IL-6. Transcriptomic and molecular analyses showed that the therapeutic mechanism of morusin-H involved suppression of the IL-17/TNF signaling pathways and downregulating the mRNA levels of Tlr2, Tlr3, Myd88, Il6, and Cxcl10 (P < 0.05 or P < 0.001), as well as the protein levels of key inflammatory mediators (IL-6, MYD88, and TLR2) (P < 0.001). Conclusion Morusin demonstrates protective effects against LPS-induced acute liver injury, likely through modulation of gut microbiota and suppression of pro-inflammatory factor expression. These findings indicate that morusin exerts its effects through the "microbiota-inflammation-liver" axis, providing a theoretical basis for its use as a multi-target plant-based drug in the treatment of metabolic inflammation-related liver diseases.

Objective:To investigate the synergistic activity and mechanism of vinegar baked radix bupleurum polysaccharides(VBCP)in combination with oxaliplatin(OXA),and to provide new ideas for the clinical treatment of primary hepatocellular carci-noma.Methods:MTT assay was used to detect the cytotoxic effect of VBCP 3-4 and VBCP 3-3 in combination with OXA on Huh7 cells;ICP-MS was used to measure the uptake rate of OXA by Huh7 cells and evaluate the in vitro synergistic pathway of VBCP 3-4 in combination with OXA;Western blotting was used to measure the expression levels of related transporter proteins in Huh7 cells and explore the synergistic mechanism of VBCP 3-4 in combination and MRP1 in Huh7 cells,and the protein expression level of multidrug resistance-associated protein(MRP)2 was upregulated to 18.11%and 25.00%,respectively(P=0.008,P=0.001),while that of MRP1 was upregulated to 28.51%(P>0.05)and 39.70%(P=0.015),respectively.After the combination of VBCP 3-4 and OXA,the protein expression of MRP2,MRP1,and breast cancer resis-tance protein(BCRP)was inhibited;MRP2 was reduced by 47.38%in the high-dose combination group(P=0.000)and 15.18%in the low-dose combination group(P=0.049);MRP1 was reduced by 64.96%in the high-dose combination group(P=0.000)and 34.63%in the low-dose combination group(P=0.000);BCRP was reduced by 29.00%(P=0.020)in the high-dose combination group.Acting on Huh7 cells alone,VBCP 3-4 significantly reduced the protein expression levels of MRP2,MRP1,and BCRP,and in the high-dose VBCP 3-4 group,MRP2 and MRP1 were reduced by 24.91%and 20.79%,respectively(P=0.004,P=0.005).VBCP 3-4 downregu-lated the protein expression level of BCRP by 15.02%in the high-dose group(P=0.003)and 13.92%in the middle-dose group(P=0.030).Conclusion:VBCP 3-4 exerts a synergistic effect by inhibiting the expression of the efflux transporter proteins MRP1,MRP2,and BCRP,promoting the intake of OXA by Huh7 cells,and increasing the intracellular effective concentration.

Objective:Malnutrition is prevalent among patients with chronic obstructive pulmonary disease(COPD)and closely associ-ated with adverse outcomes.This study aimed to evaluate the effectiveness of three nutritional indices in predicting all-cause mortality among COPD patients.Methods:Based on the National Health and Nutrition Examination Survey(NHANES),this study included 1640 patients with COPD surveyed from 1999 to 2018.The optimal cutoff values for controlling nutritional status(CONUT)score,geri-atric nutritional risk index(GNRI),and prognostic nutritional index(PNI)were determined using receiver operating characteristic curves.The predictive value of these nutritional indices was assessed using the area under the receiver operating characteristic curve and C-index.Their predictive abilities were compared using the net reclassification improvement and integrated discrimination improvement.A Cox regression analysis was conducted to explore the association of the three nutritional indices with all-cause mortality.Results:Log-rank tests revealed lower overall survival rates in patients with higher nutritional risks(P<0.001).In multivariate Cox regression adjusting for all covariates,CONUT score(hazard ratio[HR]=1.31,95%CI=1.03-1.67,P=0.030),GNRI(HR=2.02,95%CI=1.26-3.24,P=0.004),and PNI(HR=2.05,95%CI=1.53-2.75,P<0.001)were independently associated with all-cause mortality.Conclusion:This study confirms that the three nutritional indices are effective predictors of all-cause mortality in COPD patients.Compared with PNI,CONUT score and GNRI demonstrate im-proved predictive abilities,and they are recommended for routine screening for high-risk malnutrition in COPD patients.

OBJECTIVE To analyze the influential factors on trough concentration （cmin） and area under the drug concentration time curve （AUC） of voriconazole （VRZ） in pediatric patients with thalassemia undergoing hematopoietic stem cell transplantation （HSCT）. METHODS A total of 60 pediatric patients with thalassemia undergoing HSCT who used VRZ for prevention or treatment of invasive fungal infection were collected in our hospital from January 2021 to January 2024. The plasma concentration of VRZ was measured by high-performance liquid chromatography and the AUC was calculated. The factors affecting cmin and AUC of VRZ were analyzed using multiple linear regression. RESULTS A total of 120 cases of VRZ cmin in 60 pediatric patients was obtained and 27 cases of VRZ AUC in 26 pediatric patients were obtained. The median concentration of VRZ cmin was 0.31 mg/L； 46 cases had a cmin in 0.5-5 mg/L（ 38.33%）， 2 cases had a cmin＞5 mg/L（ 1.67%）， and 72 cases had a cmin＜0.5 mg/L. The median AUC of VRZ was 11.68 mg·h/L. The patient’s body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine had significant effects on VRZ cmin （P＜0.05）. Lymphocyte count and combined use of phenytoin sodium had significant effects on VRZ AUC （P＜0.05）. CONCLUSIONS The body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine are independent factors affecting VRZ cmin. Lymphocyte count and combined use of phenytoin sodium are independent factors affecting VRZ AUC.

Objective:To investigate the effect of mitochondrial division of GABAergic neurons in substantia nigra pars reticulata(SNr)on motor dysfunction in mice with acute hepatic encephalopathy(AHE).Methods:AHE mice model was established by intraperitoneal injection of thioacetamide(TAA).The changes of liver lobules in AHE mice were observed by hematoxylin-eosin(HE)staining.The changes of serum aspartate aminotransferase(AST),alanine aminotransferase(ALT)and blood ammonia in AHE mice were detected by biochemical detection kit.Then,the motor function of AHE mice was observed by rod fatigue test,elevated cross maze test and open field test.Furthermore,the changes of mitochondrial area,perimeter,roundness and other morphological indicators in SNr of AHE mice were ob-served and analyzed by transmission electron microscopy.The expression of mitochondrial division and fusion related molecules in SNr of AHE mice was observed by Western Blot.Then,the expression of mitochondrial dynamic related protein 1(DRP1)in SNr of AHE mice was targeted by AAV virus.The mitochondrial membrane potential(MMP),ATP and reactive oxygen species(ROS)in SNr were detected by fluorescence enzyme marker,and the changes of motor function of mice were observed.Results:Compared with the control group,the motor function of AHE mice was signifi-cantly decreased,the mitochondrial division of SNr was significantly enhanced,and the expression of mitochondrial divi-sion related proteins was significantly increased.The MMP in SNr of AHE mice was significantly decreased,the ATP of cells was decreased,and the ROS was increased.After targeted inhibition of DRP1 expression in SNr of AHE mice,the movement was improved;further observation found that after the mitochondrial division in SNr of AHE mice was inhibi-ted,the MMP was significantly increased,the ATP of cells was increased,and the ROS was decreased,which demon-strated that the mitochondrial function was significantly improved.Conclusion:Targeted inhibition of mitochondrial di-vision of GABAergic neurons in SNr of AHE mice can improve mitochondrial morphology and function,thus alleviating their movement disorders.

ObjectiveTo explore the characteristics and associated risk factors of diabetes in patients with schizophrenia living in communities, and to provide a basis for the prevention of diabetes comorbidity in this population. MethodsA stratified cluster sampling was used to randomly select patients with schizophrenia in Shanghai who participated in the free health examination provided by the National Basic Public Health Services in 2020. Statistical methods were employed to analyze the general demographic data, clinical characteristics, and laboratory test results of the study subjects. ResultsThe study included 3 374 individuals with schizophrenia, among which the prevalence of diabetes was 17.01%. Statistically significant differences were observed in terms of age, education level, urban area type, marital status, employment status, duration of illness, blood pressure, body mass index, total cholesterol, and triglyceride levels (all P<0.05). Multivariate logistic regression analysis revealed that living in non-central urban areas (OR=1.76, 95%CI: 1.33‒2.32), disease duration of 6‒ years (OR=2.60, 95%CI: 1.07‒6.32), disease duration of 11‒ years (OR=2.72, 95%CI: 1.17‒6.35), disease duration of 16‒ years (OR=3.38, 95%CI: 1.54‒7.42), hypertension(OR=1.73, 95%CI: 1.27‒2.36), obesity (OR=1.52, 95%CI: 1.15‒2.00), and elevated triglyceride levels (OR=2.78, 95%CI: 2.22‒3.49) were risk factors for diabetes in patients with schizophrenia. ConclusionThe prevalence of diabetes in community-dwelling patients with schizophrenia is higher than that in the general population. It is recommended that appropriate health education and rehabilitation guidance be provided as part of community-based mental health services.

Objective:To investigate the diagnostic value of density features of computed tomography(CT)of the fat around pericoronary artery of dual-source computer tomography angiography(CTA)combined with electrocardiogram(ECG)on the severity of disease condition in patients with coronary heart disease(CHD).Methods:A total of 120 CHD patients who admitted to Shanxi Bethune Hospital from March 2021 to March 2023 were selected,and they were grouped according to the New York Heart Association(NYHA).Among of them,86 cases at grade Ⅱ-Ⅲ were divided into grade Ⅱ-Ⅲ group,and 34 cases at grade Ⅳ were divided into grade Ⅳ group.A dual-source CT was used to detect the densities of different coronary branches of Pericardial Adipose Tissue(PCAT)of average coronary artery of proximal left anterior descending artery(pLAD),mid left anterior descending artery(mLAD),proximal left circumflex artery(pLCX),proximal right coronary artery(pRCA),mid right coronary artery(mRCA)and distal right coronary artery(dRCA)of all patients,and ECG was used to detect and record the value of QRS voltage,QRS time limit value and QTc interval of patients.The mean PCAT densities of pLAD,mLAD,pLCX,pRCA,mRCA and Drca,and the QRS voltage and QRS time limit,as well as QTc interval between the two groups were observed and compared.The receiver operating characteristics(ROC)curve was used to analyze the efficacies of the above indicators in single diagnosis and combined diagnosis for the severity of disease condition of CHD patients.Results:The mean PCAT density of pLAD,mLAD,pLCX,pRCA,mRCA,mRCA and dRCA,and QRS time limit and QTc interval of patients in grade Ⅱ-Ⅲ group were significantly lower than those in grade Ⅳ group,with statistically significant difference(t=58.681,5.097,5.902,13.513,P<0.05),respectively.The area under curve(AUC)values of ROC curves of ECG and CT density of the fat around pericoronary artery of CTA were larger than 0.5 for the severity of disease condition in CHD patients,and the highest AUC value of combined diagnosis was 0.966.The results of Pearson linear correlation analysis showed that there were correlations among mean PCAT density,QRS voltage,QRS time limit and QTc interval,and there were significantly negative correlations between QRS voltage and mean PCAT density,between QRS time limit and QTc interval(r=-0.754,-0.280,-0.452,P<0.05),and there were significantly positive correlations among mean PCAT density,QRS time limit,QTc interval and the severity of the disease condition of CHD patients(r=0.983,0.435,0.547,P<0.05),respectively.There was a significantly negative correlation between QRS voltage and severity of disease condition of CHD patients(r=-0.776,P<0.05).Conclusion:The combination of CT density features of the fat around pericoronary artery of coronary artery CTA and ECG QRS wave group detection is helpful to the diagnosis for the severity of disease condition of CHD patients,which can improve the accuracy of diagnosis and has a certain of application value.

Objective:To investigate the changes of mitochondria in the substantia nigra pars reticulata(SNr)in a mouse model of acute hepatic encephalopathy(AHE),and the effects of mitochondrial division inhibitor Mdivi-1 on the motor function and mitochondrial function of SNr in AHE mice.Methods:The mouse model of AHE was established by intraperitoneal injection of thioacetamide(TAA)and treated with Mdivi-1.The changes of serum aspartate aminotrans-ferase(AST),alanine aminotransferase(ALT),and blood ammonia were detected by biochemical detection kits.Open field test,rotor-rod fatigue test and elevated plus maze test were performed to observe the motor function of AHE mice.Mitochondrial membrane potential(MMP),cellular reactive oxygen species(ROS)and ATP of SNr were detected by commercial kits.Results:Compared with the control group,the levels of AST,ALT and blood ammonia in AHE mice were increased.The total movement distance of the mice in the open field was reduced,and the movement time of the rotor-rod fatigue test and the elevated plus maze test were shortened.In SNr,mitochondria became smaller and rounder,mitochondrial fission increased,MMP decreased,cellular ROS increased,and ATP production decreased.After treat-ment with Mdivi-1,the levels of AST,ALT and blood ammonia in AHE mice were decreased.In the open field,the total movement distance of mice increased,the movement time of rotorrod fatigue test and elevated plus maze test increased,the mitochondria of SNr were larger,with decreased roundness,decreased mitochondrial division,increased MMP,decreased cellular ROS,and increased ATP production.Conclusion:Mdivi-1 can improve movement disorders in AHE mice by repairing mitochondrial in the SNr.

Objective To conduct a visual analysis of the current status, hotspots, and frontiers of research on renal cell carcinoma targeted therapy using VOSviewer software. Methods Literature related to renal cell carcinoma targeted therapy published between January 1, 2006 and December 31, 2023, from the Web of Science (WOS) Core Collection database were retrieved. Eligible articles were screened and subjected to bibliometric and visual analysis using VOSviewer software. Results A total of 1, 009 articles were selected, with an overall increasing trend in annual publication volume. The top three countries in terms of publication output were the United States, China, and Italy, while the top three institutions were Harvard University, The University of Texas, and France Uni-cancer Institute. The analysis of the core author collaboration network revealed close collaboration among researchers in the United States and the United Kingdom, whereas collaboration between China and foreign countries was limited, resulting in a relatively loose collaboration network. Through co-occurrence clustering analysis of high-frequency author keywords, nine clusters were generated, with hotspots focusing on targeted and immune combination therapy, efficacy, prognosis, drug resistance, targets, and biomarkers. Conclusion Remarkable progress has been made in renal cell carcinoma targeted therapy research over the past decade; however, drug resistance and adverse reactions to targeted therapies remain challenges in clinical treatment. Research related to targeted drug resistance mechanisms, novel targeted drugs, and effective predictive biomarkers has significantly increased. Grasping the developmental trends in this fieldis crucial, and VOSviewer's visual analysis can offer an intuitive representation of the current status, hotspots, and frontiers, thereby providing researchers with a valuable reference.