Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

OBJECTIVE To investigate the therapeutic effect and mechanism of Qiwei dongqingye powder （QDP） on bronchial asthma in mice. METHODS The mice were divided into blank group （normal saline）， model group （normal saline）， dexamethasone group （2 mg/kg）， and QDP low-， medium-， and high-dose groups （200， 400， 800 mg/kg）， with 14 mice in each group. Except for the blank group， mice in all other groups were given ovalbumin via intraperitoneal injection followed by aerosol inhalation to induce a bronchial asthma model. During the modeling process， mice in each group were administered corresponding drug solutions or normal saline intragastrically/intraperitoneally. After the last medication， the number of cells in the bronchoalveolar lavage fluid （BALF） of the mice was observed and counted； the pathological changes of the bronchus and lung tissue were observed； the levels of malondialdehyde （MDA）， nitric oxide （NO）， total superoxide dismutase （T-SOD）， and glutathione peroxidase （GSH-Px） in the lung tissue of the mice were determined， and the level of interleukin-17 （IL-17） in the BALF and serum was determined. Transcriptomics was employed to predict and validate the mechanism of action of QDP against bronchial asthma. RESULTS Compared with the model group， the total cell count， neutrophil count， lymphocyte count， and macrophage counts in the BALF of the QDP high-dose group were all significantly reduced （ P ＜0.05）； the levels of MDA and NO in the lung tissue， and the levels of IL-17 in the BALF and serum were all decreased significantly （ P ＜0.05）； the levels of T-SOD and GSH-Px were significantly increased （ P ＜0.05）； the arrangement of lung tissue cells tended to normalize， with reduced infiltration of inflammatory cells and decreased exfoliation of bronchial simple columnar epithelial cells. The transcriptomic results revealed that the differentially expressed genes were B-cell receptor signaling pathway， nuclear factor κB （NF-κB） signaling pathway， ferroptosis signaling pathway， and others. Further validation revealed that， compared with the model group， the expression levels of NF-κB p65 and chemokine ligand 20， as well as the phosphorylation level of NF-κB inhibitor protein α， were significantly decreased in the lung tissues of the mice in all QDP groups （ P ＜0.05）. Conversely， the protein expression of nuclear factor erythroid 2-related factor 2 （Nrf2） and heme oxygenase 1 （HO-1） were significantly increased （ P ＜0.05）. CONCLUSIONS QDP can effectively alleviate bronchial asthma by inhibiting the NF-κB signaling pathway， activating the Nrf2/HO-1 signaling pathway， regulating oxidative stress， and reducing inflammatory responses.

Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMP-activated protein kinase(AMPK)activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis(MASH).Rhizoma Atractylodis Mac-rocephalae(RAM)has been clinically used to treat obesity-related health problems,but its therapeutic effects on MAFLD and the underlying mechanism remain unclear.Therefore,this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.Methods:The effect of RAM decoction on MAFLD was evaluated using a high-fat diet(HFD)-induced MAFLD mouse model.In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum.The underlying mechanisms were elucidated through a combination of network pharmacology analysis,immunohis-tochemistry,western blotting,and polymerase chain reaction analysis.Results:Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake.The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment.Additionally,RAM administration decreased serum levels of alanine aminotrans-ferase,aspartate transaminase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,and glucose,while reducing lipid droplet accumulation in the liver tissues of MAFLD mice.The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase(ACC),and inhibition of the expression of sterol regulatory element binding protein 1(SREBP1).However,RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α.Furthermore,the RAM-induced upregulation of phosphorylated AMPK,phos-phorylated ACC,and SREBP1 expression,as well as the downregulation of fatty acid synthase expression,were reversed by using an AMPK inhibitor.Conclusions:Through a combination of network pharmacology and experimental validation,we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.

Objective To investigate the types of diseases examined by ultrasonography in a certain island clinic,and to summarize the experience of ultrasound medical support in island area.Methods The ultrasound examination results of patients who were admitted to a certain island clinic from January 2017 to August 2022 were reviewed,and the types and characteristics of diseases examined by ultrasound were analyzed.Results A total of 2 043 patients underwent ultrasound examination.There were 76 disease categories and 1 579 diseases.The top five diseases were fatty liver(13.24%),kidney crystals(12.10%),kidney stones(10.70%),gallbladder polyps(6.33%)and ureteral stones with hydronephrosis(6.02%).Ultrasound could predict the pathological types of appendicitis and guide the clinical decision by observing the width of the appendiceal lumen and the layers of the appendiceal wall.Doppler-assessed ureteric jet could be used to determine the renal function of the affected side of ureteral calculi.Conclusion There are wide and varied disease categories in islands.Sonographers should have comprehensive abilities and qualities.This study can provide reference for the follow-up medical support on island area.

Objective:To investigate the diagnostic and prognostic value of systemic immune inflammatory index (SII) for severe traumatic brain injury secondary to acute lung injury (sTBI-ALI).Methods:A retrospective study was conducted on patients with severe traumatic brain injury admitted to the trauma center of the First Affiliated Hospital of Soochow University from January 2021 to November 2023. Patients received standard treatments including hemostasis and intracranial pressure management. Vital signs and blood routine data were collected upon admission. Patients were categorized into sTBI group and sTBI-ALI group based on established clinical diagnostic criteria for ALI to evaluate the diagnostic utility of SII. Subsequently, within the sTBI-ALI group, patients were stratified into survival and non-survival groups based on their 30-day outcomes to assess the prognostic value of SII.Results:A total of 260 sTBI patients were enrolled, of whom 113 developed ALI. Among the sTBI-ALI patients, 73 survived at 30 days. Compared to the sTBI group, the sTBI-ALI group exhibited significantly higher respiratory rates, heart rates, white blood cell counts, neutrophil counts, platelet counts, and SII levels (all P<0.05). Multivariate logistic regression analysis showed that SII index ( OR=1.003, 95% CI: 1.002-1.004, P<0.001) was an independent risk factor for ALI development in sTBI patients. The combined predictive model incorporating SII and heart rate yielded an AUC of 0.801 (95% CI: 0.740-0.862). The non-survival group had significantly higher neutrophil counts and SII levels, and significantly lower Glasgow Coma Scale scores than the survival group (all P<0.05). Multifactorial regression analysis indicated that SII index ( OR=1.002, P=0.004, 95% CI: 1.000-1.003) served as an independent risk factor for 30-day mortality in sTBI-ALI patients. The combined predictive model of SII and GCS achieved an AUC of 0.904 (95% CI: 0.848-0.960). Conclusions:SII demonstrates potential as a biomarker for predicting the development of ALI following sTBI. Furthermore, incorporating SII into predictive models significantly enhances the ability to forecast mortality risk in sTBI-ALI patients.

Objective:To assess the impact of elderly medical and nursing services pilots on the health of the elderly and its differentiated effects.Methods:Using five-period unbalanced panel data from China Longitudinal Aging Social Survey conducted between 2014 and 2023,the study employed a PSM-DID method to analyze changes in the health status of the elderly before and after the reform.Results:The pilots significantly improved the health status of the elderly,with the policy's effects most notably enhancing their psychological health.The elderly groups at a disadvantage in terms of resources,such as those with advanced age,low educational levels,or living apart from their children,can obtain greater mental health benefits from the pilots.The long-term care insurance and elderly medical care services pilots formed a policy synergy,but the implementation of multiple overlapping policies may attenuate the pilot's effects.Conclusions:The pilots have yielded initial results,but there is still considerable room for improvement.It is recommended to actively promote the integration of regional medical and nursing resources,precisely meet the needs of disadvantaged the elderly groups,and strengthen interdepartmental collaboration and information sharing.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.