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.

Functional constipation （FC） is a clinically common functional bowel disorder characterized by a protracted course and associations with various chronic disorders and psychological abnormalities. Although not life-threatening， FC significantly impairs patients' quality of life. FC subtypes include slow-transit constipation （STC）， defecatory disorder （DD）， and normal-transit constipation （NTC）. The pathological mechanisms underlying FC have not been fully elucidated， and overall clinical efficacy remains unsatisfactory. Animal models of FC serve as essential tools for the study of disease mechanisms and the development of novel therapeutics. This article systematically reviews the current state of research on the animal models of FC and identifies that rodents， particularly rats and mice， are the most commonly used species. Dogs and pigs are also employed in complex intervention studies due to their physiological similarities to humans， though their use is limited by housing challenges and ethical considerations. Induction methods vary across different FC subtypes. STC models are primarily established with chemical agents such as loperamide or compound diphenoxylate. DD modeling often involves low-fiber diets combined with methylene blue injection or rectal narrowing. NTC modeling mainly relies on low-fiber dietary interventions. In addition， disease-syndrome combination models based on traditional Chinese medicine （TCM） theory have been developed， encompassing excess patterns such as heat accumulation， cold accumulation， and Qi stagnation， as well as deficiency patterns including Qi deficiency， blood deficiency， Yin deficiency， and Yang deficiency. These are achieved through an approach of disease model + syndrome induction， enabling the integration of mechanisms from both Western and TCM perspectives. Models are evaluated from two aspects： disease and syndrome manifestations （e.g.， colonic transit， secretory function， and TCM syndrome indicators such as mental state and body weight） and disease mechanisms （e.g.， enteric nervous system， interstitial cells of Cajal， smooth muscle cells， gut microbiota， and metabolites）. However， current research still faces challenges such as poor consistency in some models， non-specific interference in mechanism interpretation， insufficient studies on NTC， and lack of TCM tongue and pulse diagnosis in evaluation. Future efforts should focus on optimizing model stability and specificity to provide a more reliable experimental basis for investigating the pathological mechanisms of FC and developing therapeutic agents.

Objective: To explore the association between problematic short video use (PSVU) and executive function among students in grades 3 to 6 of primary school, so as to provide references for intervening in primary school students PSVU. Methods: In September 2024 (T1), using a convenience sampling method, 520 students in grades 3 to 6 from a primary school in Xi an City of Shaanxi Province were selected as research subjects. They were followed up at three time points: T1, T2 (January 2025), and T3 (May 2025) using an adapted version of the Internet Addiction Test and Questionnaire of Executive Functioning of Chinese. Pearson correlation and cross lagged model were used to analyze the correlation between PSVU and executive function among primary school students at each time point. Results: The mean PSVU scores of primary school students at T1-T3 were (35.51±12.46, 34.86± 12.64 , 35.16±13.37) respectively, and the mean executive function scores were (68.31±12.95, 64.92±12.99, 66.58±14.13) respectively. Correlation analysis results indicated that PSVU scores and executive function scores were positively correlated in all three measurements ( r =0.26~0.62, all P <0.01). Cross lagged analysis results showed that executive function scores at T1 could positively predict PSVU scores at T2 ( β =0.21), and executive function scores at T2 could positively predict PSVU scores at T3 ( β = 0.20) (both P <0.01). Conclusion The level of executive function in students from grades 3 to 6 of primary school can unidirectionally predict the severity of their PSVU.

OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） as first-line therapy for advanced gastric cancer. METHODS PubMed， Web of Science， Embase， The Cochrane Library， Wanfang Data， CNKI， and VIP databases were searched to collect phase Ⅲ clinical randomized controlled trials （RCTs） on ICIs as first-line therapy for advanced gastric cancer， as well as abstracts from relevant oncology academic conferences. The search period spanned from database inception to June 1， 2025. After screening literature， extracting data， and assessing quality， a network meta-analysis was performed using R software version 4.3.2. RESULTS A total of 8 studies involving 7 801 patients were included. Network meta-analysis results showed that， in terms of efficacy， compared with chemotherapy （Chemo）， SHR-1701_Chemo， Cadonilimab_Chemo， Sintilimab_Chemo， Pembrolizumab_Chemo， and Tislelizumab_Chemo significantly prolonged median overall survival （OS） and median progression free survival （PFS） in patients （P＜0.05）； whereas Nivolumab_Chemo only significantly improved median PFS （P＜0.05）. Surface under the cumulative ranking curve （SUCRA） results indicated that the top 2 interventions for median OS were SHR-1701_Chemo and Cadonilimab_Chemo； for PFS， the top 2 were Cadonilimab_Chemo and SHR-1701_Chemo. For patients with combined positive score （CPS） ≥5 points for programmed death-ligand 1 （PD-L1）， Cadonilimab_Chemo and SHR- 1701_Chemo also demonstrated the optimal OS and PFS benefits （P＜0.05）. Regarding safety， there were no statistically significant differences among the interventions in the incidence of any adverse events （AEs） or grade ≥3 AEs （P＞0.05）. The SUCRA ranking for the incidence of any AEs showed the top 2 were SHR-1701_Chemo and Chemo； for grade ≥3 AEs， the top 2 were Chemo and Sugemalimab_Chemo. CONCLUSIONS For patients with advanced gastric cancer， Cadonilimab_Chemo and SHR-1701_Chemo demonstrate the best benefits in terms of OS and PFS， with their advantages remaining clear in patients with PD-L1 CPS≥5 points. In terms of safety， the risk of developing any AEs and grade ≥3 AEs is relatively lowest with Chemo.

Objective To study the five-year survival status and influencing factors of elderly patients with lung cancer complicated with chronic obstructive pulmonary disease (COPD). Methods A cohort study was conducted to follow up 450 patients with lung cancer and chronic obstructive pulmonary disease who were hospitalized in our hospital from January 2018 to December 2023. The endpoint of the follow-up was the end of a five-year period or death. The Life Tables method was used to calculate survival rates and plot survival curves. The Cox proportional hazards model was used to analyze the influencing factors of five-year survival. Results The results indicated that the overall five-year survival rate of patients was 4.89%, and it decreased year by year. Cox regression analysis showed that age, gender, family functioning, and psychological status significantly influenced patient survival rate (all P<0.05). Stratified analysis found that the smoking status, family functioning, and psychological status of male patients all had an impact on survival rate (all P<0.05), while the psychological status of female patients had a more significant impact on survival (P=0.008). Conclusion This study provides a scientific basis for comprehensive intervention of elderly lung cancer patients with COPD. It is recommended that clinical attention should be paid to psychological and family factors to improve patient prognosis.

ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

Objective To investigate the scientific outputs of metagenomic next-generation sequencing (mNGS) for diagnosis of infection of unknown origin in intensive care units (ICUs), and to decipher the latest advances, frontier trends and spatiotemporal evolution of research hotpots in mNGS for diagnosis of infection of unknown origin in ICUs. Methods Publications pertaining to the application of mNGS in diagnosis of infection of unknown origin in ICUs were retrieved from Web of Science Core Collection (WOSCC) from January 1, 2015 to December 31, 2024. The software Scimago Graphica 1.0.30 was employed to generate the network maps of collaboration relationships between countries, international collaborative relationships, author collaborations, institutional collaborative relationships, and a heatmap of journals, and the software VOSviewer 1.6.18 was used to create a heatmap of keywords, and maps of keyword co-occurrence clustering and keyword clustering timelines. In addition, the keyword burst map was created using the software CiteSpace 6.3.R3. Results A total of 1 707 publications were included in the final analysis, and the number of publications appeared an overall tendency towards a rise from 2015 to 2024, with the largest number of publications seen in 2024 (545 publications). The largest number of publications was recorded in China (1 390 publications), followed by in USA (190 publications) and United Kingdom (31 publications), and China led the global research in this field, with 81% of global related researches linked with China. Frontiers in Cellular and Infection and Microbiology published the largest number of articles (212 publications, 12.42%), and Joseph Derisi was the most productive author (33 publications). Author collaborations occurred within groups; however, there was a lack of close inter-group collaborations, with University of California, San Francisco and Chan Zuckerberg Biohub-based group seen as the largest collaborative group. High-frequency co-occurrence keywords included mNGS, infection, diagnosis, case report, community-acquired pneumonia and bronchoalveolar lavage fluid, and the 100 most common high-frequency co-occurrence keywords were assigned into four clusters. Keyword clustering timeline analysis revealed that the research hotspots in this field shifted from virus sequencing and sequence alignment to severe pulmonary infections, and keyword burst analysis showed identification, mNGS and virus as top three keywords with the highest burst intensity. Conclusions mNGS was mainly used for identification of viruses among patients with infections of unknown origins in ICUs from 2015 to 2024, and future research priority shifted to pathogen detection for severe pulmonary infections.

[Objective]To investigate the intervention effect of eriocitrin on intracranial aneurysm(IA)model rats based on stromal cell derived factor-1α(SDF-1α)/C-X-C motif chemokine receptor 4(CXCR4)signaling pathway.[Methods]IA rat model was established by isolating and ligating the left common carotid artery and renal artery,and removing both ovaries.The rats were randomly assigned into IA group(intragastric and intraperitoneal administration of 0.9%sodium chloride solution),eriocitrin low(intragastric 8 mg·kg-1 of eriocitrin),medium(intragastric 16 mg·kg-1 of eriocitrin)and high(intragastric 32 mg·kg-1 of eriocitrin)dose groups,and eriocitrin high dose(intragastric 32 mg·kg-1)+SDF-1α/CXCR4 pathway activator CTCE-0214(intraperitoneal administration of 10 mg·kg-1 CTCE-0214)group,and the other 10 rats only exposed the left common carotid artery,renal artery and ovaries,which were recorded as sham operation(intragastric and intraperitoneal administration of 0.9%sodium chloride solution)group.Each group was intervened once a day for 8 consecutive weeks.Tweenty-four hours after the last administration,enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and nitric oxide(NO)in each group.Elastica van Gieson staining was used to measure the length of aneurysms,the area of the aneurysm lumen and the length of internal elastic layer rupture.Hematoxylin-eosin(HE)staining was applied to detect pathological changes in arterial aneurysm tissue.Real time-polymerase chain reaction(RT-PCR)was applied to detect the mRNA expression of matrix metalloproteinase-9(MMP-9),vascular endothelial growth factor(VEGF)and MMP-2 in tissues.Western blot was applied to detect the expression of SDF-1α/CXCR4 related proteins in tissues.[Results]Compared with sham operation group,the levels of TNF-α,IL-6;aneurysm length,aneurysm cavity area,internal elastic layer rupture length;MMP-9,VEGF,MMP-2 mRNA expression;SDF-1α and CXCR4 protein expression were prominently higher in IA group,while the level of NO was obviously lower(P<0.05).Compared with IA group,the levels of TNF-α,IL-6;aneurysm length,aneurysm cavity area,internal elastic layer rupture length;MMP-9,VEGF,MMP-2 mRNA expression;SDF-1α and CXCR4 protein expression in eriocitrin low,medium and high dose groups were obviously lower,while the level of NO was prominently higher(P<0.05).Compared with eriocitrin high dose group,the levels of TNF-α,IL-6;aneurysm length,aneurysm cavity area,internal elastic layer rupture length;MMP-9,VEGF,MMP-2 mRNA expression;SDF-1α and CXCR4 protein expression in eriocitrin-high+CTCE-0214 group were prominently higher,while the level of NO was prominently lower(P<0.05).[Conclusion]Eriocitrin alleviates the inflammatory response in IA rats by regulating the SDF-1α/CXCR4 signaling pathway,improves the function of vascular endothelial cells and reduces the risk of aneurysm rupture.