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.

Randomized clinical trials are important in both clinical and academic stroke communities with increasing numbers of new design concepts emerging. One of the “less traditional” designs that have gained increasing interest in the last decade is non-inferiority trials. Whilst the concept might appear straightforward, the design and interpretation of non-inferiority trials can be challenging. In this review, we will use exemplars from clinical trials in the stroke field to provide an overview of the advantages and limitations of non-inferiority trials and how they should be interpreted in stroke research.

Objective To observe the application effect of bedside contrast-enhanced ultrasound combined with gas-water alternating injection method in severe patients with nasointestinal catheterization.Methods A total of 150 severe patients who were admitted to intensive care unit(ICU)and emergency intensive care unit(EICU)and required nasointestinal catheterization were collected.Patients were separated into the blind insertion method group(catheterization without other auxiliary equipment,n=50),the ultrasound method group(ultrasound-guided catheterization,n=53),and the combined method group(bedside contrast-enhanced ultrasound combined with gas-water alternating injection method,n=47)according to the wishes of patients or their families.The catheterization success rate,feeding standard-reaching rate within one week,catheterization time and incidence of adverse events were compared between three groups.Kappa test was used to compare the consistency of three methods with X-ray examination results after catheterization.Receiver operating characteristic(ROC)curve was used to evaluate the catheterization effect.Results The catheterization success rate and the feeding standard-reaching rate within one week were increased successively in the blind insertion method group,the ultrasound method group and the combined method group,and the catheterization time shortened in turn(P＜0.05).The consistency of blind insertion method,ultrasound method,combined method with X-ray examination was strong(Kappa=0.730),very strong(Kappa=0.835)and very strong(Kappa=0.911),respectively.Results of ROC curve showed that the areas under the ROC curve of the blind insertion method group,the ultrasound method group and the combined method group increased in turn,which were 0.838(95%CI:0.661-1.000),0.918(95%CI:0.763-1.000)and 0.988(95%CI:0.959-1.000),and the combined method group had the best catheterization effect.There were no significant differences in the incidence of adverse events such as hiccup,abdominal distension,diarrhea,aspiration and gastrointestinal bleeding between the three groups(P>0.05).Conclusion Bedside contrast-enhanced ultrasound combined with gas-water alternating injection method can improve the success rate of nasointestinal catheterization in severe patients,shorten the catheterization time and without increasing the incidence of adverse events.

Objective To explore the frequency domain characteristics of pedestrian head dynamic response in vehicle collisions and investigate the correlation between frequency domain parameters and time domain injury criteria.Methods Finite element modelling based on human body model was used to simulate the process of pedestrian head-vehicle impacts,and the wavelet packet signal analysis method was employed to obtain the frequency domain response of pedestrian head in the simulations.Results The head energy under impacts at the bonnet area was mainly dispersed in the 0-300 Hz frequency band,while the head energy under impacts at the windshield area was mainly concentrated in the 0-5 Hz frequency band.The peak energy of frequency band for pedestrian head generally increased with the increase of linear and rotational speed,and the influence of rotational speed on the peak energy of frequency band was more significant when the linear speed was higher.The linear correlation R2 between the peak energy of the head frequency band caused by the collision between the bonnet and windshield area and the time-domain criterion for skull injury were 0.85 and 0.61,respectively.But their correlation with the time-domain indicators for brain injury evaluation was relatively low(R2＜0.5).Conclusions The frequency domain response characteristics of pedestrian heads are affected by collision speed and location.The peak energy of the frequency band can potentially characterize the risk of skull injury,but the frequency band and concentration of the peak energy in the frequency band are not related to the risk of head injury.This study can provide references for the evaluation of head blunt injury combined with time-frequency response.

Objective:To investigate the radon exposure levels and health effects among non-uranium miners in Chongqing.Methods:From June 2022 to December 2023, a survey was carried out on basic information, radon exposure and occupational health status of 110 male miners with good cooperation attitudes in 6 non-uranium metal mines in normal operation in Chongqing. The logistic regression model was utilized to statistically analyze the impact of miners′ individual radon doses on abnormalities in chromosomal aberration analysis, micronucleus examination, tumor marker tests, and pulmonary CT imaging.Results:Monitoring results from passive integrated radon personal dosimeters indicated that three miners had an annual dose exceeding 2 mSv. Logistic regression analysis revealed that abnormalities in pulmonary CT imaging were associated with miners′ age, tenure, and alcohol consumption ( χ2=12.18, 9.63, 4.87, P<0.05), with no significant correlation with smoking or individual radon dose. There was a significant correlation between individual radon dose and abnormalities in tumor markers; for every additional 1 mSv of effective dose from radon and its progeny, the risk of abnormality increased by 2.25 times ( χ2=4.57, P < 0.05). Conclusions:Some miners in Chongqing are exposed to an annual dose exceeding 2 mSv, and there is a correlation between individual radon doses and abnormalities in lung cancer serum tumor markers. It is necessary to focus on monitoring the radon exposure risks for miners, carry out regular health checks, and enhance the health protection for the miner population.

This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.

Aim To investigate the effects of Ixerin Z,a sesquiterpene lactone from Ixeris sonchifolia,on bone-lipid metabolic imbalance in ApoE-/-mice and to elu-cidate its molecular mechanisms.Methods A mouse model of ApoE-/-was induced using a high-fat diet,followed by eight weeks of Ixerin Z administration at doses of 1 and 10 mg·kg-1.Serum markers related to bone-lipid metabolism and inflammatory cytokines were quantified.Bone mineral density,biomechanical prop-erties,bone tissue morphology,and bone microstructure changes were analyzed.Computational molecular doc-king was performed to identify potential target proteins of Ixerin Z,and its regulatory effects on bone-lipid me-tabolism were investigated.Results Treatment with Ixerin Z markedly decreased the serum levels of total cholesterol,triglycerides,TNF-α,and IL-1β in ApoE-/-mice.It significantly improved bone mineral density,enhanced biomechanical strength,restored tra-becular structure,and reduced fat accumulation in bone tissue.Investigations revealed that Ixerin Z activated PPARα,thereby promoting fatty acid β-oxidation in bone tissue,and stimulating the Wnt/β-Catenin signa-ling pathway to facilitate bone formation.Furthermore,Ixerin Z suppressed the OPG/RANKL/NF-κB signaling pathway,leading to reduced bone resorption,independ-ent of PPARα activation.Conclusions Ixerin Z dem-onstrates potent therapeutic effects on bone-lipid meta-bolic imbalance in ApoE-/-mice.The mechanism in-volves activating PPARα to promote fatty acid β-oxida-tion in bone tissue,activating PPARα/Wnt/β-Catenin signaling pathway to promote bone formation,and in-hibiting OPG/RANKL/NF-κB signaling pathway to re-duce bone resorption.

Objective To explore the short-term and long-term efficacy of partial splenic artery embolization(PSE)in the treat-ment of cirrhosis with hypersplenism.Methods A retrospective analysis was conducted on 35 patients with cirrhosis and hyper-splenism who underwent PSE treatment.Data on white blood cell(WBC),red blood cell(RBC),platelet count(PLT),hemoglobin(HGB),total bilirubin(TBiL),albumin(ALB),prothrombin time(PT),and D-dimer were collected at the three time points:before surgery,1 week after surgery,and 1 year after surgery.The changes in these parameters across the three time points were observed and compared.One-way ANOVA was used for repeated measurements,and time pairwise comparisons were made between the three time points.According to the formation of portal thrombosis,patients were divided into thrombus group and no-thrombus group.The D-dimer values were compared before surgery and 1 week after surgery.Results WBC and PLT were significantly higher 1 week and 1 year after surgery than those before surgery,with the most significant increase 1 week after surgery,and there was also statistically sig-nificant difference between 1 week after surgery and 1 year after surgery(P1,P2,P3<0.05).There were no significant differences in RBC and HGB between 1 week after surgery and before surgery(RBC P1=0.835,HGB P1=0.446).However,RBC and HGB 1 year after surgery were significantly higher than those before surgery and 1 week after surgery(RBC P2=0.039,P3=0.015;HGB P2=0.001,P3=0.010).There were significant differences in TBiL,ALB,PT,and D-dimer 1 week after surgery compared with those before surgery(TBiL P1=0.006,ALB P1<0.001,PT P1=0.001,D-dimer P1<0.001),but there was no significant differ-ence between 1 year after surgery and before surgery(all P2>0.05).The D-dimer of the thrombus group was significantly higher than that of the no-thrombus group 1 week after surgery,with a statistical significance(P=0.024),however,there was no signifi-cant difference in D-dimer between the two groups before surgery.Conclusion PSE in the treatment of cirrhosis with hypersplenism shows positive short-term and long-term efficacy for WBC and PLT.The short-term increase of RBC and HGB is not obvious,however the long-term efficacy is significant.In the short-term after surgery,TBiL increase,ALB decrease,PT prolonge,and liver reserve function decrease,but there was no long-term effect.The increase of D-dimer after surgery can easily induce portal thrombosis,and anticoagulation therapy can be given in the short-term after surgery.

Objective To investigate the role of long non coding RNA(lncRNA)Gm14461 in promoting trigeminal neuralgia(TN)and its potential molecular mechanisms.Methods A TN mouse model was induced by surgery for chronic compression injury of the infraorbital nerve.Short hairpin RNA(shRNA)of Gm14461 was injected into TN mice,and the expression level of Gm14461 and mechanical pain threshold(MWT)in the trigeminal ganglia of the mice were measured.A TN cell model was established in vitro using tumor necrosis factor-α(TNF-α)to induce trigeminal ganglia,and the trigeminal ganglia were treated with sh-Gm14461 and cleavage stimulation factor subunit 2(CSTF2)overexpression vector(OE-CSTF2).RNA immunoprecipitation(RIP)analysis of CSTF2 binding to Gm14461,calcitonin gene-related peptide(CGRP),purine receptors P2X3 and P2X7 mRNA.Results Compared with the sham surgery group,the expression of Gm14461 in the trigeminal ganglia of TN group mice was significantly increased(t=35.450),and the MWT value of mice decreased in a time-dependent manner(t=8.427～28.190),with statistical significance(all P<0.05).The expression levels of inflammatory factors TNF-α,IL-1 β and IL-6,as well as pain related proteins CGRP,P2X3,and P2X7,were significantly increased in the trigeminal ganglia of TN mice,and the differences were statistically significant(t=31.750～50.240,all P<0.05).Knocking down Gm14461 significantly improved MWT(t=6.019～26.548),reduced inflammatory factors(t=43.959,26.416,25.431),and pain related protein levels(t=38.709,43.257,45.807)in TN mice,with statistically significant differences(all P<0.05).Compared with the control group,TNF-α induced upregulation of Gm14461 expression in the trigeminal ganglia(t=27.710),significantly increased levels of inflammatory factors and pain related protein expression(t=23.076～29.508),and the differences were statistically significant(all P<0.05).After knocking down Gm14461,the expression of Gm14461 was significantly reduced(t=3.641),and the levels of inflammatory factors and pain related proteins in the trigeminal ganglia induced by TNF-α were significantly reduced(t=20.560～25.136),with statistical significance(all P<0.05).Gm14461 upregulates CSTF2 protein levels by binding to CSTF2,and upregulates CSTF2 protein by binding to mRNA of CGRP,P2X3,and P2X7 and promoting their expression.Overexpression of CSTF2 can reverse the inhibitory effect of Gm14461 knockdown on TNF-α-induced inflammation and pain related protein expression in trigeminal ganglia(TGs)(t=18.870～24.399,all P<0.05).Conclusion Gm14461 upregulates the expression of CGRP,P2X3,and P2X7 by recruiting CSTF2,promotes inflammatory response,thereby reducing the mechanical pain threshold of TN mice and promoting pain.