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.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

Objective To investigate the predictive value of cerebroplacental ratio(CPR),cerebro-uterine ratio(CUR)combined with cystatin C(CysC)for adverse pregnancy outcomes in preeclampsia(PE)fetuses.Methods A retrospective analysis was conducted on the clinical data of 150 PE patients admitted to the department of obstetrics and gynecology of Nuclear Industry 416 Hospital from January 2019 to December 2024,and patients were divided into the adverse-outcome group and the favorable-outcome group according to pregnancy outcomes.The clinical data,CPR,CUR and CysC level were compared between the two groups.Multivariate Logistic regression was used to analyze the independent influencing factors of adverse pregnancy outcome in PE patients;then,receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive efficiency of each index on adverse pregnancy outcome.Results The adverse-outcome group had shorter/lower gestational age at diagnosis,estimated fetal body weight,CUR,and CPR,but higher body mass index and CysC level compared to those in the favorable-outcome group,with significant differences(P<0.05).Multivariate Logistic regression identified that the elevated CysC level,and decreased CUR and CPR were related influencing factors for adverse pregnancy outcome(P<0.05).ROC curve analysis demonstrated that CUR,CPR and CysC had strong predictive value for adverse pregnancy outcome,with the area under the curve(AUC)of 0.802(95%CI:0.729 to 0.863),0.834(95%CI:0.764 to 0.890),and 0.791(95%CI:0.717 to 0.853),respectively;the combined prediction of CUR,CPR and CysC had grater AUC of 0.909(95%CI:0.851 to 0.950)than the individual prediction of the above three indicators(P<0.05).Conclusion CUR,CPR and CysC are influencing factors of adverse pregnancy outcome in PE patients,and their combined detection demonstrates good predictive value for adverse pregnancy outcome in PE patients.

Objective:To investigate the clinicopathological features and differential diagnosis of male genital system lympho-ma(MGSL).Methods:We retrospectively analyzed the clinicopathological and immunophenotypic features and prognosis of 80 ca-ses of MGSL.Results:The onset age of the MGSL patients ranged from 4 to 85(median 62)years old.All the cases showed non-specificity of the imaging features and clinical manifestations.MGSL was located mainly in the testis(n=66),followed by the pros-tate(n=7),epididymis(n=3),scrotum(n=3)and penile glans(n=1).Diffused large B cell lymphoma(DLBCL)was the most common pathological type(n=62),next came extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue(MALT)(n=7)and other rare types(n=12).During the 1-112-month follow-up of 10 of the 19 patients,1 died at 1 month af-ter diagnosed with prostatic B-lymphoblastic lymphoma(B-LBL)and another 1 died at 50 months after diagnosed with testicular DLBCL.Conclusion:MGSL is rare clinically,mainly of the DLBCL type pathologically,lacking specificity in clinical symptoms and imaging manifestation.The definite diagnosis of the malignancy depends on histopathology combined with related molecular exami-nation and immunohistochemical labeling,and R-CHOP chemotherapy is the first choice for its treatment.

Objective:To investigate the characteristics of the endometrial microbiota in patients with varying degrees of intrauterine adhesion (IUA).Methods:This single-center cross-sectional observational study enrolled 115 patients with IUA who were treated at the Hysteroscopic Center of Fuxing Hospital, Capital Medical University, from May 2022 to October 2023. After quality control and data preprocessing, 81 samples met the inclusion criteria for analysis. Patients were grouped according to an established IUA scoring and grading system into mild IUA ( n=38) and moderate-to-severe IUA ( n=43). Endometrial tissue was collected under sterile conditions. Bacterial genomic DNA was extracted, the 16S rRNA V3-V4 region was amplified, and sequencing was performed on an Illumina platform. Differences in endometrial microbiota diversity and composition were compared between the two groups. Results:Patients with varying degrees of IUA exhibited comparable species richness, evenness and diversity of endometrial microbiota. At the phylum level, the endometrial microbiota across all subjects was predominantly composed of Proteobacteria, Firmicutes, Cyanobacteriota, Bacteroidota, and Actinobacteriota, with Proteobacteria (32.29%) and Firmicutes (23.82%) showing the highest mean relative abundances. At the genus level, Ralstonia (16.67%), Lactobacillus (13.45%), and Streptococcus (7.07%) were the most abundant genera. Group comparisons showed that the abundance of Ralstonia was higher in the mild IUA group, whereas Lactobacillus, Vibrio and Pseudoalteromonas were more abundant in the moderate-to-severe IUA group; however, these differences did not reach statistical significance (all P>0.05). LEfSe analysis further indicated that Lactobacillus, Vibrio, Pseudoalteromonas, Aeromonas, Ureaplasma and Acetobacterium were relatively enriched in the moderate-to-severe IUA group, while Geobacillus, Stomatobaculum and Fusicatenibacter were more abundant in the mild IUA group. Conclusion:The composition of the endometrial microbiota differs among patients with varying IUA severity. IUA progression may be associated with alterations in the endometrial microbiota; however, causal relationships and underlying mechanisms require further investigation.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

BACKGROUND:H uman pluripotent stem cell-derived cardiomyocytes offer an ideal cellular resource for studying heart diseases,conducting drug screening,developing in vitro heart models,and exploring potential cell therapies.However,human pluripotent stem cell-derived cardiomyocytes are characterized by immaturity with limited specific gene expression,low Ca2+processing levels,and underdeveloped structural,metabolic,and electrophysiological features.These limitations significantly impede the application of human pluripotent stem cell-derived cardiomyocytes.OBJECTIVE:To review the academic progress and clinical application of promoting the maturation of human pluripotent stem cell-derived cardiomyocytes by in vitro synthetic microenvironment.METHODS:CNKI,WanFang,VIP,PubMed,Web of Science,and Medline databases were searched,with"human pluripotent stem cells,human myocardial cells,hPSC-CMs,mature,OA,human pluripotent stem cell-derived cardiomyocytes,hPSC-CMs"as English search terms and"human pluripotent stem cells,cardiomyocytes,mature,OA,hPSC-CMs"as Chinese search terms.All relevant literature published from January 2002 to July 2024 was retrieved and 82 articles were included in the review.RESULTS AND CONCLUSION:(1)In recent years,in vitro synthetic microenvironments have attracted extensive attention due to their excellent intrinsic properties such as stiffness,plasticity,nanoscale morphology,and chemical functionality.(2)Human pluripotent stem cell-derived cardiomyocytes can be used as an effective platform for the treatment of cardiovascular diseases.(3)Mechanical stimulation,electrical stimulation,addition of biochemical molecules,and three-dimensional culture methods are effective methods to promote the maturation of human pluripotent stem cell-derived cardiomyocytes,which can further promote the clinical application of human pluripotent stem cell-derived cardiomyocytes.