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 construct a preoperative medication reconciliation model assisted by a localized large language model （LLM） for gastric cancer and evaluate its clinical efficacy. METHODS A total of 249 gastric cancer patients with a history of continuous medication before admission in the Gastric Surgery Department of Jiangsu Cancer Hospital were retrospectively enrolled. Patients were divided into training set （154 cases） and validation set （95 cases） based on the order of time. Based on guidelines， drug package inserts， and other evidence， a standardized medication reconcili ation process and a structured knowledge base were constructed. DeepSeek-V3 LLM was deployed privately in the hospital， combined with retrieval-augmented generation technology， to achieve automated integration of medication information， risk screening， and generation of personalized recommendations. The quality of LLM-generated recommendations was evaluated using automatic metrics （BERT Score and ROUGE-1， 2， L） and manual scoring [seven-dimensional index （7DI） ] . Spearman correlation analysis was performed to explore the correlation between automatic scores and manual scores. Cronbach’s α coefficient was used to test the internal consistency of manual scoring results. The time consumed by manual and LLM-assisted medication reconciliation was compared across tasks of different difficulty levels （simple， moderate， and high）. RESULTS A structured knowledge base covering 8 major drug categories was finally established， covering common and high-risk preoperative medication scenarios and providing structured retrieval support for the LLM. For automatic evaluation， the precision， recall， and F1-score of BERT Score were 0.783±0.033， 0.811±0.038， and 0.796±0.028， respectively. The F1-scores of ROUGE-1， ROUGE-2 and ROUGE-L were 0.566±0.067， 0.338±0.076 and 0.468±0.082， respectively. The 7DI scores from three manual raters ranged from 32.06 to 33.45. The F1-score of automatic scoring was significantly positively correlated with the 7DI score of manual scoring （maximum coefficient of determination＝0.611， P ＜0.001）， and the internal consistency of manual scoring was good （Cronbach’s α ＝ 0.876）. In terms of efficiency， LLM-assisted medication reconciliation reduced time consumption by more than 90% compared with manual reconciliation in the simple， moderate， and high-difficulty groups （ P ＜0.001）. CONCLUSIONS The medication reconciliation model constructed based on a localized LLM and structured knowledge base shows high accuracy， consistency， and clinical applicability in complex preoperative medication scenarios for gastric cancer. It can improve the efficiency of medication reconciliation and reduce potential medication risks.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

ObjectiveProtein-protein interactions (PPIs) are fundamental to the execution of biological functions within living cells. However, traditional biochemical methods, such as co-immunoprecipitation (Co-IP), often fail to capture transient, weak, or membrane-associated interactions due to the stringent detergent requirements for cell lysis. Proximity labeling (PL) has emerged in recent years as a transformative technology for mapping the proteomes of specific subcellular compartments and identifying dynamic interactomes in situ. Golgi protein 73 (GP73, also known as GOLPH2), a resident type II Golgi transmembrane protein, is a well-recognized clinical biomarker for liver diseases, including hepatocellular carcinoma (HCC). Despite its clinical significance, the comprehensive physiological and pathological functions of GP73 remain partially understood. This study aims to establish an APEX2-mediated proximity labeling system specifically targeting GP73 to map its interactome in a living cellular environment, thereby providing new insights into its molecular roles and regulatory mechanisms. MethodsTo achieve spatial specificity, we first constructed a stable cell line expressing a fusion protein consisting of GP73 and the engineered soybean peroxidase APEX2. The localization of the GP73-APEX2 fusion protein was validated to ensure it correctly targeted the Golgi apparatus. The proximity labeling reaction was initiated by incubating the cells with biotin-phenol (BP) for 30 min, followed by a brief (1 min) treatment with1 mmol/L hydrogen peroxide (H₂O₂). This catalytic reaction converts BP into highly reactive, short-lived biotin-phenoxyl radicals that covalently attach to endogenous proteins within a small labeling radius of the GP73-APEX2 enzyme. Subsequently, the cells were quenched, and biotinylated proteins were enriched using high-affinity streptavidin-coated magnetic beads. The captured “neighbor” proteins were subjected to on-bead digestion and analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) for high-throughput identification. Rigorous bioinformatics analysis, including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction network mapping, was performed to interpret the biological significance of the identified candidates. ResultsOur results demonstrate the successful establishment of a robust and sensitive APEX2-based proximity labeling system for GP73. We identified a total of 95 high-confidence interacting proteins that were significantly enriched in the GP73 proximity proteome compared to control groups. Bioinformatics analysis revealed that these interactors were predominantly associated with biological processes such as vesicular transport, protein localization, and, most notably, molecular functions related to “ribosome binding” and “translation regulation”. This suggested an unexpected role for the Golgi-resident GP73 in the cellular translation machinery. To validate these findings, we performed targeted biochemical assays which confirmed a direct interaction between GP73 and the subunits of the eukaryotic translation initiation factor 3 (eIF3) complex, specifically EIF3G and EIF3I. Furthermore, functional validation using the surface sensing of translation (SUnSET) assay—a non-radioactive method to monitor protein synthesis—revealed that the overexpression of GP73 significantly promoted global protein translation levels in the cell, whereas its depletion or inhibition resulted in reduced translation efficiency. ConclusionThis study successfully utilized APEX2-mediated proximity labeling to provide the first systematic map of GP73 interactome in living cells. Our findings uncover a novel, unconventional function of GP73 as a regulator of cellular protein translation, likely mediated through its interaction with the eIF3 complex. This discovery significantly broadens our understanding of the biological roles of GP73 beyond its traditional function in the Golgi apparatus and suggests that it may act as a bridge between Golgi-related trafficking and the protein synthesis machinery. Furthermore, the technical framework established in this study provides a valuable template for investigating other complex organelle-associated protein networks and resolving transient macromolecular interactions in various physiological and pathological contexts.

ObjectiveBy comparing the composition and content of volatile components in raw products， wine-washed products and wine-fried products of Ligusticum sinense cv. Chaxiong rhizome（LSCR）， to investigate the influence of wine processing on the volatile components of LSCR， in order to provide a basis for the development of quality standards for LSCR and its processed products. MethodsElectronic nose was used to identify the odors of LSCR， wine-washed and wine-fried LSCR， and their volatile components were detected by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the relative mass fractions of these components were determined by peak area normalization method. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on the obtained sample data by SIMCA 14.1 software， and the differential components of LSCR， wine-washed and wine-fried LSCR were screened according to the variable importance in the projection（VIP） value>1. Pearson correlation analysis was used to explore the relationship between volatile differential flavor components and electronic nose sensors. ResultsElectronic nose detection results showed that there were significant differences in the odors of LSCR， wine-washed and wine-fried LSCR， mainly reflected in the sensors S2， S4， S5， S6， S11， S12， S13. And a total of 62 compounds were identified from LSCR and its wine-processed products， among which 46， 50 and 51 compounds were identified from LSCR， wine-fried and wine-washed LSCR， respectively. There were 21 differential components between the raw products and wine-fried products， of which 10 components were increased and 11 were decreased after processing. There were 20 differential components between the raw products and wine-washed products， of which 11 constituents increased and 9 decreased after processing. There were 17 differential components between the wine-wash products and wine-fried products. Compared with the wine-washed products， the contents of 13 components in the wine-fried products increased， and the contents of 4 components decreased. The increasing trend of the content of phthalides in the wine-washed products was more obvious than that in the wine-fried products， but the content of total volatile components was higher in the wine-fried products than the wine-washed products. Correlation analysis showed that there were different degrees of correlation between the 7 differential sensors of electronic nose and 24 differential volatile components， mainly phthalides and olefins. ConclusionThe odor and the content of volatile components in LSCR changed obviously after wine processing， and n-butylphthalide， Z-butylidenephthalide and E-ligustilide can be used as the candidate differential markers of volatile components in LSCR before and after wine processing.

To characterize the genomes of different emm-type group A Streptococcus (GAS), their virulence genes and drug resistance profiles in Tianjin City from 2011 to 2024. After PCR, a total of 42 strains with different years and emm types were selected for whole genome sequencing and multi-locus sequence typing (MLST), and the core genomes were used to generate a phylogenetic tree, after which the virulence genes and resistance genes were identified and analyzed, followed by the drug susceptibility test. In this study, the GAS strains were dominated by emm1 (50.0%) and emm12 (40.4%), and the MLST phenotypes were categorized into six types: ST36 (40.4%), ST1274 (26.1%), ST28 (23.8%), ST921 (4.7%), ST46 (2.3%), and ST403 (2.3%). There was a high consistency between their emm-types and ST types. A total of 68 virulence genes were detected in the genomes of 42 GAS strains, involving functional genes encoding exotoxin, bacterial adhesion, extracellular enzymes, etc. The virulence genes they carried were significantly different between emm1-type and emm12-type strains, such as speA. At the same time, the carrying rates of some virulence genes in the same emm-type strains changed with time, such as hyl. The resistance genes were basically the same among different emm-type strains except for the vanSE gene detected in all emm12 strains. The results of drug sensitivity showed that the GAS strains isolated in Tianjin City from 2011 to 2024 were sensitive to penicillin, cefazolin, chloramphenicol, vancomycin, and levofloxacin, while the resistance rates to erythromycin, azithromycin, clarithromycin, and clindamycin ranged from 88.5% to 100.0%, and there was a certain degree of consistency between the resistance phenotypes and the detected resistance genes. Overall, the main emm types and evolutionary features of GAS in Tianjin City from 2011 to 2024 were consistent with the dominant types in China, and the carrying rate of virulence genes and drug resistance genes differed significantly among different emm-type strains, and there were continuous evolution and variation in the prevalence of virulence genes in GAS.

OBJECTIVE To explore and establish the working mechanism for prevention and control of hospital-as-sociated infections in regional oral medical institutions so as to standardize the prevention and control of the hospi-tal-associated infections in the regional oral medical institutions.METHODS Taking an administrative division of Chongqing as example,the matrix evaluation was carried out based on the quality control mode for management of hospital-associated infections in oral medical institutions' action planning,training guidance,quality control super-vision,summary review' organically in combination with'quality control plus law enforcement',a color-co-ded management of the oral medical institutions in the region was implemented,and the effectiveness of improved work in infection control was examined.RESULTS From the perspective of the grade of medical institution,the qualified rates of hospital infection management system construction,architectural layout and process,cleaning,disinfection and sterilization of oral instruments,environmental cleaning and disinfection,isolation,safe injection,use of occupational protection supplies and disposal of medical waste of the primary and unrated medical institu-tions were respectively 26.51％,49.40％,24.10％,37.35％,31.33％,46.99％,67.47％and 51.81％before the improvement and were respectively increased to 67.47％,63.86％,45.78％,66.27％,63.86％,73.49％,84.34％and 66.27％after the improvement,and there were significant differences(P＜0.05).From the perspec-tive of the property of the medical institution,the qualified rates of the above items of the private medical institu-tions were respectively 24.66％,47.95％,21.92％,34.25％,31.51％,45.21％,69.86％and 50.68％before the improvement and were respectively increased to 65.75％,61.64％,42.47％,64.38％,63.01％,71.23％,84.93％and 63.01％after the improvement,and there were significant differences(P＜0.05).CONCLUSION The working mechanism on prevention and control of hospital-associated infections in regional oral medical institu-tions that is established based on'quality control plus law enforcement'with the introduction of social credit can effectively raise the qualified rates of the infection prevention and control measures,which achieves more remarka-ble improvement effectiveness in grass-roots oral medical institutions such as the private,primary and unrat-ed medical institutions.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

OBJECTIVE: To screen the optimal regimen of acupuncture and moxibustion for obstructive sleep apnea hypopnea syndrome (OSAHS), so as to provide the evidences for clinical decision-making. METHODS: From 7 databases in Chinese and English i.e. the Full-Text Database of China Journal Network (CNKI), Wanfang Data Knowledge Service Platform (Wanfang), VIP Information Chinese Journal Service Platform (VIP), Chinese Biomedical Literature Database (SinoMed), PubMed, Web of Science (WOS) and Cochrane Library, randomized controlled trial (RCT) articals of OSAHS treated with acupuncture and moxibustion were searched. The quality of evidence was evaluated with the modified Jadad scale, the evaluation index was established and the optimal regimen of acupuncture and moxibustion for OSAHS was screened by multi-index decision analysis. RESULTS: A total of 10 RCTs were included, and the filiform needling therapy was optimal in treatment of OSAHS. The acupoints included Lianquan (CV23), Danzhong (CV17), Zhongwan (CV12), and bilateral Kongzui (LU6), Pishu (BL20), Fenglong (ST40), Zusanli (ST36), Yinlingquan (SP9) and Zhaohai (KI6). Zusanli (ST36) received the reinforcing method, Pishu (BL20) and Fenglong (ST40) were stimulated with the reducing technique, and the rest acupoints with the uniform reinforcing-reducing. Each acupoint was manually manipulated once every 10 min during the needle retention for 30 min. Acupuncture was delivered once a day, 5 times a week and for consecutive 4 weeks. Among the included literature, the severity of disease was not reported in detail, the filiform needling was the dominant intervention, the local acupoints such as Lianquan (CV23) and Panglianquan (Extra) were mainly selected. The apnea-hypopnea index and the minimum oxygen saturation were taken as the evaluation indexes, and the effect was evaluated in reference to the generally accepted standards. The attention to safety evaluation was insufficient, the report on methodology was not adequate and the quality was low. CONCLUSION Filiform needling is the dominant therapy of acupuncture and moxibustion for OSAHS, and the local acupoints are considered specially. But the quality of clinical research should be improved.
Humans ; Moxibustion ; Acupuncture Therapy ; Sleep Apnea, Obstructive/therapy* ; Acupuncture Points ; Randomized Controlled Trials as Topic