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 clinical value of tumor-stroma ratio (TSR) in combination with KRAS, BRAF, NRAS, and microsatellite status for prognostic assessment of patients with colorectal cancer. Methods A total of 51 colorectal cancer cases meeting the inclusion and exclusion criteria were enrolled in this study. TSR levels were evaluated through optical microscopy. The KRAS/NRAS/BRAF mutation profiles and microsatellite status were determined in accordance with genetic testing results. Clinical data, pathological characteristics, and survival outcomes were systematically recorded. Results Among the 51 patients with colorectal cancer, 19 (37.3%) were categorized into the low stromal group and 32 (62.7%) into the high stromal group. Statistically significant differences were observed between the two groups in drug resistance, M stage, TNM stage, neural invasion, and microsatellite status (P<0.05). Compared with patients exhibiting high TSR, those with low TSR demonstrated significantly increased recurrence rates (5 vs. 21 cases, P=0.007), shortened disease-free survival (34.21 vs. 14.34 months, P=0.001), and reduced overall survival (38.79 vs. 23.09 months, P=0.021). Multivariate Cox regression analysis identified N stage, M stage, TNM stage, neural invasion, lymphovascular invasion, and TSR as independent risk factors for disease-free survival. N stage, M stage, neural invasion, lymphovascular invasion, and TSR emerged as independent prognostic factors for overall survival (P<0.05). Although the combined models of TSR with KRAS, NRAS, BRAF, and microsatellite status, respectively, demonstrated overall statistical significance (P<0.05), none of the dummy variables in these models reached individually statistical significance (P>0.05), and therefore cannot be considered independent prognostic factors. Conclusion TSR serves as an independent predictor of poor prognosis in advanced colorectal cancer, with patients exhibiting low TSR demonstrating a significantly higher risk of recurrence and metastasis than those with high TSR. For patients with colon cancer undergoing first-line palliative chemotherapy after postoperative recurrence, histopathological assessment of TSR in primary tumor sites holds prognostic value and may serve as a relevant factor for evaluating treatment resistance in clinical management.

AIM: To investigate the effects of Conbercept on various optical coherence tomography(OCT)biomarkers in patients with retinal vein occlusion-related macular edema(RVO-ME), and to analyze the correlation of these biomarker changes with visual prognosis.METHODS: Retrospective study. A total of 57 patients(57 eyes)with RVO-ME, including 25 patients(25 eyes)with central retinal vein occlusion(CRVO)and 32 patients(32 eyes)with branch retinal vein occlusion(BRVO), were enrolled in this study. All the patients received intravitreal injection of conbercept once a month, three times in total. The preoperative and postoperative best-corrected visual acuity(BCVA), and changes in OCT biomarkers, including central macular thickness(CMT), the length of disorganization of the retinal inner layers(DRIL), the number of hyperreflective dots(HRD), the area of intraretinal fluid(IRF), the area of subretinal fluid(SRF), and the length of ellipsoid zone(EZ)disruption were compared. Furthermore, the relationship of these changes with BCVA was analyzed.RESULTS:Compared with the baseline, at 3 mo post-treatment, BCVA(LogMAR)was improved, CMT was decreased, the length of DRIL was shortened, the number of HRD was reduced, the area of IRF was decreased, the area of SRF was reduced, and the length of EZ disruption was shortened(all P<0.05). Spearman correlation analysis showed that there was no correlation between the changes in CMT, the length of DRIL, the number of HRD, the area of IRF, the area of SRF and the change in BCVA before and after treatment(P>0.05). However, the change in the length of EZ disruption was positively correlated with the change in BCVA(rs=0.34, P=0.011), and the R2 value of the fitting curve between the change in the length of EZ disruption and the change in BCVA was 0.113(P=0.011). When comparing the pre- and post-treatment changes in BCVA, the length of DRIL, the number of HRD, the area of IRF, the area of SRF, and the length of EZ disruption between patients in the CRVO group and BRVO group, no significant differences were observed(all P>0.05). In contrast, a significant difference was found in the change in CMT between the two groups(P=0.002).CONCLUSION:Conbercept effectively improves multiple OCT biomarkers in patients with RVO-ME. Repair of EZ disruption is a key driver of visual recovery, and its stability may serve as a novel indicator for personalized decision-making in anti-vascular endothelial growth factor therapy.

Cervi Cornu Pantotrichum is a precious animal-derived Chinese medicinal material, while there are often adulterants derived from animals not specified in the Chinese Pharmacopeia in the market, which disturbs the safety of medication. This study was conducted with the aim of strengthening the quality control of Cervi Cornu Pantotrichum and standardizing the medication. To achieve digital identification of Cervi Cornu Pantotrichum from different sources, a digital identification model was constructed based on ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS~E) combined with an adaptive boosting algorithm(Adaboost). The young furred antlers of sika deer, red deer, elk, and reindeer were processed and then subjected to polypeptide analysis by UHPLC-QTOF-MS~E. Then, the mass spectral data reflecting the polypeptide information were obtained by digital quantification. Next, the key data were obtained by feature screening based on Gini index, and the digital identification model was constructed by Adaboost. The model was evaluated based on the recall rate, F_1 composite score, and accuracy. Finally, the results of identification based on the constructed digital identification model were validated. The results showed that when the Gini index was used to screen the data of top 100 characteristic polypeptides, the digital identification model based on Adaboost had the best performance, with the recall rate, F_1 composite score, and accuracy not less than 0.953. The validation analysis showed that the accuracy of the identification of the 10 batches of samples was as high as 100.0%. Therefore, based on UHPLC-QTOF-MS~E and Adaboost algorithm, the digital identification of Cervi Cornu Pantotrichum can be realized efficiently and accurately, which can provide reference for the quality control and original animal identification of Cervi Cornu Pantotrichum.
Animals ; Algorithms ; Antlers/chemistry* ; Boosting Machine Learning Algorithms ; Chromatography, High Pressure Liquid/methods* ; Deer ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Quality Control ; Reindeer ; Tandem Mass Spectrometry/methods* ; Tissue Extracts/analysis*

Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical

This study aims to investigate the mechanism of Mahuang Lianqiao Chixiaodou Decoction(MHLQ) and its main active components in treating immunoglobin A nephropathy(IgAN). The rat model of IgAN was established by a combination of measures including gavage of bovine serum albumin, subcutaneous injection of carbon tetrachloride, and tail vein injection of lipopolysaccharide. The modeled rats were randomized into model, low-, medium-, and high-dose(1.773, 3.545, and 7.090 g·kg~(-1), respectively) MHLQ, phillyrin(PHI, 0.020 g·kg~(-1)), pseudoephedrine(PSE, 0.020 g·kg~(-1)), and losartan potassium(LP, 9.003 mg·kg~(-1)) groups, and Wistar rats were used as the control. Rats were administrated with corresponding drugs by gavage, and those in the control and model groups received an equal volume of normal saline. All the groups were treated for 4 consecutive weeks. Urine, serum, liver, and kidney samples were collected from rats in each group at the end of drug administration. The 24 h urine protein and renal function were examined, and staining was performed to observe the pathological changes in the renal tissue. The immunofluorescence assay was employed to detect the expression of IgA and complement C3/C3b/C3c in the renal tissue. Electron microscopy was employed to observe the ultrastructure of the renal tissue. Enzyme-linked immunosorbent assay was performed to determine the expression of complement C3 and sublytic C5b-9 in the serum and renal tissue. Western blot was performed to determine the expression levels of hepatic and renal complement C3/C3b/C3c, C5/C5a, C5b-9, and complement factor B(CFB). Immunohistochemistry(IHC) was employed to measure the expression of complement C3 in the renal tissue. The results showed that compared with the control group, the model group had elevated levels of blood urea nitrogen and serum creatinine, proliferation of glomerular mesangial cells and extracellular matrix, and glomerular deposition of IgA immune complexes or electron-dense material. In addition, the model group showcased increased serum C3 levels and up-regulated expression of CFB, C3/C3b/C3c, C5/C5a, and C5b-9 in the renal tissue and C3/C3b/C3c and C5b-9 in the hepatic tissue. After treatment with MHLQ and its active components, all of the above indexes were reversed. In conclusion, MHLQ and its active components can improve the renal function and reduce the deposition of immune complexes and pathological damage in the renal tissue of the rat model of IgAN by inhibiting the alternative pathway complement activation.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Glomerulonephritis, IGA/genetics* ; Rats ; Male ; Disease Models, Animal ; Rats, Wistar ; Complement Activation/drug effects* ; Kidney/immunology* ; Humans

Objective: To analyze the change trends in the body shape indicators and proportions of students in Harbin from 2010 to 2024, and to investigate ergonomic compatibility of functional dimensions of school desks and chairs with current student shape indicators, so as to provide a reference for revising furniture standards of desks and chairs. Methods: Between September and November of both 2010 and 2024, a combination of convenience sampling and stratified cluster random sampling was conducted across three districts in Harbin, yielding samples of 6 590 and 6 252 students, respectively. Anthropometric shape indicators cluding height, sitting height, crus length, and thigh length-and their proportional changes were compared over the 15-year period. The 2024 data were compared with current standard functional dimensions of school furniture. The statistical analysis incorporated t-test and Mann-Whitney U- test. Results: From 2010 to 2024, average height increased by 1.8 cm for boys and 1.5 cm for girls; sitting height increased by 1.5 cm for both genders; crus length increased by 0.3 cm for boys and 0.4 cm for girls; and thigh length increased by 0.5 cm for both genders. The ratios of sitting height to height, and sitting height to leg length increased by less than 0.1 . The difference between desk chair height and 1/3 sitting height ranged from 0.4-0.8 cm. Among students matched with size 0 desks and chairs, 22.0% had a desk to chair height difference less than 0, indicating that the desk to chair height difference might be insufficient for taller students. The differences between seat height and fibular height ranged from -1.4 to 1.1 cm; and the differences between seat depth and buttock popliteal length ranged from -9.8 to 3.4 cm. Among obese students, the differences between seat width and 1/2 hip circumference ranged from -20.5 to -8.7 cm, while it ranged from -12.2 to -3.8 cm among non obese students. Conclusion Current furniture standards basically satisfy hygienic requirements; however, in the case of exceptionally tall and obese students, ergonomic accommodations such as adaptive seating allocation or personalized adjustments are recommended to meet hygienic requirements.

Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

PURPOSE: Early mortality in major trauma has decreased, but MODS remains a leading cause of poor outcomes, driven by trauma-induced cytokine storms that exacerbate injuries and organ damage. METHODS: This prospective cohort study included 79 major trauma patients (ISS >15) treated in the National Center for Trauma Medicine, Peking University People's Hospital, from September 1, 2021, to July 31, 2023. Patients (1) with ISS >15 (according to AIS 2015), (2) aged 15-80 years, (3) admitted within 6 h of injury, (4) having no prior treatment before admission, were included. Exclusion criteria were (1) GCS score <9 or AIS score ≥3 for TBI, (2) confirmed infection, infectious disease, or high infection risk, (3) pregnancy, (4) severe primary diseases affecting survival, (5) recent use of immunosuppressive or cytotoxic drugs within the past 6 months, (6) psychiatric patients, (7) participation in other clinical trials within the past 30 days, (8) patients with incomplete data or missing blood samples. Admission serum inflammatory cytokines and pathophysiological data were analyzed to develop machine learning models predicting MODS within 7 days. LR, DR, RF, SVM, NB, and XGBoost were evaluated based on the area under the AUROC. The SHAP method was used to interpret results. RESULTS: This study enrolled 79 patients with major trauma, and the median (Q₁, Q₃) age was 51 (35, 59) years (52 males, 65.8%). The inflammatory cytokine data were collected for all participants. Among these patients, 35 (44.3%) developed MODS, and 44 (55.7%) did not. Additionally, 2 patients (2.5%) from the MODS group succumbed. The logistic regression model showed strong performance in predicting MODS. Ten key cytokines, IL-18, Eotaxin, MCP-4, IP-10, CXCL12, MIP-3α, MCP-1, IL-1RA, Cystatin C, and MRP8/14 were identified as critical to the trauma-induced cytokine storm and MODS development. Early elevation of these cytokines achieved high predictive accuracy, with an AUROC of 0.887 (95% CI 0.813-0.976). CONCLUSION Trauma-induced cytokine storms are strongly associated with MODS. Early identification of inflammatory cytokine changes enables better prediction and timely interventions to improve outcomes.
Humans ; Prospective Studies ; Middle Aged ; Male ; Female ; Adult ; Aged ; Cytokine Release Syndrome/etiology* ; Adolescent ; Young Adult ; Aged, 80 and over ; Wounds and Injuries/complications* ; Cytokines/blood* ; Multiple Organ Failure/diagnosis* ; Machine Learning