Pharmacotranscriptomic profiles, which capture drug-induced changes in gene expression, offer vast potential for computational drug discovery and are widely used in modern medicine. However, current computational approaches neglected the associations within gene‒gene functional networks and unrevealed the systematic relationship between drug efficacy and the reversal effect. Here, we developed a new genome-scale functional module (GSFM) transformation framework to quantitatively evaluate drug efficacy for in silico drug discovery. GSFM employs four biologically interpretable quantifiers: GSFM_Up, GSFM_Down, GSFM_ssGSEA, and GSFM_TF to comprehensively evaluate the multi-dimension activities of each functional module (FM) at gene-level, pathway-level, and transcriptional regulatory network-level. Through a data transformation strategy, GSFM effectively converts noisy and potentially unreliable gene expression data into a more dependable FM active matrix, significantly outperforming other methods in terms of both robustness and accuracy. Besides, we found a positive correlation between RS_GSFM and drug efficacy, suggesting that RS_GSFM could serve as representative measure of drug efficacy. Furthermore, we identified WYE-354, perhexiline, and NTNCB as candidate therapeutic agents for the treatment of breast-invasive carcinoma, lung adenocarcinoma, and castration-resistant prostate cancer, respectively. The results from in vitro and in vivo experiments have validated that all identified compounds exhibit potent anti-tumor effects, providing proof-of-concept for our computational approach.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

Objective:To evaluate the clinical efficacy of endoscopic treatment of superficial non-ampullary duodenal adenoma.Methods:A retrospective analysis was performed on the clinical data and follow-up information of patients diagnosed with superficial duodenal non-ampullary adenomas via preoperative endoscopy and treated endoscopically at Peking University First Hospital between January 2013 and January 2024. The overall en bloc resection rate, complete resection rate of the lesion, perioperative complications, and recurrence rates were evaluated. Patients were categorized into three groups based on their treatment modality: endoscopic mucosal resection (EMR)（ n=46）, endoscopic submucosal dissection (ESD)（ n=16）, and modified ESD (ESD with snare, ESD-S)（ n=24）. Comparative analyses were conducted to evaluate operative time, en bloc resection rate, and complete resection rate among the three groups. Results:Among 86 patients, the overall en bloc and complete resection rates were 87.2% (75/86) and 86.0% (74/86), respectively. No case of delayed bleeding was observed during the perioperative period. Intraoperative perforation occurred in two patients, both of whom improved following conservative management. Delayed perforation was noted in four patients, and three of them were successfully managed with surgical intervention, while one case was resolved after conservative treatment. During the follow-up period, local recurrence was identified in two patients. Following re-treatment with endoscopy and continuous surveillance, no further recurrence was observed. The operative times for the EMR group, ESD-S group, and ESD group were 4 (1-36) minutes, 25 (5-190) minutes, and 46 (5-150) minutes, respectively. Significant differences were observed in operative times among the three groups ( Hc=49.892, P<0.001). The en bloc resection rates for the EMR, ESD-S, and ESD groups were 80.4% (37/46), 91.7% (22/24), and 100.0% (16/16), respectively. The complete resection rates were 80.4% (37/46), 91.7% (22/24), and 93.8% (15/16) for the respective groups. Conclusion:Endoscopic treatment demonstrates favorable efficacy and safety for superficial non-ampullary duodenal adenoma. In addition to traditional EMR and ESD, ESD-S is also an effective procedure for endoscopic treatment of non-ampullary duodenal adenoma.

With the modernization drive of traditional Chinese medicine (TCM), this perspective innovatively proposes integrating carbon dot research paradigms to facilitate the modernization of charcoal drugs in TCM. The research focuses on five core areas: analyzing and validating charcoal drugs components pharmacologically, exploring modern preparation methods, establishing a quality evaluation system, fixing preparation process parameters, and probing into the material basis. These steps aim to deepen the scientific understanding of the material basis of charcoal drugs, optimize its preparation process, and establish a comprehensive quality control system. This work provides a theoretical foundation and experimental evidence for the scientific understanding of charcoal drugs, further promoting their modernization and internationalization.

Objective To investigate the prognostic value of triglyceride-glucose index(TyG index)in non-diabetic patients with acute coronary syndrome(ACS)who underwent percutaneous coronary intervention(PCI).Methods A total of 529 non-diabetic ACS patients who had successfully underwent PCI in our hospital from January 2019 to December 2020 were selected.According to the median TyG index(8.98),the patients were divided into low TyG index group(TyG＜8.98)and high TyG index group(TyG≥8.98).All the patients were followed up for major adverse cardiovascular events(MACE).Results Overall,55(10.4％)endpoint events were documented during a 24-month follow-up.Kaplan-Meier survival curves showed that the cumulative incidence of MACE was significantly higher in patients in the high TyG group than in the low TyG group(Log Rank P=0.001).Multivariate Cox analysis showed that after adjusting other confounding factors,TyG index was an independent predictor of MACE(HR=3.50,95％CI:1.44-8.53,P＜0.01).The risk of MACE in the high TyG group was 1.12-fold increased compared with the low TyG group(95％CI:1.19-3.79,P=0.011).The subgroup analysis results were generally consistent.Conclusion TyG index is an independent predictor of MACE in non-diabetic ACS patients who underwent PCI.

Objective:To investigate the current situation of water-borne endemic fluorosis in Anhui Province, and provide basic data for the adjusting the prevention and control measures.Methods:Using cross-sectional survey method, all villages in the water-borne endemic fluorosis areas were investigated in Anhui Province from 2019 to 2022. In water-borne endemic fluorosis village, the situation of water improvement project and the fluoride level of drinking water were investigated, and dental fluorosis of all children aged 8 - 12 was examined. The criteria for determining the achievement of control targets for water-borne endemic fluorosis in affected counties were based on the "Evaluation Measures for Control and Elimination of Key Endemic Diseases (2019 Edition)".Results:From 2019 to 2022, the rate of water improvement village in water-borne endemic fluorosis areas were 88.47% (1 527/1 726), 100% (1 726/1 726), 100% (1 726/1 726) and 100% (1 726/1 726), respectively. The qualified proportion of water fluoride in water-borne endemic fluorosis villages was 33.84% (584/1 726), 63.09% (1 089/1 726), 70.74% (1 221/1 726) and 74.33% (1 283/1 726), respectively. The prevalence rates of dental fluorosis in children aged 8 - 12 were 25.48% (45 461/178 440), 15.78% (27 959/177 200), 13.68% (23 505/171 880) and 12.66% (23 315/184 200), respectively. The proportion of affected counties that had achieved the control target of water-borne endemic fluorosis was 16% (4/25), 60% (15/25), 36% (9/25) and 40% (10/25), respectively.Conclusions:The water-borne endemic fluorosis areas in Anhui Province have improved the water fluoride qualification rate and reduced the incidence of fluorosis in children through prevention and control measures such as water improvement and fluoride reduction. However, the prevention and control efforts in key areas and counties need to be further improved.

Objective To investigate the prognostic value of triglyceride-glucose index(TyG index)in non-diabetic patients with acute coronary syndrome(ACS)who underwent percutaneous coronary intervention(PCI).Methods A total of 529 non-diabetic ACS patients who had successfully underwent PCI in our hospital from January 2019 to December 2020 were selected.According to the median TyG index(8.98),the patients were divided into low TyG index group(TyG＜8.98)and high TyG index group(TyG≥8.98).All the patients were followed up for major adverse cardiovascular events(MACE).Results Overall,55(10.4％)endpoint events were documented during a 24-month follow-up.Kaplan-Meier survival curves showed that the cumulative incidence of MACE was significantly higher in patients in the high TyG group than in the low TyG group(Log Rank P=0.001).Multivariate Cox analysis showed that after adjusting other confounding factors,TyG index was an independent predictor of MACE(HR=3.50,95％CI:1.44-8.53,P＜0.01).The risk of MACE in the high TyG group was 1.12-fold increased compared with the low TyG group(95％CI:1.19-3.79,P=0.011).The subgroup analysis results were generally consistent.Conclusion TyG index is an independent predictor of MACE in non-diabetic ACS patients who underwent PCI.

Objective:To investigate the current situation of water-borne endemic fluorosis in Anhui Province, and provide basic data for the adjusting the prevention and control measures.Methods:Using cross-sectional survey method, all villages in the water-borne endemic fluorosis areas were investigated in Anhui Province from 2019 to 2022. In water-borne endemic fluorosis village, the situation of water improvement project and the fluoride level of drinking water were investigated, and dental fluorosis of all children aged 8 - 12 was examined. The criteria for determining the achievement of control targets for water-borne endemic fluorosis in affected counties were based on the "Evaluation Measures for Control and Elimination of Key Endemic Diseases (2019 Edition)".Results:From 2019 to 2022, the rate of water improvement village in water-borne endemic fluorosis areas were 88.47% (1 527/1 726), 100% (1 726/1 726), 100% (1 726/1 726) and 100% (1 726/1 726), respectively. The qualified proportion of water fluoride in water-borne endemic fluorosis villages was 33.84% (584/1 726), 63.09% (1 089/1 726), 70.74% (1 221/1 726) and 74.33% (1 283/1 726), respectively. The prevalence rates of dental fluorosis in children aged 8 - 12 were 25.48% (45 461/178 440), 15.78% (27 959/177 200), 13.68% (23 505/171 880) and 12.66% (23 315/184 200), respectively. The proportion of affected counties that had achieved the control target of water-borne endemic fluorosis was 16% (4/25), 60% (15/25), 36% (9/25) and 40% (10/25), respectively.Conclusions:The water-borne endemic fluorosis areas in Anhui Province have improved the water fluoride qualification rate and reduced the incidence of fluorosis in children through prevention and control measures such as water improvement and fluoride reduction. However, the prevention and control efforts in key areas and counties need to be further improved.

Objective:To evaluate the clinical efficacy of endoscopic treatment of superficial non-ampullary duodenal adenoma.Methods:A retrospective analysis was performed on the clinical data and follow-up information of patients diagnosed with superficial duodenal non-ampullary adenomas via preoperative endoscopy and treated endoscopically at Peking University First Hospital between January 2013 and January 2024. The overall en bloc resection rate, complete resection rate of the lesion, perioperative complications, and recurrence rates were evaluated. Patients were categorized into three groups based on their treatment modality: endoscopic mucosal resection (EMR)（ n=46）, endoscopic submucosal dissection (ESD)（ n=16）, and modified ESD (ESD with snare, ESD-S)（ n=24）. Comparative analyses were conducted to evaluate operative time, en bloc resection rate, and complete resection rate among the three groups. Results:Among 86 patients, the overall en bloc and complete resection rates were 87.2% (75/86) and 86.0% (74/86), respectively. No case of delayed bleeding was observed during the perioperative period. Intraoperative perforation occurred in two patients, both of whom improved following conservative management. Delayed perforation was noted in four patients, and three of them were successfully managed with surgical intervention, while one case was resolved after conservative treatment. During the follow-up period, local recurrence was identified in two patients. Following re-treatment with endoscopy and continuous surveillance, no further recurrence was observed. The operative times for the EMR group, ESD-S group, and ESD group were 4 (1-36) minutes, 25 (5-190) minutes, and 46 (5-150) minutes, respectively. Significant differences were observed in operative times among the three groups ( Hc=49.892, P<0.001). The en bloc resection rates for the EMR, ESD-S, and ESD groups were 80.4% (37/46), 91.7% (22/24), and 100.0% (16/16), respectively. The complete resection rates were 80.4% (37/46), 91.7% (22/24), and 93.8% (15/16) for the respective groups. Conclusion:Endoscopic treatment demonstrates favorable efficacy and safety for superficial non-ampullary duodenal adenoma. In addition to traditional EMR and ESD, ESD-S is also an effective procedure for endoscopic treatment of non-ampullary duodenal adenoma.

BACKGROUND:Cell derivative is cell-derived bioactive components,including decellularized extracellular matrix,exosome,apoptotic extracellular vesicle,and conditioned medium,has the effects on immune regulation,promoting angiogenesis,bone regeneration,ligament remodeling,and is capable of promoting stem cell chemotherapy,migration,proliferation,and adhesion.Its excellent characteristics make it a promising biomaterial for application and clinical translation in the field of periodontal tissue engineering. OBJECTIVE:To review the characteristics of cell derivatives(decellularized extracellular matrix,exosome,apoptotic extracellular vesicle,and conditioned medium)and its effect and the latest progress in the field of regenerative restoration of periodontal complex tissue structures. METHODS:We searched the articles on CNKI and PubMed databases with the search terms"regeneration,periodontal tissue,tissue engineering,decellularized matrix,exosome,apoptotic extracellular vesicle,condition medium"in Chinese and English,respectively.Finally,76 articles were included for analysis and discussion. RESULTS AND CONCLUSION:(1)Among those four cell derivatives,the decellularized extracellular matrix has the best mechanical properties and fibrous structure,serving as a biomimetic scaffold to provide physiochemical signals and participate in mechanical signaling in periodontal tissue engineering,providing supporting effect suitable for periodontal regeneration.Recently,the development of soluble decellularized extracellular matrix bioinks has enabled the fabrication of regenerative scaffolds for personalized periodontal defects.(2)Exosomes are the simplest cell derivatives that have immunomodulatory capacity,promoting cell migration and differentiation.As a carrier,they can be used to carry target molecules to regulate periodontal regeneration,promote ligament remodeling and bone regeneration,and are suitable for periodontal tissue engineering.(3)Apoptotic vesicles generated from apoptotic cells have a strong immunomodulatory effect and can recruit stem cells and macrophages,which determine the fate of stem cells through signal transduction and can enhance immunomodulation to promote periodontal regeneration.Engineered extracellular vesicle is considered to have the potential to initiate targeted internal immunomodulation.(4)The extraction of conditioned medium is simple and completely noninvasive,which provides essential nutrients and growth factors for tissue regeneration.These components are crucial for successful periodontal regeneration.Therefore,the conditioned medium is especially suitable for studying the interactions between cells in vitro and has an important role in high-throughput detection in the future.