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

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.

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.

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.

BACKGROUND:De novo adipose regeneration induced by small extracellular vesicles has become a promising method for repairing soft tissue defects.However,due to different animal models and small extracellular vesicle application dosages,it is difficult to quantitatively compare the therapeutic effect of small extracellular vesicles from various sources on adipose regeneration. OBJECTIVE:To compare the regenerative effects of small extracellular vesicles derived from stem cells and small extracellular vesicles from tissue. METHODS:Small extracellular vesicles derived from adipose-derived stem cells and from adipose tissue were isolated by ultracentrifugation.The particle number,particle size,morphology,and protein expression of small extracellular vesicles were identified by nanoparticle tracking analysis,transmission electron microscopy and western blot assay.A quantitative and evaluative subcutaneous model for adipose regeneration in C57 mice was established using a customized silicone tube.The regenerative effects of induced de novo adipose were compared by cell counting and hematoxylin-eosin staining. RESULTS AND CONCLUSION:(1)Small extracellular vesicles derived from adipose-derived stem cells and from adipose tissue were isolated by ultracentrifugation.Both small extracellular vesicles were round-shape in transmission electron microscopy with particle size between 50-200 nm,and abundant with the small extracellular vesicles marker protein CD81,CD63 and TSG101.(2)An equal number of small extracellular vesicles were mixed with matrigel in customized silicone tubes,implanted subcutaneously in the back of mice to establish a cell-free and quantifiable adipose regeneration model.(3)On days 3 and 7 after implantation,the results of cell counting and hematoxylin-eosin staining showed that both small extracellular vesicle groups recruited more host cells than the blank group,and the small extracellular vesicles derived from adipose tissue group were superior to the small extracellular vesicles derived from adipose-derived stem cell group.(4)4 weeks after implantation,hematoxylin-eosin staining of the contents in silicone tubes showed that small extracellular vesicles induced de novo adipose regeneration in vivo,and the small extracellular vesicles derived from adipose tissue group were superior to the small extracellular vesicles derived from adipose-derived stem cell group.The above results indicated that small extracellular vesicles derived from tissues have a superior effect on inducing de novo adipose regeneration compared to small extracellular vesicles derived from stem cells.

Objective:To investigate the impact of intermittent senescent cell clearance on the proliferation and differentiation of dental pulp stem cells (DPSC) in long-term, large-scale expansion, and to explore strategies for maintaining the youthful state of DPSC in vitro. Methods:Human-derived dental pulp stem cells were isolated from healthy permanent teeth extracted for orthodontic or impeding eruption reasons, provided by the Department of Oral and Maxillofacial Surgery at West China Hospital of Stomatology, Sichuan University. Long-term, large-scale in vitro expansion of DPSC was conducted. The study compared young DPSC (passage 5) with aged DPSC (passage 25) using cellular senescence-associated β-galactosidase staining, colony formation assay, and Alizarin Red S staining for osteogenic differentiation induction. To assess the differences between the two cell populations in terms of senescence and amplification and differentiation ability. Medicine screening for the most effective senolytic was compared among 5 common senolytics [Navitoclax (ABT-263), curcumin, dasatinib, fisetin, and quercetin]. The clearance efficacy was compared using cellular senescence-associated β-galactosidase staining to reflect the changes in senescent cell ratio. The senolytic with the highest efficacy was chosen for further experiments. The passage at which the proportion of senescent cells significantly increased was identified, and the selected senolytic was administered three times at three-generation intervals from that passage to remove senescent cells. Both the control and senolytic-treated groups were estimated by fluorescence cellular senescence-associated β-galactosidase staining, real-time fluorescence quantitative PCR (RT-qPCR), colony formation assay, wound healing assay, and Alizarin Red S staining for osteogenic differentiation induction. Subcutaneous heterotopic osteogenesis was performed in nude mice and the grafts were analyzed by HE staining and alkaline phosphatase (ALP) immunohistochemical staining. Results:The proportion of senescent cells increased as the expansion extended, leading to decreased proliferation and osteogenic differentiation ability of senescent DPSC compared to young DPSC ( P<0.05). Senescent DPSC exhibited altered mRNA expression levels of senescence-related genes, including p21, p16INK4a, IL-6, and Ki67 ( P<0.001). Among the five senolytics, ABT-263 had the biggest decreases in the proportion of senescent cells. After intermittent ABT-263 treatment during expansion, the proportion of senescent cells in the senolytic-treated group [(6.72±2.34)%] was significantly lower than that in the control group [(31.82±0.57)%] ( P<0.001). RT-qPCR confirmed that compared with the control group, mRNA expressions of p21, p16 INK4a, and IL-6 in the senolytic-treated group were significantly decreased ( P<0.05), while mRNA expressions of Ki67 were significantly increased ( P<0.01). Furthermore, the cell healing ability and osteogenic differentiation ability of the senolytic-treated group were higher than those of the control group ( P<0.05). In vivo experimental results indicated that the relative new bone area [(2.36±0.48)%] after DPSC transplantation in the senolytic-treated group was greater than that in the control group [(1.00±0.46)%] ( P<0.05), and the expression of ALP was higher than that in the control group ( P<0.01). Conclusions:ABT-263 can effectively eliminate senescent cells in long-term large-scale DPSC expansion. Continuous treatment with ABT-263 during cultivation can maintain the proliferation and differentiation ability of DPSC both in vivo and in vitro.

Periodontitis is a chronic inflammatory and destructive disease in which plaque acts as an initiator.Recruitment of host im-mune cells and production of multiple inflammatory mediators leads to periodontal tissue damage.Programmed cell death(PCD)is a self-destructive process that is actively initiated by cells under specific conditions and can be mainly categorized into apoptosis,necrop-tosis,autophagy,pyroptosis,ferroptosis,cuproptosis,etc.Different types of programmed cell death have their own distinctive roles in periodontitis.In this review,we summarizes the characteristics of different types of PCD and their role in the progression of periodonti-tis,in order to provide new research ideas on the pathogenic mechanism of periodontitis and more references for the precise treatment of periodontitis.

Objective:To compare the short- and mid-term clinical outcomes of robotic versus laparoscopic radical resection of right- and left-sided colon cancer.Methods:In this retrospective cohort study, clinical data on patients who had undergone robotic or laparoscopic radical resection of right and left sided-colon cancer performed by two senior physicians in the Department of Gastro-Colorectal and Anal Surgery, Daping Hospital, Army Medical University between January 2015 and December 2023 were collected. The patients were allocated to robotic ( n=117) or laparoscopic groups ( n=267). Propensity score matching in a ratio of 1∶1 was implemented to minimize the impact of imbalances in baseline information between the two groups. Propensity score matching left 228 patients in the study cohort, with 114 in each group. The participants were aged (60.8±12.1) and (60.3±13.1) years and the body mass indices were (23.1±3.0) kg/m 2 and (23.1±2.8) kg/m 2 in the robotic and laparoscopic groups respectively. After matching, relevant perioperative indicators, postoperative complications, and 3-year survival outcomes were compared between the two groups. Results:After propensity score matching, the differences in baseline information between the two groups were not statistically significant ( P>0.05). After matching, in the robotic surgery group, radical resection of right- versus left-sided colon cancer had been performed on 80 and 34 patients, respectively; compared with 78 and 36, respectively, in the laparoscopic surgery group. Compared with the laparoscopic group, the robotic group had a longer operative time ( [209.8±48.4] minutes vs. [186.7±46.9] minutes, t=3.665, P<0.001), higher hospitalization cost ( [88657.8±18548.1] yuan vs. [61179.5±13822.7] yuan, t=12.683, P<0.001), and lower rate of postoperative complications (7.9% [9/114] vs. 17.5% [20/114], χ 2=4.780, P=0.029); these differences are statistically significant. The robotic group tended to have a lower conversion rate than the laparoscopic group (0 vs. 4.4% [5/114]); however, this difference between the two groups was not statistically significant (χ 2=3.272, P=0.070). The amount of intraoperative bleeding, time to first passage of flatus, postoperative hospital stay, postoperative complications (Clavien-Dindo grade), number of resected lymph nodes, and number of positive lymph nodes did not differ significantly between the two groups (all P>0.05). Furthermore, the differences between the robotic and laparoscopic groups in 3-year disease-free survival (81.4% vs. 82.8%, P=0.863) and overall survival (83.1% vs. 86.5%, P=0.921) were not statistically significant ( P>0.05). Conclusion:Robotic radical resection of right and left-sided colon cancer is safe and feasible and an effective alternative to laparoscopic surgery. Although robotic surgery has a longer operative time and higher hospitalization costs than laparoscopic surgery, it has a lower rate of postoperative complications, and a 3-year survival outcome comparable to that of laparoscopic surgery.

Objective:To compare the short- and mid-term clinical outcomes of robotic versus laparoscopic radical resection of right- and left-sided colon cancer.Methods:In this retrospective cohort study, clinical data on patients who had undergone robotic or laparoscopic radical resection of right and left sided-colon cancer performed by two senior physicians in the Department of Gastro-Colorectal and Anal Surgery, Daping Hospital, Army Medical University between January 2015 and December 2023 were collected. The patients were allocated to robotic ( n=117) or laparoscopic groups ( n=267). Propensity score matching in a ratio of 1∶1 was implemented to minimize the impact of imbalances in baseline information between the two groups. Propensity score matching left 228 patients in the study cohort, with 114 in each group. The participants were aged (60.8±12.1) and (60.3±13.1) years and the body mass indices were (23.1±3.0) kg/m 2 and (23.1±2.8) kg/m 2 in the robotic and laparoscopic groups respectively. After matching, relevant perioperative indicators, postoperative complications, and 3-year survival outcomes were compared between the two groups. Results:After propensity score matching, the differences in baseline information between the two groups were not statistically significant ( P>0.05). After matching, in the robotic surgery group, radical resection of right- versus left-sided colon cancer had been performed on 80 and 34 patients, respectively; compared with 78 and 36, respectively, in the laparoscopic surgery group. Compared with the laparoscopic group, the robotic group had a longer operative time ( [209.8±48.4] minutes vs. [186.7±46.9] minutes, t=3.665, P<0.001), higher hospitalization cost ( [88657.8±18548.1] yuan vs. [61179.5±13822.7] yuan, t=12.683, P<0.001), and lower rate of postoperative complications (7.9% [9/114] vs. 17.5% [20/114], χ 2=4.780, P=0.029); these differences are statistically significant. The robotic group tended to have a lower conversion rate than the laparoscopic group (0 vs. 4.4% [5/114]); however, this difference between the two groups was not statistically significant (χ 2=3.272, P=0.070). The amount of intraoperative bleeding, time to first passage of flatus, postoperative hospital stay, postoperative complications (Clavien-Dindo grade), number of resected lymph nodes, and number of positive lymph nodes did not differ significantly between the two groups (all P>0.05). Furthermore, the differences between the robotic and laparoscopic groups in 3-year disease-free survival (81.4% vs. 82.8%, P=0.863) and overall survival (83.1% vs. 86.5%, P=0.921) were not statistically significant ( P>0.05). Conclusion:Robotic radical resection of right and left-sided colon cancer is safe and feasible and an effective alternative to laparoscopic surgery. Although robotic surgery has a longer operative time and higher hospitalization costs than laparoscopic surgery, it has a lower rate of postoperative complications, and a 3-year survival outcome comparable to that of laparoscopic surgery.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.