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

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Objective:To analyze the impact and mechanism of grassroots Party building in public hospitals on departmental business, and to provide reference for promoting the integration and mutual promotion of Party building and business.Methods:In November 2023, a self-designed questionnaire was used to survey clinical medical staff in a tertiary hospital in Wuhan. A cluster random sampling method was employed to investigate the evaluation of grassroots Party building work by clinical medical staff and the role of grassroots Party building in departmental business. Descriptive quantitative analysis was conducted on the questionnaire data. From November to December 2023, typical sampling was used to select Party branch committee members from clinical and medical technology departments of the hospital for semi-structured interviews. The interview content included the status of grassroots Party building work, its role in departmental business development, and the underlying mechanisms. Grounded theory was used for three-level coding of the interview data, and role theory was applied to analyze the mechanism by which grassroots Party building promotes business development.Results:A total of 1 124 valid questionnaires were collected, covering personnel from various sequences, including medical, nursing, technical, and pharmacy staff. Over 95% of the respondents rated the Party branch work highly, and more than 94% believed that grassroots Party building had a positive impact on the department′s medical care, teaching, research, talent team building, management, and cultural construction. The analysis using grounded theory and role theory revealed that the promotion of departmental business by grassroots Party building mainly originated from three aspects of standardization and normalization construction of Party branches, participation of Party branches in departmental management, and the development of characteristic activities based on Party building carriers. These three aspects enhanced personal responsibility, discipline, and service awareness through five personal-level targets (correcting work attitudes, leading by example among Party members, strengthening integrity in professional practice, improving professional skills, and improving working methods). This, in turn, facilitated medical staff to better identify their role positioning, standardize role behavior, and enhance role learning. At the departmental level, seven targets (expanding channels for departmental transparency, emphasizing practical performance, Party branch involvement in important departmental matters, enhancing external communication, increasing emotional identification, improving internal communication, and strengthening integrity building) were identified to promote fairness and justice, democratic decision-making, external cooperation, unity, and a clean atmosphere within the department. This further improved role evaluation, created an atmosphere conducive to role learning, helped strengthen role identification, and guided role standardization.Conclusions:Grassroots Party building of public hospital has a positive impact on department business work and is widely recognized by clinical medical staff. Different Party building activities have different pathways of influence. It is recommended to conduct targeted Party building activities based on actual needs.

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Pathology images,being an essential part of medical imaging,are critical for early diagnosis of diseases such as cancer.The study introduces edge computing into pathology image research,and presents an edge inference solution for medical pathological image recognition and analysis,aiming to leverage the advantages of edge computing and combine with deep learning methods to achieve real-time pathology image detection.Experimental results show that the solution protects patient privacy well,improves the efficiency and real time of medical image processing,and greatly reduces costs,demonstrating that it has high practical application value and can provide more and efficient accurate support for medical diagnosis and treatment.

BACKGROUND:Some research has suggested that regulation of gut microbiota may influence the course of intervertebral disc degeneration.However,the causal relationship of gut microbiota on intervertebral disc degeneration is unknown.OBJECTIVE:To assess the potential causal relationship between gut microbiota and intervertebral disc degeneration using a Mendelian randomization method.METHODS:Genome-wide association analysis summary statistics for 473 gut microbiota and genome-wide association analysis summary data for intervertebral disc degeneration from the R11 of the FinnGen database(46 205 cases of intervertebral disc degeneration and 322 314 controls)from the most recent publicly available publication were applied.Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between gut microbiota and intervertebral disc degeneration.Sensitivity analyses were used to test whether the results of Mendelian randomization analyses were reliable.Reverse Mendelian randomization was performed with all gut microbiota as the outcomes for effect analysis and sensitivity analysis.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method of the forward Mendelian randomization method showed that the order Trichosporonaceae,the family UBA-6960,the family Anaerobes thermophilus,the family Salmonellaceae,the genus Pseudomonas tufts,the species Gordonella and the species Euclidia showed a positive correlation with intervertebral disc degeneration.The order Spirochaetes,the order Pseudomonas,the family Spirochaetaceae,the genus CAG-776,the genus Helicobacter,the species CAG-448 sp003150135,the species CAG-776 sp000438195,the species Brautella-A sp000285855 and the species Hanson's Brautella showed a negative correlation with intervertebral disc degeneration.(2)The results of reverse Mendelian randomization showed that intervertebral disc degeneration was positively correlated with the genus Bartonella rosea,the genus Geobacillus C,the species Escherichia fumigatus,the species Propionibacterium fumigatus,the species UBA-1777 sp900319835,the species Pseudomonas aeruginosa and the species Bacillus subtilis,while negatively correlated with the species Streptomyces mingoldii,the species Prevotella sp000434975,the species Brault's A sp000285855,the species CAG-194 sp002441865 and the species CAG-590 sp000431135.(3)No heterogeneity or horizontal pleiotropy was found in the two-way sensitivity analysis.(4)The results described above indicate that the causal relationship between gut microbiota and intervertebral disc degeneration based on the Finnish database contributes to the exploration on new biomarkers for the early prediction and treatment of intervertebral disc degeneration in clinical practice.In addition,the establishment of a large database and the integration of medical data from multiple centers can be drawn upon in biomedical research in China to provide a solid foundation for studying the relationship between gut microbiota and intervertebral disc degeneration.We will strengthen communication and cooperation with research teams in other countries to jointly promote the research on the relationship between gut microbiota and diseases and contribute to the development of global medicine.

Alcohol abuse is a global public health problem.Excessive drinking not only damages digestive tract,cardiovascu-lar and endocrine systems,but also damages central nervous system(CNS).Recent studies have shown that alcohol interacts with neu-roimmune system to alter neuroimmune signaling and molecular expression,thereby leading to neuroinflammation and regulating a wide range of brain functions.Microglia is main cell of CNS involved in neuroimmune responses.Microglia is activated by alcohol and acts on neurons,leading to neuropsychiatric diseases,such as neuronal loss,abnormal synaptic connections,cognitive decline and motor dysfunction.Alcohol chronically stimulates digestive tract and also affects microglia along gut-brain axis.Neural properties of microglia and related immune factors and their important roles in neuroinflammation provide a new insight into neuroimmune mecha-nisms underlying alcohol-induced changes in brain function and behavior.This review discusses progress of role of microglia and their immune signaling in alcohol-induced neuroinflammation,and provides theoretical basis for further research on neurobiological mecha-nism and treatment of alcohol abuse.

Pathology images,being an essential part of medical imaging,are critical for early diagnosis of diseases such as cancer.The study introduces edge computing into pathology image research,and presents an edge inference solution for medical pathological image recognition and analysis,aiming to leverage the advantages of edge computing and combine with deep learning methods to achieve real-time pathology image detection.Experimental results show that the solution protects patient privacy well,improves the efficiency and real time of medical image processing,and greatly reduces costs,demonstrating that it has high practical application value and can provide more and efficient accurate support for medical diagnosis and treatment.

BACKGROUND:Some research has suggested that regulation of gut microbiota may influence the course of intervertebral disc degeneration.However,the causal relationship of gut microbiota on intervertebral disc degeneration is unknown.OBJECTIVE:To assess the potential causal relationship between gut microbiota and intervertebral disc degeneration using a Mendelian randomization method.METHODS:Genome-wide association analysis summary statistics for 473 gut microbiota and genome-wide association analysis summary data for intervertebral disc degeneration from the R11 of the FinnGen database(46 205 cases of intervertebral disc degeneration and 322 314 controls)from the most recent publicly available publication were applied.Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between gut microbiota and intervertebral disc degeneration.Sensitivity analyses were used to test whether the results of Mendelian randomization analyses were reliable.Reverse Mendelian randomization was performed with all gut microbiota as the outcomes for effect analysis and sensitivity analysis.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method of the forward Mendelian randomization method showed that the order Trichosporonaceae,the family UBA-6960,the family Anaerobes thermophilus,the family Salmonellaceae,the genus Pseudomonas tufts,the species Gordonella and the species Euclidia showed a positive correlation with intervertebral disc degeneration.The order Spirochaetes,the order Pseudomonas,the family Spirochaetaceae,the genus CAG-776,the genus Helicobacter,the species CAG-448 sp003150135,the species CAG-776 sp000438195,the species Brautella-A sp000285855 and the species Hanson's Brautella showed a negative correlation with intervertebral disc degeneration.(2)The results of reverse Mendelian randomization showed that intervertebral disc degeneration was positively correlated with the genus Bartonella rosea,the genus Geobacillus C,the species Escherichia fumigatus,the species Propionibacterium fumigatus,the species UBA-1777 sp900319835,the species Pseudomonas aeruginosa and the species Bacillus subtilis,while negatively correlated with the species Streptomyces mingoldii,the species Prevotella sp000434975,the species Brault's A sp000285855,the species CAG-194 sp002441865 and the species CAG-590 sp000431135.(3)No heterogeneity or horizontal pleiotropy was found in the two-way sensitivity analysis.(4)The results described above indicate that the causal relationship between gut microbiota and intervertebral disc degeneration based on the Finnish database contributes to the exploration on new biomarkers for the early prediction and treatment of intervertebral disc degeneration in clinical practice.In addition,the establishment of a large database and the integration of medical data from multiple centers can be drawn upon in biomedical research in China to provide a solid foundation for studying the relationship between gut microbiota and intervertebral disc degeneration.We will strengthen communication and cooperation with research teams in other countries to jointly promote the research on the relationship between gut microbiota and diseases and contribute to the development of global medicine.

Alcohol abuse is a global public health problem.Excessive drinking not only damages digestive tract,cardiovascu-lar and endocrine systems,but also damages central nervous system(CNS).Recent studies have shown that alcohol interacts with neu-roimmune system to alter neuroimmune signaling and molecular expression,thereby leading to neuroinflammation and regulating a wide range of brain functions.Microglia is main cell of CNS involved in neuroimmune responses.Microglia is activated by alcohol and acts on neurons,leading to neuropsychiatric diseases,such as neuronal loss,abnormal synaptic connections,cognitive decline and motor dysfunction.Alcohol chronically stimulates digestive tract and also affects microglia along gut-brain axis.Neural properties of microglia and related immune factors and their important roles in neuroinflammation provide a new insight into neuroimmune mecha-nisms underlying alcohol-induced changes in brain function and behavior.This review discusses progress of role of microglia and their immune signaling in alcohol-induced neuroinflammation,and provides theoretical basis for further research on neurobiological mecha-nism and treatment of alcohol abuse.