Objective To investigate the mechanism underlying gasdermin E(GSDME)-mediated pyroptosis in radiation-induced intestinal injury and to find out whether gasdermin(GSDM)family members regulate pyroptosis through similar signaling pathways.Methods Human normal colon epithelial cells(NCM460)and human colon cancer cells(HT-29)were exposed to radiation of different doses and durations before pyroptosis indicators were evaluated by observing pyroptotic bubbles,cell survival,and the cleavage of pyroptosis execution proteins.HT-29 cells overexpressing GSDME were subjected to radiation,followed by enrichment analysis of pyroptosis-related differentially expressed genes using RNA-seq.Results Radiation induced substantial pyroptosis in NCM460 cells.Overexpression of GSDME in HT-29 cells resulted in substantial radiation-induced pyroptosis.The pyroptosis state of human intestinal cells was simulated in the HT-29 model cell line.Overexpressions of GSDME-N and GSDMD-N resulted in the expression of more than 50％ of the differentially expressed genes in the pyroptosis state.Sequencing analysis showed that the genes in the pyroptosis state were mainly overrepresented in immune response,inflammatory response,and Rapl signaling pathway.Conclusion GSDME activation can mediate radiation-induced pyroptosis by producing GSDME-N fragments.GSDM family members participate in pyroptosis in a similar mode of regulation.Furthermore,radiation-induced activation of GSDME/D may regulate pyroptosis through immune response,inflammatory response,and Rap1 signaling pathway.

Hepatocellular carcinoma is one of the most common malignant tumors worldwide, posing a great threat to human health and life. Despite the tremendous progress in understanding the origin and molecular characterization of hepatocellular carcinoma, there are still few therapeutic options that can significantly increase the survival rate and improve the quality of life of patients. Protein post-translational modifications (PTMs) are regulatory mechanisms for protein activity, localization, expression, and interactions with other cellular molecules that induce changes in protein properties and functions. More and more studies have demonstrated that PTMs and immunotherapy play an important role in the development of hepatocellular carcinoma, even in the immunosurveillance of hepatocellular carcinoma and the treatment and prognosis of hepatocellular carcinoma patients. Traditional types of PTMs include phosphorylation, glycosylation, methylation, and ubiquitination. Phosphorylation affects cancer development and progression by regulating tumor cell proliferation, invasion and metastasis, and inhibiting apoptosis. There are two main types of glycosylation: O-glycosylation andN-glycosylation. Abnormal glycosylation not only promotes the proliferation and metastasis of hepatocellular carcinoma cells, but also plays an important role in immune recognition and immune escape. Common methylation modifications include DNA methylation, RNA methylation and histone methylation. Among them, histone methylation, as an important epigenetic regulatory mechanism, is of great theoretical and practical significance for understanding the mechanism of hepatocellular carcinoma as well as carrying out the corresponding prevention and immunotherapy. Ubiquitination plays an important role in the localization, metabolism, function, regulation and degradation of proteins, and it is regulated at different levels by ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), ubiquitin-conjugating enzyme (E3), and a series of deubiquitinating enzymes (DUBs) and is closely related to hepatocellular carcinoma immunotherapy. This paper begins with a brief overview of the importance of PTMs of proteins, discusses the importance of these traditional types of PTMs in hepatocellular carcinoma immunotherapy, and summarizes the most recent applications of these approaches in hepatocellular carcinoma in order to explore the mechanism of action of PTMs in hepatocellular carcinoma immunotherapy. Then, we summarize the finding that programmed death-ligand 1 (PD-L1) is associated with a variety of conventional types of PTMs, that in-depth study of the mechanisms regulating PD-L1 expression in tumor cells is expected to improve therapeutic efficacy, and that targeting PD-L1 in PTMs is expected to be a new field for exploring hepatocellular carcinoma immunotherapy in the future. Finally, we discuss the current status of research on PTMs for hepatocellular carcinoma immunotherapy and provide new insights and future research directions. In addition to the traditional types of PTMs, multiple novel PTMs have also been identified in published research reports, while the relationship between novel PTMs and hepatocellular carcinoma and the types of PTMs to other undiscovered proteins are still poorly understood, and future research will be focused on a more comprehensive knowledge and understanding of PTMs as well as on exploring new types and mechanisms of PTMs. Overall, further investigation of the role of PTMs in tumor immunity could help to discover new biomarkers and to develop more effective and personalized cancer immunotherapies and targeted therapies, expanding our understanding of cancer biology.

Objective To investigate the inhibitory effects of Wumeiwan on oxidative stress injury of ulcerative colitis mice induced by dextran sulfate sodium(DSS)by regulating Kelch-like ECH related protein 1(Keap-1)-nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathwayand.Methods Forty C57BL/6 mice were randomly divided into five groups:normal group,model group,positive control group,experimental-L,-H groups.UC mice model were induced by free access to 2％DSS water.Mice in normal and model group were orally administered with 0.9％NaCl,mice in positive control group were orally treated with Mesalazine solution(0.005 g·10 g-1·d-1),while mice in experimental groups were orally administered with Wumeiwan decoction at the dose of 0.13 and 0.26 g·10 g-1·d-1,respectively.All the drugs were administered for consecutive 7 days,1 times a day.The levels of disease activity index(DAI)and the colon length were scored.The levels of superoxide dismutase(SOD),catalase(CAT),cyclooxygenase-2(COX-2)and inducible nitric oxide synthase(iNOS)in colon tissue of mice were determined by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)method.The level of Keap-1,Nrf2,HO-1 proteins in colon tissue were determined by Western blot method.Results The levels of DAI of seventh day in normal group,positive control group,experimental-L,-H groups were 0、(2.62±0.33),(1.87±0.35),(1.87±0.35)and(1.58±0.35);the colon lengths were(8.16±0.47)、(5.98±0.24),(7.58±0.38),(7.33±0.24)and(7.48±0.51)cm;the SOD mRNA were 1.01±0.16、0.40±0.01,1.43±0.45,0.65±0.01 and 0.83±0.02;the CAT mRNA were 1.01±0.20、0.45±0.01,0.84±0.02,0.68±0.07 and 0.87±0.05;the COX-2 mRNA were 1.03±0.33、16.65±0.60,4.78±0.25,14.07±0.60 and 7.39±0.15;the iNOS mRNA were 1.04±0.40、20.71±0.66,8.09±0.93,15.44±0.68 and 11.66±0.06;the levels of Keap-1 were 1.22±0.16、1.10±0.05,1.18±0.05,1.94±0.08 and 1.17±0.08;the levels of Nrf2 were 1.12±0.16、0.76±0.15,0.65±0.13,0.70±0.16 and 0.82±0.18;the levels of HO-1 were 1.34±0.15、1.00±0.12,0.89±0.10,1.50±0.18 and 1.40±0.13,respectively.Significant difference was found between normal group and model group(P＜0.01,P＜0.05);significant difference was also found between the experimental-L,-H groups and model group(P＜0.01,P＜0.05).Conclusion Wumeiwan can inhibit oxidative stress in mice with UC,the mechanisms may be related to adjusted the expression of Keap-1-Nrf2/HO-1 signaling pathway protein in colon.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also nonmotor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target neurons of cerebellar nuclei (CN) from wild-type mice and Nlgn3R451C mutant mice, a mouse model for autism. Our results derived from 36 target nuclei show that the projections from CN to thalamus, midbrain and brainstem are differentially affected by Nlgn3R451C mutation. Importantly, Nlgn3R451C mutation altered the innervation power of CN→zona incerta (ZI) pathway, and chemogenetic inhibition of a neuronal subpopulation in the ZI that receives inputs from the CN rescues social defects in Nlgn3R451C mice. Our study highlights potential role of cerebellar outputs in the pathogenesis of autism and provides potential new therapeutic strategy for this disease.
Animals ; Mice ; Disease Models, Animal ; Cerebellar Nuclei ; Autistic Disorder/pathology* ; Neurons/metabolism* ; Mutation ; Nerve Tissue Proteins/metabolism* ; Male ; Membrane Proteins ; Cell Adhesion Molecules, Neuronal

Objective:To identify the influencing factors affecting the cosmetic facial injection treatments for cosmetic patients.Methods:Based on the purposeful sampling principle with maximum diversity and data saturation principle, patients who underwent facial injection cosmetic surgery in Plastic Surgery Hospital, Chinese Academy of Medical Sciences from June to September 2022 were selected for cross-sectional study. The qualitative study method was used to conduct semi-structured in-depth interviews with patients and collect data. After the interview, the 7-step analysis method of Colaizzi phenomenological data was used to extract the topic concepts.Results:A total of 16 patients were included, and their influencing factors for medical treatment could be divided into 5 related topics: (1) age-related; (2) occupation-related; (3) surrounding social-environment-related; (4) social media platforms contacted; (5) experience of negative appearance evaluation during adolescence.Conclusion:Many factors affect the treatment of injection patients. In the course of medical treatment, the influencing factors should be identified accurately, so as to guide patients to seek medical treatment scientifically.

Objective:To identify the influencing factors affecting the cosmetic facial injection treatments for cosmetic patients.Methods:Based on the purposeful sampling principle with maximum diversity and data saturation principle, patients who underwent facial injection cosmetic surgery in Plastic Surgery Hospital, Chinese Academy of Medical Sciences from June to September 2022 were selected for cross-sectional study. The qualitative study method was used to conduct semi-structured in-depth interviews with patients and collect data. After the interview, the 7-step analysis method of Colaizzi phenomenological data was used to extract the topic concepts.Results:A total of 16 patients were included, and their influencing factors for medical treatment could be divided into 5 related topics: (1) age-related; (2) occupation-related; (3) surrounding social-environment-related; (4) social media platforms contacted; (5) experience of negative appearance evaluation during adolescence.Conclusion:Many factors affect the treatment of injection patients. In the course of medical treatment, the influencing factors should be identified accurately, so as to guide patients to seek medical treatment scientifically.

OBJECTIVE To mine the focus and emotional attitude of the public on rare diseases， and to provide decision- making reference for relevant departments to formulate and implement relevant policies， systems and strategies for medical security of rare diseases. METHODS Latent Dirichlet allocation （LDA） topic model and sentiment analysis method were used to analyze the comment text of short videos related to the “nosinasine” medical insurance admission event on the Bilibili video website， mine the theme and sentiment tendency of the text， and put forward relevant strategy suggestions. RESULTS A total of 8 videos with tens of thousands of playback and 7 109 text data were obtained. According to the LDA analysis， online public paid attention to 9 topics related to rare diseases （the price of rare disease drugs， the inclusion of rare disease drugs in medical insurance， the status quo of research and development of rare disease drugs， the scope of medical insurance and the medical security system， the plight of rare disease patients， the prevention and screening of rare diseases， the value of rare disease drugs in medical insurance， the Chinese and western medical methods of rare diseases， and the supply and demand status of rare disease drugs）， which could be summarized into 4 categories according to the objects of concern （rare disease drugs， rare disease medical insurance， rare disease medical and health services and rare disease patient groups）. On the whole， the emotional tendency of the Internet public towards each topic showed a low positive and high negative tendency. CONCLUSIONS The public paid more attention to the price， research and development， supply and demand of rare disease drugs， and was deeply worried about the current medical status of rare diseases in China. To strengthen and improve the medical security for patients with rare diseases， such as actively carrying out public health services for rare diseases， strengthening cooperation in the diagnosis and treatment of rare diseases， and researching rare disease drugs， etc. Chinese medical and health departments can make concerted efforts in medical and health services， drug supply security， medical security and other social security.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Early diagnosis and effective management are important to reduce atrial fibrillation-related adverse events. Photoplethysmography (PPG) is often used to assist wearables for continuous electrocardiograph monitoring, which shows its unique value. The development of PPG has provided an innovative solution to AF management. Serial studies of mobile health technology for improving screening and optimized integrated care in atrial fibrillation have explored the application of PPG in screening, diagnosing, early warning, and integrated management in patients with AF. This review summarizes the latest progress of PPG analysis based on artificial intelligence technology and mobile health in AF field in recent years, as well as the limitations of current research and the focus of future research.
Humans ; Atrial Fibrillation/therapy* ; Photoplethysmography ; Artificial Intelligence ; Electrocardiography ; Biomedical Technology

Objective:To analyze the accuracy of a single-lead electrocardiogram (iECG) algorithm based on intelligent wristwatch in identifying sinus tachycardia and atrial fibrillation (AF) with rapid ventricular rate.Methods:In this non-randomized control trial, 642 patients aged ≥18 years were enrolled in the General Hospital of Chinese PLA between December 15, 2020 and May 30, 2022, with sinus tachycardia or rapid ventricular rate of AF (ranging from 111 to 145 beats/min for sinus tachycardia, from 110 to 150 beats/min for rapid ventricular rate of AF, respectively). The patients wore Huawei Watch GT2 Pro smartwatches on their left wrists, and the physiological signals detected by the smartwatches in a relaxed state were used as the measured data. The iECG algorithm developed by Huawei was used for identification. Simultaneously, 12-lead electrocardiograms (12L-ECG) were performed, and two cardiologists served as the gold standard for interpretation. Three participants who did not meet the inclusion criteria were excluded based on the detection results, and a total of 639 participants were included in the study. The accuracy of the algorithm in identifying sinus tachycardia and rapid ventricular rate AF was evaluated using metrics such as recall rate, precision rate, macro F1 score for multi-class classification.Results:Among 639 subjects, there were 469 males and 170 females. There were 389 cases of sinus tachycardia and 250 cases of rapid ventricular rate AF, with a mean age of (46.53±13.32) years. The recall rate, precision rate, and F1 value of iECG algorithm in identifying sinus tachycardia was 98.7%, 99.2% and 99.0%, respectively, while it was 98.8%, 98.0% and 98.4%, respectively for AF with rapid ventricular rate. The macro F1 of AF with rapid ventricular rate and sinus tachycardia was 98.7%. The iECG based on the intelligent wristwatch showed good consistency with the corresponding 12L-ECG waveforms.Conclusion:The intelligent wristwatch-based iECG algorithm can effectively identify sinus tachycardia and rapid ventricular rate AF, demonstrating good accuracy.