Bronchial asthma （asthma for short） is a common clinical respiratory disease mainly characterized by chronic airway inflammation， with complicated pathogenesis and a long treatment cycle. It is lingering and difficult to be cured， and lack specific drugs. Oxidative stress is a new focus in the research on the pathogenesis of asthma and a potential key target for the treatment. Under physiological conditions， the oxidative and antioxidative systems in the body are in a dynamic balance， and the two antagonize each other to maintain normal life activities. In the case of asthma attack， oxidation products such as reactive oxygen species （ROS）， malondialdehyde （MDA）， and nitric oxide （NO） are produced excessively， while the content of antioxidants such as superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） is reduced. As a result， the oxidation exceeds the removal of oxidation products， which aggravates oxidative stress. In addition， the overproduction of ROS activates oxidative stress-related signaling pathways to produce pro-inflammatory factors， exacerbating inflammation， which leads to lung and airway tissue damage. In recent years， traditional Chinese medicine has garnering increasing attention because of the unique advantages in the treatment of asthma， especially in regulating redox balance， alleviating oxidative stress in asthma patients， and reducing inflammation. On the one hand， by inhibiting the mitogen-activated protein kinase （MAPK） and transcription factor （NF）-κB signaling pathways， traditional Chinese medicine can reduce the content of oxidation products and pro-inflammatory factors from the source. On the other hand， by activating the nuclear factor-erythroid 2-related factor 2 （NrF2） signaling pathway， traditional Chinese medicine can elevate the levels of antioxidant enzymes and enhance the antioxidant system to neutralize the excessive accumulation of oxidation products. Therefore， the adjustment of redox balance state by traditional Chinese medicine may be a new means and a new direction for the prevention and treatment of asthma in the future. This paper summarizes the oxidative stress-related pathways in the pathogenesis of asthma and reviews the latest research progress in the regulation of oxidative stress-related pathways by Chinese medicine extracts and prescriptions in the treatment of asthma， with a view to providing a fuller， more solid， and more scientific theoretical basis for the clinical and basic research on the prevention and treatment of asthma by traditional Chinese medicine.

Background::Artificial intelligence (AI) technology represented by deep learning has made remarkable achievements in digital pathology, enhancing the accuracy and reliability of diagnosis and prognosis evaluation. The spatial distribution of CD3 + and CD8 + T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer (CRC). This study aimed to investigate CD3 CT (CD3 + T cells density in the core of the tumor [CT]) prognostic ability in patients with CRC by using AI technology. Methods::The study involved the enrollment of 492 patients from two distinct medical centers, with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation cohort. To facilitate tissue segmentation and T-cells quantification in whole-slide images (WSIs), a fully automated workflow based on deep learning was devised. Upon the completion of tissue segmentation and subsequent cell segmentation, a comprehensive analysis was conducted.Results::The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3 CT and CD3-CD8 (the combination of CD3 + and CD8 + T cells density within the CT and invasive margin) in predicting mortality (C-index in training cohort: 0.65 vs. 0.64; validation cohort: 0.69 vs. 0.69). The CD3 CT was confirmed as an independent prognostic factor, with high CD3 CT density associated with increased overall survival (OS) in the training cohort (hazard ratio [HR] = 0.22, 95% confidence interval [CI]: 0.12–0.38, P <0.001) and validation cohort (HR = 0.21, 95% CI: 0.05–0.92, P = 0.037). Conclusions::We quantify the spatial distribution of CD3 + and CD8 + T cells within tissue regions in WSIs using AI technology. The CD3 CT confirmed as a stage-independent predictor for OS in CRC patients. Moreover, CD3 CT shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.

Objectives:To examine the feasibility of using foundation model in computer vision for echocardiographic left ventricular ejection fraction measurement. Methods:Based on the most extensive publicly accessible repository of echocardiographic loops,EchoNet-Dynamic,featuring 10024 recordings from individual patients,a foundation model in computer vision,VideoMAE V2,was fine-tuned,validated,tested using 7460,1288,and 1276 echocardiographic loops,respectively. Results:The mean absolute error between left ventricular ejection fraction measurements of VideoMAE V2 and expert's measurements was 3.94％ (95％CI:3.79％-4.11％).The Pearson's correlation coefficient was 0.91 (95％CI:0.89-0.92).Additionally,VideoMAE V2 demonstrated exceptional accuracy in identifying patients with a left ventricular ejection fraction below 50％,achieving an AUC of 0.96 (95％CI:0.95-0.97). Conclusions:This study validates the feasibility of using foundation model in computer vision for measuring left ventricular ejection fraction in echocardiographic loops and lays the foundation for the development of a generalized multimodal automated interpretation system for echocardiography.

Promoting the transformation and development of public hospitals into clinical research-oriented hospitals is the necessary way for China to deepen the reform of medicine and health system. In August 2019, Henan Cancer Hospital deeply combined the key elements of clinical research management with the concept of multidisciplinary collaborative governance, created an offline operating end of collaborative governance (including the front collaborative recruitment system, the middle collaborative quality management system, and the terminal collaborative transformation system), built a supporting internet plus intelligent auxiliary end (including the intelligent recruitment manager, the intelligent quality manager and the intelligent transformation manager), and built a clinical research intelligent management mode covering the trinity of subject recruitment, clinical research quality control, and innovation achievements transformation. The hospital focused on management elements such as " focusing on quality, improving efficiency, and increasing motivation" , and drove the front, middle, and terminal ends of the model to work together, to ensure the quality and efficiency of clinical research and achieve a comprehensive improvement in the hospital′s clinical research level. As of December 2023, the hospital had undertaken over 2 000 clinical research projects of various types, with a cumulative amount of clinical research conversion contracts exceeding 53 million yuan. This practice had achieved good results and could provided references for other tertiary public hospitals to promote high-quality development of clinical research.

Objective:To explore the current situation and related factors of asphyxia prevention and management for the elderly in elderly care institutions, so as to provide a reference for improving the safety management of elderly care institutions.Methods:This research was a cross-sectional survey. From December 2020 to January 2021, convenience sampling was used to select 43 elderly care institutions from the China Aged Care Alliance. The self-designed questionnaire was used to collect the content related to asphyxia prevention and management for the elderly in institutions, and analyze its current situation and related factors. A total of 43 questionnaires were distributed in this survey, and 43 were recovered, with a recovery rate of 100%.Results:Among the 43 elderly care institutions, and 3 (6.98%) were state-run, and 22 (51.16%) were private, and 18 (41.86%) were public and private. The average occupancy rate was (67.63±20.59) %, and the average proportion of moderate to severe disability among the elderly residents was (80.10±20.25) %. The proportions of elderly care institutions that formulated systems and regulations for monitoring and early warning of asphyxia events, reporting of asphyxia events, analysis and improvement of asphyxia incidents in the elderly were 53.49%, 51.16%, and 51.16%, respectively. The proportions of elderly care institutions that carried out asphyxia risk screening, swallowing function assessment, and swallowing function training for the elderly residents were 65.12%, 51.16%, and 46.51%, respectively.Conclusions:Most elderly care institutions have problems in the prevention and management of asphyxia for the elderly, which needs to be improved. It is recommended that building a complete asphyxia prevention and management system, carrying out risk screening, assessment and training of swallowing function for high-risk groups, strengthening the professional training of agency leaders and caregivers, and seeking continuous external professional support so as to improve the safety management system of elderly care institutions, and ensure the quality of life and personal safety of the elderly.

Pyrroloquinoline quinone (PQQ), an important redox enzyme cofactor, has many physiological and biochemical functions, and is widely used in food, medicine, health and agriculture industry. In this study, PQQ production by recombinant Gluconobacter oxydans was investigated. First, to reduce the by-product of acetic acid, the recombinant strain G. oxydans T1 was constructed, in which the pyruvate decarboxylase (GOX1081) was knocked out. Then the pqqABCDE gene cluster and tldD gene were fused under the control of endogenous constitutive promoter P0169, to generate the recombinant strain G. oxydans T2. Finally, the medium composition and fermentation conditions were optimized. The biomass of G. oxydans T1 and G. oxydans T2 were increased by 43.02% and 38.76% respectively, and the PQQ production was 4.82 and 20.5 times higher than that of the wild strain, respectively. Furthermore, the carbon sources and culture conditions of G. oxydans T2 were optimized, resulting in a final PQQ yield of (51.32±0.899 7 mg/L), 345.6 times higher than that of the wild strain. In all, the biomass of G. oxydans and the yield of PQQ can be effectively increased by genetic engineering.
Fermentation ; Gene Knockout Techniques ; Gluconobacter oxydans ; genetics ; metabolism ; Industrial Microbiology ; methods ; Multigene Family ; genetics ; Organisms, Genetically Modified ; PQQ Cofactor ; biosynthesis ; genetics ; Promoter Regions, Genetic ; genetics

Objective Summarize and share the working practice of Investigator Research Ethics and Research Integrity Training conducted at Peking University Human Research Protection Program (PKU HRPP) ,to further explore continuing quality improvement of investigator ethical training at university level .Methods Conduct systematic review of the archiving files of PKU HRPP investigator training activities during 2012-2018 ,summarize feedback information from investigators to i-dentify possible experiences for sharing and space for improvement .Results There are some positive experiences for sharing a-bout the training mechanism and practices at PKU HRPP .Conclusions Based on the previous ethical training work and experi-ences at PKU HRPP ,possible proposals for continuing quality improvement may including :strengthening the requirements of ethical training of investigators ,encouraging and recognizing ethical training conducted by research teams ,emphasizing training Quality and the promotion of sharing and mutual recognition mechanisms for ethical training .

Objective To obtain a thyroid cancer cell line integrated with luciferase and fluorescence,and to establish a metastatic nude mouse model of papillary thyroid cancer monitored with in vivo imaging system. Methods Lentivirus carrying recombinant plasmid containing luciferase gene and mCherry gene infected high malignant papillary thyroid cancer cell line (BHP10-3SCmice). The stable thyroid cancer cell line (BHP10-3mluc) labeled with luciferase and mCherry selected by hygromycin, analyzed for fluorescence with fluorescence microscopy and bioluminescence with in vitro analysis and in vivo imaging. 0.25 ml(5×106/ml)BHP10-3mluc cell suspension were injected into the left thigh intramuscular tissue of 5-week-old nude mice to establish BALB/C nude mice metastatic tumor model. The growth and metastasis of the tumors were monitored weekly with in vivo imaging system. The nude mice were sacrificed on the 42th day and the tissues with metastatic tumors were analyzed by fluorescent imaging ex vivo. The ectopic implanted tumors and metastatic lesions were verified by tissue sections with Hematoxylin and Eosin staining. Results BHP10-3mluc cells showed similar growth characteristics to the original BHP10-3SCmice cells and stably expressed luciferase and mCherry. At the end of the first week after ectopic implantation,the xenograft tumors were found and in the 6th week,the tumors were found to metastasized to adjacent lymph nodes and lungs,which was consistent with the results of pathology.The growth and metastasis of tumors can be accurately monitored with in vivo imaging system. Conclusions A PTC cell line stably expressing bioluciferase and fluorescence was successfully established.The nude mouse model of PTC metastatic tumor generated by intramuscular inoculation of those cells can be well monitored with in vivo imaging system, which provides ideal models for researches on tumor growth, metastasis,and drug treatment.

Locoweeds are presently defined as those species of the genera Oxytropis and Astragalus (family Leguminosae) that specifically contain the key toxic constituent,swainsonine.After ingesting locoweeds,livestock can develop poisoning disease characterized by chronic dysfunction of the nervous system,which causes severe economic losses to the pastoral areas.In addition,swainsonine has attracted a great attention from toxicology and medicine fields,due to its dual role of toxicity and pharmacological activity.This review not only summarizes the latest research progress of toxicity and its poisoning mechanism,pharmacological activity,source,and biosynthesis pathway of swainsonine,but also speculates the possible regulatory enzymes involved in the synthesis pathway.Moreover,the future research on swainsonine is also looked ahead,which provide references for the prevention and treatment of locoism.