OBJECTIVE To optimize the free examination, traceability, cost settlement and privacy protection during the development of pediatric drug clinical trials by means of information technology, so as to improve the efficiency and quality of project operation. METHODS Based on the existing hospital information system, multi department joint designed and implemented an information system for the settlement of the diagnosis and treatment expenses for drug clinical trial, which realized the real-time settlement of medical costs for drug clinical trials without the need for advance reimbursement of subjects' guardians. RESULTS This system took into account both cost and function, and had good feasibility. It could effectively improve the operation efficiency of drug clinical institutions, ensure the traceability of diagnosis and treatment data, and optimize the experience and privacy protection of child subjects. CONCLUSION The development and design of this system can effectively improve the operating efficiency of pediatric drug clinical trials, and has a good reference for other new record institutions to solve such problems.

Objective To provide strategies and suggestions for the development of clinical research in children's spe-cialized hospitals.Methods With a Class A tertiary children's specialty hospital in Shanghai as an example,the SWOT model is used to analyze the strengths,weaknesses,opportunities,and threats of clinical research development in the hospital,and to propose corresponding strategies and suggestions.Results The hospital has distinguished disciplinary advantages,tremendous strength in scientific research,a strong team of talents,and steady progress in the construction of clinical research center.The weaknesses include imperfect clinical research management system,imperfect informatization construction,and insufficient allo-cation of full-time management personnel.There are now opportunities of high policy support,increasing funding support,the shift in clinical demand,and good prospects for development of investigator-initiated trials(IIT).The hospital is also faced with the threat of difficulty in conducting pediatric clinical research and fierce competition among similar hospitals.Conclusion We could promote the development of pediatric clinical research by incentivizing the conduction of clinical research,strengthening the construction of clinical research system,improving the clinical research capabilities,and building a collaborative network for ped-iatric multicenter clinical research.

The idiopathic inflammatory myopathies encompass a diverse array of autoimmune diseases,characterized by muscular inflammation and various extramuscular manifestations.These conditions have the poten-tial to impact multiple organs,including the lungs,skin,joints,gastrointestinal tract,and heart.The defining features of these conditions are muscle weakness and myalgia.Although cardiac involvement is infrequent,its clinical manifestations are subtle and easily overlooked.Cardiac damage represents a significant contributor to mortality and morbidity in patients with idiopathic inflammatory myopathy.Early and accurate identification of cardiac involve-ment may facilitate improved patient outcomes.This article provides an overview of the potential etiology,clinical presentations,risk factors,biomarkers,and imaging studies for early diagnosis of cardiac involvement in idio-pathic inflammatory myopathy.This review aims to enhance clinicians'understanding and diagnostic capabilities re-garding cardiac involvement in idiopathic inflammatory myopathy while promoting early intervention strategies for lifelong management and improved prognosis.

Osteoarthritis （OA） is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs （NSAIDs）， which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA， with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope， multiple targets， and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species （ROS）， relieve oxidative stress （OS） damage， and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde （MDA） and superoxide dismutase （SOD）. Through the modulation of signaling pathways such as nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa B （NF-κB）， c-Jun N-terminal kinase （JNK）， NOD-like receptor protein 3 （NLRP3）， and osteoprotegerin （OPG）， they downregulated the expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， thereby effectively relieving local joint inflammation， protecting chondrocytes and bone tissue， inhibiting chondrocyte apoptosis， and further alleviating the progression of OA. Currently， there are still certain limitations in the medical research status and development trends of OA， necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA， providing new directions and ideas for future research.

Objective The purpose of this article is to summarize and review the current status of the construction of clinical research evaluation systems in domestic public hospitals,identify existing problems in the evaluation system,and propose development strategies and suggestions.Methods Retrieved relevant articles,dissertations and policies from the past five years(2018-2022),screened the titles,viewed the full texts of 52 selected papers and their references,and summarized them.Results The"five-only"indicators have long been an important indicator for evaluating clinical research in public hospitals,but in today's scientific research environment and policy environment,the"five-only"evaluation system has revealed its utilitarian draw-backs and gradually evolved into a hindrance to scientific research.It is urgent to break through the"five-only"orientation and establish a clinical research evaluation system oriented towards"transforming and applying transformation of scientific research achievements".Conclusion The evaluation system for clinical research should break the previous"five-only"evaluation model based on quantity-oriented scientific research evaluation.We can draw on the framework of the research output,influence,and environment indicators in the UK's REF Excellence Framework model,combine the American APT system and the Chinese STEM indicator dimensions,explore multi-outcome evaluation,integrate developmental indicators,and continuously improve the indica-tor system and application methods in practice to promote the development of clinical research in public hospitals.

Objective:This study aimed to discuss the risks associated with investigator-initiated pediatric drug clinical trials in terms of drug management and put forward relevant suggestions to improve the standardization and quality of pediatric clinical trials.Methods:The risk in the implementation of pediatric drug clinical trials initiated by domestic researchers were discussed and the countermeasures were put forward by reviewing literature, laws and regulations, and combining with the problems related to research drugs in project management.Results:In investigator-initiated pediatric drug clinical trials, the variety of research drug sources, such as sponsor donations, hospital pharmacy supplies, and community pharmacy provisions, posed distinct management risks that would require tailored attention. Moreover, the specific risk of pediatric medication should be fully considered during study execution. It was imperative for medical institutions to strengthen comprehensive management of research drugs to ensure the trial′s smooth operation.Conclusions:Investigator-initiated pediatric drug clinical trials serve as valuable supplements that expand new drugs′ trial scope for children. While actively conducting these trials, it is recommended that medical institutions should strengthen project approval reviews from the perspectives of drug supply, subject compensation and child dosage form, implement centralized management of research drugs, attach importance to ethical review of adverse drug events, strengthen personnel training and leverage information settlement, so as to improve work efficiency and research quality-ultimately providing support for pediatric pharmaceutical development efforts as well as promoting high-quality advancements within Chinese pediatrics medicine.

Objective:To explore the correlation between the expression level of the serum CircRNA_ 0005853 and cognitive impairment in elderly patients with acute cerebral infarction (ACI).Methods:A total of 120 elderly patients with ACI admitted to Haikou Third People′s Hospital from January 2019 to March 2022 were retrospectively selected. According to the Montreal Cognitive Assessment (MoCA) score of the patients 4 weeks after treatment, they were divided into a cognitive impairment free group (MoCA score≥26, 55 cases) and a cognitive impairment group (MoCA score<26, 65 cases). The cognitive impairment group was redivided into mild group (MoCA score 21-25, 16 cases), moderate group (MoCA score 15-20, 38 cases), and severe group (MoCA score<15, 11 cases) based on the severity of cognitive impairment. The serum CircRNA_0005853 expression level of each group was compared. multivariate logistic regression analysis was applied to identify the risk factors for cognitive impairment after ACI. A receiver operating characteristic (ROC) curve was drown to analyze the value of CircRNA_0005835 expression level in predicting cognitive impairment. Using Pearson correlation analysis, the correlation between the expression level serum CircRNA_0005835 and MoCA score in patients with cognitive impairment was analyzed.Results:There were statistically significant differences in age, infarct size, and triglycerides between the cognitive impairment group and the non cognitive impairment group (all P<0.05). The MoCA score of the cognitive impairment group was lower than that of the non cognitive impairment group [(19.62±2.73)points vs (28.10±1.05)points, P<0.001]. The expression level of Serum CircRNA_0005835 in the cognitive impairment group was higher than that of the non cognitive impairment group (2.48±1.02 vs 1.25±0.46, P<0.001), and in the severe group, the expression level of the serum CircRNA_0005835 (2.90±1.26) was higher than that of the moderate group (1.87±0.84) and the mild group (0.92±0.35) ( P<0.001). Multivariate logistic regression analysis shew that age ( OR=1.662, 95% CI: 1.140-2.873), infarct size>3.0 cm 2 ( OR=1.853, 95% CI: 1.317-4.112), and CircRNA_0005835 ( OR=2.217, 95% CI: 1.635-5.540) were risk factors for cognitive impairment after ACI. The area under the curve (AUC) of CircRNA_0005835 expression level predicting cognitive impairment was 0.837(95% CI: 0.779-0.894), with a sensitivity of 80.2% and a specificity of 83.7%. The AUC of CircRNA_0005835 expression level predicting cognitive impairment was 0.837(95% CI: 0.779-0.894), with a sensitivity of 80.2% and a specificity of 83.7%. The correlation analysis shew that the expression level of serum CircRNA_0005835 in elderly ACI patients was negatively correlated with MoCA score ( r=-0.773, P<0.001). Conclusions:The increased expression level of serum CircRNA_0005853 is related to the occurrence and development of cognitive dysfunction after elderly ACI, and has certain value in predicting cognitive dysfunction.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

ObjectiveTo analyze the characteristics of death and premature death of 4 major chronic diseases （cardiovascular and cerebrovascular diseases， malignant tumors， chronic respiratory diseases and diabetes） in Taizhou City from 2011 to 2018，and provide data basis for the government to formulate chronic disease prevention planning. MethodsThe death data of household registration residents in Taizhou City from 2011 to 2018 were derived from the Chronic Disease Surveillance Information Management System in Zhejiang Province. The death toll ratio of chronic diseases， the mortality rate of chronic diseases， the probability of premature death of chronic diseases were analyzed. The standardization rate was calculated six times in 2010. Population composition of the census. The Joinpoint Regression Program 4.2 software was used for calculating annual percent change （APC） and its statistical test results. ResultsFrom 2011 to 2018， there were 231 724 chronic disease deaths in Taizhou City， with a mortality rate of 486.52/10⁵ and a standardized mortality rate of 381.55/10⁵. The proportion of chronic disease deaths to total deaths was 79.89%， of which males were higher than females and rural areas were higher than urban areas.From 2011 to 2018， the standardized mortality and early death probability of cardiovascular and cerebrovascular diseases， malignant tumors and chronic respiratory diseases in Taizhou showed a downward trend （P<0.05）， the standardized mortality of diabetes （P=0.46） and the early death probability （P=0.22） did not decline， and the mortality of all age groups of the above four types of chronic diseases in rural areas was higher than that in urban areas. The mortality of the four types of chronic diseases from high to low are cardiovascular and cerebrovascular diseases， malignant tumors， chronic respiratory diseases and diabetes， and the mortality tends to increase with age. From 2011 to 2018， the probability of premature death from four types of chronic diseases in Taizhou City showed a downward trend， from 13.49% in 2011 to 10.49% in 2018， with an average annual decrease of 2.97%. The difference was statistically significant （t=‒5.83，P<0.05）. ConclusionChronic disease death is the main cause of death in Taizhou City. In order to reduce the mortality rate of chronic diseases， effective prevention and control measures for chronic diseases should be carried out， especially the prevention and control of diabetes and male chronic diseases.

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.