ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

OBJECTIVE To provide suggestions for improving the path and system construction of patient engagement in drug regulation in China. METHODS By reviewing initiatives and experiences from the United States （U. S.）， European Union （EU）， and Japan in promoting patient engagement， this study summarizes the roles and contributions of patients in the entire drug regulatory process internationally. Combining China’s current progress and challenges in patient engagement， specific proposals are formulated to refine regulatory pathways and institutional systems. RESULTS & CONCLUSIONS With growing global emphasis on patient engagement as a regulatory strategy， countries or regions such as the U.S.， EU， and Japan have established clear policies， designated oversight agencies， and developed diversified pathways for patient engagement. Patients contribute to regulatory processes through advisory meetings， direct decision-making roles， and leveraging lived experiences and expertise to optimize drug evaluation and monitoring. In contrast， China’s patient engagement remains primarily limited to clinical value- oriented drug development， lacking formal policy guidance. It is recommended that China， based on its existing policy system， further strengthen the construction of a safeguard system for patient engagement， improve the capacity building and pathway models for patient participation in pharmaceutical regulation， and promote the continuous development of patient engagement in pharmaceutical regulation in our country.

The traditional Chinese medicine （TCM） myocardial infarction （MI） unit is a standardized， regulated， and continuous integrated care unit guided by TCM theory and built upon existing chest pain centers or emergency care units. This unit emphasizes multidisciplinary collaboration and forms a restructured clinical entity without altering current departmental settings， offering comprehensive diagnostic and therapeutic services with full participation of TCM in the treatment of MI. Its core medical model is patient-centered and disease-focused， providing horizontally integrated TCM-based care across multiple specialties and vertically constructing a full-cycle treatment unit for MI， delivering prevention， treatment， and rehabilitation during the acute， stable， and recovery phases. Additionally， the unit establishes a TCM-featured education and prevention mechanism for MI to guide patients in proactive health management， reduce the incidence of myocardial infarction， and improve quality of life.

Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO₂), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO₂ plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.

Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

Background::We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse model.Methods::In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups ( n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and hiPSC-CMs. Results::After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMs via enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significantly suppressed the production of malondialdehyde and lactate dehydrogenase and the reduction in glutathione content induced by hypoxia in both HUVECs and hiPSC-CMs in vitro. Conclusions::MLB significantly enhanced the potential of hiPSC-CMs in repairing injured myocardium by improving endothelial cell function via the NF-κB/ICAM1 pathway and inhibiting hiPSC-CMs apoptosis via the DUSP2/STAT3 pathway.

OBJECTIVE To explore the applicablity of 'BlueScreen HC'(BSHC),a high throughput genotoxicity screening system based on human growth arrest and DNA damage inducible 45α(GADD45α)gene,in detecting the genotoxicity of migrants mixtures from food contact materials(FCM).METHODS The 2000 bp sequence upstream of the open reading frame of human GADD45α gene was used as the promoter to construct the lentiviral plasmid pEZX-LvPG04,which was double labeled by purinamycin and Gausluciferase(Gluc),and the lentiviral plasmid was infected with human lymphoblastocyte TK6 to obtain a stable transmutation cell line TK6-Gluc.Methyl methylate(MMS)at concentrations of 0,1.56,3.13,6.25,12.5,25.0 and 50.0 mg·L-1 was selected as the genotoxin without liver S9,cyclophosphamide(CTX)0,0.78,1.56,3.13,6.25,12.5,25.0 mg·L-1 was selected as the pre-genotoxin with liver S9,and dimethyl sulfoxide(DMSO)0,0.35,0.69,1.38,2.75,5.5 and 11.0 g·L-1 was selected as the non-genotoxin.The constructed BSHC was verified with the above known genetic positive and negative substance respectively.Polybutyleneadipate-co-terephthalate(MS/PBAT)was tested using 4% (V/V)acetic acid,and 10%,20%,50% and 95% (V/V)ethanol as food simulants at 40℃for 24 hours to obtain 5 multi-component migrants of MS/PBAT that were obtained by using DMSO as a solvent.TK6-Gluc cells were treated with 5 multi-component migrants of MS/PBAT at concentrations of 0,0.38,0.76,1.53,3.05,6.10 and 12.20 g·L-1 with or without liver S9.Cells were treated without liver S9 for 48 h.Cells treated with liver S9-mix were incubated for 3 h at a final concen-tration of 1% (V/V)liver S9 before being washed and re-suspended in fresh recovery media for another 45 h.After exposure,the cell viability was detected using the CCK-8 cell activity kit,and the Gluc Lumi-nescence in the medium was detected with Secrete-PairTM Gaussia Luciferase Assay Kit.In addition,the mutagenicity on Salmonella typhimurium TA98 and TA100 was detected by micro-fluctuation Ames test with 5 multi-component migrants of MS/PBAT at concentrations of 3.05 and 12.20 g·L-1.The in vitro mammalian cell chromosome aberration test was performed on CHL cells with 5 multi-component migrants of MS/PBAT at concentrations of 3.05 and 12.20 g·L-1 to detect the chromosomal aberration.The results of genotoxicity were compared with those of BSHC.RESULTS The lowest effect centra-tion(LEC;<80% relative cell viability)and the coytotoxicity(<30% relative cell viability)was defined.A positive genotoxicity result threshold was determined at 1.8-fold relative induction.For the liver S9 protocol,the same process was followed,and the decision threshold derived was 1.5-fold relative Gluc induction.It is considered as genetic substance only when a positive genotoxicity result was reached and there was no cytotoxicity.Compared with the vehicle control group,no genotoxicity was observed at all concentration of DMSO by BSHC.MMS 12.5,25.0 and 50.0 mg·L-1 produced genotoxicity without liver S9 while CTX 6.25,12.5 and 25.0 mg·L-1 produced genotoxicity with liver S9.Significant cell growth inhibition was observed in 95% ethanol migrants of MS/PBAT at concentrations of 6.10 and 12.20 g·L-1,and in 50% ethanol migrants of MS/PBAT at a concentration of 12.20 g·L-1 without liver S9.No cytotoxicity with a relative cell viability below 30% was observed in any of the treatment groups,and no high expression of Gluc was observed.Therefore,none of the 5 multi-component migrants produced genotoxicity without liver S9.Significant cell growth inhibition was observed in 95% ethanol migrants of MS/PBAT at a concentration of 12.20 g·L-1,and in 4% acetic acid migrants of MS/PBAT at concentrations of 6.10 and 12.20 g·L-1 with liver S9.No cytotoxicity with a relative cell viability below 30% was observed in any of the treatment groups.No high expression of Gluc was observed.There-fore,none of the 5 multi-component migrants produced genotoxicity with liver S9.In the micro fluctua-tion Ames test,when 5 multi-component migrants of MS/PBAT were treated with concentrations of 3.05 and 12.20 g·L-1 on TA98 and TA100 strains,there was no significant difference in the number of muta-genic positive wells compared with DMSO control group with or without liver S9,indicating that no mutagenic effect was produced.When CHL cells were treated with 5 multi-component migrants of MS/PBAT at concentration of 3.05 and 12.20 g·L-1,compared with DMSO control group,there was no signifi-cant difference in chromosome aberration rate of CHL cells with or without liver S9.CONCLUSION BSHC based on GADD45α gene has been established,which can be used for in vitro genotoxicity eval-uation of migrants mixtures of FCM,but further exploration of its minimum effective concentrations is still needed,and more types of mixtures need to be applied for further validation.