Diabetic cardiomyopathy is a distinct form of cardiomyopathy that can lead to heart failure, arrhythmias, cardiogenic shock, and sudden death. It has become a major cause of mortality in diabetic patients. The pathogenesis of diabetic cardiomyopathy is complex, involving increased oxidative stress, activation of inflammatory responses, disturbances in glucose and lipid metabolism, accumulation of advanced glycation end products (AGEs), abnormal autophagy and apoptosis, insulin resistance, and impaired intracellular Ca²⁺ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor‑α (PPAR‑α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR‑α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone.

Oromucosal drug delivery preparations offer advantages such as convenient administration,suitability for patients with dysphagia,rapid onset of action,and avoidance of first-pass metabolism in the liver.The 2020 edition of the Chinese Pharmacopoeia,EP11.0,BP2022,USP44-NF39,and JP18 all include relevant standards for the quality control of different oromucosal drug delivery systems.This article compares the differences in general re-quirements for oromucosal formulations among different countries and provides an overview of inspection items for marketed oral mucosal formulations and those documented in pharmacopoeias both domestically and internationally.Foreign pharmacopoeias include a wide range of oromucosal drug delivery formulations,with more refined quality control measures for systemic action.These findings can serve as a reference for the improvement and enhancement of standards for oromucosal drug delivery systems in China.

Objective:To explore the real experience and needs of parents of adolescent patients with non-suicidal self-injury.Methods:Using the descriptive phenomenological research method. A total of 20 parents of non-suicidal self-injury adolescent patients who received treatment at the Second Affiliated Hospital of Xinxiang Medical University (Henan Provincial Psychiatric Hospital) from May to October 2022 were selected by purposive sampling for semi-structured interviews. Colaizzi 7-step analysis method was used to analyze, summarize and extract the subjects of the data.Results:The real experience of parents of adolescents with non-suicidal self-injury could be summarized into five themes, which were complex psychological reaction in the early stage, negative impact on the family, desire for more professional support, benefit and growth and negative coping in the later stage.Conclusions:Medical staff should pay attention to the mental health of parents of adolescents with non-suicidal self-injury and the negative effect of non-suicidal self-injury on their families, meet the emotional and knowledge needs of parents of adolescents with non-suicidal self-injury, especially pay attention to their negative coping in the later stage and formulate targeted intervention plans according to different stages, so as to build a good family rehabilitation environment and reduce the incidence of non-suicidal self-injury in adolescents.

Objective To compare the effect of 8-week high-intensity interval training(HIIT)and moderate-intensity continuous training(MICT)on body composition and cardiovascular risk biomarkers in middle-aged and elderly obese women,so as to provide theoretical and practical basis for future in-tervention.Methods Thirty-four middle-aged and elderly obese women were randomly divided into an HIIT group(n=13),a MICT group(n=12)and a CON group(n=9).All subjects underwent a laboratory VO2max test before intervention to determine their corresponding exercise load.Then,HIIT group rode a power bicycle for 2 minutes at 80%～85%VO2max intensity and 1 minute at 30%VO2max intensity,re-peated 10 times,while MICT group rode at 65%VO2max intensity for 30 minutes,3 times a week for 8 weeks.CON group did exercise.Before and after intervention,all groups were measured their body weight,body fat,muscle mass,body fat rate,as well as the serum levels of high-sensitivity c-reac-tive protein(hs-CRP),endothelin-1(ET-1),lipoprotein(a)[Lp(a)]and homocysteine(Hcy).Results Af-ter intervention,there was a significant decrease in the body fat and body fat rate(P<0.05)and a sig-nificant increase in muscle mass(P<0.05)in the HIIT group,while there were no significant changes in the above three values in the MICT group(P>0.05).Moreover,there was a significant decrease in hs-CRP and ET-1 of the HIIT group(P<0.01),and a significant increase in Hcy and Lp(a)of the CON group(P<0.01).Meanwhile,the decrease in hs-CRP(P<0.05),Lp(a)(P<0.05)and Hcy(P<0.01)of the HIIT group,as well as that in Hcy(P<0.05)of the MICT group were significantly higher than the CON group.What's more,no significant differences were observed between HIIT and MICT groups in their effects(P>0.05).Conclusions HIIT is superior to MICT in improving body composition and reducing serum levels of hs-CRP and ET-1 in middle-aged and elderly obese women.Moreover,it has a positive effect on improving chronic inflammatory state and vascular endothelial function,to a certain extent,and lowering their risk of suffering from cardiovascular diseases.

OBJECTIVE To explore suitable storage and transportation conditions for “internet plus drug delivery” under high- temperature conditions. METHODS A survey on high-temperature conditions in summer in Beijing was conducted； a retrospective analysis was conducted on “internet plus drug delivery” orders in our hospital from July 2021 to June 2022， summarizing the proportion and delivery range of drugs under different storage and transportation conditions. Additionally， simulation and validation experiments were performed to investigate optimal drug storage and transportation devices for “internet plus drug delivery” in Beijing under high-temperature conditions in summer. RESULTS The monthly average temperature in Beijing from June to August consistently exceeded 25.0 ℃ between 1991 and 2022. From July 2021 to June 2022， a total of 104 drugs were required to be stored below 25.0 ℃， accounting for 31.23% of the 333 drugs listed in our hospital’s “internet plus drug delivery” catalog in Beijing. These drugs were delivered 1 058 times， accounting for 19.63% of the total deliveries. Simulation and validation experiments demonstrated that the average maximum temperature during the next-day delivery process of “carton + foam box + composite aluminum film pearl cotton + 500 g ice bag×2 + gas column bag” was 9.6 ℃， the average minimum temperature was 2.7 ℃， and all the temperatures remained below 15.0 ℃， which could effectively ensure the quality of drugs. CONCLUSIONS Under the high-temperature conditions in summer in Beijing， the storage and transportation device of “carton + foam box + composite aluminum film pearl cotton + 500 g ice bag×2 + gas column bag” can meet the temperature requirements specified in the drug storage instructions for Beijing intra-city drug delivery.

Moyamoya angiopathy is a chronic progressive occlusive intracranial vasculopathy, and CT angiography, MRI, digital subtraction angiography are the auxiliary examinations. Headache is a common symptom in Moyamoya angiopathy (MMA ) patients, and the phenotypes of headache attributed to MMA mainly include migraine-like headache and tension type-like headache; mechanism involves in dilatation of intracranial and extracranial arteries and leptomeningeal collaterals, cerebral hypoperfusion, vascular endothelial damage, genetic susceptibility, and mental stress. Strategies such as surgical revascularization and medical treatment are given. This article focuses on clinical manifestations, pathogenesis, diagnoses, treatments and prognoses of headache attributed to MMA, in order to deepen the understanding of clinical workers on this symptom.

[摘 要] 目的：探讨贝母素乙对结肠癌HCT116细胞增殖的抑制作用及其分子机制。方法：利用不同浓度的贝母素乙处理人结肠癌细胞HCT116和正常结肠上皮细胞CCD841 CON，通过CCK-8法和结晶紫染色法检测贝母素乙对HCT116和CCD841 CON细胞增殖活力的影响，流式细胞术和WB法检测贝母素乙对HCT116细胞周期及其细胞周期相关蛋白表达的影响。构建HCT116移植瘤裸鼠模型和AOM/DSS结肠癌小鼠模型，观察贝母素乙对小鼠模型肿瘤生长和OS的影响，免疫组化法和WB法检测对移植瘤或肿瘤组织中细胞周期相关蛋白CDK4、CDK6和cyclin D1表达的影响。结果：贝母素乙可显著抑制结肠癌HCT116细胞的增殖能力（P<0.01），诱导HCT116细胞周期G0/G1期阻滞（P<0.01），降低CDK4、CDK6和cyclin D1的蛋白表达水平（均P<0.01）。荷瘤小鼠实验结果显示，贝母素乙（0.75 mg/kg）显著抑制HCT116细胞移植瘤的生长并延长荷瘤裸鼠的OS（P<0.05或P<0.01），降低AOM/DSS模型小鼠的体质量、延长OS、减少癌变肠组织的肿瘤个数和肿瘤体积，下调肿瘤组织中CDK4、CDK6和cyclin D1的蛋白表达（P<0.01或P<0.05）。结论：贝母素乙通过下调CDK4、CDK6和cyclin D1的表达水平，引起细胞周期G0/G1期阻滞，从而抑制结肠癌HCT116细胞的增殖。

AIM: To investigate the preoperative ocular symptoms and the characteristics of asymptomatic ocular surface abnormalities in hospitalized patients with primary pterygium.METHODS: Cross-sectional study. Hospitalized patients diagnosed with primary pterygium and scheduled to receive pterygium excision surgery at the Xiamen Eye Center of Xiamen University from August 2022 to October 2022 were enrolled. Ocular surface disease index questionnaire(OSDI), six examinations including non-invasive tear film break-up time, Schirmer I test, tear meniscus height, lid margin abnormality, meibomian gland dropout and tear film lipid layer thickness, and anterior segment optical coherence tomography(AS-OCT)were performed and statistically analyzed.RESULTS: A total of 178 cases(178 eyes), with a mean age of 54.39±10.75 years old, were recruited, including 75 males(42.1%)and 103 females(57.9%). The average values of ocular surface parameters in these patients included OSDI: 11.47±9.69, tear film break-up time: 7.10±3.86 s; tear meniscus height: 0.16±0.07 mm, Schirmer I test values: 14.39±7.29 mm/5 min, and pterygium thickness: 504.74±175.87 μm. Totally 161 eyes(90.4%)presented with abnormal lid margin, 44 eyes(24.7%)presented with meibomian gland dropout score ≥4, 52 eyes(29.2%)presented with low lipid layer thickness. In the 6 objective examinations, abnormalities in at least 4 of these tests were found in 85.4% of eyes. Pterygium morphology was classified into four grades: 10 eyes(5.6%)of grade Ⅰ, 93 eyes(52.2%)of grade Ⅱ, 60 eyes(33.7%)of grade Ⅲ, and 15 eyes(8.4%)of grade Ⅳ. In patients with a higher grade of pterygium, the tear film break-up time was lower, and the proportion of abnormal lid margin was also significantly higher(P<0.05). The patients were further divided into two subgroups, including 121 eyes(68.0%)with normal OSDI <13 in the normal group and 57 eyes(32.0%)with OSDI ≥13 in the abnormal group. No significant difference was found in the proportion of meibomian gland dysfunction between the two groups of patients(71.9% vs. 71.9%, P=0.872). In addition, there were differences in the number of abnormal objective examinations(4.11±0.85 vs. 4.91±0.99, P<0.001).CONCLUSIONS: Asymptomatic ocular surface abnormalities were present preoperatively in patients hospitalized for primary pterygium. A comparable high incidence of structural or functional meibomian gland dysfunction existed in pterygium patients with or without apparent ocular discomfort. More attention should be paid to the ocular surface abnormalities in those asymptomatic patients before primary pterygium surgery.

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.