Objective To explore the adverse event signals of children using macrolide drugs （azithromycin, clarithromycin, and erythromycin）, and provide reference for rational medicine use in clinical practice. Methods Data from children under 12 years old were extracted from the US FAERS database spanning from the first quarter of 2004 to the second quarter of 2023. The adverse drug reaction （ADR） signal mining for three macrolide antibiotics was conducted using the Reporting Odds Ratio （ROR） and Bayesian Confidence Propagation Neural Network （BCPNN） methods. Special emphasis was placed on analyzing and contrasting the differences in adverse events among the three drugs. Results A total of 1 615 reports for children under 12 years old were retrieved from the FAERS database, including 1 024 reports of azithromycin, 460 reports of clarithromycin, and 131 reports of erythromycin. Among azithromycin and erythromycin, there were more reports from boys than girls, while for clarithromycin, there were more reports from girls than boys. Oral administration was the most common route of administration for all three drugs. Regarding the outcome of adverse events reported, azithromycin and clarithromycin were primarily associated with other serious adverse events, whereas erythromycin was mainly associated with hospitalization and other serious adverse events. The number of adverse events reported decreased with increasing age, with a higher number of reports in the 0-3 age group. Using the ROR and BCPNN methods for signal detection, 86 signals were identified for azithromycin, 91 for clarithromycin, and 34 for erythromycin. These signals involved 22 System Organ Classes （SOCs）, with azithromycin mainly concentrated in skin and subcutaneous tissue disorders （n=21）, clarithromycin in gastrointestinal disorders （n=15）, and erythromycin in gastrointestinal disorders （n=8）. Twenty-four signals of moderate to high risk were detected, with 13 for azithromycin, 9 for clarithromycin, and 2 for erythromycin. Conclusion The adverse events induced by the three drugs with different risks in different systems. When clinically treating Mycoplasma pneumoniae pneumonia in children, the risk profiles of drugs in different systems should be considered, and personalized dosing should be implemented.

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

Objective To investigate the effects of Xuetong capsule on blood lipids and liver lesion in hyperlipidemic model animals. Methods Sixty ICR mice were randomly divided into six groups. The normal control group was fed with normal diet, the other groups were fed with high-fat diet to induce hyperlipidemia. After four weeks feeding, the three groups were given low, middle, and high doses of Xuetong capsules （0.5, 1.0, and 2.0 g/kg） by gavage, and the positive drug control group was given atorvastatin calcium （1.5 mg/kg） by gavage. The model group was given solvent （0.5% carboxymethyl cellulose sodium）. After treatment for 8 weeks, the body weight, organ index, blood lipids, blood glucose and liver function index were measured. The liver oil red staining was used to determine the lipid droplet content, and quantitative PCR was used to detect the expression of inflammatory factors TNF-α, IL-6, and IL-1β. Results The body weight, the weight of liver and spleen were significantly increased by high-fat diet. High-fat diet increased the organ indexes of the liver and spleen, the degree of liver oil red staining, and also significantly increased the levels of glucose, triglyceride （TG）, cholesterol （CHOL）, and low-density lipoprotein cholesterol （LDL-C） in serum. Compared with the model group, the level of TG has no significant change in low, middle and high doses groups. The level of CHOL in serum was reduced by Xuetong capsule with a dose dependent manner. There were significant difference between the model group and middle, high doses groups. The results of LDL-C were similar, the level of LDL-C was significantly reduced by middle and high doses groups [middle dose (0.55±0.21) mmol/L, high dose (0.52±0.22) mmol/L vs (0.81±0.29) mmol/L in model group, P<0.05]. Compared with the normal control, there was no significant difference in HDL-C levels between the high-fat model and each drug-treated group. Liver function showed that Xuetong capsules significantly reduced the degree of liver oil red staining and decreased the level of alanine aminotransferase （ALT） induced by high-fat diet. The body weight, the weight and organ indexes of liver and spleen were significantly reduced by positive drug control group. The levels of CHOL, LDL-C, and TG, and the degree of liver oil red staining were also significantly reduced in positive drug control group. Further studies have shown that high dose of Xuetong capsules significantly reduced the expression of TNF-α and IL-6 induced by high-fat diet （P<0.05）, while the reduction of IL-1β was not so significant （P>0.05）. Conclusion Xuetong capsules significantly reduced the body weight of animals with high fat, liver size, fat deposition, inflammatory damage and also significantly reduced blood lipid CHOL and LDL-C levels and transaminase elevation. The above effects may be related to Xuetong capsules reducing the expression of inflammatory factors such as TNF-α and IL-6 in the liver.

Objective To investigate the effects of Xuetong capsule on blood lipids and liver lesion in hyperlipidemic model animals. Methods Sixty ICR mice were randomly divided into six groups. The normal control group was fed with normal diet, the other groups were fed with high-fat diet to induce hyperlipidemia. After four weeks feeding, the three groups were given low, middle, and high doses of Xuetong capsules （0.5, 1.0, and 2.0 g/kg） by gavage, and the positive drug control group was given atorvastatin calcium （1.5 mg/kg） by gavage. The model group was given solvent （0.5% carboxymethyl cellulose sodium）. After treatment for 8 weeks, the body weight, organ index, blood lipids, blood glucose and liver function index were measured. The liver oil red staining was used to determine the lipid droplet content, and quantitative PCR was used to detect the expression of inflammatory factors TNF-α, IL-6, and IL-1β. Results The body weight, the weight of liver and spleen were significantly increased by high-fat diet. High-fat diet increased the organ indexes of the liver and spleen, the degree of liver oil red staining, and also significantly increased the levels of glucose, triglyceride （TG）, cholesterol （CHOL）, and low-density lipoprotein cholesterol （LDL-C） in serum. Compared with the model group, the level of TG has no significant change in low, middle and high doses groups. The level of CHOL in serum was reduced by Xuetong capsule with a dose dependent manner. There were significant difference between the model group and middle, high doses groups. The results of LDL-C were similar, the level of LDL-C was significantly reduced by middle and high doses groups [middle dose (0.55±0.21) mmol/L, high dose (0.52±0.22) mmol/L vs (0.81±0.29) mmol/L in model group, P<0.05]. Compared with the normal control, there was no significant difference in HDL-C levels between the high-fat model and each drug-treated group. Liver function showed that Xuetong capsules significantly reduced the degree of liver oil red staining and decreased the level of alanine aminotransferase （ALT） induced by high-fat diet. The body weight, the weight and organ indexes of liver and spleen were significantly reduced by positive drug control group. The levels of CHOL, LDL-C, and TG, and the degree of liver oil red staining were also significantly reduced in positive drug control group. Further studies have shown that high dose of Xuetong capsules significantly reduced the expression of TNF-α and IL-6 induced by high-fat diet （P<0.05）, while the reduction of IL-1β was not so significant （P>0.05）. Conclusion Xuetong capsules significantly reduced the body weight of animals with high fat, liver size, fat deposition, inflammatory damage and also significantly reduced blood lipid CHOL and LDL-C levels and transaminase elevation. The above effects may be related to Xuetong capsules reducing the expression of inflammatory factors such as TNF-α and IL-6 in the liver.

Background/Aims: The purpose of this study was to develop a diagnostic model utilizing multimodal ultrasound parameters to aid in the detection of cervical lymph node metastasis in papillary thyroid cancer (PTC) patients. Methods: The study included 84 suspicious lymph nodes from 69 PTC patients, all of whom underwent fine needle aspiration with pathological results. Data from conventional grayscale ultrasound, shear wave elastography (SWE), and superb microvascular imaging were analyzed. Key ultrasound features were compared between benign and metastatic groups to create a diagnostic model using Fisher’s stepwise discriminant analysis. The model’s effectiveness was assessed with self-testing, cross-validation, and receiver operating characteristic curve analysis. Results: Four features, namely lymphatic hilum (X1), cortical hyperechogenicity (X2), vascular pattern (X4), and SWEmean (X7), were integral to the discriminant analysis, resulting in the equation: Y1 = -3.461 + 2.423X1 + 0.321X2 + 1.620X4 + 0.109X7, Y2 = -8.053 + 0.414X1 + 2.600X2 + 2.504X4 + 0.192X7. If Y1 < Y2, the LN would be diagnosed as metastatic lymph nodes. The model demonstrated an area under the curve of 0.833, with a sensitivity of 83.33% and specificity of 83.33%. Conclusions The multimodal ultrasound diagnostic model, established through Fisher’s stepwise discriminant analysis, proved effective in identifying metastatic lymph nodes in PTC patients.

Background/Aims: The purpose of this study was to develop a diagnostic model utilizing multimodal ultrasound parameters to aid in the detection of cervical lymph node metastasis in papillary thyroid cancer (PTC) patients. Methods: The study included 84 suspicious lymph nodes from 69 PTC patients, all of whom underwent fine needle aspiration with pathological results. Data from conventional grayscale ultrasound, shear wave elastography (SWE), and superb microvascular imaging were analyzed. Key ultrasound features were compared between benign and metastatic groups to create a diagnostic model using Fisher’s stepwise discriminant analysis. The model’s effectiveness was assessed with self-testing, cross-validation, and receiver operating characteristic curve analysis. Results: Four features, namely lymphatic hilum (X1), cortical hyperechogenicity (X2), vascular pattern (X4), and SWEmean (X7), were integral to the discriminant analysis, resulting in the equation: Y1 = -3.461 + 2.423X1 + 0.321X2 + 1.620X4 + 0.109X7, Y2 = -8.053 + 0.414X1 + 2.600X2 + 2.504X4 + 0.192X7. If Y1 < Y2, the LN would be diagnosed as metastatic lymph nodes. The model demonstrated an area under the curve of 0.833, with a sensitivity of 83.33% and specificity of 83.33%. Conclusions The multimodal ultrasound diagnostic model, established through Fisher’s stepwise discriminant analysis, proved effective in identifying metastatic lymph nodes in PTC patients.

ObjectiveTo explore the mechanism by which the ethanol extract of Epimedium brevicornu （EEBM） intervenes in mesenchymal adipose-derived stem cells （ADSCs） to delay aging in castrated rats. MethodsForty-five 3-month-old SPF female SD rats were ovariectomized and randomly divided into model group， ADSCs treatment group， and ADSCs groups treated with low， medium， and high concentrations of EEBM （1， 50， 100 μg·L^-1）， referred to as the AE low， medium， and high concentration groups， with 9 rats in each group. After tail vein injection of 200 μL of the corresponding stem cell suspension， aging-related indicators including cyclin-dependent kinase inhibitor （p21）， tumor suppressor gene （p53）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， superoxide dismutase （SOD）， malondialdehyde （MDA）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cysteine-aspartic acid protease-3 （Caspase-3）， and lipofuscin were measured using enzyme-linked immunosorbent assay （ELISA） and Western blot. ResultsCompared with the model group， the IL-6 content in the AE low， medium， and high concentration groups was significantly decreased （P<0.05）. Lipofuscin， MDA， and IL-8 levels in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.01）， while SOD content was significantly increased （P<0.05， P<0.01）. Compared with the ADSCs treatment group， lipofuscin and IL-8 levels in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）. The MDA content was significantly decreased in the AE medium concentration group （P<0.01）. Compared with the model group， protein levels of p21， p53， Bax， and Caspase-3 in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， while the Bcl-2 protein level was significantly increased （P<0.01）. Compared with the ADSCs treatment group， protein levels of p21， p53， Bax， and Caspase-3 in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， and the Bcl-2 protein level in the AE low concentration group was significantly increased （P<0.01）. ConclusionThe results of this experiment show that EEBM-treated ADSCs or ADSCs may delay aging in castrated rats by inhibiting cell apoptosis， reducing cell cycle inhibitors and pro-inflammatory factors， enhancing antioxidant capacity， and reducing oxidative reactions. Moreover， EEBM-treated ADSCs demonstrate stronger anti-aging effects than ADSCs alone. This study provides experimental evidence supporting the clinical use of EEBM to intervene in ADSCs and delay aging.

As a patented characteristic medicine of Yi ethnic minority， Pingxuan capsules have the effects of nourishing the liver and kidney， pacifying the liver， and subduing Yang. With the main indications of dizziness， headache， palpitations， tinnitus， insomnia， dreaminess， waist and knee soreness caused by liver-kidney deficiency and liver Yang upward disturbance， Pingxuan capsules are widely used in the treatment of posterior circulation ischemic vertigo， vestibular migraine， benign paroxysmal positional vertigo. However， the current knowledge is limited regarding the efficacy， syndrome differentiation， and safety of this medicine. On the basis of summarizing the experience of clinicians and the existing evidence， this study invites clinical experts of traditional Chinese and Western medicine， pharmaceutical experts， and methodological experts from relevant fields across China to conduct evidence-based evaluation of Pingxuan capsules. The evaluation follows the Specifications for the Development of Clinical Expert Consensus on Chinese Patent Medicines issued by the Standardization Office of the China Association of Chinese Medicine， and reaches 5 recommendations and 16 consensus suggestions. The consensus clarifies the clinical applications， efficacy， dose， course of treatment， combination of medicines， precautions， and contraindications of Pingxuan capsules in the treatment of vertigo and explains the safety of clinical application. This consensus is applicable to clinicians （traditional Chinese medicine， Western medicine， and integrated traditional Chinese and Western medicine） and pharmacists in tertiary hospitals， secondary hospitals， and community-level medical and health institutions across China， providing a reference for the rational use of Pingxuan capsules in the treatment of vertigo. It is hoped that the promotion of this consensus can facilitate the rational use of drugs in clinical practice， reduce the risk of drug use， and give full play to the advantages of Pingxuan capsules in the treatment of vertigo diseases. This consensus has been reviewed and published by the China Association of Chinese Medicine， with the number GS/CACM330-2023.

BACKGROUND: The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis. METHODS: Restenosis and atherosclerosis rat models of type 2 diabetes ( n   =  20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student's t -test and one-way analysis of variance were used for statistical analysis. RESULTS: C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitroC/EBPβ overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBPβ knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBPβ hypomethylation. Additionally, Lin28a overexpression reduced C/EBPβ methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells. CONCLUSION Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis.
Animals ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Muscle, Smooth, Vascular/metabolism* ; Rats ; DNA Methylation/physiology* ; CCAAT-Enhancer-Binding Protein-beta/genetics* ; Male ; Myocytes, Smooth Muscle/cytology* ; Rats, Sprague-Dawley ; RNA-Binding Proteins/genetics* ; Cells, Cultured ; Coronary Restenosis/metabolism*

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female