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.

Definitive chemoradiotherapy (dCRT) has become a cornerstone in the treatment of locally advanced esophageal cancer; however, local control remains suboptimal, and persistent lesions or locoregional recurrences after treatment are not uncommon. For patients without distant metastases but with local failure, whether surgical intervention can still offer curative potential remains a major clinical dilemma. Salvage esophagectomy (SE) offers potential long-term survival for selected patients, but this procedure is performed in the context of severe fibrosis, impaired local blood supply, and obscured anatomical planes following chemoradiotherapy, resulting in significantly higher perioperative risk compared to primary esophagectomy. Consequently, controversies exist regarding patient selection, preoperative restaging, choice of surgical approach, extent of lymphadenectomy, gastrointestinal reconstruction, and perioperative management. In recent years, with the refinement of restaging modalities such as PET/CT, the accumulation of experience in high-volume centers, and emerging evidence from clinical studies, the clinical role of SE has gradually shifted from a "high-risk salvage measure" to a "selective curative strategy aimed at achieving long-term survival in carefully selected patients". Nevertheless, standardized guidelines for patient selection, technical approaches, and perioperative management are still lacking. Based on current evidence and clinical experience, experts organized by the Integrated Esophageal Cancer Committee of Chinese Anti-Cancer Association systematically reviewed key issues regarding SE, including its definition, indications, preoperative evaluation, choice of surgical approach, lymphadenectomy, gastrointestinal reconstruction, and perioperative management, and formulated a Chinese expert consensus. This consensus aims to provide guidance for standardized assessment, appropriate referral, individualized surgical decision-making, and optimized perioperative management of patients with locoregional failure after dCRT. Ultimately, this will increase the likelihood of R0 resection, reduce the risk of severe complications, and promote the safer, more judicious, and standardized implementation of SE in high-risk scenarios.

OBJECTIVE To establish a quality control method for Jinbei oral liquid based on multi-wavelength switching high performance liquid chromatography （HPLC） fingerprint， chemical pattern recognition and multi-index content determination. METHODS A total of 15 batches of Jinbei oral liquid were used as test samples. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （ Version 2012 ） was adopted to establish multi-wavelength switching HPLC fingerprints， followed by chromatographic peak identification and similarity evaluation. Cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were applied to conduct chemical pattern recognition on the 15 batches of samples. The multi-wavelength switching HPLC method was used to simultaneously determine the contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， forsythoside A， baicalin， salvianoli c acid B and wogonoside in samples. RESULTS A total of 25 common peaks were calibrated in the fingerprints of 15 batches of Jinbei oral liquid， among which 7 common peaks were unambiguously identified. The similarity of all samples was higher than 0.960. Chemical pattern recognition results showed that samples S1-S8 were clustered into group 1， and samples S9-S15 were clustered into group 2. Baicalin， wogonoside， neochlorogenic acid， chlorogenic acid and salvianolic acid B were identified as the differential quality markers. The average contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， forsythoside A， baicalin， salvianolic acid B and wogonoside in 15 batches of Jinbei oral liquid were 0.213 7， 0.085 3， 0.104 9， 0.287 3， 0.420 1， 0.062 1， 0.176 0 mg/mL， respectively. CONCLUSIONS The established quality control method for Jinbei oral liquid combining multi-wavelength switching HPLC fingerprint， chemical pattern recognition and multi-index content determination is stable and reliable， which can provide a reference for the formulation of quality standards of this preparation.

OBJECTIVE To establish a quality control method for Jinbei oral liquid based on multi-wavelength switching high performance liquid chromatography （HPLC） fingerprint， chemical pattern recognition and multi-index content determination. METHODS A total of 15 batches of Jinbei oral liquid were used as test samples. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （ Version 2012 ） was adopted to establish multi-wavelength switching HPLC fingerprints， followed by chromatographic peak identification and similarity evaluation. Cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were applied to conduct chemical pattern recognition on the 15 batches of samples. The multi-wavelength switching HPLC method was used to simultaneously determine the contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， forsythoside A， baicalin， salvianoli c acid B and wogonoside in samples. RESULTS A total of 25 common peaks were calibrated in the fingerprints of 15 batches of Jinbei oral liquid， among which 7 common peaks were unambiguously identified. The similarity of all samples was higher than 0.960. Chemical pattern recognition results showed that samples S1-S8 were clustered into group 1， and samples S9-S15 were clustered into group 2. Baicalin， wogonoside， neochlorogenic acid， chlorogenic acid and salvianolic acid B were identified as the differential quality markers. The average contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， forsythoside A， baicalin， salvianolic acid B and wogonoside in 15 batches of Jinbei oral liquid were 0.213 7， 0.085 3， 0.104 9， 0.287 3， 0.420 1， 0.062 1， 0.176 0 mg/mL， respectively. CONCLUSIONS The established quality control method for Jinbei oral liquid combining multi-wavelength switching HPLC fingerprint， chemical pattern recognition and multi-index content determination is stable and reliable， which can provide a reference for the formulation of quality standards of this preparation.

ObjectiveTo establish the specific chromatogram of Chuanxiong Rhizoma dispensing granules（CRdg）， and to evaluate its quality by chemometrics and two reference substances for determination of multiple components（TRSDMC）. MethodsHigh performance liquid chromatography（HPLC） specific chromatograms were established using 13 batches of CRdg from 7 manufacturers， and preliminary quality evaluation was performed by similarity evaluation and chemometrics analysis. Eight characteristic peaks in the specific chromatogram of CRdg were measured on 22 different types of C₁₈ columns， and the actual retention times were recorded. Taking chlorogenic acid（peak 1） and senkyunolide A（peak 8） as double standard compounds， the retention times of the eight characteristic peaks were predicted by linear calibration using two reference substances（LCTRS）， and the method was validated on three other columns of different brands. Taking chlorogenic acid as reference peak， the relative correction factor method（RCFM） was used to quantify cryptochlorogenic acid， caffeic acid， ferulic acid， senkyunolide I and senkyunolide A， and the results were compared with the external standard method（ESM）. ResultsThe similarities of specific chromatograms of 13 batches of CRdg were all >0.90， and a total of 8 characteristic peaks were calibrated， and six of them were identified， including chlorogenic acid（peak 1）， cryptochlorogenic acid（peak 2）， caffeic acid（peak 3）， ferulic acid（peak 5）， senkyunolide I（peak 6） and senkyunolide A（peak 8）. Through chemometric analysis， it was found that ferulic acid， chlorogenic acid， senkyunolide I and cryptochlorogenic acid were the main components causing quality difference in CRdg， and the accuracy of LCTRS in predicting the retention time of 8 characteristic peaks was superior to that of the relative retention time method（RRT）. Further comparison of the results obtained from RCFM and ESM showed that there was no statistically significant difference between the two methods. ConclusionA quality evaluation method for CRdg based on HPLC specific chromatogram and TRSDMC is established， its qualitative accuracy is better than that of RRT， the quantitative accuracy is similar to that of ESM， and 4 quality-differentiated components among different manufacturers are found. This method is stable and reliable， and has reference value for the quality evaluation of other dispensing granules.

ObjectiveTo establish the specific chromatogram of Chuanxiong Rhizoma dispensing granules（CRdg）， and to evaluate its quality by chemometrics and two reference substances for determination of multiple components（TRSDMC）. MethodsHigh performance liquid chromatography（HPLC） specific chromatograms were established using 13 batches of CRdg from 7 manufacturers， and preliminary quality evaluation was performed by similarity evaluation and chemometrics analysis. Eight characteristic peaks in the specific chromatogram of CRdg were measured on 22 different types of C₁₈ columns， and the actual retention times were recorded. Taking chlorogenic acid（peak 1） and senkyunolide A（peak 8） as double standard compounds， the retention times of the eight characteristic peaks were predicted by linear calibration using two reference substances（LCTRS）， and the method was validated on three other columns of different brands. Taking chlorogenic acid as reference peak， the relative correction factor method（RCFM） was used to quantify cryptochlorogenic acid， caffeic acid， ferulic acid， senkyunolide I and senkyunolide A， and the results were compared with the external standard method（ESM）. ResultsThe similarities of specific chromatograms of 13 batches of CRdg were all >0.90， and a total of 8 characteristic peaks were calibrated， and six of them were identified， including chlorogenic acid（peak 1）， cryptochlorogenic acid（peak 2）， caffeic acid（peak 3）， ferulic acid（peak 5）， senkyunolide I（peak 6） and senkyunolide A（peak 8）. Through chemometric analysis， it was found that ferulic acid， chlorogenic acid， senkyunolide I and cryptochlorogenic acid were the main components causing quality difference in CRdg， and the accuracy of LCTRS in predicting the retention time of 8 characteristic peaks was superior to that of the relative retention time method（RRT）. Further comparison of the results obtained from RCFM and ESM showed that there was no statistically significant difference between the two methods. ConclusionA quality evaluation method for CRdg based on HPLC specific chromatogram and TRSDMC is established， its qualitative accuracy is better than that of RRT， the quantitative accuracy is similar to that of ESM， and 4 quality-differentiated components among different manufacturers are found. This method is stable and reliable， and has reference value for the quality evaluation of other dispensing granules.

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*