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.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

OBJECTIVE To investigate the mechanism of Bushen huoxue formula in improving pregnancy outcomes in mice with antiphospholipid antibody-related recurrent spontaneous abortion （aPL-RSA）. METHODS SPF female BALB/c mice were randomly divided into normal control group， adjuvant control group， model group， and Bushen huoxue formula group. The aPL-RSA mouse model was established by immunization with β 2 glycoproteinⅠcombined with Freund’s adjuvant. From gestational day 0， the Bushen huoxue formula group was administered 1.653 6 g/（kg·d） of the prescription by gavage， while the other three groups received an equal volume of normal saline， twice daily for 15 consecutive days. The uterine appearance of pregnant mice was observed； individual embryo weight was recorded， and the embryo resorption rate was calculated. The proportion of activated CD41 + CD62p + platelets in platelet-rich plasma （PRP） was detected. Serum levels of thromboxane B2 （TXB2） and platelet factor 4 （PF4） were measured. Morphological changes of placental tissue were observed. The cell apoptosis rate of placental tissue was detected. The levels of malondialdehyde （MDA） content， tot al superoxide dismutase （T-SOD） activity， the interleukin-1β （IL-1β） and IL-18， the protein expressions of matrix metalloproteinase-3 （MMP-3）， MMP-9， nuclear proliferation antigen-67 （Ki67）， superoxide dismutase 2 （SOD2）， Nod-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， and caspase-1， as well as the mRNA expressions of superoxide dismutase 2（SOD2）， NLRP3， ASC and caspase-1 of placental tissue were detected. RESULTS Compared with the normal control group and adjuvant control group， the model group showed significant decreases in individual embryo weight， T-SOD activity of placental tissue， and relative expression levels of SOD2 mRNA and protein （ P ＜0.05）； while significant increases were observed in embryo resorption rate， proportion of activated CD41 + CD62p + platelets in PRP， serum levels of TXB2 and PF4， placental cell apoptosis rate， MDA content in placental tissue， relative protein expressions of MMP-3， MMP-9 and Ki67， relative protein and mRNA expression levels of NLRP3， ASC and caspase-1 as well as IL-1β and IL-18 levels （ P ＜0.05）. The model group also exhibited irregular uterine morphology with localized atrophy in some uterine horns； placental tissue showed fragmentation of decidual cells， extensive vacuolization and necrosis of trophoblast cells in the labyrinthine zone， accompanied by vascular reduction. After intervention with Bushen huoxue formula， the above indicators were significantly reversed （ P ＜0.05）， and uterine morphology and pathological damage were markedly improved. CONCLUSIONS Bushen huoxue formula can effectively improve pregnancy outcomes in aPL-RSA model mice， and its mechanism may be closely related to inhibiting platelet activation， reducing oxidative stress injury， enhancing trophoblast cell function， and suppressing the inflammatory response mediated by the NLRP3 inflammasome pathway.

Breast cancer is one of the most common malignant tumors among women worldwide, with an increasing incidence rate year by year, making it a significant public health concern. With the continuous advancement of tumor biology research, N 6-methyladenosine (m 6A) modification, as an important form of RNA modification, has attracted growing attention. The m 6A modification, the most prevalent RNA modification in eukaryotes, occurs in almost all types of RNA and plays a critical role in the occurrence, progression, and metastasis of breast cancer. It influences cell proliferation, apoptosis, and alterations in the tumor microenvironment, though the specific mechanisms underlying these effects require further in-depth investigation. Moreover, the specific patterns of m 6A modification demonstrate its potential as a novel biomarker for breast cancer, which could provide new directions for early diagnosis and prognosis evaluation.

Objective:To analyze the molecular mechanism of Huangqin Decoction in the treatment of acute lung injury (ALI) with network pharmacology; To conduct experimental validation.Methods:Active compounds and corresponding targets of Huangqin Decoction were retrieved from the TCMIP database. ALI-related targets were obtained from GeneCards, DisGeNet, TTD, and OMIM, and the intersection targets were obtained. The intersection targets were imported into the string database to build the PPI network, and the core targets were obtained through topology analysis by Cytoscape 3.10.1 software. GO and KEGG pathway enrichment analyses were conducted using clusterProfiler software. 16 SD rats were divided into two groups ( n = 8 per group) with random number table method: control and Huangqin Decoction. Rats in the Huangqin Decoction group received Huangqin Decoction by gavage at a dosage of 40 mg/kg, while the control group was administered an equal volume of distilled water. After seven consecutive treatments, drug-containing serum was collected. A549 cells were divided into four groups: control, model, Huangqin Decoction, and received relevant drugs as intervention for 24 h. Levels of SOD, MDA, GSH-Px, IL-1β, TNF-α, and IL-6 in the culture supernatant were measured by ELISA. Apoptosis was analyzed by flow cytometry. The expressions of PI3K, p-PI3K, Akt, p-Akt, mTOR, p-mTOR, LC3Ⅱ/Ⅰ, and Beclin-1 proteins were determined by Western blot. Results:A total of 137 active compounds and 178 common targets were identified in Huangqin Decoction, with TP53, AKT1, STAT3, TNF, IL6, and ESR1 as core nodes. GO enrichment indicated involvement in oxidative stress and responses to lipopolysaccharides, bacterial molecules, and hypoxia. KEGG analysis revealed enrichment in lipid and atherosclerosis, PI3K-Akt signaling pathway, hepatitis, MAPK signaling pathway, prostate cancer, small-cell lung cancer, and mTOR signaling pathway. In cell experiments, compared with the model group, Huangqin Decoction and inhibitor groups showed increased A549xibo ( P<0.05); levels of IL-1β, TNF-α, IL-6, and MDA in the supernatant were reduced ( P<0.05 or P<0.01), while SOD and GSH-Px levels were elevated ( P<0.05 or P<0.01); the apoptosis rate decreased ( P<0.05 or P<0.01); the expressions of LC3-Ⅱ/Ⅰ and Beclin-1 proteins decreased ( P<0.05 or P<0.01), whereas the expressions of p-mTOR/mTOR, p-Akt/Akt, and p-PI3K/PI3K increased ( P<0.05 or P<0.01). Conclusion:Huangqin Decoction exerts protective effects against ALI mainly by reducing cellular autophagy, and its mechanism may be related to the activation of the mTOR/Akt/PI3K signaling pathway.

Objective:To explore the value of prenatal three-dimensional ultrasonography（3DUS）in displaying auricular morphotyping and dimensions for predicting congenital aural atresia（CAA）.Methods:A retrospective collection of 227 fetuses who underwent ultrasound scans and retained auricular 3DUS volumes from January 2018 to December 2023 at the First Affiliated Hospital of Sun Yat-sen University was conducted. Fetuses were divided into two groups：a CAA group（52 fetuses，62 auricles）and a non-CAA group（175 fetuses，202 auricles），based on the presence or absence of external auditory canal identified through postnatal examination. According to 3DUS auricular contour and presence or absence of the concha，the auricles were divided into 4 types：type Ⅰ，C-shaped auricle with a concha；type Ⅱ，Irregular auricle with a concha；type Ⅲ，C-shaped auricle without a concha；type Ⅳ，Irregular auricle without a concha. And auricular length（AL）and width（AW）were measured to calculate the product of the auricular length and width（ALW）. Normal reference ranges for ALW from the non-CAA group were developed. Differences of the auricular morphotyping and Z-score of ALW（ALWZ）were compared between the two groups. Receiver operating characteristic（ROC）curves were used to evaluate the diagnostic efficiency of auricular morphotyping，ALWZ and the regression model. A Logistic regression model for CAA based on auricular morphotyping and ALWZ were established.Results:The auricular morphotyping and ALWZ between the two groups were different statistically（both P<0.05）. The AUC of the auricular morphotyping and ALWZ predicting CAA were 0.960（95% CI = 0.923 - 0.997）and 0.975（95% CI = 0.959 - 0.991）individually. Formula for CAA prediction model combining the two indicators（5.379 × morphotyping - 2.386 × ALWZ - Conclusions:The auricular morphotyping and dimensions can effectively predict CAA.

Objective A random forest model was used to analyze the risk of immune reconstitution dysfunction(INR)after antiviral therapy(HAART)in HIV/AIDS patients.Methods A total of 67 HIV/AIDS patients treated in our hospital from January 2019 to December 2022 were selected and all of them received HAART treatment.After 18 months of follow-up,patients were divided into INR group and non-INR group according to prognosis.The clinical data of the two groups were compared,and the importance of the indicators affecting INR in patients was ranked by random forest model,and the related factors affecting INR in HIV/AIDS patients after HAART were analyzed by Logistic regression model.Results During the follow-up period of 18 months,a total of 13(19.40％)of 67 HIV/AIDS patients developed INR.There were statistically significant differences in the time interval from diagnosis to treatment and baseline CD4+T lymphocyte count between INR group and non-INR group(P＜0.05).Random-forest model results showed that variables were ranked in descending order of importance as baseline CD4+T lymphocyte count and time interval between diagnosis and treatment.Logistic multivariate regression analysis showed that more than 1 year between diagnosis and treatment and baseline CD4+T lymphocyte count≤ 200/μl are all risk factors for INR in HIV/AIDS patients after HAART treatment(P＜0.05).Conclusion More than 1 year between diagnosis and treatment and baseline CD4+T lymphocyte count≤200/μl are all risk factors for INR in HIV/AIDS patients after HAART.In addition,the random forest model is of great significance for health care workers to identify high-risk groups of INR after HAART and formulate intervention plans.

Objective:To investigate the clinical efficacy of anterolateral thigh free fat flap (hereinafter referred to as fat flap) transplantation with vascular anastomosis for reconstructing facial depressed scars.Methods:This study was a retrospective observational study. Twelve patients (5 males and 7 females, aged 15-67 years) with facial depressed scars who met the inclusion criteria were treated at the First Affiliated Hospital of Air Force Medical University from June 2017 to September 2023. Before surgery, the patient and observer scar assessment scale (POSAS) was used to evaluate the facial scar condition of the patients. Scar depression area was measured ranging from 5 cm×4 cm to 14 cm×7 cm, with a depth from 6 to 12 mm. All cases were reconstructed with fat flaps. The harvested fat flaps ranged 6 cm×5 cm to 15 cm×8 cm in size, with vascular pedicle lengths ranging from 4 to 7 cm. Intraoperatively, the number of perforator vessels observed was as follows: 1 perforator in 2 cases, 2 perforators in 7 cases, and 3 perforators in 3 cases. Fat flaps were transplanted to the recipient sites, with the main trunks of its perforator vessels and accompanying veins anastomosed to the recipient arteries and veins. Donor site wounds were closed primarily. Postoperatively, the survival of fat flap, vascular crisis, and the healing of donor site incision were observed. During follow-up, the facial contour was observed, the long-term reintervention at recipient sites was recorded, and the scars formed at both donor and recipient incisions were observed. The function of donor limb was assessed. At the last follow-up, the scar condition at recipient site was evaluated using the two subscales of POSAS (the observer scale and the patient self-rating scale), respectively.Results:One patient developed a mild hematoma due to bleeding within 24 hours after surgery. After timely removal of the hematoma and enhanced drainage, the fat flap survived. The fat flaps of the other patients survived completely with no vascular crisis occurred. The donor site incision of 1 patient developed infection 7 days after surgery and healed after timely dressing changes, while the donor site incisions of the remaining patients all healed smoothly. During the follow-up of 6-26 months, significant improvement in facial symmetry was observed in all patients, with natural fullness achieved. Autologous microlipofilling was performed in 2 patients at 6 months and 10 months postoperatively, respectively. Local liposuction contouring was conducted in 1 patient at 12 months postoperatively. The scars at the donor and recipient sites were mild. No functional impairment at donor sites was recorded, and the motor and sensory functions of the affected limbs were normal. At the last follow-up, the observer scale assessment showed that the scores for vascularity, thickness, roughness, pliability, pigmentation, and overall assessment of the scars in the recipient areas were 2.1±0.5, 1.9±0.7, 3.0±0.7, 2.1±1.2, 3.8±1.1, and 2.8±0.5, respectively, which were significantly lower than 4.2±0.9, 5.1±1.0, 4.2±1.5, 4.6±1.4, 4.8±1.2, and 5.2±1.0 before surgery (with t values of 7.24, 11.70, 4.31, 9.57, 4.17, and 9.30, respectively, P<0.05). The patient self-rating scale assessment showed that the scores for pain, pruritus, color, stiffness, irregularity, thickness, and overall satisfaction of the scars in the recipient areas were 1.3±0.5, 1.3±0.4, 1.9±1.0, 2.3±1.1, 1.8±0.8, 1.9±0.8, and 1.9±0.7, respectively, which were significantly lower than 2.9±1.0, 2.6±0.9, 4.2±1.5, 5.3±2.0, 4.0±1.2, 4.6±1.3, and 4.8±1.4 before surgery (with t values of 6.09, 5.20, 8.07, 9.17, 8.00, 8.60, and 8.81, respectively, P<0.05). Conclusions:Transplantation of the fat flaps with vascular anastomosis can safely and effectively reconstruct facial depressed scars, and significantly improve the aesthetic contour and scar-related symptoms. This technique yields stable long-term outcomes with high patient satisfaction, demonstrating high value of clinical application.

Objective To explore the mechanism of Shengmai Decoction in improving heart failure by regulating mitochondrial apoptosis based on network pharmacology and experimental verification;To provide a basis for its clinical application.Methods The active components and targets of Shengmai Decoction were obtained through TCMSP and TCMID databases.Heart failure and mitochondrial apoptosis related targets were retrieved from GeneCards,OMIM,DrugBank,PharmGKB and TTD databases.A protein-protein interaction(PPI)network at the intersection of drugs and diseases was constructed using the STRING database,and a component-target network was constructed using Cytoscape 3.8.2 software.GO and KEGG pathway enrichment analysis was performed on intersecting targets using the DAVID database.Molecular docking was conducted to assess the binding affinity of key components to core target proteins.A rat model of heart failure was established,and the cardiac function of rats were detected by echocardiogram,ELISA was used to detect serum contents of BNP and NT-proBNP,mitochondrial ultrastructure was observed by transmission electron microscope,and Western blot was used to detect protein expressions of Bcl-2/Bax/Caspase-3 signaling pathway.Results A total of 66 active components and 146 targets of Shengmai Decoction were identified,and 22 intersecting targets with heart failure and mitochondrial apoptosis,including key proteins such as TNF,Bcl-2,Bax and Caspase-3.GO enrichment analysis revealed that the intersecting targets were closely associated with inflammation and cell signaling,while KEGG pathway analysis showed that the targets were primarily involved in the TNF signaling pathway,IL-17 signaling pathway,and mitochondrial function regulation.Molecular docking results indicated that Ginsenoside rh2,Beta-sitosterol and other components of Shengmai Decoction exhibited strong binding affinities with Bcl-2,Bax and Caspase-3.Animal experiments demonstrated that Shengmai Decoction significantly improved cardiac function(P<0.05,P<0.01),reduced serum BNP and NT-proBNP contents(P<0.01),alleviated mitochondrial damage,and inhibited mitochondrial apoptosis by upregulating Bcl-2 and downregulating Bax and Caspase-3 protein expression(P<0.01),thereby protecting cardiomyocytes.Conclusion Shengmai Decoction can target and regulate the Bcl-2/Bax/Caspase-3 signaling pathway,improving pathological processes associated with heart failure,which can provide a foundation for clinical optimization of Shengmai Decoction.

Objective:To investigate the characteristics, influencing factors, consequences, coping strategies, and preventive measures of workplace violence in medical consortiums.Methods:Medical professionals from a specialized hospital in South China and its consortium members (2 primary-level, 1 secondary-level, and 1 tertiary-level hospitals) were surveyed in December 2022 and July 2023. Quantitative research included 1013 participants, while qualitative research involved 35 participants. Workplace violence was assessed using the "National Case Study Tool for Workplace Violence in Healthcare Institutions-Survey Questionnaire", with qualitative analysis conducted through semi-structured interviews. Inter-group comparisons employed chi-square tests or Fisher's exact probability test, with logistic regression models for bivariate analysis.Results:The overall incidence rates of violence, psychological violence, and physical violence in this medical consortium were 31.7% (321/1, 013) , 30.6% (310/1, 013) , and 3.3% (33/1, 013) , respectively. Specifically, the overall violence rates in Level 1, Level 2, and Level 3 hospitals were 22.7% (41/181) , 27.4% (43/157) , and 35.1% (237/675) . The physical violence rates were 1.1% (2/181) , 10.2% (16/157) , and 2.2% (15/675) , respectively. The psychological violence rates stood at 22.7% (41/181) , 24.8% (39/157) , and 34.1% (230/675) . The total violence in tertiary hospitals was significantly higher than that in tertiary hospitals ( F=10.10, P=0.002) , and the incidence of psychological violence in tertiary hospitals was significantly higher than that in tertiary hospitals ( Flevel 1 vs level 3=8.61, P=0.003; Flevel 2 vs level 3=4.96, P=0.026) , incidence of verbal insults ( Flevel 1 vs level 3=8.25, P=0.004; Flevel 2 vs level 3=6.36, P= 0.012) was significantly higher than that of level 1 and level 2 hospitals. The incidence of physical violence in secondary hospitals was significantly higher than that of other two-level hospitals ( P<0.001) . Compared with other types of violence, the incidence of verbal insults is highest in hospitals at all levels. Higher anxiety about violence was a risk factor for psychological violence in hospitals at all levels ( Flevel1 hospital=15.44, P=0.004; Flevel2 hospital=22.87, P<0.001; Flevel3 hospital=84.12, P<0.001) . Health workers in all three levels of hospitals has a high level of approval of existing workplace violence interventions. The main causes of workplace violence were poor communication between doctors and patients (13.2%) , service attitude problems (12.5%) and patient illness (16.9%) . Conclusion:Workplace violence remains prevalent within this medical consortium. Targeted measures should be implemented based on hospital size, functions, and patient demographics.