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 explore the effect of Chaibei Zhixian Decoction on intestinal flora and T helper 17/regulatory T cell(Th17/Treg)immune balance in epileptic rats by regulating mammalian target of rapamycin/hypoxia-inducible factor-1α(mTOR/HIF-1α)pathway.Methods:Sixty rats were randomly divided into Sham group,Model group,low-dose Chaibei Zhixian Decoction group(CBZXD-Low)and high-dose Chaibei Zhixian Decoction group(CBZXD-High),with 15 rats in each group.Lateral ventricular injec-tion 1 μl kainic acid(1.5 μg/μl)was used to prepare epileptic rat model,Sham group was injected with an equal amount of physiological saline.CBZXD-Low group and CBZXD-High group were given Chaibei Zhixian Decoction by gavage daily(8.48 g/kg,16.96 g/kg),while Sham group and model group were given an equal amount of physiological saline by gavage.After continuous gavage for 4 weeks,HE staining and Nissl staining were used to detect pathological damage in hippocampal tissue;RT-qPCR was used to detect Th17/Treg related marker mRNA levels in spleen tissue and mTOR,HIF-1α mRNA levels in hippocampus tissue;flow cytometry was used to de-tect Th17/Treg cell ratio in spleen tissue;16S rRNA sequencing of feces in colon segment was performed;Western blot was used to de-tect mTOR and HIF-1α protein levels in hippocampal tissue.Results:Compared with Sham group,Model group rats suffered from spontaneous epilepsy,the arrangement of hippocampal neurons was disordered and severely lacking,intracellular Nissl bodies was de-creased,RORγt,IL-17A mRNA levels in spleen tissue were increased,Foxp3,CTLA-4 and GITR mRNA levels were decreased,the proportion of Th17 cells and Th17/Treg were increased,the proportion of Treg cell was decreased,intestinal flora α/β diversity were decreased,the proportion of harmful bacteria such as Cronobacter and Heliobacillus were increased,the proportion of beneficial bacte-ria such as Bacteroides,Lactobacillus,Prevotella and Akkermansia were decreased;mTOR and HIF-1α mRNA levels,p-mTOR/mTOR,HIF-1α protein levelsin hippocampal tissue were increased(P<0.05);compared with Model group,the seizures of rats in CBZXD-Low group and CBZXD-High group were significantly reduced,and the damage to hippocampal neurons was alleviated,RORγt,IL-17A mRNA levels in spleen tissue were decreased,Foxp3,CTLA-4 and GITR mRNA levels were increased,the propor-tion of Th17 cells and Th17/Treg were decreased,the proportion of Treg cell was increased,intestinal flora α/β diversity were in-creased,the proportion of harmful bacteria such as Cronobacter and Heliobacillus were decreased,the proportion of beneficial bacte-ria,such as Bacteroides,Lactobacillus,Prevotella,and Akkermansia were increased;mTOR and HIF-1α mRNA levels,p-mTOR/mTOR,HIF-1α protein levels in hippocampal tissue were decreased(P<0.05);and it showed a dose-dependent effect of Chaibei Zhixian Decoction(P<0.05).Conclusion:Chaibei Zhixian Decoction can restore intestinal flora and Th17/Treg cell immune balance in epileptic rats,it possibly plays a role by regulating mTOR/HIF-1α pathway.

AIM To investigate the clinical effects of Mahuang Fuzi Xixin Decoction combined with non-immunosuppressive treatment on patients with focal segmental glomerulosclerosis due to Spleen-Kidney Yang Deficiency.METHODS Sixty patients were randomly assigned into control group(30 cases)for 24-week intervention of non-immunosuppressive treatment,and observation group(30 cases)for 24-week intervention of both Mahuang Fuzi Xixin Decoction and non-immunosuppressive treatment.The changes in clinical effects,TCM syndrome effects,TCM syndrome score,24 h UTP,ALB,eGFR,Nephrin,Podocin and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate and TCM syndrome effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome score,24 h UTP,Nephrin,Podocin(P＜0.05),and increased ALB(P＜0.05),especially for the observation group(P＜0.05).No obvious adverse reactions occured in the two groups.CONCLUSION For the patients with focal segmental glomerulosclerosis due to Spleen-Kidney Yang Deficiency,Mahuang Fuzi Xixin Decoction combined with non-immunosuppressive treatment can improve TCM syndromes,whose action mechanism may be contribute to the alleviation of podocyte injury.

Objective To summarize the current status of outcome indicators in randomized controlled trials of TCM intervention in pediatric myocarditis,to explore the existing problems,and to provide a reference for the construction of a core set of indicators for the treatment of pediatric myocarditis with TCM.Methods Randomized controlled trial literature on the treatment of pediatric myocarditis with TCM was retrieved from CNKI,Wanfang Data,VIP,SinoMed,PubMed,Embase,Cochrane Library and Web of Science from the establishment of the databases to 16th,Nov.2024.The basic characteristics,diagnostic criteria,TCM evidence,interventions and outcome indicators of the studies were extracted.The risk of bias was assessed for the selected studies using the Cochrane Collaboration's risk of bias tool(RoB 2.0),and the outcome indicators were statistically analyzed using Excel 2019.Results Finally,totally of 250 articles were included in the literature.The outcome indicators were counted to obtain 187 outcome indicators with a cumulative total of 1 540 occurrences,which were categorized into six indicator domains:symptoms and signs,physicochemical testing,TCM symptoms/signs,clinical efficacy evaluation,safety evaluation and quality of life evaluation;among them,the physicochemical testing indicators(112 types,926 times)had the highest frequency of occurrences,followed by the clinical efficacy evaluation(13 types.340 times),and safety evaluation(24 types,193 times).Conclusion The overall quality of randomized controlled trials of TCM treatment of pediatric myocarditis is low,and there are problems with primary and secondary differentiation of outcome indicators and lack of TCM characteristics.There is an urgent need to improve the core set of endpoint indicators that highlight the characteristics of TCM in order to improve the quality of clinical research.

This article summarized the clinical experience of national TCM master Zhang Zhen in treating gastroesophageal reflux cough by applying the theory of"dredging and regulating qi".Professor Zhang Zhen believes that the pathogenesis of gastroesophageal reflux cough lies in the abnormal ascending and descending of qi movement in the viscera.Specifically,it is manifested as weakness of the spleen and stomach,dysfunction of the pivot mechanism,failure of the liver to dredge and disperse,failure of the lung qi to descend,insufficiency of kidney yang,and failure of the kidney to receive qi.Clinically,the treatment method of dredging and regulating qi is adopted,and the Shutiao Decoction is used as the basic prescription.The disease is treated from three aspects,namely strengthening and regulating the spleen and stomach,soothing the liver and purifying the lung,and tonifying the kidney and helping it receive qi.The regulation of the qi movement of the whole body is organically combined with that of the local areas to jointly smooth the operation of the qi movement throughout the body.It is hoped that this can provide references and ideas for the treatment of gastroesophageal reflux cough in TCM.

Different animals in Xinjiang carry Escherichia coli O157:H7(E.coli O157:H7),but the connection between these strains is not clear.This study aims to understand the evolutionary sub-group of E.coli O157:H7,the distribution of the dominant genetic lineage,the biofilm formation ability,the carriage of mobile genetic elements and their drug resistance profile.E.coli O157:H7 was identified by PCR.Multilocus sequence typing(MLST)protocol was used for E.coli O157 to detect ST type,plasmid replicon and integron genes.Biofilm formation ability was determined by crystal violet microplate,and Kirby-Bauer was used to detect drug resistance.The results showed that 46.7％(7/15)of E.coli O157:H7 belongs to Group A,53.3％(8/15)of E.coli O157:H7 be-longs to Group E.Sheep source were mainly prevalent in Group A(4/6).Cattle sources are mainly Group E(6/7).A total of six ST types were detected:ST11(8/15),ST-206(1/15),ST-6126(3/15),ST-1640(1/15),ST-178(1/15),ST-4550(1/15).Two strains had a moderate biofilm-form-ing capacity,two strains had a weak biofilm-forming capacity,10 strains have no biofilm-forming capacity.All were multidrug-resistant strains,with complete resistance to lincomycin,oxacillin,clindamycin,vancomycin,midemycin and cefthiophene,and 88％-94％resistance to poly-myxin B,ampicillin,penicillin G and erythromycin,they are highly drug resistant.The five resist-ance genes detected were acrA(66.66％,10/15),tolC(73.33％,11/15),qurS(13.33％,2/15),floR and qurA(6.67％,1/15).Four plasm id replicons were detected,they were IncP(66.66％,10/15),IncFrepB(86.67％,13/15),IncFIA(6.67％,1/15),IncFIB(66.66％,10/15).Two class Ⅰ integrons were detected and they were ISCR1(33.33％,5/15),ISECP1(20％,3/15).The re-sults showed that E.coli O157:H7 in Xinjiang was predominantly prevalent in Group A and Group E.Sheep sources were predominantly prevalent in Group A,and cattle sources were predominantly prevalent in Group E.The ST types were widely distributed,with ST11 types being the predomi-nant type,the biofilm-forming ability was weak,and the resistance was strong,all of them were multi-drug-resistant strains,and the resistance genes were mainly externally excreted from the pumps,and the resistance genes had more spreading elements.

AIM To study the chemical constituents from Inula japonica Thunb.and their anti-asthmatic activity.METHODS Separation and purification were performed using silica gel and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The effect of compounds on the release rate of β-Hex was evaluated by substrate coloration method.RESULTS Twenty-three compounds were isolated and identified as dehydrodontic acid(1),vitexin(2),alternariol(3),globuxanthone(4),1,3,6,7-tetrahydroxyxanthone(5),hydroxyhydrolapachol(6),isoscopoletin(7),elephanmollen(8),benzoylcholine(9),hoconobiflavone(10),clovandiol(11),hydroxydihydrobovolide(12),5,7-dihydroxycoumarin(13),scopoletin(14),orlichenol glucoside(15),urolignoside(16),9-angeloyloxythymol(17),6,3′,4′-trihydroxyaurone(18),flufuran(19),sweroside(20),guajadial(21),5,7,4′-trimethoxy-4-phenylcoumarin(22),dibutylphthalate(23).After intervention with compounds 9 and 16,the release rates of β-Hex were(56.64±2.37)％and(58.07±2.29)％,respectively.CONCLUSION Compounds 1-23 are isolated from Ⅰ.japonica for the first time.Compounds 9 and 16 have anti-asthmatic activity.

Objective To investigate the efficacy of surface electromyography biofeedback combined with respiratory training on post-stroke dysphagia and its impacts on serum neuron specific enolase(NSE)and insulin-like growth factor 1(IGF-1)in patients.Methods Totally 120 patients with post-stroke dysphagia in our hospital were stochastically assigned into the control group and the combined group,with 60 patients in each group.Both groups were given conventional treatment first,while the control group received respiratory training treatment.The combined group received surface electromyography biofeedback treatment on the top of the control group.The efficacy,serum NSE,central nervous system specific protein(S100β),IGF-1,functional oral intake scale(FOIS)score,standard swallowing function assessment scale(SSA)score,respiratory function,pharyngeal contraction rate and duration of pharyngeal contraction were compared between the two groups.Results After treatment,the total effective rate was higher in the combined group(x2=4.876,P＜0.05).Compared with before treatment,NSE,S100β,SSA score and pharyngeal contraction rate decreased after treatment in both groups,and those were even lower in the combined group(t=5.193,9.000,8.976,10.614,P＜0.05).Compared with before treatment,IGF-1,FOIS score,force vital capacity(FVC),forced expiratory volume in one second(FEV1),peak expiratory flow rate(PEF)and duration of pharyngeal contraction increased after treatment in both groups,with even higher levels in the combined group(t=4.212,6.220,3.765,6.935,5.020,4.249,P＜0.05).Conclusion Surface electromyography biofeedback combined with respiratory training can improve neuronal damage in patients with dysphagia,enhance swallowing efficiency,reduce serum NSE,S100β levels and pharyngeal retention time,with significant curative effect.

BACKGROUND:The asymmetrical biomechanical environment of adolescent idiopathic scoliosis can lead to further wedge deformation of the vertebral body,which may affect cardiopulmonary function and compress nerves in severe cases.Adolescent idiopathic scoliosis with different degrees of scoliosis should be treated with exercise,bracing,and surgery.However,the mechanical mechanism of selecting an orthopedic approach remains unclear due to the individual variability of patients.OBJECTIVE:To investigate the biomechanical mechanism of different orthopedic modalities for the treatment of adolescent idiopathic scoliosis to provide a basis for clinical selection of treatment modalities based on the spine model of adolescent idiopathic scoliosis patients.METHODS:Based on the CT images of an adolescent idiopathic scoliosis patient,a scoliosis model(C7-L5)was reconstructed in Mimics software in three dimensions,and lateral thrust force was applied at the T8/T9 thorax and vertical distraction force was applied over the C7 vertebra with the magnitude of 20,40,60,80,100,and 120 N.The intervertebral disc stress and vertebral displacement in concave and convex sides,and Cobb angle of the spine were analyzed under two orthopedic modalities.RESULTS AND CONCLUSION:(1)With lateral thrust,there was no significant change in the C7T1-T7T8 intervertebral disc.The concave and convex stress of T7T8-L4L5 segment decreased first and then increased with the increase of lateral thrust force.The correction effect of lateral thrust on the segment near T8T9 was obvious and weakened with the extension of the segment to the cephalic and caudal ends.At 120 N of lateral thrust,the thoracic Cobb angle changed from 53.2° to 32.5° and the lumbar Cobb angle changed from 50.2° to 43.9°.(2)With the vertical distraction,the thoracic intervertebral disc stresses first decreased and then increased,and all the lumbar disc stresses decreased.The C7 displacement was the most obvious,and the correction effect gradually diminished with the segment extended to the caudal end.At a vertical distraction force of 120 N,the thoracic Cobb angle changed from 53.2° to 39.4° and the lumbar Cobb angle changed from 50.2° to 47.6°.(3)It is concluded that both orthopedic modalities provide improvement in the degree of scoliosis,with the thoracic correction being greater than the lumbar correction.Also,the asymmetric stress distribution on the concave and convex sides is improved,which contributes to normal bone growth.A vertical distraction approach is appropriate for larger Cobb angles,and a lateral thrust approach is appropriate for smaller Cobb angles.The results of this study help to understand the mechanism of spinal orthosis and provide a theoretical basis for the choice of orthopedic approach.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.