Objective To investigate the effect of miR-29b-3p targeting insulin-like growth factor-1(IGF-1)on high glucose-induced injury in human retinal microvascular endothelial cells(HRMECs)and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods HRMECs were di-vided into the following groups:control group(normal culture),high glucose(HG)group(treated with 30.0 mmol·L-1 glucose for 48 h),inhibitor-NC group,miR-29b-3p inhibitor group,miR-29b-3p inhibitor+si-NC group,miR-29b-3p inhib-itor+si-IGF-1 group(all transfected with corresponding plasmids for 24 h after HG treatment),and LY294002 group(treated with 40 μmol·L-1 LY294002 for 24 h).The expression level of miR-29b-3p was detected by quantitative real-time PCR(qRT-PCR).Cell viability was assessed using the Cell Counting Kit-8(CCK-8)assay.Intracellular reactive oxygen species(ROS)levels were measured by immunofluorescence.The expression levels of malondialdehyde(MDA),superox-ide dismutase(SOD),and glutathione peroxidase(GSH-Px)were determined using enzyme-linked immunosorbent assay(ELISA).Cell apoptosis was analyzed by flow cytometry.Autophagosome formation was observed under a transmission electron microscope.The protein expression levels related to apoptosis,autophagy,IGF-1,and the PI3K/Akt/mTOR path-way were examined by Western blot.The targeting relationship between miR-29b-3p and IGF-1 was verified by a dual-lucif-erase reporter assay.Results Compared with the Control group,the HG group showed significant increases in the ex-pression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;whereas the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the number of autophagosomes were significantly decreased(all P＜0.05).Compared with the in-hibitor-NC group,the miR-29b-3p inhibitor group exhibited significant decreases in the expression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;while the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the num-ber of autophagosomes were significantly increased(all P＜0.05).Compared with the miR-29b-3p inhibitor+si-NC group,the miR-29b-3p inhibitor+si-IGF-1 group demonstrated significant increases in the expression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;whereas the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the number of autophagosomes were significantly decreased(all P＜0.05).Compared with the HG group,the LY294002 group showed significant decreases in the expression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;while the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the number of autophagosomes were significantly increased(all P＜0.05).The dual-luciferase activity was significantly lower in cells co-transfected with IGF-1-WT and miR-29b-3p mimic compared to miR-NC cells(P＜0.05).Conclusion Inhibition of miR-29b-3p can target upregulation of IGF-1 expression levels,thereby inhibiting the PI3K/Akt/mTOR pathway and improving high glucose induced cell damage in HRMECs.

Objective To investigate the role and molecular mechanism of SOX4 in Helicobacter pylori(H.pylori)-mediated gastric mucosal epithelial dysplasia.Methods The expression of SOX4 in gastric tissues and cells was analyzed with reverse transcription-polymerase chain reaction(RT-PCR),Western blotting,and immunohistochemical staining.The effects of SOX4 on gastric epithelial cell proliferation and colony formation were determined with CCK-8 and colony formation assays.A PCR array was used to screen downstream target genes involved in H.pylori-induced dysplasia mediated by SOX4.The transcriptional regulation and binding sites of the target gene MLH3 by SOX4 were elucidated with luciferase reporter assay,promoter truncation assay,and chromatin immunoprecipitation(ChIP).Results SOX4 expression was significantly increased in H.pylori-infected gastric tissues(P<0.05).Overexpression of SOX4 markedly enhanced the proliferation and colony formation abilities of normal gastric epithelial cells(P<0.05).Elevated SOX4 led to the dysregulation of MLH3 and other DNA damage repair-related molecules after H.pylori infection in gastric epithelial cells(|logFC|>1,P<0.05).H.pylori promoted MLH3 expression in gastric epithelial cells through SOX4.SOX4 transcriptionally activated MLH3 expression by binding to the 5th site of the MLH3 promoter.The increased expression of SOX4 and MLH3 is associated with poor prognosis of gastric cancer patients.Conclusion SOX4 is closely associated with H.pylori-induced dysplasia in gastric epithelial cells.Upregulation of SOX4 promotes H.pylori-related dysplasia by transcriptionally activating MLH3,leading to the imbalance of proliferation and colony formation in gastric epithelial cells.

Patient-Reported Outcomes(PRO)is a subjective outcome indicator based on the concept of"patient-centered",in which patients report their own information such as health status,functional status,and treatment feelings,which is an ef-fective supplement to traditional objective outcome indicators.Based on the development status of the Patient Reported Outcome Measure(PROM),it systematically analyzed the concepts related to PRO with the goal of clarifying the Patient Experience Data(PED)with research value,and proposed six core types of PROs in the medical field,including health-related quality of life,health preference,health behavior,symptom burden,functional status and patient-reported experience.For each type of PRO,the key characteristics of the study were analyzed,the evidence and application directions of related PED and the production based on PED were described,and the existing international mainstream PROMs were reviewed.It is hoped that the connotation of PRO-related concepts can be comprehensively expounded,and PEDs with research significance and value can be explored,so as to provide guidance for the focus of PRO-related research in China,so as to promote the application and development of PRO in China.

Patient-Reported Outcomes(PRO)refers to a subjective outcome measure based on the concept of"patient-cen-tered",in which patients report their own health status,functional status,treatment feelings and other information,which is an ef-fective supplement to traditional objective outcome indicators.With the continuous promotion of PRO research,its application in the world is also constantly enriched.It takes the different application scenarios of PRO as the starting point and the evidence-based evidence that PRO can generate as the evaluation object,reviews the application status of PRO in the US,the European Union,the UK,Canada and other countries,regions or organizations,and summarizes the main application methods of PRO in different medical decision-making scenarios,in order to provide international experiences for the application research of PRO in China.

OBJECTIVE To analyze the bacterial spectrum characteristics and drug resistance of midstream urine culture-positive cases in patients with urinary tract infection(UTI),and to provide reference for rational use of antibiotics.METHODS A retrospective analysis was conducted on 6 029 patients with urinary tract infections who had positive midstream urine cultures at the First Affiliated Hospital of Guangzhou Medical University from 2013 to 2023,with a total of 8 495 infectious bacterial detected,and the characteristics of the pathogens,antimicrobial susceptibility tests and the epidemiological features were analyzed.RESULTS There were 2 086 males and 3 943 fe-males.A total of 8 495 pathogens were isolated,of which 1 492 stains of gram-positive bacteria accounted for 17.56％,5 850 strains of gram-negative bacteria accounted for 68.86％,1 150 strains of fungi accounted for 13.54％,with Escherichia coli(42.30％),Klebsiella pneumoniae(7.59％),and Enterococcus faecalis(6.19％)being predominated.The major gram-negative bacteria had low resistance rates to meropenem,imipen-em and ertapenem(＜20％),and high resistance rates to ampicillin and cefazolin(＞34％).The major gram-posi-tive bacteria had low resistance rates to teicoplanin and quinupristin/dalfopristin(＜12％),very low resistance to linezolid(＜1％),and high resistance rates to erythromycin(＞40％).The main fungi had low resistance rates to flucytosine and amphotericin B(＜3％),while Candida tropicalis had high resistance rates to itraconazole,flu-conazole,and voriconazole(37.93％-42.18％).CONCLUSION The three most frequently isolated pathogens in the midstream urine cultures of patients with UTI are Escherichia coli,Klebsiella pneumoniae,and Group D En-terococcus faecalis,which show low resistance to tigecycline and high resistance to ciprofloxacin,ampicillin and levofloxacin,and these findings provide important references for clinical treatment of urinary tract infections.

Objective To investigate the effect of miR-29b-3p targeting insulin-like growth factor-1(IGF-1)on high glucose-induced injury in human retinal microvascular endothelial cells(HRMECs)and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods HRMECs were di-vided into the following groups:control group(normal culture),high glucose(HG)group(treated with 30.0 mmol·L-1 glucose for 48 h),inhibitor-NC group,miR-29b-3p inhibitor group,miR-29b-3p inhibitor+si-NC group,miR-29b-3p inhib-itor+si-IGF-1 group(all transfected with corresponding plasmids for 24 h after HG treatment),and LY294002 group(treated with 40 μmol·L-1 LY294002 for 24 h).The expression level of miR-29b-3p was detected by quantitative real-time PCR(qRT-PCR).Cell viability was assessed using the Cell Counting Kit-8(CCK-8)assay.Intracellular reactive oxygen species(ROS)levels were measured by immunofluorescence.The expression levels of malondialdehyde(MDA),superox-ide dismutase(SOD),and glutathione peroxidase(GSH-Px)were determined using enzyme-linked immunosorbent assay(ELISA).Cell apoptosis was analyzed by flow cytometry.Autophagosome formation was observed under a transmission electron microscope.The protein expression levels related to apoptosis,autophagy,IGF-1,and the PI3K/Akt/mTOR path-way were examined by Western blot.The targeting relationship between miR-29b-3p and IGF-1 was verified by a dual-lucif-erase reporter assay.Results Compared with the Control group,the HG group showed significant increases in the ex-pression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;whereas the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the number of autophagosomes were significantly decreased(all P＜0.05).Compared with the in-hibitor-NC group,the miR-29b-3p inhibitor group exhibited significant decreases in the expression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;while the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the num-ber of autophagosomes were significantly increased(all P＜0.05).Compared with the miR-29b-3p inhibitor+si-NC group,the miR-29b-3p inhibitor+si-IGF-1 group demonstrated significant increases in the expression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;whereas the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the number of autophagosomes were significantly decreased(all P＜0.05).Compared with the HG group,the LY294002 group showed significant decreases in the expression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;while the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the number of autophagosomes were significantly increased(all P＜0.05).The dual-luciferase activity was significantly lower in cells co-transfected with IGF-1-WT and miR-29b-3p mimic compared to miR-NC cells(P＜0.05).Conclusion Inhibition of miR-29b-3p can target upregulation of IGF-1 expression levels,thereby inhibiting the PI3K/Akt/mTOR pathway and improving high glucose induced cell damage in HRMECs.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

ObjectiveTo observe the clinical effectiveness of horticultural therapy involving the planting of Chinese medicinal herbs （mint and lily potted plants） combined with intradermal needling therapy for generalized anxiety disorder （GAD） of liver depression transforming into fire syndrome under transcranial magnetic stimulation and basic psychological therapy， and to explore the possible mechanisms of action. MethodsA total of 180 patients with GAD of liver depression transforming into fire syndrome were randomly divided into three groups， horticultural therapy group， intradermal needling group， and horticultural therapy+intradermal needling group， with 60 patients in each. All groups received basic treatment including basic psychological therapy and transcranial magnetic stimulation. The horticultural therapy group received horticultural therapy in addition to the basic treatment； the intradermal needling group received intradermal needling therapy once a week for 8 weeks in addition to the basic treatment； the horticultural therapy+intradermal needling group received both horticultural therapy and intradermal needling therapy， following the same procedures and duration. Hamilton Anxiety Rating Scale （HAMA）， Self-Rating Anxiety Scale （SAS）， and Pittsburgh Sleep Quality Index （PSQI） scores were assessed at baseline and after 2， 4， 6， and 8 weeks of treatment. Serum levels of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） were measured before treatment and after 8 weeks of treatment. Motor-evoked potential （MEP） baseline levels were recorded before treatment， and MEP amplitude ratios were compared after 1 week and 8 weeks of treatment. Clinical effectiveness and safety were evaluated after 8 weeks of treatment. Pearson correlation analysis was used to examine the relationships between serum ACTH and CORT levels， MEP amplitude， and anxiety. ResultsIn the horticultural therapy group and intradermal needling group， HAMA， SAS and PSQI scores after 4， 6， and 8 weeks treatment were lower than baseline scores （P＜0.05）. In the horticultural therapy+intradermal needling group， these scores showed a significant decline starting after 2 weeks treatment and continuing through 8 weeks after treatment （P＜0.05）. The HAMA， SAS， and PSQI scores in the horticultural therapy+intradermal needling group were significantly lower than those in the other two groups after 2， 4， 6， and 8 weeks treatment （P＜0.05）. After 8 weeks of treatment， serum CORT and ACTH levels in the horticultural therapy+intradermal needling group were significantly lower than baseline levels （P＜0.05） and were also lower than those in the horticultural therapy group and intradermal needling group at the same time point （P＜0.01）. When comparing the level after 8 weeks treatment to that after 1 week treatment， under PAS10 stimulation， the MEP amplitude ratio in the intradermal needling group decreased at 30 minutes， while in the horticultural therapy+intradermal needling group， the MEP amplitude ratio decreased at all time points （P＜0.05 or P＜0.001）； under PAS25 stimulation， the MEP amplitude ratio in the horticultural therapy group increased at 20 minutes， and in the intradermal needle group at 10 minutes （P＜0.05）. In the horticultural therapy+intradermal needling group， the MEP amplitude ratio increased significantly at all time points after treatment （P＜0.001）. The cure rate in the horticultural therapy+intradermal needling group （74.14%， 43/58） was significantly higher than that in the horticultural therapy group （30.00%， 18/60） and the intradermal needling group （48.28%， 28/58， P＜0.05）. Correlation analysis revealed that serum ACTH and CORT levels were positively correlated with HAMA scores （r = 0.488， P＜0.01； r = 0.428， P＜0.01）. Following PAS10 intervention， the MEP amplitude ratio was positively correlated with HAMA scores （r = 0.458， P＜0.01）， whereas after PAS25 intervention， the MEP amplitude ratio was negatively correlated with HAMA scores （r = -0.562， P＜0.01）. ConclusionHorticultural therapy combined with intradermal needling treatment， under transcranial magnetic stimulation and basic psychological therapy， demonstrates significant clinical effectiveness in patients with GAD of liver depression transforming into fire syndrome. Its mechanism of action may be related to the regulation of hyperactivation of the hypothalamic-pituitary-adrenal （HPA） axis and the reduction of cortical excitability.

Objective:This study investigated the expression level of phosphatidylserine-specific phospholipase A1(PLA1A)in colorectal can-cer(CRC)and analyzed its correlations with clinicopathological features,prognosis,and immune infiltration.Methods:The expression level of PLA1A in CRC was screened,and the influence of this expression level on patient prognosis was analyzed using bioinformatics methods.A cohort of 192 patients diagnosed with CRC at Shanxi Province Cancer Hospital from January to December 2020 were selected.The PLA1A ex-pression level in those with CRC was determined using immunohistochemistry(IHC)and real-time quantitative reverse transcription PCR(RT-qPCR).The relationship between PLA1A level and the clinicopathological features of the patients with CRC was analyzed using the chi-square test.The expression levels of immune cell markers CD4 and CD8 as well as immunosuppressive checkpoints PD-1,TIM-3,and CTLA-4 in CRC were detected via IHC,and their correlations with PLA1A level were analyzed using the chi-square test.Results:The results of bioinformatics analysis showed that the expression level of PLA1A in CRC tissue was higher than paracancerous tissue,which correlated with overall surviv-al(OS)(P<0.05).The IHC and RT-qPCR results showed that PLA1A expression level was significantly upregulated in CRC tissiue(P<0.05).High PLA1A level was closely associated with the TNM stage,degree of differentiation,and lymph node metastasis(P<0.05).The IHC results demonstrated that PLA1A positively correlated with the infiltrating CD8+T cell level(P<0.05).In addition,the elevated PLA1A levels upregu-lated the expressions of immunosuppressive checkpoints PD-1,TIM-3,and CTLA-4(P<0.05).Conclusions:PLA1A is highly expressed in CRC,which is closely related to immune infiltrating cells and immunosuppressive checkpoints,suggesting that PLA1A plays an important role in immune infiltration in CRC,a finding that provides guidance in the treatment of CRC.

Objective To explore and analyze adverse drug events(ADE)signals of azithromycin,identify common adverse events and suspected adverse reactions that occur easily in the real clinical application of azithromycin.Methods The adverse drug event reports related to azithromycin recorded in the US FDA Adverse Event Reporting System database from October 1,2003,to October 1,2023,were mined using the OpenVigil 2.1 drug surveillance platform.Signal detection and analysis were carried out using the reporting odds ratio(ROR)and Bayesian confidence propagation neural network method(BCPNN).Results A total of 5498 ADE signals were identified,with a total of 112485 reports.Eventually,31,041 azithromycin-associated adverse event reports were extracted,involving 898 positive signals,27 system organ classes,mainly concentrated in respiratory system diseases,infections,gastrointestinal system diseases,and others.Additionally,some adverse reactions possibly caused by azithromycin were discovered,such as asthma,wheezing,and potential reactions like incomplete abortion.Conclusion When using azithromycin,besides paying attention to the adverse reactions listed in the drug instructions,we should also pay attention to some adverse reactions that have not been timely recorded or updated,in order to prevent the medication safety risks caused by outdated instructions,provide reasonable medication advice,and ensure the medication safety of patients.