Aim To investigate the key targets and mechanisms of diabetic gastroparesis(DGP)by in-tegrating network pharmacology and molecular docking technology with animal experiments,and to specifically focus on exploring the effects of hedysarum polybotrys polysaccharide(HPS)on DGP through animal experi-mentation to validate its potential as a treatment for di-abetic gastroparesis.Methods The chemical constit-uents of HPS were analyzed,and the active chemical components of Radix Astragali were identified using the TCMSP database.The Swisstarget database was utilized to screen for HPS active ingredient targets,while DGP-related targets were identified from disease databases such as TTD,GeneCards,Drugbank,and DisGeNET.The STRING database was used to construct the PPI network,and Cytoscape 3.10.1 software was employed for network topology analysis and selection of key tar-gets.Subsequently,a compound-target-pathway net-work diagram was constructed.Key targets underwent GO function(biological function,molecular function,and cellular function)and KEGG pathway enrichment analysis using the Metascape database.Molecular doc-king was performed using Pymol 2.5 and AutoDock software.DGP rat model was established to observe the histopathological changes in small intestine after eight weeks of HPS intervention through HE staining.Addi-tionally,Western blot was conducted to detect the ex-pression of AGEs,RAGE,and NF-κB in eggs.The re-sults revealed a total of 302 key targets.Results A total of 302 key targets which were further analyzed for gene GO function and KEGG pathway enrichment.CUL3,YWHAZ,and NTRK1 were predicted as the key targets with critical pathways including the AGE-RAGE signaling pathway in diabetic complications,viral carci-nogenesis,hepatitis B,and alcoholism signaling path-way among others.Furthermore,in vivo experiments confirmed that HPS could improve small intestine histo-pathology in DGP rats,resulting in significant protective effects on this organ.It also reduced the expression of AGEs,RAGE,and NF-κB protein,hence achieving its purpose of treating DGP.Conclusion HPS has the characteristics of multi-component,multi-target and multi-pathway action,which may affect the regulatory role of AGE-RAGE signaling pathway on DGP,and provide new ideas for the subsequent clinical improve-ment of DGP.

Aim To investigate the key targets and mechanisms of diabetic gastroparesis(DGP)by in-tegrating network pharmacology and molecular docking technology with animal experiments,and to specifically focus on exploring the effects of hedysarum polybotrys polysaccharide(HPS)on DGP through animal experi-mentation to validate its potential as a treatment for di-abetic gastroparesis.Methods The chemical constit-uents of HPS were analyzed,and the active chemical components of Radix Astragali were identified using the TCMSP database.The Swisstarget database was utilized to screen for HPS active ingredient targets,while DGP-related targets were identified from disease databases such as TTD,GeneCards,Drugbank,and DisGeNET.The STRING database was used to construct the PPI network,and Cytoscape 3.10.1 software was employed for network topology analysis and selection of key tar-gets.Subsequently,a compound-target-pathway net-work diagram was constructed.Key targets underwent GO function(biological function,molecular function,and cellular function)and KEGG pathway enrichment analysis using the Metascape database.Molecular doc-king was performed using Pymol 2.5 and AutoDock software.DGP rat model was established to observe the histopathological changes in small intestine after eight weeks of HPS intervention through HE staining.Addi-tionally,Western blot was conducted to detect the ex-pression of AGEs,RAGE,and NF-κB in eggs.The re-sults revealed a total of 302 key targets.Results A total of 302 key targets which were further analyzed for gene GO function and KEGG pathway enrichment.CUL3,YWHAZ,and NTRK1 were predicted as the key targets with critical pathways including the AGE-RAGE signaling pathway in diabetic complications,viral carci-nogenesis,hepatitis B,and alcoholism signaling path-way among others.Furthermore,in vivo experiments confirmed that HPS could improve small intestine histo-pathology in DGP rats,resulting in significant protective effects on this organ.It also reduced the expression of AGEs,RAGE,and NF-κB protein,hence achieving its purpose of treating DGP.Conclusion HPS has the characteristics of multi-component,multi-target and multi-pathway action,which may affect the regulatory role of AGE-RAGE signaling pathway on DGP,and provide new ideas for the subsequent clinical improve-ment of DGP.

Aim To investigate the role of FRMD4A in autophagy of placental trophoblast cells in preeclampsia(PE).Methods The placental tissues and clinical data of normal pregnancy and PE were obtained,and the histopathological changes were observed by HE staining.An in vitro model of hypoxia-induced HTR-8/SVneo trophoblast cells was established.The expres-sions of LC3B Ⅱ/Ⅰ and p62 in placental tissues and hypoxic cell models were analyzed by Western blot.The expression of FRMD4A was detected by qRT-PCR,Western blot and immunofluorescence,and the correlation between the expression level of FRMD4A and the clinical characteristics of the subjects was ana-lyzed by Pearson correlation analysis.Hypoxia induced trophoblast cells were transfected with si-FRMD4A,and the expression of LC3 B Ⅱ/Ⅰ and p62 was analyzed by Western blot.Results Compared with the normal group,the expression of LC3B Ⅱ/Ⅰ in PE placental tissues and hypoxia-induced trophoblast models was significantly upregulated,while the expression of p62 was significantly downregulated.Meanwhile,the ex-pression of FRMD4A increased significantly.Moreo-ver,its expression was positively correlated with the maternal systolic blood pressure,diastolic blood pres-sure,and platelet count,but negatively correlated with the neonatal weight(P＜0.01).In addition,hypoxia-induced trophoblast cells transfected with si-FRMD4A showed a significant decrease in LC3B Ⅱ/Ⅰ and an increase in p62 expression.Conclusions The expres-sion of FRMD4A is upregulated in PE placenta and hy-poxia-induced trophoblast cell model.Interfering with it can significantly hinder the autophagy process of trophoblast cells,suggesting that it may serve as a po-tential molecular target to participate in the pathologi-cal process of PE.

Aim To establish an animal model of diabetic kidney disease(DKD)integrating blood stasis syndrome and syndrome evaluation indicators.Methods Twenty-five SD rats were ran-domly divided according to body weight into a control group(8 rats)and a modeling group(17 rats).The modeling group was fed a high-sugar and high-fat diet for four weeks and induced to form diabetic rats by intraperitoneal injection of 30 mg·kg-1 streptozocin.The modeling rats were randomly divided into the DKD group and blood stasis syndrome combination group accord-ing to 24-hour urinary protein(24-hUP).The blood stasis syn-drome combination group was induced to replicate the DKD blood stasis syndrome model by injecting 10％high molecular weight D-glucoside three times at a dose of 0.05 mg·kg-1 via tail vein.The model was evaluated based on random blood glu-cose level,24-hUP level,syndrome assessment,pathological staining etc,and differential metabolites were selected using metabolomics.Results The comprehensive evaluation of syn-drome manifestations and pathological staining in the combined model of blood stasis syndrome in rats demonstrated successful replication.Utilizing the technique of liquid chromatography-mass spectrometry,22 differential metabolites were identified,with associated pathways showing a certain relevance to blood stasis syndrome in DKD.Conclusions The successful replica-tion of an animal model combining the syndrome of blood stasis in DKD has been achieved in this study.Evaluation of indicators and results from metabolomics studies consistently demonstrate a correlation with the syndrome of blood stasis in DKD.

Purpose To investigate the clinicopathological features and possible tumor-associated immune micro-environment in CD23-positive diffuse large B-cell lymphoma(DLBCL).Methods The clinicopathological data of 12 cases of CD23-positive DLBCL patients were analyzed retrospectively.The clinical and pathological features were ana-lyzed,and the clinical correlation and tumor-associated immune invasion were studied.Results CD23-positive DL-BCL accounted for 9.45％of all DLBCL.There were 6 males and 6 females.The mean age of onset was 64.83 years old.Four DLBCL cases occurred in lymph nodes and 8 cases occurred outside lymph nodes.Nine DLBCL cases were in advanced stage(Ⅲ-Ⅳ)and 3 cases DLBCL were in early stage(Ⅰ-Ⅱ).Among the patients,3 cases were untreated and lost to follow-up.One case deteriorated and died after operation.Two cases died,1 case progressed and 5 cases partially recovered after chemotherapy.Microscopically,the tumor cells were diffusely infiltrated and destroyed the nor-mal tissue structure.The tumor cells were observed to be centroblastic,immunoblastic and anaplastic large cells.No blastoid transformation and plasmacytoid differentiation were observed in morphology.According to Hans algorithm,11 cases were non-GCB phenotype except 1 case was GCB phenotype.Bioinformatics studies revealed that CD23 expres-sion was correlated with regulatory T cells,NK cells,plasma-like dendritic cells and neutrophils.Conclusion CD23-positive DLBCL patients are mainly middle-aged and elderly,and most of them occur outside lymph nodes and in ad-vanced stage(Ⅲ-Ⅳ).Follow-up results show that their prognosis is poor.Morphologically,there is no significant difference between DLBCL and conventional DLBCL.The Hans classification suggests that most cases originated from activated B cells.CD23 expression may play a role in the immune microenvironment of DLBCL.

Objective To observe the clinical efficacy of multi-target repetitive transcranial magnetic stimulation on freezing of gait in Parkinson's disease. Methods A total of 45 Parkinson's disease patients with freezing of gait in our hospital from January 2023 to January 2024 were selected and randomly divided into primary motor cortex(M1) treatment group (M1 group),dorsolateral prefrontal cortex (DLPFC) group (D group),and M1+DLPFC group (MD group),with 15 cases in each group. The stimulation site of patients in M1 group was bilateral M1 region lower limb innervation region,the stimulation site of patients in D group was bilateral DLPFC,and the left M1 region and DLPFC region of patients in MD group were stimulated on alternate days. The efficacy of Parkinson's disease patients with freezing of gait and the changes of mood scores were compared among the groups. Results One patient in D group and one in MD group were lost to follow-up,and 43 patients were eventually included. The freezing of gait questionnaire (FOGQ) scores,timed up and go test (TUGT) total time,modified standing-start 180° turn test (SS-180) time,unified Parkinson's disease rating scale part Ⅲ(UPDRS Ⅲ) scores,Hamilton depression scale (HAMD) scores and Hamilton anxiety scale (HAMA) scores of patients after treatment were improved compared with those before treatment in all three groups (P<0.05),and the improvement effect of MD group was significantly better than those of M1 group and D group (P<0.05). Conclusion High-frequency repetitive transcranial magnetic stimulation targeting bilateral M1 region and DLPFC region can improve freezing of gait,walking ability,and motor function,and alleviate symptoms of depression and anxiety of Parkinson's disease patients.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.