ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide （APS） on inhibitor of differentiation1 （ID1） and protein kinase B （Akt） in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625， 1.25， 2.5， 5， 10， 20 mg·L^-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8（CCK-8） method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer， gastric tumor， and stomach cancer were searched against GeneCards， UniProt， DisGeNET， and Online Mendelian Inheritance in Man （OMIM） for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets， and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR， respectively. ResultsCompared with the adjacent normal gastric tissue， the gastric adenocarcinoma tissue showed increased positive expression of ID1 （χ² =81.00， P<0.01）. Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase （PI3K） /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil （0.1 mg·L^-1） and APS （10， 20 mg·L^-1） groups showed decreased cell proliferation， migration， and colony formation. Compared with the control group， 10， 20 mg·L^-1 APS inhibited the proliferation of MGC-803 cells （P<0.01）， with 10 mg·L^-1 APS demonstrating stronger inhibitory effect. In addition， APS at 10， 20 mg·L^-1 inhibited the migration （P<0.01） and colony formation （P<0.05， P<0.01） of MGC-803 cells. Compared with the control group， APS at 10， 20 mg·L^-1 down-regulated the protein levels of ID1 （P<0.01） and Akt （P<0.05） and the mRNA levels of ID1 （P<0.05， P<0.01） and Akt （P<0.05， P<0.01） in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue， which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects， which is expected to provide new therapeutic targets for gastric cancer treatment.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.

Objective: To investigate the clinical efficacy of oral microscope-assisted microflap periodontal bone grafting in treating class Ⅱ furcation involvement in mandibular molars, and to provide clinical evidence for its treatment in furcation involvement. Methods: This study was reviewed and approved by the institutional ethics committee, and informed consent was obtained from all patients. Sixty mandibular molars with class II furcation involvement caused by periodontitis were enrolled in a randomized controlled clinical study, utilizing a random number table method. Patients were categorized into a control group (n=30) and an experimental group (n=30) based on the surgical procedure employed. The control group underwent periodontal flap surgery with an internal oblique incision and vertical incision; this procedure was performed without the aid of a microscope. Conversely, the experimental group underwent micro flap periodontal bone grafting surgery without vertical incision; an oral microscope was used for this procedure. Both groups were analyzed 6 months after surgery, and postoperative gingival recession (GR), probing depth (PD), bleeding index (BI), vertical bone height increase (VBHI), pain level, and complications were recorded. Results: Both groups showed improvement in PD and BI after 6 months compared to preoperative levels: the control group had a preoperative PD of (7.33 ± 1.72 mm) and a 6-month postoperative PD of (3.37 ± 0.96 mm), with statistically significant differences (P<0.001). The preoperative PD of the experimental group was (7.27 ± 1.57 mm), and the 6-month postoperative PD was (3.00 ± 0.69 mm), with statistically significant differences (P<0.001). The BI of the control group decreased from 3.03 ± 1.03 before surgery to 0.77 ± 0.82 at 6 months after surgery (P<0.001), while the BI of the experimental group decreased from 3.20 ± 1.09 before surgery to 0.73 ± 0.64 at 6 months after surgery (P<0.001), and the differences were statistically significant. The experimental group showed a significant improvement in GR (0.70 ± 0.59 mm) compared to preoperative GR (1.26 ± 0.94 mm) at 6 months after surgery (P=0.007), while the control group showed an increase in GR (1.37 ± 0.89 mm) at 6 months after surgery compared to preoperative GR (1.13 ± 0.97 mm), but the difference was not statistically significant (P=0.337). The inter group comparison results showed that there were no statistically significant differences in PD and BI between the two groups at 6 months after surgery (PD: P=0.096, BI: P=0.861); The GR of the experimental group was lower than that of the control group, and the difference was statistically significant (P=0.001). There was no statistically significant difference in postoperative VBHI between the two groups (P=0.128). The pain level scores of the experimental group were lower than those of the control group at 4 and 24 hours after surgery (P<0.001). None of the patients experienced complications. Conclusion Microflap periodontal bone grafting assisted by an oral microscope effectively improves the periodontal condition of patients with grade Ⅱ root bifurcation lesions of mandibular molars, and the bone grafting effect is good, with mild pain and good safety.

Objective To mine the adverse drug event(ADE)signals of galcanezumab based on U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)to provide reference for clinical drug safety.Methods The data from the FAERS database from the third quarter of 2018 to the fourth quarter of 2023 were extracted.After data cleaning and standardization,the duplicate data was removed using structured query language,ADE reports with galcanezumab as the main suspected drug were screened.ADE reports were standardized and categorized using the Medical Dictionary for Drug Regulatory Activities.The reporting odds ratio(ROR)method and information component(IC)method were applied for signal detection.Results A total of 60 ADE signals were detected after screening,11 system organ classes were involved,mainly general disorders and administration site conditions.The ADE signals that occurred most frequently were a variety of discomfort reactions at the injection site,consistent with the most common ADEs documented in the drug insert.The top 3 new ADE signals in order of occurrence frequency were alopecia,weight increased and constipation,and in order of ROR and IC values were injection site pustule,vertebral artery dissection and Raynaud's phenomenon.Conclusion ADE related to galcanezumab mainly involve systemic diseases and various reactions at the site of administration,among which vertebral artery dissection and Raynaud's phenomenon are stronger signals and newer ADEs.The patient's disease progression should be closely monitored during the treatment period to avoid serious consequences.

Objective:To investigate the efficacy and safety of liposomal amphotericin B (L-AmB) for the salvage treatment of invasive fungal disease (IFD) in patients with hematological diseases.Methods:Data were retrospectively collected from 80 patients with hematological issues treated with L-AmB between June 2023 and December 2023 after failure of previous antifungal therapy. Baseline patient information, clinical efficacy, and factors affecting the efficacy of L-AmB were analyzed by logistic regression. Moreover, adverse effects associated with L-AmB were evaluated.Results:Among the 80 patients, 9 (11.2%) had proven IFD, 43 (53.8%) had probable IFD, and 28 (35.0%) had possible IFD. The efficacy rate of L-AmB salvage therapy for IFD was 77.5%, with a median daily dose of 3 (range: 1-5) mg·kg -1·d -1 and a median dosing course of 14 (range: 8-25) days. Multivariate logistic regression analysis showed that the disease remission status ( OR=4.337, 95% CI 1.167-16.122, P=0.029) and duration of medication ( OR=1.127, 95% CI 1.029-1.234, P=0.010) were independent factors affecting the efficacy of L-AmB. The incidence of infusion reactions associated with L-AmB, including fever and chills, was 5.0%. The incidence of hypokalemia was 28.8% (predominantly grades 1-2), and the incidence of nephrotoxicity was 11.3% (predominantly grades 1-2) . Conclusion:L-AmB is safe and effective in the treatment of patients with IFD who are intolerant to or who have experienced no effect of previous antifungal therapy, with a low rate of adverse reactions.

The study analyzes the upgrade and application of LightSpeed VCT Console,aiming to explore the principle,method and advantages of this technology,and verify its effectiveness in practical scenarios.After the introduction of the basic principle of LightSpeed VCT Console which uses machine learning algorithms and large-scale image training data to improve and transform low-quality images,the application cases of LightSpeed VCT Console in reducing noise and suppressing artifacts after upgrading are discussed in details,and the excellent performance of this technology in improving image quality is demonstrated.Finally,the characteristics and differences of LightSpeed VCT Console and other image transformation technologies are compared,and the further development direction of Lightspeed VCT Console in image processing is discussed.

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation

Objective To investigate the anti-inflammatory effects of Bupi Yichang Pills on mice with experimental colitis and its potential mechanism of action.Methods Dextran sulfate sodium(DSS)was used to model the experimental colitis,and low-,medium-and high-doses of Bupi Yichang Pills(1.5,3.0,6.0 g·kg-1·d-1)and Mesalazine(300 mg·kg-1·d-1)were fed at the same time.Mice were observed for general behavior and weighed.Hematoxylin-eosin staining was used to observe the pathological injury of colonic tissues.qPCR and ELISA were used to detect the levels of inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10,IL-35 and TGF-β1),qPCR and Western Blot were used to detect the mRNA and protein levels of glucose transporters and glycolytic kinases.Results Low-,medium-and high-doses of Bupi Yichang Pills significantly down-regulated disease activity index in colitis mice(P＜0.05,P＜0.01).The body mass and colon length were significantly increased,while colon mass,colon mass index and unit colon mass index were significantly reduced(P＜0.05,P＜0.01),and ulcer formation and inflammatory cell infiltration in colonic tissue were significantly improved.In addition,medium-and high-doses of Bupi Yichang Pills significantly down-regulated the mRNA levels and concentrations of pro-inflammatory cytokines including TNF-α,IL-1β and IL-6(P＜0.01),while significantly up-regulated the mRNA levels and concentrations of anti-inflammatory cytokines such as IL-10,IL-35 and TGF-β1(P＜0.01).We further found that high-dose of Bupi Yichang Pills significantly down-regulated the mRNA and protein expressions of glucose transporters(Glut1,Glut2,Glut4)and glycolytic kinases(HK2,Aldolase A,PKM2)in colonic tissue(P＜0.01).Conclusions Bupi Yichang Pills effectively alleviates DSS-induced experimental colitis,and its specific mechanism of action is related to the improvement of glycolytic metabolic pathways and the regulation of inflammatory cytokine expression.