OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group， model group and T. mongolicum total flavonoid group， with 8 mice in each group. Except for the blank group， the other 2 groups were given a high-fat diet， while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/（kg·d）] intragastrically， once a day， for 8 consecutive weeks. During the experiment， the food intake of each group of mice was recorded. After the last medication， the body mass， fat weight， blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing； the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group， the body weight of mice in T. mongolicum total flavonoids group was decreased significantly （P＜0.05）； the levels of total lipid cholesterol， triglycerides， and LDL cholesterol were all decreased significantly （P＜0.01）， and the level of HDL cholesterol was increased significantly （P＜0.01）； the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced （P＜0.05）； significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved； mRNA expressions of COX7A1 and COX8B were significantly upregulated （P＜0.05）. The results of bacterial colony detection showed that compared with the model group， there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group， and the Sobs index characterization and β diversity were increased significantly （P＜0.05）. Relative abundances of Blautia， norank_f_Ruminococcaceae， Bilophila， Alistipes， classified_f_Ruminococcaceae， Parabacteroides， norank_f_Desulfovibrionaceae， Anaerotruncus were significantly up-regulated（P＜0.05）， while those of Faecalibaculum， Erysipelatoclostridium， GCA-900066575， Tuzzerella， Lactobacillus， norank_f_norank_o_RF39， achnospiraceae_FCS020_group were significantly down-regulated （P＜0.05）. CONCLUSIONS T. mongolicum total flavonoids can reduce body mass， fat weight and blood lipid levels， and repair the pathological damage to liver and epididymal fat in obese mice， which is related to improving intestinal flora disorders caused by high-fat diet.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Giant cell-rich osteosarcoma(GCRO)is a special subtype of osteosarcoma,and is rare.This paper reported the clinical and imaging data of the patient with GCRO who had special imaging manifestations,and to provide the reference for clinical diagnosis and treatment of GCRO.The patient,a 69-year-old female,was admitted to the hospital due to the discovery of a mass in the right lower leg for 1 month.The X-ray imaging manifestations showed that the cortical bones on the opposite edges of the tibia and fibula presented mild moth-eaten changes.The plain CT scan imaging manifestations showed that there was a mass within the muscle,and the cortical bones on the opposite edges of the tibia and fibula were destroyed.The tumor only involved the superficial cortical bones and did not invade the deep cortical bones and the medullary cavity.The MRI imaging manifestations showed that the local bones of the tibia and fibula adjacent to the tumor were destroyed,and the medullary cavity was not invaded.An extended resection of the mass was performed,and the postoperative pathological diagnosis was GCRO.The patient received chemotherapy after the operation.However,a tumor in the right lower leg recurred 15 months after the operation.The patient passed away 21 months after the operation.Giant cell-rich osteosarcoma often leads to misdiagnosis or missed diagnosis due to its non-specific clinical manifestations.This paper explored the clinical manifestations and imaging data of the patient with GCRO in order to improve the clinical understanding level and the level of diagnosis and treatment of the clinicians about this disease.

Objective To investigate the effects of artesunate(Art)on the proliferation,apoptosis,and autophagy of nephroblastoma cell line(SK-NEP-1).Methods SK-NEP-1 cells were intervened with different concentrations of Art(0,10,20,40 and 80 μmol/L),and MTT method was applied to calculate the cell proliferation inhibition rate to screen the optimal intervention concentration;SK-NEP-1 cells were separated into control group,Art group,3-MA group(Art+autophagy inhibitor,3-methyladenine),and Rapa group(Art+autophagy activator rapamycin).EdU and flow cytometry were applied to detect cell proliferation and apoptosis,respectively;MDC staining was applied to detect autophagy in cells;the level of reactive oxygen species(ROS)in cells was detected by DCFH-DA fluorescent probe;the expression of proliferating cell nuclear antigen(PCNA),anti apoptotic factor B cell lym-phomatoma-2(Bcl-2),Bcl-2 associated X protein(Bax),microtubule junction protein 1 light chain 3 Ⅱ/3 Ⅰ(LC3 Ⅱ/LC3 Ⅰ),selective autophagy junction protein 1(p62),and benzyl chloride 1(Beclin-1)proteins in cells were detected by Western blot.Results Compared with 0 μmol/L Art,the proliferation inhibition rate of SK-NEP-1 cells was gradually increased after 10,20,40 and 80 μmol/L Art treatment(P＜0.05),and the IC50 value was 46.881 μmol/L,so 40 μmol/L Art was selected for follow-up experiments.Compared with the control group,the apoptosis rate,relative autophagy fluorescence intensity,ROS level,Bax,LC3 Ⅱ/LC3 Ⅰ,Beclin-1,PINK1,and Parkin protein expression levels of SK-NEP-1 cells in the Art group were obviously increased,the EdU positive cell rate,PCNA,Bcl-2,and P62 protein expression levels were obviously reduced(P＜0.05);The auto-phagy inhibitor 3-MA inhibited the promoting effect of Art on apoptosis and autophagy of nephroblastoma cells and inhibit proliferation(P＜0.05).Conclusions Art inhibits the proliferation of nephroblastoma cell line SK-NEP-1,and promotes autophagy and apoptosis.

Objective: To investigate the regulatory role of Porphyromonas gingivalis(Pg) infection on the EGFR/GSK3β signaling axis, and its impact on epithelial-mesenchymal transition(EMT) and cetuximab(Ctx) resistance in esophageal squamous cell carcinoma(ESCC). Methods: Single cell RNA sequencing was employed to perform differential analysis of cellular subpopulations, identifying differentially expressed genes in ESCC tissues infected and non-infected with Pg. IHC was conducted to assess the expression of Pg and epidermal growth factor receptor(EGFR) in ESCC tissues. Western blot, RT-PCR, and IF staining were performed to evaluate EGFR expression in Pg infected ESCC cell lines KYSE70 and TE1. ESCC cells were treated with Pg and EGFR inhibitor Ctx, and divided into four groups: control(NC) group, Pg group, Ctx group, Pg+Ctx group. Cell proliferation, migration and invasion abilities were evaluated using CCK-8, plate cloning, wound healing and Transwell assay. Western blot analysis was performed to detect the expression of EMT and EGFR/GSK3β signaling pathway-associated proteins and their phosphorylation levels. Transforming growth factor-β1(TGF-β1) was used to induce EMT in ESCC cells, promoting a transition from the epithelial phenotype to mesenchymal-like phenotype. The differential effects of Ctx on these two phenotypic states were subsequently compared. Results: Epithelial cells were predominantly enriched in Pg-positive tissues, and Pg infection promoted the upregulation of EGFR expression in ESCC cells. Compared to the NC group, Pg treatment significantly enhanced the proliferation, invasion and migration capabili-ties of ESCC cells, and also increased chemoresistance to Ctx and reduced its antitumor efficacy. Pg induced EMT in ESCC cellsviathe EGFR/GSK3β signaling pathway. Notably, Ctx exhibited markedly weaker inhibitory effects on mesenchymal-like cells compared to epithelial ESCC cells. Conclusion Pg promotes ESCC cells proliferation, invasion and migration by regulating EMT through the EGFR/GSK3β signaling pathway, and enhances chemoresistance to Ctx.

Objective:To investigate the current status of disease burden and its influencing factors among welder's pneumoconiosis patients, and provide scientific basis for taking targeted intervention measures.Methods:From June 2022 to June 2023, the patients with welder's pneumoconiosis in Jiangsu Province were selected from 1956 to 2020 as the research objects, and disability adjusted life years (DALY) were used as the comprehensive index to study the disease burden. The direct and indirect economic losses caused by the diseases were calculated, and the factors affecting the disease burden were discussed by multiple linear regression method.Results:A total of 974 cases of welder's pneumoconiosis were reported in Jiangsu Province, the cumulative loss of DALY was 6300.73 person-years, and the per capita loss was 6.47 person-years. Among them, the healthy life years lost due to disability (YLD) was 6156.50 person-years (97.71%) , and the healthy life years lost due to premature death (YLL) was 144.23 person-years (2.29%) . Multiple linear regression analysis showed that the main factors affecting DALY were disability grade, diagnostic age, pneumoconiosis grade and length of dust exposure ( P<0.05) . The total economic loss caused by 974 welder's pneumoconiosis patients was 1831838160.18 yuan, and the per capita loss was 1880737.33 yuan. Among them, the direct economic loss was 970917563.75 yuan (53.00%) , and the indirect economic loss was 860920596.43 yuan (47.00%) . Conclusion:Welder's pneumoconiosis causes serious disease burden to patients, and at the same time causes huge economic losses to individuals and society, which seriously hinders the development of society. Taking effective control measures to prevent the incidence of welder's pneumoconiosis is the key to reduce the disease burden.

Objective:To investigate the current status of disease burden and its influencing factors among welder's pneumoconiosis patients, and provide scientific basis for taking targeted intervention measures.Methods:From June 2022 to June 2023, the patients with welder's pneumoconiosis in Jiangsu Province were selected from 1956 to 2020 as the research objects, and disability adjusted life years (DALY) were used as the comprehensive index to study the disease burden. The direct and indirect economic losses caused by the diseases were calculated, and the factors affecting the disease burden were discussed by multiple linear regression method.Results:A total of 974 cases of welder's pneumoconiosis were reported in Jiangsu Province, the cumulative loss of DALY was 6300.73 person-years, and the per capita loss was 6.47 person-years. Among them, the healthy life years lost due to disability (YLD) was 6156.50 person-years (97.71%) , and the healthy life years lost due to premature death (YLL) was 144.23 person-years (2.29%) . Multiple linear regression analysis showed that the main factors affecting DALY were disability grade, diagnostic age, pneumoconiosis grade and length of dust exposure ( P<0.05) . The total economic loss caused by 974 welder's pneumoconiosis patients was 1831838160.18 yuan, and the per capita loss was 1880737.33 yuan. Among them, the direct economic loss was 970917563.75 yuan (53.00%) , and the indirect economic loss was 860920596.43 yuan (47.00%) . Conclusion:Welder's pneumoconiosis causes serious disease burden to patients, and at the same time causes huge economic losses to individuals and society, which seriously hinders the development of society. Taking effective control measures to prevent the incidence of welder's pneumoconiosis is the key to reduce the disease burden.

Tetralogy of Fallot is the most common cause of cyanotic congenital heart disease,and it is related with the high incidence of pulmonary regurgitation in repaired tetralogy of Fallot that usually requires pulmonary valve replacement.Transcatheter pulmonary valve replacement can replace traditional surgery in treating pulmonary regurgitation,which can make up for the shortcoming of large injury.Echocardiography is important in assessing ventricular function,however,conventional echocardiographic parameters have several limitations.This study reviewed the application of two-dimensional speckle tracking imaging in evaluating the right and left ventricular function after transcatheter pulmonary valve replacement in pulmonary valve regurgitation after repaired tetralogy of Fallot.

The most effective treatment for acute ischemic stroke is early recanalization of the occlusive vessels, including intravenous thrombolysis and endovascular thrombectomy. But the time window is narrow and limited patients can actually benefit from these therapies. In recent years, with the development of neuroimaging techniques such as CT perfusion and MRI, as well as advanced image analysis software applicated in clinical research, the time window of these two methods has been significantly extended. This article reviews the evolution and future development of the time window for early recanalization of the occlusive vessels in acute ischemic stroke, especially the extended time window, in order to provide some references for clinical work.

Objective To investigate the vowel acoustic characteristics of patients with voice disorders and the reasonable way of administering vocal space area(VSA)and language in the Mandarin system.Methods A total of 40 subjects(20 males and 20 females)with voice disorder and normal healthy controls were recruited.The differ-ences in VSA between the disorder and healthy control groups were analyzed under different corpora and different vowel vertex numbers.Results The differences in VSA between the voice disorder and the control groups were highly significant in both the vowel and long sentence corpus.The differences in VSA between 4 vowels and 3 vow-els and 5 vowels were not significant,and 5 vowels were more suitable for VSA measurement in Mandarin.Conclu-sion The vowel articulation of patients with voice disorder is less clear than that of normal speakers.It is more ac-curate to use 5 vowels to measure VSA under the Mandarin system and it is better for measuring oral motility.Both single vowels and continuous speech are suitable for the measurement of VSA.