Background Carbendazim (CBZ), a widely used benzimidazole fungicide, has raised increasing concerns regarding the health risks associated with its residues. However, the toxic effects and associated mechanisms of CBZ on the skeletal system have not been reported. Objective To elucidate the effects of carbendazim on osteogenic differentiation and its underlying mechanisms. Methods MC3T3-E1 mouse pre-osteoblastic cells were treated with 1, 10, and 100 μmol·L⁻¹ CBZ for 24 h to examine cell viability, alkaline phosphatase (ALP) activity, bone nodule formation, reactive oxygen species (ROS) level, malondialdehyde (MDA) content, and nitric oxide synthase (NOS) activity. Transcriptomics was used to identify differentially expressed genes (DEGs) in osteoblasts exposed to CBZ. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were employed to analyze the potential biological pathways of DEGs. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to validate changes in gene and protein expression. Results Exposure to 10 and 100 μmol·L⁻¹ CBZ significantly reduced osteoblast viability, ALP activity, bone nodule formation, and NOS activity, while increasing intracellular ROS levels. CBZ at 100 μmol·L⁻¹ concentration significantly elevated MDA level (P < 0.05). The transcriptomic analysis revealed that 1 μmol·L⁻¹ CBZ treatment resulted in 385 significantly DEGs. The KEGG enrichment analysis revealed that CBZ significantly affects hormone regulation pathways (including parathyroid hormone, growth hormone, dopamine, and oxytocin), mitogen-activated protein kinase (MAPK) and cyclic GMP-dependent protein kinase G (cGMP-PKG) signaling pathways, focal adhesion and adherens junction, as well as the NOD-like receptor signaling pathway and the mRNA surveillance (NMD) pathway. The results of GSEA showed that CBZ significantly inhibited the bile acid metabolism and the Wnt/β-catenin pathway in osteoblasts. The validation results demonstrated that CBZ significantly suppressed the mRNA expression of Wnt3a and β-catenin, as well as the protein expression of Runx2 and Osterix in the Wnt/β-catenin pathway. Conclusion CBZ exposure exhibits potential skeletal toxicity, and its mechanism is through promoting oxidative stress, interfering with the Wnt/β-catenin pathway in osteogenic differentiation, thereby inhibiting the bone formation function of osteoblasts.

Objective To explore the mechanism of action of Huaier (Vanderbylia robiniophila) against pancreatic cancer. Methods The chemical components and targets of Huaier (Vanderbylia robiniophila) were searched through the Herb database. Pancreatic cancer-related targets were screened from GeneCards, NCBI, and DisGeNET online databases, and a Venn diagram was drawn to obtain the intersection targets of drugs and diseases. The protein-protein interaction (PPI) network was constructed using the String platform, and a series of network diagrams were drawn using Cytoscape 3.8.0 software to screen core targets and perform GO analysis and KEGG pathway enrichment analysis on the target genes. Finally, the key active components were molecularly docked with potential target genes using AutoDock software. The KEGG enrichment top 20 pathways and the whole-genome association analysis data of pancreatic cancer were used to further validate the results using the Open GWAS database through Mendelian randomization analysis. Results A total of 4 effective components of Huaier (Vanderbylia robiniophila) were identified, 112 drug-disease intersection targets, the main active components were kaempferol, rutin, genistein, and glucuronic acid, and the core targets were mitogen-activated protein kinase 8 (MAPK8), uridine diphosphate(UDP)-glucuronic acid transferase 1 family peptide A1 (UGT1A1), and superoxide dismutase 2 (SOD2). The mechanism of action may be related to pancreatic cancer, tumor necrosis factor(TNF) signaling pathway, and interleukin(IL)-17 signaling pathway. The molecular docking showed that the main active components had good docking activity with the key targets. After screening, 73 genes were retained, and 24,195,229 single nucleotide polymorphism(SNP) were used for two-sample Mendelian randomization analysis. The analysis results showed that MAPK8 may be an important therapeutic target for pancreatic cancer. Conclusions Huaier (Vanderbylia robiniophila) may exert an anti-pancreatic cancer effect by acting on MAPK8, providing initial theoretical evidence for further verifying the mechanism of action of Huaier in treating pancreatic cancer.

Palliative care is the final link in the whole lifecycle health management and is an important part of promoting a healthy China. In order to further improve service efficiency and the quality of end-of-life care, Shanghai Jiading Yingyuan Hospital has constructed a new interdisciplinary team collaboration model for palliative care from the perspective of integrated medical theory, and applied this model to clinical practice. By elaborating on the theory of team integration, member composition and division of labor, implementation process and preliminary effects, this study aims to provide a theoretical basis and reference for other regions to carry out the integration path and collaborative model of interdisciplinary services in palliative care.

OBJECTIVE To study the neuroprotective effects of Shenzao jianna o oral liquid （SZJN）on Alzheimer ’s disease （AD）model mice and its mechanism. METHODS The mice were randomly divided into sham operation group ，model group ， Donepezil hydrochloride tablet group （0.65 mg/kg），SZJN low-dose ，medium-dose and high-dose groups （0.3，1.5 and 7.5 g/kg， calculated by crude drug quantity ），with 12 mice in each group ，half male and half female. Each group was given relevant medicine（intragastric administration of water at constant volume in sham operation group and model group ），twice a day ，for consecutive 28 d. On the 15th day of administration ，intracerebroventricular injection of β-amyloid 1-42（Aβ1-42）combined with intraperitoneal injection of scopolamine hydrobromide were used to induce AD model. Morris water maze was used to detect the learning and memory ability of mice. HE staining and Nissl staining were used to evaluate the pathological changes of brain tissue in mice. The levels of MDA and SOD in brain tissue of mice were detected. The phosphorylation level of cyclic adenosine monophosphate response element binding protein （CREB） and expression of brain-derived neurotrophic factor （BDNF） in hippocampal tissues were detected by Western blot. RESULTS Compared with sham operation group ，the escape latency of the model group was significantly prolonged ，and the number of crossing the platform and the percentage of residence time in the target quadrant were significantly reduced （P＜0.01）. The level of SOD in brain tissue ，the phosphorylation level of CREB and the expression level of BDNF in hippocampus decreased significantly （P＜0.01），while the level of MDA increased significantly （P＜ 0.01）. In hippocampal CA 1 area and cortical tissue ，nerve cells showed significantly decreased number ，the disordered arrangement and large gap ；the shape of nucleus was irregular and deeply stained ，and Nissl body was blurred ，loosely arranged and the number decreased. Compared with model group ，the escape latency of mice in each dose group of SZJN was significantly shortened ，and the times of crossing the platform and the percentage of residence time in the target quadrant were significantly jing- increased（P＜0.01）. Above indexes of brain tissue in mice were reversed sig nificantly in SZJN high-dose group （P＜0.01），and pathological damage of brain tiss ue was improved. CONCLUSIONS SZJN can significantly improve the learning and memory ability of AD model mice ，and alleviate the pathological injury and oxidative stress of brain tissue ，which may be related to the activation of CREB/BDNF signaling pathway.

Objective To explore the diagnostic value of intravoxel incoherent motion diffusion-weighted imaging(IVIM-DWI)in diagnosis of different pathological types of lung cancer.Methods 45 patients were performed traditional MR and multi-b value DWI scan by GE discovery 750 MR.The values of Slow-ADC,Fast-ADC and ffast measured on a AW4.5 workstation were analyzed between the different pathological types of lung cancers.The correlations between these IVIM-DWI parameters and the serum tumor markers of lung cancer were analyzed.The diagnostic efficiency of these parameters were evaluated by receiver operator characteristic curve (ROC).Results 27 cases NSCLC(13 cases squamous carcinoma;14 cases adenocarcinoma )and 18 cases SCLC were finally included in this study.There were significant differences in Slow-ADC values between SCLC group and NSCLC group (P =0.00),the adenocarcinoma group (P=0.03),the squamous carcinoma group(P=0.01).There were no significant difference in Fast-ADC as well as ffast value between any two groups.The AUC of Slow-ADC value was 0.874.There existed negative correlation between squamous cell carcinoma antigen(SCC-Ag)of squamous carcinoma group and Slow-ADC(r=-0.730).Conclusion The Slow-ADC of IVIM-DWI parameters is useful in differential diagnosis of NSCLC and SCLC,which has the largest diagnostic efficiency.The correlation between SCC-Ag and Slow-ADC value has a certain meaning in diagnosing different pathological types of lung cancers.

Objective To evaluate whether the size,number or location of fibroids affect therapeutic efficacy of uterine artery embolization (UAE).Methods 84 patients with symptomatic uterine fibroids who had received uterine fibroid embolization with the use of polyvinyl alcohol(PVA)or gelfoam sponge particles(GSP).According to the lesion's size,number or location,all patients were divided into different groups and following -up as outpatients. Patient's symptomatic improvement and imaging following -up was assessed after UAE.Results A technically suc-cessful embolization was done in all patients.Postoperative 12 -month following -up was performed in 77 cases.No major life -threatening complications were found and the clinical symptoms were improved after UAE.In the different groups,the uterine size and the leiomyoma size after UAE were markedly decreased(t =5.842,P <0.05).Further comparison showed that the mean reduction in fibroids volume after UAE was not significant between the two groups, so was the mean reduction in uterine volume.Solitary leiomyoma group showed no significant difference in volume reduction rate of fibroids and uterine after UAE as compared with multiple leiomyoma group.Changes were not signifi-cantly in Submucosal uterine fibroids,Subserosal uterine fibroids,Intramural uterine fibroids.Conclusion UAE is an effective treatment for uterine fibroids.In this study,the size,number,and location of fibroids did not affect therapeutic efficacy or the complication rate of UAE.

Objective To evaluate the efficacy of dual stent placements for the treatment of occlusion/stenosis of subclavian artery associated with stenosis of adjacent vertebral artery initial site. Methods The clinical data of 9 patients with occlusion/stenosis of subclavian artery associated with stenosis of adjacent vertebral artery initial site were retrospectively analyzed. Stent implantations in the affected subclavian artery and vertebral artery were separately performed; the patients were followed up for 3-12 months after the treatment. The therapeutic efficacy was evaluated with the clinical symptoms and Doppler ultrasonic examination. Results Successful implantation of two stents was accomplished in all 9 patients, with the technical success rate of 100%. After the treatment, the blood flow in both the subclavian and vertebral arteries was unobstructed. Following-up examination showed that the subjective symptoms were obviously improved in all 9 patients, and no serious procedure-related complications occurred. Doppler ultrasound examination showed that no in-stent restenosis or stent displacement was observed. Conclusion For the treatment of occlusion/stenosis of subclavian artery associated with stenosis of adjacent vertebral artery initial site, dual stent placement technique is a safe and feasible means with satisfactory effect in improving vertebro-basilar arterial insufficiency.

The cytotoxicity of medical ultrasonic couplant was tested by MTT assay and agar overlay test. By MTT assay, when the inoculum density was high, the cytotoxicity level was low, or vice versa. The cytotoxicity grade tested by agar overlay was not accord to MTT assay's too. MTT assay is suitable to test the cytotoxicity of medical ultrasonic couplant because it is quantitative and more sensitive, however, the experimental condition and the preparative method of extraction should be determined.
Animals ; Cell Line ; Colorimetry ; Cytotoxicity Tests, Immunologic ; methods ; Mice ; Ultrasonics

Objective To compare the efficacy and safety of E1B gene-deleted adenovirus (H101)and ethanol in treating advanced pancreatic carcinomas by intratumoral injection combined with intravenous gemcitabine.Methods We constructed an orthotopic nude mouse model of pancreatic carcinoma through cancer cell injection into pancreas.A total of 54 nude mice were randomly allocated to 6 groups to accept H101,ethanol or saline (control) intratumoral injection,combined with or without intravenous gemcitabiein.The animals were sacrificed 4 weeks after the treatment and the pancreatic tumors were collected to determine the size,existence of metastasis,distribution of virus by indirect immunofluorescence and apoptosis in tumor by TUNEL and electron microscope.Results All mice completed the scheduled treatment,while 3 died in 48 hours after ethanol injection resulting in a mortality of 16.7％ (3/18).On the contrary,no mice died in the adenovirus injcction group.The average tumor size in group of H101 intratumoral injection combined with intravenous gemcitabie was significant smaller than that in group of saline injection with or without systemic gemcitabie (P =0.008,0.040,respectively).Similar differences were observed between ethanol intratumoral injection and control groups (P =0.012,0.041).Meanwhile,the H101 was absent in all the other organs except the pancreas,which meant that the selectivity of the H101 was tremcndous.The virus combine gemcitabie group had higher apoptosis rate in tumor (83.2 ± 35.7) ％,determined by TUNEL.Conclusion E1B gene-deleted adenovirus intratumral injection in combination with intravenous gemcitabine treating pancreatic carcinomas is efficient and safe,in spite of its lower effectiveness than ethanol.