To explore the inhibitory effect of ginkgolide B (GB) on MH7A human fibroblast-like synoviocytes (FLS) and its potential mechanism. Firstly, 20 μg/L tumor necrosis factor-α (TNF-α) was pretreated with MH7A to establish a cell model of arthritis. After incubation of MH7A cells with various concentrations of GB, CCK-8 assay, Transwell assay, and flow cytometry (FCM) were separately used to detect cell viability, cell invasion, and cell apoptosis rate and cell cycle; Real-time quantitative PCR and Western blot assay were performed to detect the apoptosis- and cycle-related gene transcriptions and protein expressions, respectively. The results showed that compared with the control group, GB dose- and time-dependently suppressed cell viability to a greater extent; GB significantly reduced cell invasive ability and increased cell apoptosis rate and proportion of G0/G1 phase in MH7A cells, along with increased transcription levels of Bcl-2-associated X protein (Bax) and p21 mRNA and decreased transcription levels of Bcl-2, myeloid cell leukemia 1(Mcl-1), protein kinase B (PKB; AKT), IP3K, Cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA; GB remarkably increased expression levels of Bax, p21, and cleaved-Caspase 3 protein and decreased expression levels of Bcl-2, Mcl-1, p-AKT, p-PI3K, Cyclin D1, and CDK4 protein, with decreased ratios of p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax. In conclusion, GB blocks the G1-to-S cell cycle transition, suppresses cell viability and cell invasion and induces cell apoptosis of MH7A human RA-FLS via suppressing the PI3K/AKT signaling pathway.

This paper aims to discuss the ideas and experience about the radiology residency training system of Canada with a presentation of its base accreditation standards for five aspects, competency goals for seven roles, four stages of training arrangement, and two types of final assessment questions. Although the Canada's radiology residency program differs from China's standardized resident and specialist training programs for radiology, there are still several points that are worth referencing, including emphasizing the training priority of competency goals, providing a specific basis for the stratification of training, offering clear guidance for the implementation of training content, and improving assessment methods to focus on competency goals. These points are of great value for improving the standardized radiology resident and specialist training programs in China, so as to provide a reference for the training of excellent radiologists in China.

Objective:To determine the relative correction factor of pre-vitamin D and simplify the calculation method of vitamin D assay.Methods:By studying the calculation method of vitamin D content in drug standards of various countries,HPLC was used to determine the relative correction factor of pre-vitamin D,and the influencing factors of determination were investigated.Results:The relative correction factors of pre-vitamin D at 254 nm and 265nm wavelength were determined by statistical analysis of 7 laboratories in China.Conclusion:Using the pre-vi-tamin D relative correction factor method to calculate the total amount of vitamin D simplified the experimental steps can be simplified by the pre-vitamin D relative correction factor method to calculate the total amount of vitamin D and the random operating errors can be avoided.The method is rapid and accurate,and lay a solid foundation for further improving the standard of vitamin D preparations.

Pyroptosis is a kind of inflammatory cell death mediated by the Gasdermin family,which has made great progress in tumor therapy in recent years.Basing on that cell pyroptosis can activate the anti-tumor immune response,and tumor immunotherapy is a new field of tumor therapy,the regulation of cell pyroptosis exhibits great potential for tumor therapy.Meanwhile,nanotechnology is the key means of tumor precision treatment with the advantages of precise targeting and continuous release.Based on these current situations,this paper summarizes the drugs that activate pyroptosis and the nanocarriers that use nanotechnology to promote pyroptosis to participate in tumor therapy,and summarizes the mechanism and application of their action on pyroptosis.This paper is aimed to provide certain references for anti-tumor therapy based on pyroptosis.

Objective:To investigate the protein expression characteristics of bone metastatic breast cancer cells and the underlying molecu-lar mechanism driving bone metastasis.Methods:A firefly luciferase-overexpressing human breast cancer cell line,MCF-7-luc,and its bone metastasis subline,MCF-7-BOM-luc,were established.Additionally,a nude mouse model of breast cancer bone metastasis was established by injecting the aforementioned cells into the left ventricle.Bone metastasis and trabecular changes were assessed using micro-computed tomography(Micro-CT).Cell migration,and invasion were evaluated using the Transwell assays.Differential protein expression and epithelial-mesenchymal transition(EMT)were analyzed using proteomics,Western blot,and reverse transcription-quantitative PCR(qPCR).We meas-ured the glucose uptake,L-lactic acid content,and cell energy metabolism parameters using 2-NBDG,ELISA,and a Seahorse energy metabol-izer.Results:MCF-7-BOM-luc cells exhibited stronger migration,invasion,and EMT characteristics as well as more pronounced bone meta-stasis capabilities than the MCF-7-luc cells.Proteomic analysis revealed increased S100 calcium-binding protein A(S100A4)expression in MCF-7-BOM-luc cells,with other differentially expressed proteins being primarily involved in metabolic pathways.Additionally,MCF-7-BOM-luc cells displayed increased expression of E-box binding homeobox 1/2(zinc finger E-box binding homeobox 1/2,ZEB1/2)and Vimentin and reduced E-cadherin expression.MCF-7-BOM-luc cells also exhibited enhanced glucose uptake,L-lactic acid production,and glycolysis rates as well as increased phosphorylation levels of extracellular signal-regulated kinases 1/2(ERK1/2)and signal transducer and activator of tran-scription 3(STAT3).Conclusions:MCF-7-BOM-luc cells promote S100A4 expression through ERK1/2 and STAT3 signaling pathway activation,which in turn enhances the EMT process and glycolysis rate,thereby contributing to malignant bone metastasis.Proteomic analysis of breast cancer bone metastasis-related protein characteristics could offer potential targets for the diagnosis,prevention,and treatment of breast cancer bone metastasis.

Objective To observe the effects of Renshen Yimai Prescription on oxidative stress and vascular aging in ApoE-/-mice;To explore its mechanism of intervention in vascular aging.Methods Forty ApoE-/-mice were divided into model group,Western medicine group(rosuvastatin,2.6 mg/kg),TCM low-and high-dosage group(Renshen Yimai Prescription,4.29,8.58 g/kg),with 10 mice in each group.Another 10 C57BL/6J mice were set as normal group.A vascular aging model was established by ApoE-/-mice fed with a Western diet.Each medication group was given corresponding drugs by gavage for 12 consecutive weeks,the normal group and model group were given equivalent volume of pure water.HE staining and Masson staining were used to observe the morphological changes of aortic tissue,and ox-LDL content in serum was detected by ELISA,the contents of ROS,GSH,GPX and NAD+in serum were detected by colorimetric method,the expressions of SIRT1,p53,p21 and NOX4 protein in aortic tissue were detected by Western blot.Results Compared with the normal group,the model group mice showed significant fat deposition in the aorta,thickening of the intima and media,a significant decrease in elastic fibers,and an increase in collagen fibers;the serum contents of ox-LDL and ROS significantly increased(P<0.01),while the contents of GSH,GPX and NAD+significantly decreased(P<0.01);the expression of SIRT1 protein in the aortic tissue significantly decreased(P<0.05),the expressions of p21 and p53 protein significantly increased(P<0.01,P<0.05).Compared with the model group,a small amount of lipid deposition was observed in the intima of aorta in each medication group,with clearer membrane structures in each layer and reduced collagen fiber;the serum contents of ox-LDL and ROS in each medication group were significantly decreased(P<0.01),while the GSH content significantly increased(P<0.05,P<0.01),the NAD+content in TCM low-dosage group significantly increased(P<0.05);the expressions of p21 and NOX4 protein in aortic tissue of the TCM high-dosage group significantly increased(P<0.05,P<0.01).Compared with the Western medicine group,the TCM high-dosage group showed a significant decrease in ROS content(P<0.01)and a significant decrease in p53 protein expression(P<0.05).Compared with the TCM low-dosage group,the TCM high-dosage group showed a significant decrease in p21 protein expression(P<0.01)and a significant increase in NOX4 protein expression(P<0.01).Conclusion Renshen Yimai Prescription may reduce vascular endothelial damage by regulating oxidative stress levels and related protein expression,thereby playing a role in improving vascular aging.

BACKGROUND:Nano-zirconium dioxide has good application potential in the field of bone tissue repair.Studying the effect of nano-zirconium dioxide on osteogenic differentiation will help to promote the clinical application of nano-zirconium dioxide in the treatment of bone defects. OBJECTIVE:To explore the effect of nano-zirconium dioxide on the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa. METHODS:Ectomesenchymal stem cells derived from rat nasal mucosa were isolated and cultured,and the biotoxicity of nano-zirconium dioxide to the cells was detected by CCK-8 assay.The biosafety concentration was selected according to the cytotoxicity,and the cells were randomly divided into a control group,a nano-zirconium dioxide group,and a nano-hydroxyapatite group.Osteogenic differentiation of cells was directionally induced in each group.On day 7 of induced differentiation,alkaline phosphatase staining was performed.qRT-PCR and western blot assay were used to detect the expression of early osteogenic markers(Runx2 and Osx).On day 21 of induced differentiation,alizarin red staining was conducted.qRT-PCR and western blot assay were utilized to determine the expression levels of late osteogenic markers(OPN and OCN). RESULTS AND CONCLUSION:(1)The median lethal concentration of nano-zirconium dioxide on ectomesenchymal stem cells in nasal mucosa was 0.6 mg/mL.In the experiment,the mass concentration of 200 μg/mL was selected for intervention.Zirconium dioxide had no significant effect on the proliferation of the cells.(2)Compared with the control group,the alkaline phosphatase staining of the cells in the nano-zirconium dioxide group was more obvious and the level of cell mineralization was higher,but there was no significant difference compared with the nano-hydroxyapatite.(3)Compared with the control group,the expression of bone-related genes and proteins increased significantly,but there was no significant difference compared with nano-hydroxyapatite.(4)The results show that nano-zirconium dioxide has good biological safety and can promote the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa.This promoting effect is equivalent to that of nano-hydroxyapatite.

Objective To assess the tear film stability and morphological characteristics of the tarsal gland in myopic children.Methods In this prospective descriptive study,myopic children who performed refractive examinations in the Pediatric Ophthalmology & Refraction Clinic,Jinan Mingshui Eye Hospital from November 2021 to November 2022 were in-cluded.An Ocular Surface Disease Index(OSDI)questionnaire survey was carried out;tear meniscus height(TMH),non-invasive first breakup time(NIf-BUT)and images of the tarsal glands were obtained by OCULUS Keratograph 5M compre-hensive ocular surface analyzer.In addition,the atrophy and tortuosity of tarsal glands were scored to analyze the tear film stability and clinical characteristics of tarsal glands in myopic children.Results A total of 48 myopic children(91 eyes)aged from 7 to 16(10.25±2.23)years were recruited,including 27 males(56.25％)and 21 females(43.75％).The aver-age TMH was(0.19±0.04)mm(95％CI:0.18-0.19)and the average NIf-BUT was(5.40±2.62)s(95％CI:4.90-5.94);the TMH was positively correlated with NIf-BUT(r=0.223,P=0.034).The tarsal gland atrophy score was 1(0,1).The tortuosity score of the upper and lower tarsal gland was 0(0,1)and 0(0,0),respectively,with a statistically significant difference(Z=3.692,P＜0.001).In all subjects,49 eyes(53.85％)had tarsal gland atrophy,and 37 eyes(40.66％)had tarsal gland tortuosity.There were significant differences in TMH and NIf-BUT between children aged＜12 years and children aged ≥12 years(both P＜0.05).There was a significant difference in TMH between children with an OSDI score＜13 and children with an OSDI score ≥ 13(t=2.305,P=0.026).There was a significant difference in NIf-BUT between mild and moderate myopia children(t=2.300,P=0.024);the spherical equivalent was positively correlated with NIf-BUT(r=0.283,P=0.023).Conclusion Children with mild to moderate myopia show low tear film stability and a certain proportion of abnormal morphology in tarsal glands.In addition to the refractive status of children,attention should also be paid to ocular surface health in the refraction clinic.

AIM: To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe its effect on miR-26a-5p and its target gene PTEN in the retinal of diabetic mice.METHODS: Diabetic mice models were established and they were gavaged by fenofibrate. H& E staining and transmission electron microscopy were used to observe the impairments of retinal neurons. Real-time PCR was used to examine the expression of miR-26a-5p, and Western blotting was employed to measure the expression of phosphatase and tensin homologue(PTEN)in the retina of diabetic mice. The expression level of nuclear factor-κB(NF-κB), interleukin-1β(IL-1β)and the morphology of neural tissues were observed.RESULTS: When compared with the diabetic mice, fenofibrate significantly attenuated the damage to retinal ganglion cells and the atrophy of retinal nerve fiber layer. While the level of miR-26a-5p was increased and the levels of PTEN and inflammatory mediators were significantly decreased in the retina of fenofibrate treated diabetic mice, with significant statistical significance(P<0.05).CONCLUSIONS: Fenofibrate protects against diabetic retinal neurodegeneration by upregulating miR-26a-5p and inhibiting PTEN, attenuating the inflammatory response and alleviating retinal cell injury.

Objective:To investigate the predictive ability of Glypican-3 (GPC3) positive hepatocellular carcinoma based on the hepatobiliary specific contrast agent gadoxetate disodium enhancement of the liver imaging reporting and data system version 2018 (LI-RADS v2018) imaging features, and to assess the relevant clinical imaging features for postoperative recurrence in GPC3 positive HCC patients.Methods:This study was a cohort study. A total of 122 hepatocellular carcinoma patients who underwent gadoxetate disodium enhanced MRI examination with hepatic tumor resection in Henan Provincial People′s Hospital from January 2017 to December 2021 were retrospectively collected, including 96 GPC3 positive and 26 GPC3 negative patients. The imaging features defined by LI-RADS v2018 of HCC lesions were analyzed. Patients were followed up for 40 months to determine recurrence free survival (RFS). The logistic regression was used to analyze the risk factors of GPC3 positivity. An imaging model, and a clinical-imaging model which combined the patient′s alpha-fetoprotein levels were constructed. The efficacy of the model for predicting GPC3 positivity was assessed using receiver operating characteristic curves. Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the RFS between GPC3 positive and negative patients. Risk factors affecting the recurrence of GPC3 positive HCC were assessed by Cox regression.Results:The results of logistic multivariate regression analysis confirmed that rim enhancement ( OR=5.685, 95% CI 1.229-26.287, P=0.026) and irregular tumor margin at hepatobiliary phase ( OR=4.431, 95% CI 1.684-11.663, P=0.003) were independent risk factors for GPC3 positive HCC. The area under the curve for predicting GPC3 positivity was 0.745 (95% CI 0.636-0.854) for the imaging model and 0.776 (95% CI 0.677-0.876) for the clinical-imaging model. The mean RFS in the GPC3 positive group was 22 months, and it was 32 months in the negative group. There was a statistically significant difference in RFS between the two groups ( χ2=5.15, P=0.023). The multivariate Cox regression analysis showed that the arterial rim enhancement ( HR=5.460, 95% CI 1.966-15.162, P=0.001), microvascular invasion ( HR=2.402, 95% CI 1.210-4.769, P=0.012), portal vein tumor thrombus ( HR=3.226, 95% CI 1.114-9.344, P=0.031) were independent risk factors for recurrence after hepatic tumor resection for GPC3-positive HCC. Conclusions:A model based on the LI-RADS v2018 imaging features of hepatobiliary specific contrast agent gadoxetate disodium enhancement can effectively predict GPC3 positive HCC. The arterial rim enhancement, microvascular invasion and portal vein tumor thrombus are independent risk factors for postoperative recurrence of GPC3 positive HCC.