BACKGROUND:Long non-coding RNA(LncRNA)plays an important role in nervous system development and neurological diseases.Previous studies by the research team have demonstrated that human umbilical cord mesenchymal stem cells overexpressing erythropoietin(EPO-MSCs)under ischemic and hypoxic conditions have better neuroprotective functions and significantly activate the expression of LncRNA XIST.Research suggests that XIST is related to the pathogenesis of hypoxic-ischemic encephalopathy,but the role and mechanism of its regulation by EPO-MSCs in protecting ischemic-hypoxic neurons remain unclear.OBJECTIVE:To explore the new mechanism by which LncRNA XIST,in response to EPO-MSC signaling,affects the apoptosis of ischemic-hypoxic SH-SY5Y cells.METHODS:(1)SH-SY5Y cell lines with knockdown of LncRNA XIST(sh-XIST)and negative control(NC-XIST)were constructed through lentiviral transfection.Oxygen-glucose deprivation was used to induce ischemic-hypoxic injury in the cells.Transwell chambers were used to create a non-contact co-culture system with EPO-MSCs,sh-XIST,and NC-XIST ischemic-hypoxic SH-SY5Y cells.Cell proliferation ability was detected using the CCK-8 assay.Cell migration ability was assessed using the scratch assay,and cell apoptosis was measured by flow cytometry.(2)RNA-seq bioinformatics analysis was performed to screen for differentially expressed genes and pathways between sh-XIST and NC-XIST cell lines.Dual-luciferase experiments were used to verify the relationship between miR-124-3p and the target genes XIST and GRIN1.qRT-PCR was conducted to validate the expression levels of downstream miR-124-3p and GRIN1 genes.(3)miR-124-3p inhibitors and mimics were added to verify phenotypic changes in SH-SY5Y cells after ischemic-hypoxic injury and co-culture with EPO-MSCs.RESULTS AND CONCLUSION:(1)Compared with the NC-XIST group,SH-SY5Y cells in the sh-XIST group showed reduced proliferation and migration abilities and increased apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs.(2)Dual-luciferase experiments showed that miR-124-3p interacted with the target gene XIST.SH-SY5Y cells transfected with miR-124-3p mimics and co-cultured with EPO-MSCs showed decreased apoptosis after ischemic-hypoxic injury,while SH-SY5Y cells transfected with miR-124-3p inhibitors showed increased apoptosis after co-culture with EPO-MSCs.(3)Transcriptomic sequencing and bioinformatics analysis of sh-XIST revealed significant downregulation of the neuroactive ligand-receptor pathway and the key receptor gene GRIN1 for central nervous system development.(4)Dual-luciferase experiments showed that miR-124-3p interacted with GRIN1.GRIN1 expression was significantly downregulated in the sh-XIST group after ischemic-hypoxic injury compared with the NC-XIST group.These findings indicate that LncRNA XIST promotes GRIN1 expression by upregulating miR-124-3p,thereby reducing cell apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs and enhancing proliferation and migration.sh-XIST can block this protective function.

BACKGROUND:Long non-coding RNA(LncRNA)plays an important role in nervous system development and neurological diseases.Previous studies by the research team have demonstrated that human umbilical cord mesenchymal stem cells overexpressing erythropoietin(EPO-MSCs)under ischemic and hypoxic conditions have better neuroprotective functions and significantly activate the expression of LncRNA XIST.Research suggests that XIST is related to the pathogenesis of hypoxic-ischemic encephalopathy,but the role and mechanism of its regulation by EPO-MSCs in protecting ischemic-hypoxic neurons remain unclear.OBJECTIVE:To explore the new mechanism by which LncRNA XIST,in response to EPO-MSC signaling,affects the apoptosis of ischemic-hypoxic SH-SY5Y cells.METHODS:(1)SH-SY5Y cell lines with knockdown of LncRNA XIST(sh-XIST)and negative control(NC-XIST)were constructed through lentiviral transfection.Oxygen-glucose deprivation was used to induce ischemic-hypoxic injury in the cells.Transwell chambers were used to create a non-contact co-culture system with EPO-MSCs,sh-XIST,and NC-XIST ischemic-hypoxic SH-SY5Y cells.Cell proliferation ability was detected using the CCK-8 assay.Cell migration ability was assessed using the scratch assay,and cell apoptosis was measured by flow cytometry.(2)RNA-seq bioinformatics analysis was performed to screen for differentially expressed genes and pathways between sh-XIST and NC-XIST cell lines.Dual-luciferase experiments were used to verify the relationship between miR-124-3p and the target genes XIST and GRIN1.qRT-PCR was conducted to validate the expression levels of downstream miR-124-3p and GRIN1 genes.(3)miR-124-3p inhibitors and mimics were added to verify phenotypic changes in SH-SY5Y cells after ischemic-hypoxic injury and co-culture with EPO-MSCs.RESULTS AND CONCLUSION:(1)Compared with the NC-XIST group,SH-SY5Y cells in the sh-XIST group showed reduced proliferation and migration abilities and increased apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs.(2)Dual-luciferase experiments showed that miR-124-3p interacted with the target gene XIST.SH-SY5Y cells transfected with miR-124-3p mimics and co-cultured with EPO-MSCs showed decreased apoptosis after ischemic-hypoxic injury,while SH-SY5Y cells transfected with miR-124-3p inhibitors showed increased apoptosis after co-culture with EPO-MSCs.(3)Transcriptomic sequencing and bioinformatics analysis of sh-XIST revealed significant downregulation of the neuroactive ligand-receptor pathway and the key receptor gene GRIN1 for central nervous system development.(4)Dual-luciferase experiments showed that miR-124-3p interacted with GRIN1.GRIN1 expression was significantly downregulated in the sh-XIST group after ischemic-hypoxic injury compared with the NC-XIST group.These findings indicate that LncRNA XIST promotes GRIN1 expression by upregulating miR-124-3p,thereby reducing cell apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs and enhancing proliferation and migration.sh-XIST can block this protective function.

The construction of a medication safety culture is important for medication safety management and rational drug use.The construction of medication safety culture standards is formulated based on relevant national policies and regulations,accreditation standards for hospitals,expert opinions,the current situation,and the development trend of the healthcare industry.With scientificity,general applicability,instructive guidance,and practicality,they standardized basic requirements,management processes,and improvement of the construction of medication safety culture.To facilitate understanding and the implementation of the standards,we describe the process of standards formulation and explain the key points of the standards.

With the increasing life span of the population and the increasing proportion of the elderly population, the elderly with osteoporosis are prone to hip fractures, which brings heavy economic burdens to the family and society. The progress in predicting hip fractures from the aspects of the proximal femur geometry, bone mineral density (BMD), fracture risk assessment tool (FRAX) and finite element analysis (FEA) based on computed tomography (CT) imaging was reviewed, in order to understand the influencing factors of fracture risk, improve the accuracy of hip fracture risk prediction for the elderly, detect the high fracture risk group at an early stage, and hence to reduce the occurrence of fractures with appropriate preventing measures, and provide theoretical references for the prevention and treatment of hip fractures.

Objective: The present study was designed to evaluate the clinical significance of serum GP73 in patients with alcohol liver disease. Methods: Thirty-two patients with alcoholic liver disease (ALD), 40 patients with non-alcohol fatty liver disease(NFLAD), and 40 apparently healthy individuals were included in this study. Results: Compared with Those of healthy control population(43.91±19.02 ng/ml), the serum GP73 levels in ALD patients(93.39±66.91 ng/ml) were significantly increased, and also markedly higher than those of NFLAD patients (55.38±21.00 ng/ml). Taken the NFALD as"healthy controls" population, and ALD population as"patients" , the GP73 may be used to differentiate the ALD from NFLAD. The area of ROC analysis was 0.66(95%CI: 0.52~0.80, P=0.02). We set 75.65 ng/ml as the cut-off value for ALD diagnosis, the sensitivity and specificity were 50.0% and 85.0% respectively. Conclusion Serum GP73 levels in ALD patients were significantly higher than those of NFALD patients. GP73 may be a new marker for differentiating ALD from NFALD.

Currently,the toxicity study of traditional Chinese medicine is faced with the following problems. Firstly,the evaluation in vitro cannot fully reflect the true state of the body. Secondly,the traditional method is not sensitive enough to the early toxicity. Lastly,the toxicity evaluation indexes cannot determine whether the compatibility of traditional Chinese medicine produces toxicity or increases toxicity systematically. The paper proposed a synthesized early evaluation research method for target organ toxicity induced by traditional Chinese medicine:screening,validation,optimization and application. This method mainly inoolves early target organ toxicity biomarkers in screening,optimi?zation,validation,biological significance explanation,and application to the traditional Chinese medicine incompatibility based on the metabolic dynamic fingerprint spectrum in order to obtain biomarkers of target organ toxicity that are sensitive and precede conventional biochemical indices for early evaluation . We attempted to analyze the pattern of chang of the biomarkers for animals acted by″18 incompatible medicaments″compatibility combination. We found that Radix Aconiti Lateralis Preparata with cardiotoxicity were compatible with Rhizoma Pinelliae,and that Trichosanthes kirilowii Maxim,Fritillaria,Ampelopsis Radix and Bletilla striata without non-cardiotoxicity produced and increased cardiotoxicity systematically.

[ ABSTRACT] AIM:To evaluate the effects of 1α, 25-dihydroxyvitamin D3 on T helper cell 17 ( Th17 cells) and its related cytokines in a mouse model of corneal allograft transplantation.METHODS:C57BL/6 mice were transplanted with corneal grafts from BALB/c mice and treated intraperitoneally with 1.0μg 1α, 25-dihydroxyvitamin D3 or soybean oil every other day after operation.The transparency of the corneal grafts was evaluated for potential rejection signs by slit lamp biomicroscopy and histopathology.The expression levels of IL-17, RORγt and IFN-γin the spleen were measured by real-time PCR.Moreover, the protein expression of RORγt and IL-17 in the peripheral blood was analyzed by Western blotting. IL-17 and IFN-γin peripheral blood were measured by flow cytometry.RESULTS:1α, 25-dihydroxyvitamin D3 signifi-cantly inhibited the rejection of the corneal allograft and reduced the numbers of inflammatory infiltrates in the corneal graft. In the spleen, 1α, 25-dihydroxyvitamin D3 treatment reduced the expression levels of IL-17, RORγt and IFN-γ.In the pe-ripheral blood, 1α, 25-dihydroxyvitamin D3 treatment downregulated the expression levels of RORγt, IL-17 and IFN-γ. CONCLUSION:The effects of 1α, 25-dihydroxyvitamin D3 on suppressing corneal transplantation-induced allograft rejec-tion in mice are closely associated with its modulation on IL-17 and related cytokine RORγt.

Background Interleukin (IL)-1a-889C/T,IL-1β-S11C/T,+ 3962C/T and IL-1Ra-2 are different morphology of single nucleotide of interleuki-1 (IL-1).The potential relationship of IL-1 polymorphisms with Beh(c)et disease has been studied in several populations and groups.However,study outcomes are controversial for a long duration.Objective This Meta-analysis was to determine whether the IL-1 gene polymorphisms is associated with the pathogenesis and development of Beh(c)et disease.Methods The literature of the assoiation between IL-1 polymorphisms and Beh(c)et disease was retrieved from Medline,EMBASE,Cochrane Library,Web of knowledge,Google Scholar,Wanfang and CNKI databases.All the published original articles (case-control studies) were reviewed with the deadline May 31,2013,and the languages were limited to English and Chinese.Included reports were evaluated based on Newcastle-Ottawa Scale (NOS) score.The potential influence of IL-1α-889TT gene,IL-1β-3962C,IL-1β-511T and IL-1Ra-2 polymorphisms on Beh(c)et disease were analyzed.RevMan5.0,the Cochrane collaboration software program,was used to prepare and complete this review.The effect size was assessed using fixed effect model in the index with lower heterogeneity (I2 ＜50％) or randomized effect model in the index with higher heterogeneity (I2＞50％).Results The literature search resulted a total of 370 cases-controlled studies,and 7 studies met the included criteria,with the NOS scores ≥ 8.The total patients were 499 and normal controls were 708.Meta-analysis was performed on several populations.Overall,the polymorphisms of IL-1β-3962C allele increased the susciptibility of Beh(c)et disease (OR =1.41,95％ CI:1.06-1.88,P =0.02),and IL-1α-889TT genotype reduced the risk of Beh(c)et disease (OR =0.61,95 ％ CI:0.40-0.92,P =0.02).However,There was no significant association between variants of IL-1β-511T allele (OR =0.84,95％ CI:0.58-1.23,P=0.38) or IL-1RA-2 allele (OR =1.25,95％ CI:0.50-3.14,P=0.63) and Beh(c)et disease susciptibility.Conclusions These results suggest that Beh(c)et disease is associated with the IL-1 gene polymorphisms at the locations α-889C/T and β-3962C/T.A larger sample size clinical data still are need to confirm this conclusion.