Objective To explore the mechanism of high mobility group AT-hook 1(Hmga1)in regulating the osteogenic differentiation of bone marrow mesenchymal stem cell(BMSC)through the Wnt/β-catenin pathway in the treatment of osteopo-rosis.Methods Hmga1-overexpressing lentiviral vector(LV)was constructed in vitro to transfect rat BMSC,and the Wnt signal inhibitor Dickkopf-1(DKK1)was used for intervention.Osteogenic differentiation-related indices were analyzed by qRT-PCR,Western blot,alkaline phosphatase(ALP)activity detection and Alizarin red staining.Ovariectomized(OVX)osteoporosis rat model was established,and Hmga1-LV was injected into the bone marrow cavity.Micro-CT,histological staining and immuno-fluorescence techniques were used to evaluate the bone microstructure and the expression of osteogenic differentiation-related proteins.Results Hmga1 expression was upregulated in a time-dependent manner during osteogenic differentiation of BMSC,while Hmga1 expression was significantly decreased in the bone tissue of OVX rats.Overexpression of Hmga1 significantly en-hanced the ALP activity and mineralized nodule formation of BMSC,and upregulated the expression of Runt-related transcrip-tion factor 2(Runx2)and osteocalcin(Ocn).The effect was partially reversed by DKK1.Hmga1 overexpression activated the Wnt/β-catenin pathway by promoting the nuclear translocation of β-catenin.In vivo experiments showed that Hmga1-LV treat-ment significantly improved trabecular thickness(Tb.Th)and bone volume fraction(BV/TV)in OVX rats,and reduced trabecu-lar separation(Tb.Sp),but had no significant effect on osteoclast differentiation.Conclusion Hmga1 promotes BMSC osteogen-ic differentiation and reverses OVX-induced bone loss by activating the Wnt/β-catenin signaling pathway,providing a potential target for gene therapy of postmenopausal osteoporosis.

Objective To explore the mechanism of Cistanche phenylethanoid glycosides(CPhGs)in treating osteoporosis by regu-lating osteogenic differentiation via SIRT2-C/EBPβ-AREG axis.Methods An osteoporosis mouse model was established using ova-riectomy.Trabecular number/thickness,bone formation rate,and tissue morphology were evaluated using micro-computed tomography,calcein double labeling,and hematoxylin and eosin staining,respectively.SIRT2,C/EBPβ,AREG,proteins related to the SIRT2-C/EBPβ-AREG axis,were analyzed by Western blotting and co-immunoprecipitation.The mRNA expression of osteogenic differentiation marker genes OCN,OPN,RUNX2,C/EBPβ,and AREG were detected by real-time quantitative PCR.Results CPhGs intervention significantly improved the trabecular microarchitecture and promoted bone formation in mice undergoing ovariectomy,and the mechanism involved the activation of SIRT2-mediated deacetylation of C/EBPβ,which in turn upregulated AREG expression.Cell experiments confirmed that CPhGs significantly increased the activity of alkaline phosphatase and the expression of osteogenic genes such as OCN,OPN,and RUNX2 in MC3T3-E1 cells by enhancing the interaction between SIRT2 and C/EBPβ.Notably,this effect could be reversed by SIRT2 knockdown.Conclusion CPhGs regulate the osteogenic differentiation process through the SIRT2-C/EBPβ-AREG axis,providing a new molecular target and theoretical basis for the treatment of osteoporosis with the active ingredients of traditional Chinese medicine.

Objective To explore the mechanism of Cistanche phenylethanoid glycosides(CPhGs)in treating osteoporosis by regu-lating osteogenic differentiation via SIRT2-C/EBPβ-AREG axis.Methods An osteoporosis mouse model was established using ova-riectomy.Trabecular number/thickness,bone formation rate,and tissue morphology were evaluated using micro-computed tomography,calcein double labeling,and hematoxylin and eosin staining,respectively.SIRT2,C/EBPβ,AREG,proteins related to the SIRT2-C/EBPβ-AREG axis,were analyzed by Western blotting and co-immunoprecipitation.The mRNA expression of osteogenic differentiation marker genes OCN,OPN,RUNX2,C/EBPβ,and AREG were detected by real-time quantitative PCR.Results CPhGs intervention significantly improved the trabecular microarchitecture and promoted bone formation in mice undergoing ovariectomy,and the mechanism involved the activation of SIRT2-mediated deacetylation of C/EBPβ,which in turn upregulated AREG expression.Cell experiments confirmed that CPhGs significantly increased the activity of alkaline phosphatase and the expression of osteogenic genes such as OCN,OPN,and RUNX2 in MC3T3-E1 cells by enhancing the interaction between SIRT2 and C/EBPβ.Notably,this effect could be reversed by SIRT2 knockdown.Conclusion CPhGs regulate the osteogenic differentiation process through the SIRT2-C/EBPβ-AREG axis,providing a new molecular target and theoretical basis for the treatment of osteoporosis with the active ingredients of traditional Chinese medicine.

Objective To explore the mechanism of high mobility group AT-hook 1(Hmga1)in regulating the osteogenic differentiation of bone marrow mesenchymal stem cell(BMSC)through the Wnt/β-catenin pathway in the treatment of osteopo-rosis.Methods Hmga1-overexpressing lentiviral vector(LV)was constructed in vitro to transfect rat BMSC,and the Wnt signal inhibitor Dickkopf-1(DKK1)was used for intervention.Osteogenic differentiation-related indices were analyzed by qRT-PCR,Western blot,alkaline phosphatase(ALP)activity detection and Alizarin red staining.Ovariectomized(OVX)osteoporosis rat model was established,and Hmga1-LV was injected into the bone marrow cavity.Micro-CT,histological staining and immuno-fluorescence techniques were used to evaluate the bone microstructure and the expression of osteogenic differentiation-related proteins.Results Hmga1 expression was upregulated in a time-dependent manner during osteogenic differentiation of BMSC,while Hmga1 expression was significantly decreased in the bone tissue of OVX rats.Overexpression of Hmga1 significantly en-hanced the ALP activity and mineralized nodule formation of BMSC,and upregulated the expression of Runt-related transcrip-tion factor 2(Runx2)and osteocalcin(Ocn).The effect was partially reversed by DKK1.Hmga1 overexpression activated the Wnt/β-catenin pathway by promoting the nuclear translocation of β-catenin.In vivo experiments showed that Hmga1-LV treat-ment significantly improved trabecular thickness(Tb.Th)and bone volume fraction(BV/TV)in OVX rats,and reduced trabecu-lar separation(Tb.Sp),but had no significant effect on osteoclast differentiation.Conclusion Hmga1 promotes BMSC osteogen-ic differentiation and reverses OVX-induced bone loss by activating the Wnt/β-catenin signaling pathway,providing a potential target for gene therapy of postmenopausal osteoporosis.

Objective:The standardized medical device clinical trials in China began in a short time, and the quality of trials needs to be improved.This article intends to explore possible ways for the improvement of quality management of the medical device clinical trials.Methods:Through working practice and literature review, analyze the current status of medical device clinical trials and in vitro diagnostic reagent in China; put forward targeted improved measures for the quality management system; as well as verify its feasibility through practice.Results:This article summarizes three factors that limit the improvement of the quality of medical device clinical trials, including the insufficient research and development strength of sponsors, the limited professional level of research teams, and the differences in verification and drugs, based on the risk-based quality management concepts, puts forward improved measures from three aspects, which including building risk-based quality certification system, making full use of electronic information systems to ensure the trial quality, and strengthening training of clinical trial capacity of researchers, and verifies the feasibility of these measures via the practical experience of our hospital since 2016.Conclusions:The application of risk-based quality management system, electronic information system and clinical trial capacity training can improve the management quality for medical device clinical trial centers.

To study the anticoagulant effect of Xiang-Qi-Tang (XQT),the mice model of endotoxemia was established to detect the expression of coagulation factors and their regulatory proteins in serum and aorta.The results showed that XQT could decrease the expression of TF and increase the expression of tPA in the aorta of mice with endotoxemia,and also decrease the expression of sEPCR in the serum.We further found that XQT caused the decrease of sEPCR through the regulation of PKC δ and ADAM17 to contribute the anticoagulation in mice.This study may provide a new strategy for treating endotoxin-induced disease and provide evidences for further researching the pharmacological action of XQT.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide with a trend of increasing morbidity and prevalence. It usually links to a high disability and mortality rate. Stroke is the most important and severe complication of AF, as a core strategy to prevent it, anticoagulation therapy is recommended to reduce the risk of stroke events. However, management risks including poor treatment adherence, individual difference and bleeding risk can′t be ignored. In the western countries, they have successively established a nurse-led integrated chronic care program for patients with atrial fibrillation. We can use it to guide our future work. Anticoagulation therapy is a long-term managing process. To integrate the existing medical resources, nurses must give their full play to access the deep needs and guide them to learn the core skills of management, thus improving the adherence to anticoagulation therapy.

Objective To study the effect and mechanisms of berberine (BBR) on the proliferation of papillary thyroid cancer K1 cells induced by high glucose.Methods K1 cells were cultured under 5.5 mmol/L or 25 mmol/L glucose condition with or without different concentration of BBR (0,10,40 and 80 μmol/L) for 24 hours.The proliferations of K1 cells in each condition were detected by MTT.Western blot was used to measure the expression of nuclear factor erythroid 2-related factor 2 (Nrt2),phosphoinositide 3-kinase (PI3K),protein kinase B (Akt) and phosphorylated-Akt (p-Akt).The distribution pattern of Nrf2 in K1 cells was determined using immunofluorescent staining.Results Compared with 5.5 mmol/L condition,the proliferation rate [(126.64 ± 5.41) ％ vs (87.31 ± 3.67) ％],expression levels of PI3K (0.425 ±0.019 vs 0.272 ±0.039),p-Akt/Akt (0.446 ±0.021 vs 0.168 ±0.035) and Nrf2 (0.597 ± 0.014 vs 0.308 ± 0.026),and Nrf2 distribution (93.0％ vs 23.1％) in nuclear of K 1 cells under 25 mmol/L condition were significantly elevated,respectively (all P ＜0.01).Addition of BBR in 25 mmol/L condition dose dependently (10,40,80 μmol/L) lowered the proliferation rate of K1 cells [(111.76 ± 4.10)％,(70.03 ±2.18)％,(32.41 ±3.76)％ vs (126.64 ±5.41)％,all P＜0.05],and suppressed the expression of PI3K,p-Akt/Akt,Nrf2,and Nrf2 nuclear distribution (P ＜ 0.05).Conclusions BBR dose dependently inhibited the proliferation of high glucose-induced K1 cells.This effect was associated with the suppression on of PI3K/Akt signaling activation,Nrf2 expression and its nuclear translocation.

Objective To discuss the clinical diagnosis and treatment of primary thyroid lymphoma (PTL) by reporting a case and reviewing relevant literatures.Methods Clinical data of a case diagnosed as PTL by pathology was retrospectively analyzed,and literatures related to this disease were reviewed.Results A male patient aged 71 years with a progressive enlargement of neck mass and hoarseness was suspected to have a malignant thyroid tumor and admitted to our hospital.Changes in a fine needle aspiration cytopathology before operation were considered as a malignant thyroid lesion.A final diagnosis of bilateral mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid was confirmed by the thyroid tissue pathological changes of surgical resection specimen.Chemotherapies were carried out.Recurrence of primary thyroid lymphoma was not found after following up to this day.Conclusions Primary thyroid lymphoma is a rare disease and easy to be misdiagnosed as Hashimoto's thyroiditis or thyroid cancer due to the lacking of specificities in clinical manifestations and in imaging examinations.Its diagnosis is based on pathological biopsy and immunohistochemistry.The optimal treatment is based on its pathological type,clinical stage and patients' age.

Objective To investigate the relationship between homocystine (Hcy) ,methylenetetra hydrofolate reductase(M T H-FR) C677T and gestational diabetes mellitus (GDM ) .Methods A total of 91 GDM cases(GDM group) and 123 cases with normal pregnancy(control group) were detected for the C677T polymorphism of M T HFR and serum levels of Hcy and glucose .Results Serum Hcy level in GDM group was remarkable higher than that of control group (P< 0 .05) .Hcy level was positively correlated with fasting plasma glucose ( P < 0 .05) .The genotype frequencies (CC ,CT ,TT ) of M T HFR C677T in GDM group and control group were with significantly difference(P< 0 .05) .Hcy was significantly higher in women with C677T TT genotype than those with CC genotype(P< 0 .05) .Conclusion Hcy could be related to GDM .The mutation of M T HFR might affect serum Hcy level , and be involved in the occurrence and development of GDM .