ObjectiveTo investigate the effect of circSLC8A1_005 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe effect of adenovirus-mediated overexpression of circSLC8A1_005 on the expression of fibrosis-related genes， collagen type I alpha 1 chain （Col1a1）， collagen type Ⅲ alpha 1 chain （Col3a1） and smooth muscle actin alpha 2 （Acta2）， in mouse cardiac fibroblasts （mCFs） were detected. The proliferation and migration activities of mCFs were detected by EdU and wound-healing assay， respectively. Dual luciferase reporter gene assay was performed to detect the activity of potential internal ribozyme entry site （IRES） in circSLC8A1_005. CircSLC8A1_005-translated protein， SLC8A1-605aa， and its intracellular distribution was identified by Western blot assay. The effect of SLC8A1-605aa protein on transcription activity of Sod2 gene was detected by the dual luciferase reporter gene assay. RNA binding protein immunoprecipitation （RIP） was utilized to verify the interaction between SLC8A1-605aa and superoxide dismutase 2 （Sod2） mRNA. Actinomycin D treatment was used to detect the effect of SLC8A1-605aa on Sod2 mRNA stability in mCFs. ResultsAn efficient adenovirus-mediated overexpression of circSLC8A1_005 was achieved in mCFs. The enforced expression of circSLC8A1_005 suppressed proliferation and migration of mCFs， and inhibited the expression of fibrosis-related genes in mCFs. The dual luciferase reporter gene assay revealed the activities of 2 IRES in circSLC8A1_005. Results of Western blot assay showed that circSLC8A1_005 could translate protein SLC8A1-605aa with the prospected molecular weight of 70 ku， which is predominantly distributed in the nucleus. Overexpression of the circSLC8A1_005 and SLC8A1-605aa could consistently inhibit the fibrotic phenotype of mCFs. SLC8A1-605aa could up-regulate superoxide dismutase 2 （Sod2） expression， but not at the transcriptional level. RIP assay indicated that SLC8A1-605aa could specifically interact with Sod2 mRNA， and the results of actinomycin D assay showed that SLC8A1-605aa could enhance the stability of Sod2 mRNA in mCFs. ConclusionCircSLC8A1_005 inhibits the fibrotic phenotype of cardiac fibroblasts via translating SLC8A1-605aa protein， and SLC8A1-605aa may be a potential target for the treatment of myocardial fibrosis.

Visual hallucination(VH)is a common symptom of schizophrenia,the underlying mechanism has not been fully elucidated.It has been found that the dysfunction of dopamine(DA)system,the overactivation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate(AMPA)receptor in glutamate system and the dysfunction of γ-aminobutyric acid(GABA)ergic neurons can induce VH in patients with schizophrenia.In addition,abnormalities in brain structural and functional networks and visual networks are also closely related to the occurrence of VH.The purpose of this paper is to review the neurochemistry and nerve injury mechanism of VH in schizophrenic patients to deeply understand the characteristics of VH,and make more accurate judgment in the early diagnosis,condition evaluation and treatment plan of schizophrenic patients.

Objective:To explore the collaborative development of drug clinical trial institutions and Contract Research Organizations from the perspective of " government-application-industry-academia-research" , and facilitate faster and better conducting of clinical trials.Methods:Based the combination of literature review and the working practice in drug clinical trial management, problems existed during the implementation of clinical trials were summarized, and then the collaborative development of drug clinical trial institutions and Contract Research Organizations were discussed from the perspective of " government-application-industry-academia-research" partnership.Results:Problems identified during the implementation of clinical trials including uneven capacity of CROs, lack of effective supervision department and insufficient cooperation with clinical trial institutions, which resulted difficulties in sharing clinical trial resources and also negatively impacted the quality of clinical trials. Some proposals were offered in this article, including making good use of the " visible hand" of the government to strengthen the supervision of CROs, accelerating the construction of innovation alliance between clinical trial institutions and CROs, establishing the incentive mechanism of collaborative development and the talent team construction, strengthening the personnel professional training.Conclusions:The application of " government-application-industry-academia-research" model in clinical trials would promote the collaboration between drug clinical trial institutions and Contract Research Organizations, which play important roles in the development of clinical trials.

Objective:To explore the effectiveness and safety of tirofiban in patients with reocclusive ischemic stroke after intravenous thrombolysis with alteplase.Methods:Eighty-four patients with re-occlusive ischemic stroke after intravenous thrombolysis with alteplase, admitted to our hospital from January 2018 to May 2020, were prospectively chosen; these patients were divided into tirofiban group and routine (non-tirofiban) group ( n=42). In addition to thrombolysis, patients in the routine group received intensive lipid-lowering, collateral circulation improvement, blood glucose control, and early rehabilitation therapy; after thrombolysis for 24 h, patients without intracranial hemorrhage were given oral aspirin, 0.1 g/d, for 90 d. After thrombolysis and re-occlusion, patients in the tirofiban group were intravenously pumped with 0.4 μg/(kg·min), which was changed to 0.1 μg/(kg·min) after 30 min for 24 h; at 24 h after thrombolysis, brain CT was reexamined: tirofiban was discontinued for patients with intracranial hemorrhage, and intravenous pumping of tirofiban was continued for patients without intracranial hemorrhage for 24 h. Effectiveness was evaluated by comparing the general clinical data, National Institutes of Health Stroke Scale (NIHSS) scores 7 d after treatment, and modified Rankin Scale (mRS) scores 90 d after treatment between the two groups. Safety was assessed by comparing the intracranial hemorrhage, symptomatic intracranial hemorrhage, and mortality within 90 d of treatment between the two groups. Results:There were no significant differences in age, gender, underlying diseases, risk factors, baseline NIHSS scores, time from onset to start of treatment, infarction sites, and TOAST classification between the 2 groups ( P>0.05). NIHSS scores 7 d after treatment ([10.05±4.73] min vs. [7.93±4.68] min), mRS scores 90 d after treatment (3.48±1.48 vs.2.55±1.93), and good prognosis rate 90 d after treatment (21.4% vs. 42.9%) showed significant differences between the routine group and tirofiban group ( P<0.05). In terms of safety, there were no significant differences in intracranial hemorrhage rate (4.76% vs. 7.14%), symptomatic intracranial hemorrhage incidence (2.38% vs. 2.38%) and mortality (2.38% vs. 2.38%) between the 2 groups ( P>0.05). Conclusion:It is safe and effective for tirofiban in patients with re-occlusive ischemic stroke after intravenous thrombolysis with alteplase.

Objective: To evaluated the application of General Provisions of Safety and Health for Writing Boards(GB 28231-2011), and to provide basis for the revision and improvement of the standard. Methods: From June to October 2018, a questionnaire survey was conducted among 852 people engaged in the evaluation, use and production of writing boards in 8 districts of Beijing, Liaoning and Jiangsu. The contents of the survey include the awareness, implementation of the standard and evaluating the use of various parameters in the standard by personnel from different institutions. Results: The overall awareness ratio of the standard among staffs from health, education and enter prise was 78.26%. For the nominal size of the writing board and the vertical distance between the lower edge and the platform, the reasonableness considered lower by health professionals(62.50%, 37.50%) than that of education professionals(90.00%, 90.00%) and enterprise staffs(90.00%, 90.00%)(P<0.05); For the frequency and reasonableness of the nine parameters such as gloss and adhesion, the perception of each institution were significantly different(P<0.05), with proportion of professionals in health lower than experts in education and enterprise. For the two parameters of color and light resistance, each institution considered the maneuverability was not strong(P>0.05). Conclusion Propagation and implement is still needed to strengthen comprehension, because different institutions have different understandings towards the standard. There are still some problems waiting to be solved, such as different standard limits, poor enforceability of two parameters which are writing board color and light resistance.

AIM To observe the effects of Huangdi Anxiao Capsules (Puerariae lobatae Radix,Eriobotryae Folium,Notoginseng Radix et Rhizoma,etc.) on blood glucose and insulin resistance in GK rats with type 2 diabetes mellitus (T2DM) and its possible mechanism of action.METHODS GK rats with T2DM included in the experiment were randomly divided into model group,rosiglitazone (1.44 mg/kg) group,Shenqi Jiangtang Granules (1.08 g/kg) group,Huangdi Anxiao Capsules high,medium and low (12,6,3 g/kg) group and normal control group of Wistar rats.After six weeks of consecutive administration,fasting blood glucose (FBG),serum insulin (FINS),fasting plasma glucose (FPG),and insulin resistance index (HOMA-IR) were measured in all groups.Serum biochemical indexes of (TG,TC,HDL-C,LDL-C),glycosylated hemoglobin (HbA1c),glucagon-like peptide (GLP-1) and insulin-like growth factor (IGF-1) were measured.The pancreatic tissue was obtained by routine paraffin embedding and HE staining to observe the pathological changes.RESULTS Compared with the normal group,FBG,FPG,FINS,HOMA-IR,TG,TC,HDL-C,LDL-C and HbA1c of the model group were significantly higher (P ＜0.01),and GLP-1 and IGF-1 expressions were markedly decreased (P ＜ 0.01).Compared with the model group,the levels of FBG,FPG,FINS,HOMA-IR,TG,TC,HDL-C,LDL-C and HbA1 c in Huangdi Anxiao Capsules high-,medium-and low-dose group were significantly decreased (P ＜ 0.05,P ＜0.01);GLP-1 and IGF-1 expressions were markedly increased (P ＜0.05,P ＜0.01),compared with the model group,the structure changes of pancreatic tissue in Huangdi Anxiao Capsules high-,medium-and low-dose groups largely reduced.CONCLUSION Huangdi Anxiao Capsules can reduce GK rats fasting blood glucose,insulin resistance,and its mechanism may be related to promoting the emergence and proliferation of pancreatic islet cells,improving the function of islet beta cells,and increasing insulin secretion.

Aim To determine the function of nuclear factor-κB ( NF-κB ) in immunological liver injury of rat model and its effect on CYP2E1 expression, content and metabolic activity. Methods The immunological liver injury rat model was prepared by injection of Ba-cillus Calmette Guérin ( BCG,125 mg · kg-1 ) for 14 days. The hepatic tissue injury was revealed by hema-toxylin and eosin ( HE ) method and serum concentra-tion of alanine aminotransferase( ALT) , aspartate ami-notransferase ( AST ) respectively. CYP450 total con-tent in hepatic homogenate was determined by spectro-photography. The expression of CYP2E1 protein was detected by Western blot analysis. The enzyme kinetics of CYP2 E1 probe drug chlorzoxazone was evaluated by high-performance liquid chromatography ( HPLC ) as-say. Results The results showed that BCG-pretreat-ment ( 125 mg · kg-1 ) significantly increased the weight of liver and spleen, serum levels of ALT and AST(P<0. 01) , and decreased CYP2E1 expression, content and metabolic activity ( P <0. 05 ) . Adminis-tration of ammonium pyrrolidine dithiocarbamate (PDTC) (50, 100, 200 mg·kg-1) reversed the a-bove hepatic injury stimulated by BCG in vivo. Moreo-ver, PDTC dose-dependently inhibited the down regu-lation of CYP2 E1 ( P<0. 05 ) . Conclusion Passiva-tion of NF-κB can inhibit the down regulation of CYP2 E1 in liver tissue of immunological liver injury rats;NF-κB may be involved in CYP2 E1 down-regula-tion.

Objective To explore the effect of peer education on the practical teaching of fundamental nursing for male nursing students .Methods Thirty-six male nursing undergraduate students from Grade 2011 were chosen as the observation group , and received the peer education .Thirty-two male nursing undergraduate students from Grade 2010 were chosen as the control group , and received the traditional teaching .The teaching effect was evaluated by the score of final examination and questionnaire in two groups .Results The scores of theory and practice test were respectively (57.68 ±4.34), (26.34 ±3.11) in the observation group, and were higher than (54.34 ±4.15), (24.58 ±2.93) in the control group, and the differences were statistically significant (t=3.233,2.393, respectively; P <0.05).The result of questionnaire on the teaching effect showed that the professional identification , learning interest , self-confidence , communications and collaboration abilities in the observation group were better than those of the control group (P<0.05), and no differences were found in the abilities of operation, problem analysis and innovation between two groups (P >0.05). Conclusions Peer education can improve the professional identification in the male nursing students , and increase their learning interest and self-confidence , and improve their scores of theory and practice test in the fundamental nursing , and increase their abilities of communications and collaboration .

Objective To evaluate the therapeutic efficacy and treatment-related toxicity of stereotactic body radiation therapy(SBRT)in patients with medically inoperable stage Ⅰ/Ⅱ non-small cell lung cancer(NSCLC). Methods SBRT was applied to 30 patients, including clinically staged T1 ,T2(≤5cm)or T3(chest wall primary tumors only), N0, M0 ,biopsy-confirmed NSCLC. All patients were precluded from lobotomy because of physical condition or comorbidity. No patients developed tumors of any T-stage in the proximal zone. SBRT was performed with the total dose of 50 Gy to 70 Gy in 10 - 11 fractions during 12 - 15 days. prescription line was set onthe edge of the PTV. Results The follow-up rate was 100%. The number of patients who completed the 1-, and 2-year follow-up were 15, and 10, respectively. All 30 patients completed therapy as planned. The complete response(CR), partial response(PR)and stable disease(SD)rates were 37%, 53% and 3%, respectively. With a median follow-up of 16 months(range,4-36 months), Kaplan-Meier local control at 2 years was 94%. The 2-year overall survival was 84% and the 2-year cancer specific survival was 90%. Seven patients(23%)developed Grade 2 pneumonitis, no grade ＞ 2 acute or late lung toxicity was observed. No one developed chest wall pain. Conclusions It is feasible to deliver 50 Gy to 70 Gy of SBRT in 10 - 11 fractions for medically inoperable patients with stage Ⅰ / Ⅱ NSCLC. It was associated with low incidence of toxicities and provided sustained local tumor control.The preliminary investigation indicated the cancer specific survival probability of SBRT was high. It is necessary to perform similar investigation in a larger number of patients with long-term follow-up.

Objective:To construct a RNAi lentiviral vector targeting rat CD80 gene and detect its effect of gene silencing in NRK and IEC6 cells.Methods:The effective sequence of siRNA targeting rat CD80 gene was confirmed in our previous work.Oligo-DNA fragment containing short hairpin frame was synthesized and reannealed,and then cloned into pGCSIL-GFP lentiviral expression vector.PCR and sequencing analysis were made for verifying the positive clones.The virus packaging plasmids were transfected into 293T cells to harvest shRNA lentivirus.After infection in NRK and IEC6 cells,Real-time PCR was performed to determine the expressing level of CD80.Results:PCR and sequencing revealed that shRNA plasmids was correctly constructed.Virus with a titer of 4×10~8 TU/ml was successfully packaged.CD80 expression in NRK and IEC6 cells could be knockdown by virus infection as characterized by 66.9% and 63.5% decrease of CD80 mRNA in NRK and IEC6 cells respectively,compared with negative control lentivirus.Conclusion:The recombinant lentiviral shRNA expressing vector targeting rat CD80 gene has been successfully constructed and packaged.CD80 mRNA could be down-regulated availably in NRK and IEC6 cells.