Toll-like receptor 3 (TLR3), as an important pattern recognition receptor (PRR), dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases. Atherosclerosis is proved as an inflammatory disease, and inflammatory events involved in the entire process of initiation and deterioration. However, the contribution of TLR3 to atherosclerosis remains unclear. Herein, we identified the clinical relevance of TLR3 upregulation and disease processes in human atherosclerosis. Besides, activation of TLR3 also directly led to significant expression of atherogenic chemokines and adhesion molecules. Conversely, silencing TLR3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell formation. Given the aberrance in TLR3 functions on atherosclerosis progression, we hypothesized that TLR3 could serve as novel target for clinical atherosclerosis therapy. Therefore, we developed the novel ellipticine derivative SMU-CX24, which specifically inhibited TLR3 (IC₅₀ = 18.87 ± 2.21 nmol/L). In vivo, atherosclerotic burden was alleviated in Western diet fed ApoE^-/- mice in response to SMU-CX24 treatment, accompanying notable reductions in TLR3 expression and inflammation infiltration within atherosclerotic lesion. Thus, for the first time, we revealed that pharmacological downregulation of TLR3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression, thereby proposing a new strategy and probe for atherosclerosis therapy.

Objective:To explore the effect of the teaching model based on the theory of planned behavior in intern nursing students of the Department of Hematology.Methods:From May 2018 to May 2020, 80 intern nursing students in the Department of Hematology from the Yantai Affiliated Hospital of Binzhou Medical University were selected as the research object by the convenience sampling method. Intern nursing students were randomly divided into a control group and an observation group, with 40 cases in each group. The control group adopted conventional nursing teaching, and the observation group conducted a nursing teaching model based on the theory of planned behavior on the basis of the control group. This study compared the two groups of nursing students' nursing skills assessment scores, core competence, empathy ability and personal evaluation of teaching effect.Results:The nursing skill assessment score and Core Competency Scale score of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . After the intervention, the total empathy ability score and scores in each dimension of the two groups were higher than those before the intervention, and those of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . The scores of 5 items of personal evaluation of teaching effect of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The teaching model based on the theory of planned behavior has a good effect when applied to practical nurses in the Department of Hematology, which can improve their nursing skills, core competence, empathy ability, and increase the satisfaction of the nursing students with the teaching effect.

Objective:To investigate the risk factors of Crohn′s disease (CD)-related gastrointestinal stenosis, and to summarize and analyze the corresponding treatments.Methods:From January 2010 to December 2018, 122 patients diagnosed with CD and hospitalized in the Seventh Medical Center, PLA General Hospital were selected including 72 patients in gastrointestinal stenosis group and 50 patients in non-gastrointestinal stenosis group. The gender, age of onset, course of disease, location of lesions involved (Montreal classification), disease activity, extraintestinal manifestations, application of therapeutic drugs, and complications were compared between the two groups. The treatment of CD patients with gastrointestinal stenosis was analyzed. Multivariate logistic regression was used to analyze the risk factors of CD patients with gastrointestinal stenosis. The independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:The age of onset of patients in gastrointestinal stenosis group was older than that in non-gastrointestinal stenosis group ((37.6±15.1) years old vs. (30.8±14.7) years old), and course of disease was longer than that of non-gastrointestinal stenosis group (72 months, 11 to 492 months vs. 45 months, 3 to 240 months); and the differences were statistically significant ( t=-2.044, Z=-2.770; P=0.018, 0.006). The proportion of patients with ileum involvement of the gastrointestinal stenosis group was lower than that of the non-gastrointestinal stenosis group (69.4%, 50/72 vs. 86.0%, 43/50), and the proportion of severe patients was higher than that of the non-gastrointestinal stenosis group (15.3%, 11/72 vs. 4.0%, 2/50); and the differences were statistically significant ( χ2=4.463 and 3.942, P=0.035 and 0.047). There were no significant differences in gender, use of therapeutic drugs, extraintestinal manifestations, application of therapeutic drugs or the incidence of complications between the patients of two groups (all P>0.05). The results of multivariate logistic regression showed that the age of onset and course of disease were risk factors of CD-related gastrointestinal stenosis ( β=0.028, odds ratio ( OR)=1.028, 95% confidence interval ( CI) 1.000 to 1.056, P=0.046; β=0.008, OR=1.008, 95% CI 1.002 to 1.015, P=0.013). Further stratified analysis revealed that the incidence rates of CD-related gastrointestinal stenosis in patients with age of onset over 40 years old and course of disease more than five years were higher than those of patients with age of onset less than 40 years old and course of disease less than five years (76.3%, 29/38 vs. 51.2%, 43/84; 68.4%, 39/57 vs. 50.8%, 33/65), and the differences were statistically significant ( OR=3.072, 95% CI 1.298 to 7.272, P=0.009; OR=2.101, 95% CI 1.002 to 4.406, P=0.048). Among the 72 CD patients with gastrointestinal stenosis, 15 cases (20.8%) were treated with medicine and nutrition, without endoscopic or surgical treatment. Fifty-two patients (72.2%) underwent surgical treatment, among them six patients (11.5%) received twice surgery, the interval between the two operations was 46 months (1 to 204 months), and eight patients (15.4%) had postoperative complications. Twenty-one patients (29.2%) were treated with endoscopic dilatation, and no complications occurred after surgery. Five patients (23.8%) underwent surgical treatment during the follow-up period. Conclusions:The age of onset over 40 years old and the course of disease more than five years are the risk factors of CD-related gastrointestinal stenosis. Individualized medical treatment is the basis for the treatment of CD-related gastrointestinal stenosis. Surgery is still the main treatment. The endoscopic treatment is safety and can delay or avoid surgery to a certain extent.

Accelerated forgetting has been identified as a feature of Alzheimer's disease (AD), but the therapeutic efficacy of the manipulation of biological mechanisms of forgetting has not been assessed in AD animal models. Ras-related C3 botulinum toxin substrate 1 (Rac1), a small GTPase, has been shown to regulate active forgetting in Drosophila and mice. Here, we showed that Rac1 activity is aberrantly elevated in the hippocampal tissues of AD patients and AD animal models. Moreover, amyloid-beta 42 could induce Rac1 activation in cultured cells. The elevation of Rac1 activity not only accelerated 6-hour spatial memory decay in 3-month-old APP/PS1 mice, but also significantly contributed to severe memory loss in aged APP/PS1 mice. A similar age-dependent Rac1 activity-based memory loss was also observed in an AD fly model. Moreover, inhibition of Rac1 activity could ameliorate cognitive defects and synaptic plasticity in AD animal models. Finally, two novel compounds, identified through behavioral screening of a randomly selected pool of brain permeable small molecules for their positive effect in rescuing memory loss in both fly and mouse models, were found to be capable of inhibiting Rac1 activity. Thus, multiple lines of evidence corroborate in supporting the idea that inhibition of Rac1 activity is effective for treating AD-related memory loss.

Objective To analyze the application effect of escitalopram in the patients with acute schizophrenia with depression and influence situation for the disease related blood indexes.Methods 84 patients with acute schizophrenia with depression in our hospital from February 2015 to August 2016 were selected as the study object, and they were randomly divided into control group(conventional treatment group)42 cases and observation group( conventional treatment and escitalopram group ) 42 cases, then the total effective rates, plasma free amino acids and stress hormones indexes before and after the treatment of two groups were compared.Results The total effective rates of observation group at different time after the treatment were all higher than those of control group, the difference was statistically significant (P<0.05), the plasma free amino acids after the treatment were all higher than those of control group, the difference was statistically significant (P<0.05), serum stress hormones were all lower than those of control group, the difference was statistically significant (P<0.05), the differences of two groups were all significant.Conclusion The application effect of escitalopram in the patients with acute schizophrenia with depression is better, and it also has active improvement role for the disease related blood indexes of patients.

BACKGROUND:Transplantation of mesenchymal stem cels to prevent and treat degeneration of the intervertebral disc is a feasible method. Mesenchymal stem cels co-transfected by SRY-related high mobility group-box gene 9 (SOX-9) and growth differentiation factor-5 (GDF-5) can differentiate into nucleus pulposus cels, in order to obtain greater effect of induction and proliferation of nucleus pulposus cels. OBJECTIVE:To investigate the effect of SOX-9 and GDF-5 co-transfection on the differentiation of rabbit bone marrow mesenchymal stem cels into nucleus pulposus cels. METHODS: We separated and cultured bone marrow mesenchymal stem cels from the bone marrow of rabbit aged 4 months. Passage 3 cels were divided into five groups andin vitro induced to differentiate into nucleus pulposus cels: non-transfected group, empty vector transfection group, SOX-9 transfection group, GDF-5 transfection group, SOX-9 and GDF-5 co-transfection group. At 14 days after transfection, RT-PCR was employed to assay SOX-9, GDF-5 and colagen type II mRNA expressions in bone marrow mesenchymal stem cels. The marker of nucleus pulposus cels-KRT19 expression was also detected by immunohistochemical staining. RESULTS AND CONCLUSION:In the co-transfection group, the mRNA expressions of SOX-9, GDF-5, and colagen type II were significantly higher than those in the SOX-9 transfection group, GDF-5 transfection group, and both these two groups, respectively (P < 0.05). Cels were positive for KRT19 in the SOX-9 and GDF-5 groups, and strongly positive for KRT19 in the co-transfection group. These findings indicate that double gene-transfected bone marrow mesenchymal stem cels are better than single gene-transfected cels with regard to differentiation into nucleus pulposus cels and secretion of extracelular matrix.

BACKGROUND:Percutaneous kyphoplasty for osteoporotic vertebral fractures with posterior vertebral wal breakage can relieve pain rapidly, but there is a risk of leakage of bone cement. OBJECTIVE: To observe the effect of bone filing mesh container in percutaneous kyphoplasty for osteoporotic vertebral fractures with posterior vertebral wal breakage. METHODS: Forty senile patients with osteoporotic vertebral compression fractures were enroled, whose CT and MRI showed different degrees of posterior vertebral wal breakage, including 19 males (21 vertebral bodies) and 21 females (28 vertebral bodies), aged 50-87 years. These 40 patients were subjected to percutaneous kyphoplasty, and bone filing mesh container was used to deliver bone cement. Then, changes in visual analogue scale score, vertebral height and leakage of bone cement were observed in patients before and after treatment. RESULTS AND CONCLUSION:The surgery was successful in al the 40 patients, and no pulmonary embolism, cement leakage, and spinal cord and nerve root injuries appeared. Al the patients were folowed for 10-12 months. The visual analogue scale scores and vertebral height were improved significantly at both 1 week and 3 months after treatment compared with those before treatment, but there was no difference in the visual analogue scale scores and vertebral height at 1 week and 3 months after treatment. These findings indicate that percutaneous kyphoplasty with bone filing mesh container is effective to prevent bone cement leakage.

OBJECTIVETo investigate the clinical effect of modified Koyanagi technique with coverage by tunica vaginalis of testis in severe hypospadias.

METHODS49 cases with severe hypospadias treated from Jan. 2009 to Sep. 2011 were retrospectively studied. 25 patients underwent Koyanagi technique with coverage by tunica vaginalis of testis. 24 cases underwent one-stage Duplay + Duckett technique in the same term. The patients were followed up for 7-24 months.

RESULTSAmong the 25 children treated with Koyanagi procedure, 20 cases were cured, 5 patients had postoperative complications, including urethral fistula in 3 cases,urethral stenosis in 2 cases. At the same time, in the Duplay + Duckett group, 17 cases were cured, 7 children had postoperative complications, including urethral fistula in 4 cases, and urethral stenosis in 3 cases. All the patients with urethral fistula were repaired successfully 6 months after the first surgery; The urethral stenosis were cured by dilatation within 1 to 3 months. The successful rate in the 2 groups had no significant difference(P >0.05).

CONCLUSIONSKoyanagi technique with coverage by tunica vaginalis of testis is relatively simple with similar effect as Duplay + Duckett technique for severe hypospadias.

Child ; Child, Preschool ; Humans ; Hypospadias ; surgery ; Male ; Postoperative Complications ; etiology ; therapy ; Retrospective Studies ; Surgical Flaps ; transplantation ; Testis ; surgery ; Urethral Diseases ; etiology ; therapy ; Urethral Stricture ; etiology ; therapy ; Urinary Fistula ; etiology ; surgery

Objective To explore the function and clinical effect of automatic nerve retractor in micro-endoscopic discectomy.Methods From August 2009 to December 2010,350 patients with lumbar disc hemiation were treated by micro-endoscopic discectomy,including 196 males and 154 females,aged from 17 to 68 years (average,42 years).Three cases were at L1-2,8 at L2-3,12 at L3-4,186 at L4-5 and 141 at L5S1.The automatic nerve retractor was used in all micro-endoscopic discectomy.The visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate clinical outcomes.Results All patients were followed up for 6 to 16 months (average,9 months).The mean VAS score decreased from preoperative 8.79±1.15 to 3.80±1.14 3 months after operation and 3.65±1.14 6 months after operation.The mean ODI score decreased from preoperative 78％±1.71％ to 28％±1.72％ 3 months after operation and 28％±1.88％ 6 months after operation.Postoperative VAS and ODI scores decreased significantly compared with those before operation.The VAS and ODI scores 6 months after operation were not significantly improved compared with those 3 months after operation.No spinal cord and nerve root injury and epidural hematoma formation occurred in all cases.Conclusion In micro-endoscopic discectomy,the automatic nerve retractor can help the operator obtain effective exposure,protect nerves from injury,alleviate workload of the operators,therefore it has a great clinical application value.

BACKGROUND:Intervertebral disc can bear load but lack vessels. Nucleus pulposus cel s have the problem of phenotype loss during in vitro culture that can lead to degenerative changes. The mechanism of intervertebral disc degeneration remains unclear.
OBJECTIVE:To explore the approaches of isolation, adherence culture, amplification and identification of the rabbit nucleus pulposus cel s in vitro, to observe the growth characteristics of nucleus pulposus cel s in different generations.
METHODS:Type Ⅱ col agenase digestion method plus explants culture method was used to isolate and purify nucleus pulposus cel s and then amplify in vitro. The morphology and growth of primary and passaged cel s was observed under the inverted microscope, the number of cel s was counted and the growth curve was draw. The morphology of the cel s was observed under light microscope after hematoxylin-eosin staining, and the expressions of col agen type Ⅱ and aggrecan were examined by immunocytochemistry.
RESULTS AND CONCLUSION:Nucleus pulposus cel s of rabbit were isolated, cultured and amplified in vitro successful y. Growth activity was observed, and found that the 1-3 generation nucleus pulposus cel s proliferated more rapidly and vigorously. The proliferation of nucleus pulposus cel s was decreased while the cel passaged more generations. These isolated and cultured nucleus pulposus cel s could positively express the col agen type Ⅱ and aggrecan. In vitro combination of type Ⅱ col agenase digestion method and explants culture method could obtain high purity nucleus pulposus cel s, and the cultured nucleus pulposus cel s were grew in round or polygonal. The 1-3 generation of cel s had strong activity.