Systematic Review on Safety of Chinese Medicines Combined with Tripterygium wilfordii Preparations in Treatment of Rheumatoid Arthritis and Exploration on Underlying Network Regulatory Mechanisms of Enhancing Efficacy and Reducing Toxicity / 中国实验方剂学杂志

ObjectiveTo systematically evaluate the safety of Chinese medicines combined with Tripterygium wilfordii polyglycoside tablets/Tripterygium wilfordii tablets （TWPT/TWT） in the treatment of rheumatoid arthritis （RA）， and to explore the network regulatory mechanisms of enhancing efficacy and reducing toxicity of commonly used combination regimes. MethodThe literature involving the adverse reactions of TWPT/TWT in treating RA was searched and collected from three Chinese databases （CNKI， Wanfang Data， VIP） and three English databases （PubMed， Cochrane Library， Embase） from the inception of the databases to July 2021. All studies were assessed by the Cochrane risk of bias tool， and the data were extracted and analyzed by Stata 15.0. Furthermore， Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine 2.0 （TCMIP v2.0，http：//www.tcmip.cn/） was used to construct a "drug target-symptom gene of efficacy and toxicity" interaction network， to explore the underlying network regulatory mechanisms of enhancing efficacy and reducing toxicity of common T. wilfordii preparation combinations. ResultA total of 2 132 articles on Chinese medicines combined with TWPT/TWT in the treatment of RA were retrieved， and 18 of them were finally included. The systematic review showed that the adverse reactions of TWPT/TWT against RA mainly occurred in the digestive system， blood system， and reproductive system， of which digestive system had the highest incidence of damages. However， the combination with Chinese medicines effectively alleviated the adverse reactions caused by TWPT/TWT ［RR （95% CI）=0.45 （0.30， 0.66）， P<0.01］. In addition， the subgroup analysis indicated that the age of RA patients， course of disease， combination regimen， medication dosage and duration of treatment all affected the occurrence of adverse reactions of TWPT/TWT. It was found in clinical studies that total glucosides of paeony （TGP） and TWPT/TWT was most widely combined， and the effect of TGP in reducing TWPT/TWT-induced hepatotoxicity was also more significant than that of other Chinese medicines. Moreover， taking this combination regime as an example， this paper explored the "efficacy-toxicity" association mechanisms of TGP-TWPT/TWT against RA. The "drug target-symptom gene of efficacy and toxicity" interaction network revealed that the core network targets of TGP-TWPT/TWT enhanced efficacy and reduced toxicity mainly through regulating immunity-inflammation-related pathways， metabolic pathways and cell signal transduction. Especially， interleukin-4 （IL-4） and interleukin-13 （IL-13）， which were involved in the "immunity-inflammation" module， were the common targets of TGP-TWPT/TWT to enhance efficacy and reduce toxicity. The endogenous sterols， bile acids and bile salts， insulin secretion and other metabolic pathways in the "body metabolism" module were closely associated with the mechanisms of TWPT/TWT inducing hepatotoxicity and TGP reducing hepatotoxicity. While cell function regulation pathways， such as stem cell factor （SCF）/tyrosine kinase receptor （KIT） signaling pathway and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）signaling pathway were involved in both anti-RA effects and hepatotoxicity of TWPT/TWT. ConclusionClinical application of suitable Chinese medicines combined with TWPT/TWT in the treatment of RA can effectively improve the rheumatism and reduce the adverse reactions of TWPT/TWT， and TGP-TWPT/TWT has the most significant toxicity-reducing effect. Further biological network-based investigation indicates that the toxicity-reducing mechanism of TGP-TWPT/TWT may be related to the regulation of interleukin signaling pathway and bile acid metabolism pathway， and the synergistic efficacy-enhancing effect of the combination may be achieved by acting on interleukin signaling pathway and cell function regulation pathway.

Exploration on the Medical Ethics Education Path of "Combining Moral and Technical Education" of Vocational Medical Students under the Concept of "Three-wide Education" / 中国医学伦理学

The educational purpose of "three-wide education" is in line with the overall goal of talent cultivation in colleges and universities, and fits the development laws of ideological and political work in colleges and universities in the new era. It is an important measure to leverage the joint efforts of education and improve the quality of education. Under the concept of "three-wide education", medical ethics education in higher vocational medical colleges lacks systematization and big data support, medical students’ "knowing morality" and "conducting morality" are not unified, the content of medical ethics teaching is outdated, and teaching methods are single, which is inconsistent with students’ innovative cognitive thinking and derailed from clinical and social real needs, making it difficult to arouse students’ interest in learning. Against the backdrop of continuously improving professional literacy requirements for medical students, this paper explored the medical ethics education path of "combining moral and technical education" for vocational medical students under the concept of "three-wide education", and formed training paths such as "three integration of medical ethics, three progressions of knowledge and action", the coordinated education of ideological and political courses and ideological and political education in the course, the "trinity" of school, family, and society, the innovative multi-dimensional medical ethics education teaching methods, the construction of a medical ethics practice platform, and the establishment of medical ethics cultural education data management platforms, with a view to providing reference ideas for the cultivation of medical ethics among vocational medical students.

Current and prospective clinical applications of autoantibodies associated with paraneoplastic neurological syndromes / 中华检验医学杂志

Paraneoplastic neurological syndrome (PNS) is an autoimmune syndrome involving the nervous system caused by tumors through distant effects. The diagnosis of PNS is difficult, and PNS-associated autoantibodies are crucial for disease diagnosis, classification, and individualized treatment. PNS-associated autoantibodies are classified into high-, intermediate-, and low-risk antibodies based on their predictive risk of tumors. Their laboratory detection is mainly carried out through indirect immunofluorescence, immunohistochemical analysis, immunoblotting, and other methods. The correct application and interpretation of antibody detection results is crucial for the diagnosis and treatment of PNS. This article reviews the current status and future prospects of the clinical application of autoantibodies related to PNS.

Clinical relevance of autoantibodies targeting peptidylarginine deiminases 2 and 4 in rheumatoid arthritis / 中华检验医学杂志

Objective:To evaluate the clinical performance of anti-peptidylarginine deiminase 2 (PAD2) and anti-PAD4 antibodies combined testing in a Chinese rheumatoid arthritis (RA) cohort.Methods:A total of 148 RA inpatients and 35 patients with non-RA arthritis as controls (DC) were recruited from November, 2018 to November, 2019 in Peking University People′s Hospital. In addition, a total of 44 healthy controls (HC) who went to Peking University People′s Hospital for annual physical examination were collected from June 2019 to July 2019. The α-PAD2 and α-PAD4 level in clinical specimens were determined by ELISA. Statistical analysis was performed by the Mann-Whitney U test, the Kruskal-Wallis (KW) test, the χ 2 test or the Fisher′s Exact Test, as necessary. Correlation analysis were performed by logistic regression. Results:α-PAD2 and α-PAD4 were present in 26.4% (39/148) and 20.9% (31/148) patients with RA, 5.7% (2/35) and 5.7% DC (2/35) and 4.5% (2/44) and 2.3% HC (2/44), respectively. α-PAD4-positive RA patients displayed significantly longer disease duration compared to α-PAD4-negative RA patients (17.3±13.2 years vs 8.6±10.2 years, P<0.001). α-PAD4-positive RA patients showed a significantly higher incidence of interstitial lung disease (ILD) compared to those without α-PAD4 (54.8% vs 25.6%, P=0.002). No associations between α-PAD2 and ILD were found ( OR: 0.797, P=0.579). In contrast, significant associations between α-PAD4 and ILD were found ( OR: 3.521, P=0.002). In seropositive RA, α-PAD4 displayed a weak correlation with ILD ( OR: 2.324, P=0.046), but this association was greatly enhanced when combined with α-PAD2 [anti-PAD2 (-)] ( OR: 4.059, P=0.007). Conclusions:The findings delineate the clinical relevance of α-PAD2 and α-PAD4 in RA and suggest that the combined testing for α-PAD2 and α-PAD4 may provide additional diagnostic value to the current clinically available assays in RA, in particular in identifying patients at risk of RA-ILD.

Effect of intercellular adhesion molecule-1-targeted miR-133a-5p on lipopolysaccharide-induced alveolar epithelial A549 cell injury / 中华实用儿科临床杂志

Objective:To investigate the effect of intercellular adhesion molecule-1 (ICAM1) targeted miR-133a-5p on lipopolysaccharide (LPS)-induced alveolar epithelial A549 cell injury.Methods:Dual lucife-rase reporter assay was used to verify the ICAM1 targeted effect of miR-133a-5p.A549 cells were induced by LPS in vitro and divided into the control group, LPS group, LPS+ negative control(miR-NC) group, LPS+ miR-133a-5p group, LPS+ small interfering RNA(si)-NC group, and LPS+ si-ICAM1 group.The expression levels of miR-133a-5p and ICAM1 mRNA were detected by real-time fluorescent quantitative PCR.Apoptosis was detected by flow cytometry.The expression levels of ICAM1, Bcl-2, Bax and cleaved caspase-3 protein that could activate cysteine were detected by Western blot.The expression levels of interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were detected by enzyme linked immunosorbent assay kit. Results:Compared with the control group, the LPS group had a decreased expression level of miR-133a-5p (0.39±0.04 vs.1.00±0.09) in A549 cells, increased expression of ICAM1 (0.86±0.08 vs.0.39±0.03), an increased apoptotic rate [(27.65±2.47)% vs.(8.13±0.89)%], and increased secretion of IL-6 [(624.59 ± 51.42) ng/L vs.(194.25±18.43) ng/L] and TNF-α [(548.35±51.42) ng/L vs.(174.26±19.43) ng/L]. The differences were significant (all P<0.05). Compared with the LPS+ miR-NC group, the apoptosis rate of A549 cells [(13.46±1.38)% vs.(28.71±2.54)%] in LPS+ miR-133a-5p group were significantly decreased, and the secretion of IL-6 [(296.43±23.51) ng/L vs.(635.86±55.41) ng/L] and TNF-α [(321.14±30.56) ng/L vs.(563.24±49.52) ng/L] was significantly decreased (all P<0.05). Compared with LPS+ si-NC group, the apoptosis rate of A549 cells [(13.65±1.64)% vs.(23.51±2.33)%] in LPS+ si-ICAM1 group was significantly decreased, and the secretion of IL-6 [(324.15±29.41) ng/L vs.(625.39±52.59) ng/L] and TNF-α [(334.65±20.46) ng/L vs.(534.97±51.42) ng/L] were significantly decreased (all P<0.05). Conclusions:miR-133a-5p can alleviate LPS-induced alveolar epithelial cell injury, and the mechanism may be related to down-regulation of ICAM1 expression.

Expression and significance of SIAH2 in epithelial ovarian carcinoma / 实用医学杂志

Objective To analyze the expression and clinicopathological significance of seven in absentia homolog 2 (SIAH2) in epithelial ovarian carcinoma, and to discuss its role in the development of epithelial ovarian carcinoma. Methods The expression of SIAH2 was determined by immunohistochemical S-P method in 165 cases of ovarian samples and SIAH2 expression was examined by Western blot. In the combination with follow-up data, survival curves were calculated using the Kaplan-Meier method and relationship between SIAH2 expression and prognosis of ovarian carcinoma patients was analyzed by the log-rank test. Cox proportional hazards regression model was used to examine the independent predictive factors in the patients with epithelial ovarian carcinoma.Results SIAH2 expression in epithelial ovarian cancer (76.4％) was higher than that of borderline ovarian tumors (41.7％) , benign ovarian cysts (5.13％) and normal ovarian tissues (2.86％) , and there were significant differences (all P < 0.05). No statistical significance of SIAH2 expression was found between benign ovarian cysts and normal ovarian tissues (P> 0.05). The expression of the SIAH2 was significantly correlated to histological grade, FIGO stage and lymph node metastasis (P < 0.05).The relative expression of SIAH2 in normal ovarian tissue, benign ovarian cyst, borderline ovarian tumor and epithelial ovarian cancer was 0.12 ± 0.05, 0.11 ± 0.04, 0.57 ± 0.08 and 1.05 ± 0.10, respectively. No difference of SIAH2 expression was found between normal ovarian tissues and benign ovarian cysts (P> 0.05). The expression of SIAH2 increased from ovarian tissues/benign ovarian cysts to borderline ovarian tumor to epithelial ovarian cancer and the difference was statistically significant (all P < 0.05).The survival curves of patients with SIAH2 (+) differed from those of patients with SIAH2 (-) and the difference was statistically significant (P < 0.05). Multiple factor analysis revealed that the higher expression of SIAH2 was an independent prognostic factor for overall survival. Conclusions The over-expression of SIAH2 plays an important role in the tumorigenesis and progression of epithelial ovarian cancer. The over-expression of SIAH2 may serve as a biomarker for poor prognosis of epithelial ovarian cancer patients.

The therapeutic effect of piperacillin sodium and sulbactum sodium(PIP/SBT)for injection in children bronchopneumonia / 中国生化药物杂志

Objective To analyzed the therapeutic effect of piperacillin sodium and sulbactum sodium(PIP/SBT)for injection in children bronchopneumonia.Methods 162 bronchopneumonia children who were admitted to pediatrics department during January 2014 to January 2016 were enrolled for this study and randomly divided into the observation group and the control group.The observation group received piperacillin sodium and sulbactum sodium therapy, while the control group received azithromycin.The symptom scores of coughing, wheezing, wheezing sound and the difficulty of expectoration in the 3rd day and 7th day were compared.The therapeutic effect of the two groups were evaluated.Results The observation group and the control group could both improve the symptom scores of coughing, wheezing, wheezing sound and the difficulty of expectoration in the 3rd day and 7th day, while the scores of observation group were significantly lower than the control ones.And the effective rate of observation group(97.5%)was significantly higher than the control one(90.1%).Conclusion Piperacillin sodium and sulbactum sodium(PIP/SBT)for injection had significantly clinical effect applying in children bronchopneumonia treatment, which was worthy of further popularization and application.

Effect of WeChat follow-up for the relatives of diabetic retinopathy patients / 中华健康管理学杂志

Objective To investigate the effects of WeChat follow-up of relatives on knowledge cognition, change of behavior, visual acuity and blood glucose for diabetic retinopathy (DR) patients.Methods Totally 107 typeⅡdiabetic patients from January 2014 to December 2015 in the Department of Endocrinology were enrolled in the study, with the inclusion criteria of 60 years of age and older and diagnosed with diabetic retinopathy. Subjects were divided into the WeChat group (53 cases) and the control group (54 cases) based on the order of enrollment. The control group was given routine care and health education, while the WeChat group was given additional follow-up of relatives through WeChat with distribution of health education messages for the management of DM and DR once each week for 12 months. Questionnaires were used to collect information on patient's knowledge of DR prevention & treatment and behavior change, FBG, PBG, and HbA1c, and visual acuity were also collected to assess the effectiveness of the intervention. Chi-square test was used to compare the patients' cognitive rate, behavioral change and stage of retinopathy. The t-test was used to compare fasting blood glucose, 2 hours postprandial blood glucose, glycosylated hemoglobin and visual acuity. Results Cognitive Knowledge change on DR were analyzed for the following questions:the time of the first fundus examination after diagnosis of diabetes and occurrence of systemic complications; what are key measures for prevention of early blindness in patients with DR;fundus checkup requirements while blood glucose control is ideal;types of major eye complications for diabetic patients; when laser treatment should be done for DR patients; how long apart should patients check the fundus;what is the normal range of blood glucose;and the types of server damages of DR;etc. The cognitive rates of WeChat group after follow-up were as follows 88.7%, 67.9%, 56.6%, 96.2%, 79.2%, 67.9%, 69.8%, 94.3%, 75.5%. WeChat group compared with the Control group after follow-up (χ2 values were 16.77, 30.76, 16.30, 7.75, 9.68, 36.03, 9.25, 10.57and 9.41, respectively, all P0.05). The two groups of patients were compared in balanced diet, regular eating time, meal volume, wearing loose clothing and exercise shoes and socks before each exercise, exercising for more than 30 min, weekly checkup of blood glucose, blood sugar test before and after the exercise and other measurements of behavior changes were significantly different (χ2 values were 11.54, 11.77, 13.68, 5.89, 10.23 and 8.72, respectively, all P0.05). Conclusions The practice of WeChat follow-up of relatives can improve cognition ability for DR patients aged 60 years and older, it can promote the healthy behavior and the BG monitoring effectively.

Risk factors analysis and nursing intervention of multidrug-resistant organism infection in patients of traditional Chinese medicine hospital / 中国实用护理杂志

Objective To discuss the risk factors and nursing intervention of multidrug-resistant organism (MDRO) infection in patients of traditional Chinese medicine hospital (TCM). Methods By investigating the patients admitted to Beijing Xuan Wu Hospital of Traditional Chinese medicine from June 2015 to June 2016, 756 patients of them who were confirmed with clinical diagnosis of infection and pathogen detection with positive, which were divided into MDRO group including 97cases and non-MDRO group including 659 cases, then the pathogens of MRDO infection species and distributionwere counted, and analyzed risk factors for infection. Results A total of 756 cases were detected positive strains 816 strains, including 611 strains of monitoring target strains, 116 strains of MRDO. The top three were methicillin-resistant staphylococcus aurous 30.17%(35/116), Pseudomonas aeruginosa 18.97% (22/116) and Klebsiella pneumonia 18.10% (21/116). Single factor analysis results showed that the patients' age, hospitalization days, the history of other hospital admission, invasive procedure, basic chronic disease (diabetes, cerebrovascular disease, lung disease) and combined use of antibiotics were MDRO infection risk factors (χ2=9.470-198.609, P < 0.01); multivariate Logistic regression analysis showed that the independent risk factors of MDRO infection were the history of other hospital admission (OR=2.085, 95%CI1.040-4.179), invasive procedure (OR=3.063,95% CI1.526- 6.150), diabetes (OR=2.037,95% CI1.070- 3.877), cerebrovascular disease (OR=4.349,95%CI 2.035-9.293)and combined use of antibiotics (OR=18.723,95% CI9.202-38.094). Conclusions Patients of TCM have many characteristics, such as with more basic diseases, longer length of stay, elder and so on. So we should be alert to the risk of MDRO infection and take nursing interventions to prevent and strengthen the isolation prevention.

Effect of administrative intervention on smoking cessation of the medical personnel / 中华健康管理学杂志

Objective To investigate the effect of the administrative intervention on smoking cessation of medical personnel and demonstrate the feasibility and the validity of this approach.Methods Two comparable hospitals were selected,one hospital with 136 smoking medical staff members was used as the intervention group;the other hospital which had 127 smoking medical staff members was used as the control group.We applied administrative intervention and health education to the intervention group and health education only to the control group.The intervention time was 10 months,we used the questionnaire survey before and after intervening to evaluate the smoking rate,the intention to quit smoking,the willingmess to accept the help of quitting and the proportion of those who quitted smoking.Results The smoking rate of intervention group (37.4％) was lower than that of control group (77.2％),the difference was statistically significant (x2=40.99,P＜0.01).The proportion of control group smokers in planning(51.1％) is statistically significant as compared with intervention group (46.18％) (x2=46.18,P＜0.01).The proportion of people who were willing to accept the help from families and friends and smoking cessation counseling in intervention group was significanly higher than that in the control group.(x2=10.04,x2=7.73,x2=7.58;P＜ 0.01).But the proportion of accepting the medicine for quitting smoking was not significantly different (x2=0.16,P＞0.05).The proportion of smokers who wanted to quit smoking on their own willingness in control group was significantly higher than that in intervention group (x2=36.27,P＜0.01).After10 months,61 people (46.6％) in the intervention group succeeded in quitting smoking and 13 (10.6％) people in control group succeeded (x2=28.21,P＜0.01).Conclusion Administrative intervention has feasibility and validity when hospitals take activities for smoking cessation.

Effects of uterine adenomyosis on clinical outcomes of infertility patients treated with in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effects of uterine adenomyosis on the clinical outcomes of infertility patients treated with in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET).</p><p><b>METHODS</b>A retrospective study was conducted of 61 IVF/ICSI-ET cycles as the study group, diagnosed with uterine adenomyosis by transvaginal ultrasound, and 164 IVF/ICSI-ET cycles of patients with tubal infertility as the control group. The baseline characteristics, ovary response and clinical outcomes were compared between the two groups.</p><p><b>RESULTS</b>The implantation rate, clinical pregnancy rate and live birth rate decreased significantly in the study group (P<0.05), and early abortion rate increased significantly (P<0.05). For patients with adenomyosis, GnRH-antagonist cycles tended to decrease clinical pregnancy rate and increase abortion rate (25.0% vs 45.0%, P=0.184; 66.7% vs 27.8%, P=0.247), and significantly decrease live birth rate (0% vs 30.8%, P=0.025), compared with GnRHa agonist cycles.</p><p><b>CONCLUSION</b>Uterine adenomyosis decreases implantation rate, clinical pregnancy rate and birth rate, and increases abortion rate significantly in patients with IVF/ICSI-ET. GnRH-antagonist cycles have adverse effects on the outcomes of adenomyosis; GnRH agonist long protocol cycles may increase clinical pregnancy rate and decrease abortion rate.</p>

Successful pregnancy following repeated implantation failure in patients with polycystic ovary syndrome: report of three cases / 南方医科大学学报

We report 3 cases of polycystic ovary syndrome (PCOS) in which the patients had successful pregnancy after repeated implantation failure in at least 8 in vitro fertilization and embryo transfer (IVF-ET) cycles. The patients were treated with gonadotropin-releasing hormone antagonist (GnRH-ant) protocol and gonadotropin-releasing hormone angonist (GnRHa) for triggering ovulation, and successful pregnancy and normal deliveries were achieved after 9 IVT-ET cycles. For young patients with PCOS but a good ovarian reserve and a high ovarian response, treatment with GnRH antagonist protocol and GnRHa alone with appropriate management of the factors that may affect implantation can prevent severe ovarian hyperstimulation syndrome to achieve favorable clinical outcomes.

Effect of group psychological intervention and relaxation training on nurses' job burnout / 中华健康管理学杂志

Objective To evaluate the effect of group psychological intervention and relaxation training on nurses' job burnout.Methods A total of 236 female registered nurses [mean age (27±4) years,and mean employment (17±3) years] were randomly assigned to the intervention group (n=120) and the control group (n=116).The intervention group had 60-minute group psychological intervention,10-minute psychological relaxing exercises and 20-minute progressing muscle relaxing exercises per week for 8 weeks.The control group did not receive any instrument.The participants were assessed at the 1st and 8th week by using the Job Burnout Scale.Results There was no statistical significance in three dimensions of the Job Burnout Scale between the two groups at baseline (P＞0.05).However,after the intervention,the intervention group had lower scores of EE (13.62±7.86 vs.19.83±4.89) and DP (5.25±3.27 vs.6.55±3.43) and higher scores of PA (38.28±6.34 vs.32.13±7.06) than the control group (all P＜0.01),and had lower scores of EE (18.92±8.36 vs.13.62±7.86) and DP (6.44±3.56 vs.5.25±3.27) and higher scores of PA (28.39±7.78 vs.38.28 ± 6.34) than baseline (all P＜0.01).The control group showed no significant difference in those parameters before and after the intervention (P＞0.05).In the intervention group,1-9 years employment subgroup had lower scores of EE (13.21±7.32 vs.16.91±5.63) and DP (5.61±4.33 vs.7.80±4.59) and higher scores of PA (36.34±7.28 vs.31.39±6.88) than the control group; 10-19 years employment subgroup had lower scores of EE (11.68±5.95 vs.15.14±6.43) and DP (5.11±3.65 vs.7.82±5.21) and higher scores of PA (31.24±8.90 vs.27.33±5.96) than the control group (all P＜0.01); 20-29 years employment subgroup had lower scores of EE (12.37±5.23 vs.15.36±4.98) than the control group (P＜0.01).Conclusions Group psychological intervention and relaxation training could effectively relieve nurses' job burnout.

Wnt/β-catenin pathway regulating glucocorticoids-mediated Alzheimer' s disease-like pathological changes / 中华神经科杂志

Objective To investigate the role of Wnt/β-catenin pathway in the glucocorticoids (GC)-mediated Alzheimer' s disease-like pathological changes in vitro.Methods Human embryonic kidney 293 (HEK293/wt) cells stably transfected with the longest human tau (tau441,HEK293/tau) and wild-type HEK293 cells were employed to study the role of GC.Cell viabilities of the two cell lines were examined by cell counting kit-8 ( CCK-8 ).Levels of phosphorylated tau ( p-T205 ) and dephosphorylated tau (Tau-1),β-catenin,phosphorylated β-catenin (p-β-catenin),glycogen synthase kinase-3β (GSK-3β),phosphorylated GSK-3β at Ser9 (ps9-GSK-3β) and Bcl-2 were determined by Western blotting.Results Treatment with 1 μmol/L GC for 48 h decreased the viability of HEK293/wt and HEK293/tau cells to 95.5％ ±3.2％ and 77.8％ ± 4.4％ (t =6.60,P ＜ 0.05 ).Moreover,GC treatment decreased the levels of ps9-GSK-3β,Tau-1,β-catenin and Bcl-2 to 47.8％ ± 10.4％,53.9％ ± 11.7％,50.9％ ±7.6％,48.4％ ±6.5％ of control groups ( t =7.01,3.86,7.09,7.30,all P ＜ 0.05 ),and increased the relative levels of pT205,p-β-catenin to 180.5％ ± 22.2％,201.3 ％ ± 27.6％ of control groups (t =5.51,5.27,both P ＜0.05) only in HEK293/tau cells.Finally,LiCI efficiently prevented the above effects of GC in HEK293/tau cells.Conclusion GC may trigger Alzheimer' s disease-like pathological changes by inhibiting the Wnt/β-catenin pathway and these pathological processes seem to specifically depend on the presence of human tau.

Targeted silencing of heparanase gene by small interfering RNA inhibits invasiveness and metastasis of osteosarcoma cells / 华中科技大学学报（医学）（英德文版）

The effects of targeted silencing of heparanase gene by small interfering RNA (siRNA) on invasiveness and metastasis of osteosarcoma cells (MG63 cells) were investigated in the present study. Two complementary oligonucleotide strands were synthesized and inserted into pGenesil-1 vector based on the mRNA sequence of heparanase gene. The expression vector containing short hairpin RNA (pGenesil-shRNA) was constructed successfully. MG63 cells were randomly allocated into 3 groups: blank group, empty vector (pGenesil) transfected group and expression vector (pGenesil-shRNA) transfected group. Under the induction of Lipofectamine 2000, the recombinants were transfected into MG63 cells. Heparanase gene expression level was detected by RT-PCR and Western blotting. Cell proliferation was measured by MTT assay. Cell invasiveness and metastasis were examined by cell adhesion and Transwell-ECM assays. HUVECs migration assay was applied for the detection of angiogenesis. As compared with negative controls, the mRNA and protein expression levels of heparanase were down-regulated by 76.1% (P<0.01) and 75.3% (P<0.01) respectively in the pGenesil-shRNA transfected group. Meanwhile, the proliferation, adhesiveness, invasiveness and angiogenesis properties of MG63 cells were all significantly inhibited. It was suggested that targeted silencing of heparanase gene by siRNA could dramatically inhibit the invasiveness and metastasis of osteosarcoma cells.

A randomized controlled trial of pramipexole versus fluoxetine in the treatment of depression in Parkinson's disease / 中华老年医学杂志

Objective To investigate the efficacy and safety of pramipexole versus fluoxetine in the treatment of depression in Parkinson's disease ( PD). Methods A randomized, clinical trial of pramipexole versus fluoxetine treatment for 12 weeks in 50 patients suffering from combined PD and depression was accomplished. The efficacy and safety assessments of the treatments were performed at different time points. Results For the intent-to-treat (ITT) population, the Hamilton Depression Rating Scale (HAMD) scores decreased progressively in both the pramipexole and the fluoxetine group, and a between-time statistical analysis was significant for both groups. The efficacy proportion of patients who responded to the treatment, as defined by at least a 50% reduction in HAMD score, was 56. 0% in the pramipexole group versus 48. 0% in the fluoxetine group (χ~2 =0. 321, P>0. 05). Similarly, the proportion of patients who recovered, as defined by a final HAMD score ≤8, was 52. 0% in the pramipexole group versus 32. 0% in the fluoxetine group (χ~2 =2. 053, P>0. 05) , but the difference between the two treatments showed no statistical significance. At the endpoint, both the Unified Parkinson's Disease Rating Scale (UPDRS) part Ⅱ and part Ⅲ subscores improved in the pramipexole group, by a mean of 2. 9±3. 7 (t= 2.366, P<0.05) and7.2±5.1 (t=2.654, P< 0.05), respectively, and the latter was significantly different from the change in this variable of the fluoxetine group (P<0. 05). Spearman analysis showed that no relationship between HAMD score and UPDRS Part II or Part III subscore. The findings for the per-protocol (PP) population were consistent with the above results, except that the proportion of patients who recovered in the pramipexole group was significantly larger than that in the fluoxetine group. The adverse events in both groups were mild dizziness, nausea and anorexia. No significant difference was found in the frequencies of the adverse events between the pramipexole and fluoxetine group. Conclusions Pramipexole is effective and safe in the treatment of Chinese PD patients combined with depression.

Biocompatibility of KLD-12 peptide hydrogel as a scaffold in tissue engineering of intervertebral discs in rabbits / 华中科技大学学报（医学）（英德文版）

KLD-12 peptide with a sequence of AcN-KLDLKLDLKLDL-CNH(2) was synthesized and its biocompatibility was assessed in animals. Rabbit MSCs were cultured in the hydrogel for 2 weeks. Live cells were counted by using Calcein-AM/PI fluorescence staining. MTT was employed to assess the viability of MSCs cultured in KLD-12 peptide solution of 0.01%, 0.03%, and 0.05%. Hemolysis test, skin irritation test and implantation test were conducted to evaluate its biocompatibility with host tissues. Our results demonstrated that the MSCs in hydrogel grew well and maintained round shape. Cell survival rate was 92.15% (mean: 92.15%+/-1.17%) at the 7th day and there was no difference in survival rate between day 7 and day 14. Cell proliferation test showed that the A value of the KLD-12 solutions was not significantly different from that of control groups (complete culture media) (P>0.05) at the 24th and 48th h. The hemolysis rate of KLD-12 solution was 0.112%. Skin irritation test showed that the skin injected with KLD-12 solution remained normal and the score of skin irritation was 0. The histological examination with HE staining exhibited that the skin layers were clear and there was no infiltration with neutrophilic granulocytes and lymphocytes. It is concluded that KLD-12 peptide hydrogel had a good biocompatibility with host rabbit and MSCs, and KLD-12 peptide hydrogel can provide an appropriate microenvironment for MSCs.

The molecular characteristics of heteroresistant vancomycin-intermediate Staphylococcus aureus in China / 中华检验医学杂志

Obiective To investigate the molecular characteristics of heteroresistant vancomycinintermediate Staphylococcus aureus(hVISA)in China and analyze the differences of the molecular characteristics between hVISA and VSSA(vancomycin-susceptible Staphylococcus aureus)isolates.Methods A total of 3 15 non-repetitive MBSA were collected from the national surveillance program in China in 2007.The isolates of hVISA were confirmed by modified population analysis profile-area under the curve(PAP-AUC).The genotypes of agr and SCCmec were determined by multiplex PCR,and spa typing was performed bv PCR and DNA sequencing.The pvl gene was detected bv PCR Results The prevalence of hVISA was 9.5%(30/315).Among 315 MRSA,SCCmec Ⅲ was the most popular type,which was found in 234 isolates(234/315,74.3%),followed by SCCmec Ⅱ,which was identified in 56 isolates (56/315,17.8%).The rate of SCCmec Ⅱ in hVISA(46.7%)was significantly hisher than in VSSA (14.7%,X~2=18.93,P＜0.001).The most prevalent agr type among 315 MRSA was agr 1 accounting for 73.6%(232/315).The agr 2 accounted for 18.7%(59/315),and agr 3 and agr 4 were very rare in clinical isolates.It was different in agr types between the two groups.The rate of agr 2 in hVISA(53.4%)was higher than in VSSA(15.1%).X~2 value was 26.08 and P value was less than 0.001 through X~2 test.There was a statistical significance in the result.There were 4 spa types in hVISA isolates,including t002 (13 isolates),t037(9 isolates),t030(6 isolates),and 1548(2 isolates).The pvl positive MRSA isolates were very low,accounting for 1.6%(5/315).Conclusions The prevalence of hVISA was relatively higher in China.Compared to VSSA,the majority(53.4%)of the hVISA strains were agr 2,which was obviously different from VSSA.hVISA isolates were more diverse by spa typing,

Progress in stem cell therapy for Alzheimer's disease / 国际生物医学工程杂志

Stem ceils transplantation is one of the potential therapeutic strategies for Alzheimer's disease (AD). Many animal models following stem cell transplantation showed improvement in memory and cognitive function. However, the pathological changes in AD, such as arnyloid beta deposits, negatively affect the survival and differentiaition of stem cells. Stem cells transfectcd with neprilysin or administration of phenserine could at-tenuate these adverse effects. Genetic modification of stem cell by over expression of neurotrophic factors could attenuate the adverse effects not only on stem cells but also on degenerative neurons. Further investigation on how to overcome the adverse effects of phathological factors in AD on stem cells and maximize the therapeutic effects of stem cells would support the hope for introduction of stem cells transplation into clinical application.

Depression in patients with Parkinson's disease and the associated features / 华中科技大学学报（医学）（英德文版）

The study was aimed to examine the prevalence of depression in patients with Parkinson's disease (PD) and identify its features. A total of 131 out-patients, diagnosed as having idiopathic PD in accordance with the United Kingdom Parkinson's Disease Society Brain Bank criteria, were interviewed with questionnaire and evaluated by Mini-Mental State Examination (MMSE), Unified Parkinson's Disease Rating Scale (UPDRS), Hohen &Yahr staging (H&Y staging) and Hamilton Rating Scale for Depression (HRSD). Patients were divided into three groups in terms of HRSD score: depression group, sub-threshold depression group and non-depression group. The clinical variables and symptom profiles were obtained and compared among the three groups. The results showed that 27 patients (20.6%) fell into the depression group, 71 (54.2%) into the sub-threshold depression group, and 33 (25.2%) into the non-depression group. There were no differences in age, gender or tremor score among the groups (P>0.05). Significant differences were found in duration of PD, UPDRS score, rigidity score and H&Y stage between the sub-threshold depression group (or the depression group) and the non-depression group (P<0.05). Moreover, the clinical variables in the subthreshold depression group had the trend of increasing with the severity of PD and their values were similar to those in the depression group. Anhedonia, feeling of incapability, sleep disturbance, gastrointestinal symptoms and depressive moods were most common in the depression group. And these symptoms also were more common in the other two groups. It is concluded that depression and sub-threshold depression are common in PD and share similar clinical features. Furthermore, subthreshold depression might be the prodrome of depression and may develop into depression as the condition progresses.