Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.

Objective:To evaluate the diagnostic efficiency and safety of endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)in lymph node staging of non-small cell lung cancer(NSCLC)in elderly patients.Methods:Thirty-five patients aged ≥70 years and 58 patients aged 60-69 years with NSCLC receiving EBUS-TBNA in our hospital from March 2015 to December 2018 were enrolled.All patients underwent EBUS for all visible mediastinal and hilar lymph nodes, and those with enlarged lymph nodes(short axis ≥6 mm)were further examined with TBNA.The diagnostic efficiency and safety of EBUS-TBNA were analyzed.Results:The sensitivity of EBUS-TBNA was 0.94, the specificity was 1.00, the Yoden index was 0.94, the positive predictive value was 1.00, and the negative predictive value was 0.82.Tumor staging was changed in 20 patients after EBU-TBNA, resulting in changes in assessment on tumor resectability in 5 cases.EBUS-TBNA had excellent agreement with postoperative pathology in evaluating resectability(Kappa=0.95). The sensitivity and specificity were 1.00 and 0.97, respectively.The incidence of complications of EBUS-TNBA was 6.5%.The elderly group had a worse performance status( P<0.05)compared with the control group, but the complication rates(5.7% vs 6.9%, P>0.05)were similar between the two groups. Conclusions:EBUS-TBNA is highly effective and safe in the diagnosis of NSCLC in patients aged 70 and older.

Objective: To investigate the efficacy and safety of Rivaroxaban for elderly patients with thrombotic diseases. Methods: This was a retrospective study.A total of 301 elderly patients taking Rivaroxaban from October 2012 to November 2017 at the Second Medical Center of the Chinese PLA General Hospital were consecutively selected.The ages ranged from 60 to 102 years, with an average age of(86.5±8.4)years.Anticoagulation regimens were developed based on comprehensive evaluation of indications, creatinine clearance, ischemia and bleeding risk.Patients were divided into a Rivaroxaban 2.5-5.0 mg/d group(n=72), a 10.0 mg/d group(n=205), and a 15.0-20.0 mg/d group(n=24). Hepatic function, renal function, and coagulation indexes were measured before and after the administration of Rivaroxaban.Fatal bleeding, cardiovascular deaths, all-cause deaths, non-fatal bleeding and thromboembolic events were recorded during the follow-up period. Results: The average dose of Rivaroxaban was(9.3±3.0)mg/d, and the minimum dose was 2.5 mg/d.The average follow-up time was(14.9± 13.9)months and the longest follow-up time was 48 months.One patient had intracranial bleeding.Twenty patients(6.6%)died with a cumulative incidence of 25.2%, three(1.0%)died of cardiac events, and 55.0% died of pneumonia and multiple organ failure.Forty patients(13.3%)had non-fatal hemorrhagic events with a cumulative incidence of 42.4%.Seven patients(2.3%)had thromboembolic events with a cumulative incidence of 16.0%, including 2 cases of non-fatal myocardial infarction, 3 cases of cerebral infarction and 2 cases of deep vein thrombosis.After treatment, levels of prothrombin time and fibrinogen significantly increased while levels of D-dimer significantly deceased(P<0.05). Conclusions Compared with previous reports, low-dose Rivaroxaban is safe and effective for elderly patients with thrombotic diseases.However, the risk of bleeding and ischemia should be comprehensively evaluated, and appropriate doses of Rivaroxaban should be selected individually.

Objective:To investigate the effect of Rab7 on cytokine induced by TLR7 (Toll like receptor-7) R848 activated in Raw264.7,and discusses the influence of Rab7 on MAPK signal transduction.Methods: TLR7 downstream cytokines such as TNF-α,IL-6,IFN-α,IFN-β and IP-10 activated by R848 were detected through Q-PCR in Rab7 silenced mouse macrophages,and then analysis of phosphorylation of MAPK determined with Western blot showed the effect of Rab7 on signal transduction of MAPK.Results: Rab7 inhibit production of cytokine activated by TLR7,and also,Rab7 had an inhibitory effect on MAPK signal pathway.Conclusion: The experimental results further illustrate that the Rab7 is the TLR7 signal transduction pathway negative regulatory factor,and to participate in MAPK signaling pathway.

PurposeTo evaluate the feasibility of a low-dose contrast medium protocol for 64-slice spiral CT angiography (CTA) of cerebral and carotid using a low-tube-voltage setting, and to compare the display effect of cerebral and carotid arteries by low-tube-voltage low-dose contrast medium and routine-tube-voltage routine-dose contrast medium scanning, and to assess the effect on radiation dose.Materials and MethodsEighty consecutive patients were prospectively selected to perform cerebral and carotid CTA inspection. The patients were randomly divided into control group and low dose group with 40 people in each group. The voltage in control group was 120 kV and the contrast agent was 80 ml; those in low dose group were 80 kV and 50 ml, respectively. The artery image quality was evaluated and venous interference was scored. The CT value, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and radiation dose in both groups were statistically analyzed.Results The consistency of uniform in artery image quality score and venous interference score was rather high according to the assessment of two physicians (Kappa=0.782 and 0.867). There was no statistical difference in artery image quality score, venous interference score, SNR and CNR between the two groups (Z=-0.864--0.032,P>0.05). The CT value in low dose group was higher than that in control group (differences with statistical significance,t=-8.789-1.715,P<0.05). The CT dose index of volume, dose-length product and effective dose in low dose group were all signiifcantly lower than those in control group (Z=-8.888,t=78.092 and 78.350, respectively,P<0.05).Conclusion The use of low tube voltage and low contrast dose in cerebral and carotid CTA examination can result in high quality images which meets the diagnostic needs and obviously reduce radiation dosage.

ObjectiveTo investigate the molecular response of adult and neonate ovine articular cartilage to acute mechanical injury.MethodsAn established in vitro model was used to compare gene expression difference of ovine articular cartilage explants at different developmental stages 24 hours after mechanical injury and the gene expression was compared between these models and that of the uninjured controls by microarray analysis.Total RNA was isolated from the tissue samples,linearly amplified,and applied to a 15 208 Ovine probes cDNA microarray(Agilent).Validation for selected genes(PPARγ,GRO TNC and LDHA) was obtained by real-time polymerase chain reaction.Comparisons between groups were performed by variance analysis.ResultsThere was significant difference in gene expression in adult and neonatal ovine articular cartilage after mechanical injury.Eighty-six genes were significantly manipulated at least 2-fold following mechanical injury for neonate sheep and 83 genes for adult sheep (P＜0.05).Conclusion Our findings indicate that mechanical injury to adult and neonatal ovine articular cartilage results in the activation of a series of signaling responses.We could identify four significant genes that are up or downregulated in response to acute mechanical injury.Significant functional clusters including genes associated with wound healing,articular protection,repair integration,and energy metabolism.Of these,PPARG could be specifically identified as novel target molecules and potential chondroprotective agent involved in traumatic cartilage injury and cartilage integrated repair.

Objective To study the levels of Th1 and Th2 type cytokines in 3-nitrobenzene sulfonate(TNBS) and oxazolone(OXZ) colitis without or with Trichinella spiralis( T. spiralis) infection. Methods Female BALB/c mice were randomly divided into 4 groups: 50% Ethanol, T. spiralis only, TNBS or OXZ,T. spiralis +TNBS or OXZ(at least 6 in each group when mice were killed). The levels of IFN-γ, IL-12,IL-4, IL-10 in colon in mice with colitis induced by TNBS or OXZ without or with T. spiralis infection 3 d and 7 d post-induction were assessed using ELISA method. Results Colonic protein levels of IFN-γand IL-12 were significantly increased 3 d and 7 d after intra-colonic injection of TNBS( P ＜0.05 ). Concurrent infection with T. spiralis prevented this rise in IFN-γand IL-12 secretion and tended to induce a rise in colonic IL-4 and IL-10 content(P ＜0. 05). The levels of IFN-γ, IL-4 and IL-10 protein in colitic mice colon with prior nematode infection on days 3 and 7 post-induction of colitis were significantly higher than that seen in colitic mice without prior nematode infection ( P ＜ 0.05 ). Conclusion T. spiralis infection significantly attenuates TNBS-induced colitis in mice. The local immunologic mechanism is that T. spiralis can down-regulate strongly Th1-type immune response of colitis and up-regulate Th2 response, Tr1-cytokines. According to the change of Th1/Th2 cytokines, prior T. spiralis infection doesn't reduce the severity of OXZ-induced colitis, but without aggravating colitis. The exactly immunologic mechanism deserve to be explored deeply.

Objective To explore the effect of Acanthopanax senticosus injection (ASI) on brain multi-infract dementia rats. Methods Thirty-six male Wistar rats were randomly divided into 3 groups:control group, model group and ASI group. The multi-infract dementia rat models were set up by injecting mini-sludged blood in carotis internal arteries, learning and memory function of rats were determined by Morris water maze and Step-down test, the section of rat cerebral cortex and hippocampus were stained with haematoxylin eosin (HE). Results Compared with model group, latency in ASI group shortened significantly at 2nd,5th and 6th day, the distance shortened at 1st,2nd,5th and 6th day. The seeking tactics of ASI trgated rats improved in the Morris water maze test. The error times of ASI treated rats decreasd at 1st and 2nd day in Step-down test; ASI did not reduce significantly pathological changes of vascular dementia rats. Conclusion ASI has effect of treatment on multi-infract dementia rats.

Objective To explore the mechanism of therapeutic effect of Donepezil hydrochloride on Alzheimer's disease(AD) rats.Methods According to weight,36 rats were divided into normal group,model group and Donepezil hydrochloride group.AD rat model was set up by injecting D-galactose into abdominal cavity for seven weeks,learning and memory function of rats was determined by using Morris water maze and Step-down test.The section of rat cerebral cortex and hippocampus were stained with haematoxylin eosin(HE),and the effect of Donepezil hydrochloride was observed by detecting the MDA content and SOD activity in cerebral tissue.Results Compared with model group,latency and distance of Donepezil hydrochloride rats shortened on the fourth day and the fifth day,starting angle of Donepezil hydrochloride rats shortened on the fourth day and the fifth day in the Morris water maze test,error times of Donepezil hydrochloride rats decreased on the first day and the second day in Step-down test;MDA content in cerebral tissue of Donepezil hydrochloride rat was deceased(P

0.05).Conclusion Donepezil hydrochloride do not improve the learning and memory function of normal under age rats.