The Efficacy of Denosumab in Patients With Rheumatoid Arthritis: A Systematic Review and Pooled Analysis of Randomized or Matched Data.

Objective: The purpose of this study was to evaluate the efficacy of denosumab treatment in patients with rheumatoid arthritis (RA). Methods: The Medline, Embase and Cochrane Library databases were searched for relevant clinical studies. Studies that assessed the efficacy of denosumab in patients with RA were identified. The primary endpoints were the percent changes in bone mineral density (BMD), and the changes in modified total Sharp score (mTSS), modified Sharp erosion score and joint space narrowing (JSN) score. Pooled analyses were calculated using random-effect models. Results: After searching the literature and performing further detailed assessments, 10 studies with a total of 1758 patients were included in the quantitative analysis. Pooled analyses showed that denosumab treatment significantly increased the percent changes in lumbar spine BMD [mean difference (MD): 5.12, confidence intervals (CI): 4.15 to 6.09], total hip BMD (MD: 2.72, 95% CI: 1.80 to 3.64) and femoral neck BMD (MD: 2.20, 95% CI: 0.94 to 3.46) compared with controls. Moreover, denosumab treatment significantly decreased the changes in mTSS (MD: -0.63, 95% CI: -0.86 to -0.41) and modified Sharp erosion score (MD: -0.62, 95% CI: -0.88 to -0.35). Subgroup analysis indicated that denosumab was superior to bisphosphonates for the improvement of BMD and the mitigation of joint destruction. Conclusion: Denosumab treatment was associated with increased BMD and alleviated progression of joint destruction in RA patients, even when compared with bisphosphonates.

In-situ detection of cadmium with aptamer functionalized gold nanoparticles based on smartphone-based colorimetric system.

Cadmium is a heavy metal pollutant in environment with high toxicity that severely threats human health. A simple and sensitive method for rapid detection of cadmium ions in water sample is of significant importance. In this paper, a colorimetric method based on aptamer-functionalized gold nanoparticles (AuNPs) for specific recognition were proposed to realize Cd2+ detection. AuNPs aggregate in high-salt solutions because of the shielding of salt to electrostatic repulsion among AuNPs, while aptamers can strengthen the stability of AuNPs and avoid the aggregation. After adding Cd2+ ions, the specific interaction between aptamers and Cd2+ leads to a decrease of free aptamers, which weakens the stability of the AuNPs and results in the color change of the solution. The colorimetric change can be rapidly captured and analyzed by a self-developed smartphone-based colorimetric system (SBCS) within 10 min, which implements the quantitative detection of Cd2+. The results show that Cd2+ ions can be detected with high selectivity and sensitivity with a linear range of 2-20 µg/L and a detection limit of 1.12 µg/L. Compared with other methods, the proposed approach features high sensitivity, high simplicity, easy implementation and high throughout, which provides a promising means for in-situ determination of Cd2+ in practical applications.

Sex-related differences in catheter ablation of atrial fibrillation: a systematic review and meta-analysis.

AIMS: The sex-related differences in the clinical outcomes of rhythm and safety after catheter ablation remain unclear. The purpose of this study was to compare the clinical outcomes of catheter ablation for atrial fibrillation (AF) in women and men. METHODS AND RESULTS: The Medline and EMBASE databases were searched for published articles up to December 2018. Studies that met our predefined inclusion criteria were included. The primary endpoints were freedom from AF/atrial tachycardia (AT) recurrence, stroke/transient ischaemic attack (TIA), and all-cause mortality. After literature search and detailed assessment, 19 observational studies (151 370 patients; 34% women) were identified. Our analyses showed that the rate of freedom from AF/AT recurrence was lower in women than men at the 2.4-year follow-up [odds ratio (OR): 0.75, 95% confidence interval (CI) 0.69-0.81; P < 0.0001]. Moreover, women had an increased risk of stroke/TIA (OR: 1.42, 95% CI 1.21-1.67; P < 0.0001) and all-cause mortality (OR: 1.53, 95% CI 1.02-2.28; P = 0.04). Nevertheless, for the endpoint of all-cause mortality, there was no significant difference between the two genders in the subgroup of prospective studies (OR: 1.19, 95% CI 0.69-2.05; P = 0.53). Additionally, women were more likely to experience major complications compared with men (pericardial effusion/tamponade, major bleeding requiring transfusion, and pacemaker implantation). CONCLUSIONS: Women who underwent catheter ablation of AF might experience lower efficacy and a higher risk of stroke/TIA and major complications than men. The reasons for these sex-related differences need to be further studied.

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Chronic Kidney Disease: A Meta-Analysis.

OBJECTIVE: The aim of this meta-analysis was to compare the clinical outcomes of transcatheter aortic valve replacement (TAVR) with those of surgical aortic valve replacement (SAVR) in patients with chronic kidney disease (CKD). DESIGN: Meta-analysis of 10 observational studies. SETTING: Hospital. PARTICIPANTS: Patients with CKD (9,619) undergoing aortic valve replacement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Medline, Cochrane Library, and Embase databases were searched for clinical studies published from January 2000 to October 2018. Studies that fulfilled the predefined inclusion criteria were included. The primary clinical outcomes included early all-cause mortality and postoperative stroke. Random-effects modeling was used to calculate odds ratio (OR) and 95% CI. After a literature search of the major databases, 10 observational cohort studies with a total of 9,619 patients were identified. Pooled analysis indicated that, when compared with SAVR, TAVR was associated with a lower risk of early all-cause mortality (6.1% v 10.2%; OR: 0.71; 95% CI: 0.51-0.98) and stroke (1.1% v 2.2%; OR: 0.53; 95% CI: 0.37-0.75). Although TAVR increased the risk of pacemaker implantation (OR: 2.06; 95% CI: 1.16-3.66), it reduced the risk of blood transfusion (OR: 0.50; 95% CI: 0.39-0.65), infection (OR: 0.30; 95% CI: 0.13-0.70), acute kidney injury (AKI) (OR: 0.46; 95% CI: 0.38-0.55), and AKI requiring dialysis (OR: 0.66; 95% CI: 0.58-0.75). There were not significant differences in the incidence rates of cardiac tamponade (OR: 0.60; 95% CI: 0.26-1.36) and major vascular damage (OR: 1.12; 95% CI: 0.81-1.55) between the 2 groups. CONCLUSION: Transcatheter aortic valve replacement might be a preferable approach to SAVR in patients with CKD. A large, prospective, randomized controlled trial is warranted.

Graphene FET Array Biosensor Based on ssDNA Aptamer for Ultrasensitive Hg2+ Detection in Environmental Pollutants.

Invisible mercury ion is an extremely poisonous environmental pollutant, therefore, a fast and highly sensitive detection method is of significant importance. In this study, a liquid-gated graphene field-effect transistor (GFET) array biosensor (6 × 6 GFETs on the chip) was fabricated and applied for Hg2+ quantitate detection based on single-stranded DNA (ssDNA) aptamer. The biosensor showed outstanding selectivity to Hg2+ in mixed solutions containing various metal ions. Moreover, the sensing capability of the biosensor was demonstrated by real-time responses and showed a fairly low detection limit of 40 pM, a wide detection ranged from 100 pM to 100 nM and rapid response time below one second. These results suggest that the GFET array biosensor based on ssDNA aptamer offers a simple fabrication procedure and quite fast method for mercury ion contaminant detection and are promising for various analytical applications.

Bifidobacterial recombinant thymidine kinase-ganciclovir gene therapy system induces FasL and TNFR2 mediated antitumor apoptosis in solid tumors.

BACKGROUND: Directly targeting therapeutic suicide gene to a solid tumor is a hopeful approach for cancer gene therapy. Treatment of a solid tumor by an effective vector for a suicide gene remains a challenge. Given the lack of effective treatments, we constructed a bifidobacterial recombinant thymidine kinase (BF-rTK) -ganciclovir (GCV) targeting system (BKV) to meet this requirement and to explore antitumor mechanisms. METHODS: Bifidobacterium (BF) or BF-rTK was injected intratumorally with or without ganciclovir in a human colo320 intestinal xenograft tumor model. The tumor tissues were analyzed using apoptosis antibody arrays, real time PCR and western blot. The colo320 cell was analyzed by the gene silencing method. Autophagy and necroptosis were also detected in colo320 cell. Meanwhile, three human digestive system xenograft tumor models (colorectal cancer colo320, gastric cancer MKN-45 and liver cancer SSMC-7721) and a breast cancer (MDA-MB-231) model were employed to validate the universality of BF-rTK + GCV in solid tumor gene therapy. The survival rate was evaluated in three human cancer models after the BF-rTK + GCV intratumor treatment. The analysis of inflammatory markers (TNF-α) in tumor indicated that BF-rTK + GCV significantly inhibited TNF-α expression. RESULTS: The results suggested that BF-rTK + GCV induced tumor apoptosis without autophagy and necroptosis occurrence. The apoptosis was transduced by multiple signaling pathways mediated by FasL and TNFR2 and mainly activated the mitochondrial control of apoptosis via Bid and Bim, which was rescued by silencing Bid or/and Bim. However, BF + GCV only induced apoptosis via Fas/FasL signal pathway accompanied with increased P53 expression. We further found that BF-rTK + GCV inhibited the expression of the inflammatory maker of TNF-α. However, BF-rTK + GCV did not result in necroptosis and autophagy. CONCLUSIONS: BF-rTK + GCV induced tumor apoptosis mediated by FasL and TNFR2 through the mitochondrial control of apoptosis via Bid and Bim without inducing necroptosis and autophagy. Furthermore, BF-rTK + GCV showed to repress the inflammation of tumor through downregulating TNF-α expression. Survival analysis results of multiple cancer models confirmed that BF-rTK + GCV system has a wide field of application in solid tumor gene therapy.

Interleukin-10-1082 G/a polymorphism and acute renal graft rejection: a meta-analysis.

OBJECTIVE: The aim of this study was to investigate the association between interleukin (IL)-10-1082 (G/A) promoter polymorphism and acute rejection (AR) in renal transplant recipients. METHODS: We searched MEDLINE, EMBASE, Web of Science, and Cochrane Central Register from the inception to March 2015 for relevant studies. Data concerning publication information, population characteristics, and transplant information were extracted. Odds ratios (ORs) was calculated for the association between IL-10-1082 GG genotype (or IL-10-1082 G allele) and AR risk. RESULTS: This meta-analysis included 22 case-control studies including 2779 cases of renal transplant recipients. The pooled estimate showed that the IL-10-1082 GG genotype was not significantly associated with AR risk (ORrandom=1.07, 95% CI 0.80-1.43, p = 0.64). Similarly, the pooled estimate showed that the IL-10-1082 G allele was not significantly associated with AR risk (ORfixed=1.02, 95% CI 0.90-1.16, p = 0.74). None of subgroup analyses yielded significant results in the association between IL-10-1082 GG genotype (or IL-10-1082 G allele) and AR risk. Meta-regression confirmed that there was no significant correlation between the pre-selected trial characteristics and our study results. CONCLUSIONS: This meta-analysis suggests that IL-10-1082 G/A polymorphism is not significantly associated with AR risk in renal transplant recipients.

Preoperative statin therapy decreases early mortality in patients undergoing isolated valve surgery: result from a meta-analysis.

OBJECTIVE: The purpose of this meta-analysis was to assess the role of preoperative statin therapy on adverse cardiovascular events in patients undergoing valve surgery. DESIGN: Meta-analysis of 10 observational studies. SETTING: Hospital. PARTICIPANTS: 22,158 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Medline, Cochrane, and Embase databases were searched for clinical studies published up to June 2014. Studies that evaluated the effects of preoperative statin therapy on valve surgery were included. After a literature search in the major databases, 10 observational studies with 22,518 patients were identified. Pool analysis indicated that preoperative statin therapy was associated with a significantly lower risk of early all-cause mortality (Odds ratio [OR]: 0.69; 95% confidence interval [CI] 0.50-0.95, p = 0.03). The benefits of preoperative statin therapy were more obvious in studies with isolated valve surgery, resulting in a 1.9% absolute risk and a 38% odds reduction of early mortality (2.4 v 4.3%; OR: 0.62; 95% CI 0.49-0.77, p<0.0001). A significant reduction by statin therapy also was observed for atrial fibrillation (OR 0.88, 95% CI: 0.80-0.98, p = 0.02). However, statin therapy was not associated with a lower risk of postoperative stroke (OR: 0.74; 95% CI 0.46-1.19, p = 0.21), myocardial infarction (OR: 1.02; 95% CI 0.78-1.34, p = 0.87), and renal failure (OR: 0.91; 95% CI 0.57-1.44, p = 0.68). CONCLUSIONS: Preoperative statin therapy was associated with a significantly lower risk of early mortality in patients undergoing isolated valve surgery. A prospective, randomized, controlled trial is warranted.

Sequencing analysis and characterization of the plasmid pBIF10 isolated from Bifidobacterium longum.

A resident plasmid, pBIF10, was isolated from Bifidobacterium longum B200304, and the full-length sequence of pBIF10 was analyzed. In this sequence, we identified at least 17 major open reading frames longer than 200 bp. A tetracycline resistance gene, tetQ, was identified and verified to confer antibiotic resistance to tetracycline. The plasmid replicon with replication protein B gene (repB) and a typical iteron was identified in pBIF10. An artificial clone vector was constructed with the replicon of pBIF10; the results showed that repB controlled plasmid replication in other bifidobacteria host cells at low transformation frequency. Taken together, the analysis and characterization of pBIF10 provided necessary information for the understanding of antibiotic resistance mediated by a plasmid in a Bifidobacterium strain. GC% and repB sequence analyses indicated that pBIF10 was a molecular hybrid of at least 2 other bacterial genera plasmids.

Meta-analysis of the effects of preoperative renin-angiotensin system inhibitor therapy on major adverse cardiac events in patients undergoing cardiac surgery.

The purpose of this meta-analysis was to assess the role of preoperative renin-angiotensin system inhibitor (RASI) therapy on major adverse cardiac events (MACE) in patients undergoing cardiac surgery. The Medline, Cochrane Library and Embase databases were searched for clinical studies published up to May 2014. Studies that evaluated the effects of preoperative RASI therapy in cardiac surgery were included. Odds ratio (OR) estimates were generated under a random-effects model. After a literature search in the major databases, 18 studies were identified [three randomized prospective clinical trials (RCTs) and 15 observational trials] that reported outcomes of 54 528 cardiac surgery patients with (n = 22 661; 42%) or without (n = 31 867; 58%) preoperative RASI therapy. Pool analysis indicated that preoperative RASI therapy was not associated with a significant reduction of early all-cause mortality [OR: 1.01; 95% confidence interval (CI) 0.88-1.15, P = 0.93; I(2) = 25%], myocardial infarction (OR: 1.04; 95% CI 0.91-1.19, P = 0.60; I(2) = 16%), or stroke (OR: 0.93; 95% CI 0.75-1.14, P = 0.46; I(2) = 38%). Meta-regression analysis confirmed that there was a strong negative correlation between the percentage of diabetics and early all-cause mortality (P = 0.03). Furthermore, preoperative RASI therapy significantly reduced mortality in studies containing a high proportion of diabetic patients (OR: 0.84; 95% CI 0.71-0.99, P = 0.04; I(2) = 0%). In conclusion, our meta-analysis indicated that although preoperative RASI therapy was not associated with a lower risk of MACE in cardiac surgery patients, it might provide benefits for diabetic patients.

The long-term efficacy of cryoballoon vs irrigated radiofrequency ablation for the treatment of atrial fibrillation: A meta-analysis.

OBJECTIVES: The main purpose of this meta-analysis was to compare the long-term efficacy of cryoballoon ablation (CBA) with irrigated radiofrequency catheter ablation (RFCA) for the treatment of atrial fibrillation (AF). METHODS: The Medline, Cochrane Library and Embase Database were searched for clinical studies published up to October 2014. Studies that fulfilled our predefined inclusion criteria were included. The primary clinical outcome was the proportion of patients free from AF (follow-up≥3months), and the secondary clinical outcomes included acute pulmonary vein (PV) isolated rate, fluoroscopy time, procedure time and complications. RESULTS: After a literature search in the major databases, three randomized controlled trials (RCTs) and eight retrospective trials with a total of 1216 patients were identified. Pool-analysis demonstrated that, as compared RFCA, CBA was associated with a similar proportion of patients free from AF at a mean 16.5months follow-up (66.9% vs 65.1%; relative risk [RR]: 1.01; 95% CI: 0.94 to 1.07, P=0.87). Acute PV isolation rate (RR: 0.92; 95% CI: 0.82 to 1.03) and fluoroscopy time (weighted mean difference WMD: -8.60; 95% CI: -18.29 to 3.69) were not statistically significant difference. The procedure time was shorter in CBA group ([WMD]: -31.94; 95% CI: -60.43 to -3.45). Transient phrenic nerve palsy was uniquely observed in the CBA group (5.4%, P<0.00001) and resolved in all during the follow-up period, total complication was similar in both groups (RR: 1.30; 95% CI: 0.91 to 1.85). CONCLUSIONS: CBA was as effective as RFCA for the treatment of atrial fibrillation during long-term follow-up with comparable procedural features.

[Enterotoxigenic Escherichia coli heat-labile enterotoxin B subunit can efficiently induce and enhance the mucosal immune response to enterovirus 71].

OBJECTIVE: To detect the immunogenicity of enterotoxigenic Escherichia coli heat-labile enterotoxin B subunit (LTB) and evaluate the immune effect of enterovirus 71 (EV71) capsid protein VP1 together with LTB by the intranasal route. METHODS: The LTB gene was cloned into the plasmid pET32a. The 6×His-LTB fusion protein was purified with Ni(2+)-NTA resin and used to vaccinate the New Zealand white rabbits to prepare the LTB-specific antiserum. The titer was determined by ELISA. BALB/c mice were immunized with normal saline, purified EV71 VP1 alone and EV71 VP1 together with LTB by the intranasal drip respectively. The sera as well as lung and intestinal mucosa lavage fluids were collected and determined for IgG and secretory IgA (sIgA) by indirect ELISA. RESULTS: Recombinant plasmid pET32a-LTB was constructed successfully. The expressed fusion protein 6×His-LTB, with a relative molecular mass of about 30 000, existed mostly in a form of inclusion body. The serum antibody titer induced with it was 1:125 000 in the New Zealand white rabbits. The levels of specific IgG and sIgA in mice immunized with EV71 VP1 plus LTB were significantly higher than those in the ones with EV71 VP1 alone and normal saline. CONCLUSION: Fusion protein 6×His-LTB was successfully expressed in E.coli BL21 (DE3) and showed both good immunogenicity and adjuvant activity. The LTB can efficiently enhance specific serum antibody response and induce mucosal immune response by intranasal drip.

Bevacizumab in the treatment of pterygium: a meta-analysis.

PURPOSE: The aim of this study was to assess the efficacy and safety of bevacizumab in the treatment of pterygium and to mainly explore its effects on recurrence rate and complications. METHODS: We searched MEDLINE, EMBASE, Web of Science, and Cochrane Central Register from the inception to July 2013 for relevant randomized controlled trials that examined bevacizumab therapy for pterygium. Data concerning study design, patient characteristics, treatment, and outcomes were extracted. The methodological quality of the studies included was assessed using the Jadad score. Relative risk (RR) was calculated for recurrence rate and complications. RESULTS: A total of 474 patients with 482 eyes in 9 randomized controlled trials were analyzed. The pooled estimate showed that bevacizumab had no statistically significant effect on preventing pterygium recurrence [RR 0.90, 95% confidence interval (CI) 0.77-1.07, P = 0.23]. None of the subgroup analyses yielded significant results in favor of bevacizumab (surgery group: RR 0.77, 95% CI 0.50-1.18, P = 0.23; nonsurgery group: RR 0.98, 95% CI 0.86-1.11, P = 0.76; primary pterygium group: RR 0.82, 95% CI 0.53-1.26, P = 0.36; recurrent pterygium group: RR 0.95, 95% CI 0.82-1.09, P = 0.44). There were no statistically significant differences in the complications between the 2 groups (RR 1.00, 95% CI 0.73-1.37, P = 1.00). However, the bevacizumab group was associated with a higher risk of developing subconjunctival hemorrhage (RR 3.34, 95% CI 1.07-10.43, P = 0.04). CONCLUSIONS: Topical or subconjunctival bevacizumab was relatively safe and well tolerated, but it had no statistically significant effect on preventing pterygium recurrence. A large-scale trial with a suitable dosage and a longer follow-up would be required to rule out the possibility of any treatment benefit.