The efficacy of dapagliflozin for type 1 diabetes: a meta-analysis of randomized controlled studies

Introduction: The efficacy of dapagliflozin for type 1 diabetes remains controversial. We conduct a systematic review and meta-analysis to explore the treatment efficacy of dapagliflozin versus placebo in patients with type 1 diabetes. Methods: We have searched PubMed, EMbase, Web of science, EBSCO and Cochrane library databases through May 2019 for randomized controlled trials (RCTs) assessing the effect of dapagliflozin versus placebo for type 1 diabetes. This meta-analysis is performed using the random-effect model. Results: Six RCTs are included in the meta-analysis. Overall, compared with control group for type 1 diabetes, dapagliflozin treatment shows favorable impact on glycated hemoglobin HbA1c ( standard mean difference SMD=-3.93; 95% confidence interval CI =-4.44 to -3.48; P<0.00001), HbA1c reduction of 650.5% (risk ratio RR=1.98; 95% CI=1.65 to 2.39; P<0.00001), and fasting plasma glucose FPG (SMD=-0.93; 95% CI=-1.77 to -0.10; P=0.03). There is no statistical difference of hypoglycemia (RR=1.09; 95% CI=0.66 to 1.79; P=0.75) or adverse events (RR=1.07; 95% CI=0.96 to 1.20; P=0.20) between two groups, but the incidence of ketone-related events is higher than those in control group (RR=0.28; 95% CI=3.96 to 11.52; P=0.01). Conclusions: Dapagliflozin treatment benefits to reduce HbA1c and FPG for type 1 diabetes

The cadmium–mercaptoacetic acid complex contributes to the genotoxicity of mercaptoacetic acid-coated CdSe-core quantum dots

Quantum dots (QDs) have many potential clinical and biological applications because of their advantages over traditional fluorescent dyes. However, the genotoxicity potential of QDs still remains unclear. In this paper, a plasmid-based system was designed to explore the genotoxic mechanism of QDs by detecting changes in DNA configuration and biological activities. The direct chemicobiological interactions between DNA and mercaptoacetic acid-coated CdSecore QDs (MAA–QDs) were investigated. After incubation with different concentrations of MAA–QDs (0.043, 0.13, 0.4, 1.2, and 3.6 μmol/L) in the dark, the DNA conversion of the covalently closed circular (CCC) DNA to the open circular (OC) DNA was significantly enhanced (from 13.9% ± 2.2% to 59.9% ± 12.8%) while the residual transformation activity of plasmid DNA was greatly decreased (from 80.7% ± 12.8% to 13.6% ± 0.8%), which indicated that the damages to the DNA structure and biological activities induced by MAA–QDs were concentration-dependent. The electrospray ionization mass spectrometry data suggested that the observed genotoxicity might be correlated with the cadmium–mercaptoacetic acid complex (Cd–MAA) that is formed in the solution of MAA–QDs. Circular dichroism spectroscopy and transformation assay results indicated that the Cd–MAA complex might interact with DNA through the groove-binding mode and prefer binding to DNA fragments with high adenine and thymine content. Furthermore, the plasmid transformation assay could be used as an effective method to evaluate the genotoxicities of nanoparticles

Treatment of avulsion fracture of posterior cruciate ligament tibial insertion by minimally invasive approach in posterior medial knee

ObjectiveThe study aims to explore the feasibility and clinical effect of posterior minimally invasive treatment of cruciate ligament tibial avulsion fracture.MethodsPosterior knee minimally invasive approach was used to treat avulsion fracture of posterior cruciate ligament (PCL) tibia in 15 males and 11 females. The length of the incision, intraoperative blood loss, operation time, postoperative hospital stay, residual relaxation, and fracture healing time were analyzed to evaluate the curative effect, learning curve, and advantages of the new technology. Neurovascular complications were recorded. During the postoperative follow-up, the International Knee Joint Documentation Committee (IKDC), Lysholm knee joint score, and knee joint range of motion were recorded to evaluate the function.ResultsAll 26 patients were followed up for 18–24 months, with an average of 24.42 ± 5.00 months. The incision length was 3–6 cm, with an average of 4.04 ± 0.82 cm. The intraoperative blood loss was about 45–60 ml, with an average of 48.85 ± 5.88 ml. The operation time was 39–64 min, with an average of 52.46 ± 7.64 min. The postoperative hospital stay was 2–5 days, with an average of 2.73 ± 0.87 days. All incisions healed grade I without neurovascular injury. All fractures healed well with an average healing time of 9.46 ± 1.33 weeks (range, 8–12 weeks). The Lysholm score of the affected knee was 89–98 (mean, 94.12 ± 2.49) at 12-month follow-up. The IKDC score was 87–95 with an average of 91.85 ± 2.19, and the knee range of motion was 129–148° with an average of 137.08 ± 5.59°. The residual relaxation was 1–3 mm, with an average of 1.46 ± 0.65 mm.ConclusionThis minimally invasive method provides sufficient exposure for internal fixation of PCL tibial avulsion fractures without the surgical complications associated with traditional open surgical methods. The process is safe, less invasive, and does not require a long learning curve

Insulin Resistance and Oxidative Stress: In Relation to Cognitive Function and Psychopathology in Drug-Naive, First-Episode Drug-Free Schizophrenia

Objective: The present study aimed to examine whether insulin resistance and oxidative stress are associated with cognitive impairment in first-episode drug-free schizophrenia (SZ) patients. Methods: Ninety first-episode SZ patients and 70 healthy controls were enrolled. Fasting insulin (FINS) and markers of oxidative stress [oxidized glutathione (GSSG), superoxide dismutase (SOD), nitric oxide (NO) and uric acid (UA) levels] were measured in serum before pharmacological treatment was initiated. Psychiatric symptoms and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB), respectively. In addition, the homeostatic model assessment of insulin resistance (HOMA-IR) was also studied. Results: HOMA-IR and serum levels of GSSG and NO were significantly higher in SZ patients than in healthy controls (P \u3c 0.001), while the serum levels of SOD were significantly lower than in healthy controls (P \u3c 0.001). HOMA-IR, GSSG and NO levels were significantly correlated to the total cognitive function scores of the patient group (r = -0.345,-0.369,-0.444, respectively, P \u3c 0.05). But these factors were not co-related to the cognitive functions in the healthy control group. And, levels of SOD, UA were not associated with the total cognitive function scores in both the patient and the healthy control groups. NO was positively correlated with general pathological and the total score in the PANSS, and was negatively correlated with six cognitive domains (r = -0.316 to -0.553, P \u3c 0.05). Conclusions: The levels of insulin resistance and oxidative stress are elevated, and correlated with the severity of cognitive impairment in drug-naive, first-episode SZ patients. Treatment approaches targeting on reducing insulin resistance and oxidative stress may improve cognitive function in SZ patients

Machine learning reveals neutrophil-to-lymphocyte ratio as a crucial prognostic indicator in severe Japanese encephalitis patients

Japanese encephalitis (JE) is a severe infectious disease affecting the central nervous system (CNS). However, limited risk factors have been identified for predicting poor prognosis (PP) in adults with severe JE. In this study, we analyzed clinical data from thirty-eight severe adult JE patients and compared them to thirty-three patients without organic CNS disease. Machine learning techniques employing branch-and-bound algorithms were used to identify clinical risk factors. Based on clinical outcomes, patients were categorized into two groups: the PP group (mRs ≥ 3) and the good prognosis (GP) group (mRs ≤ 2) at three months post-discharge. We found that the neutrophil-to-lymphocyte ratio (NLR) and the percentage of neutrophilic count (N%) were significantly higher in the PP group compared to the GP group. Conversely, the percentage of lymphocyte count (L%) was significantly lower in the PP group. Additionally, elevated levels of aspartate aminotransferase (AST) and blood glucose were observed in the PP group compared to the GP group. The clinical parameters most strongly correlated with prognosis, as indicated by Pearson correlation coefficient (PCC), were NLR (PCC 0.45) and blood glucose (PCC 0.45). In summary, our findings indicate that increased serum NLR, N%, decreased L%, abnormal glucose metabolism, and liver function impairment are risk factors associated with poor prognosis in severe adult JE patients

Carnosic Acid Mitigates Early Brain Injury After Subarachnoid Hemorrhage: Possible Involvement of the SIRT1/p66shc Signaling Pathway

Carnosic acid (CA) has been reported to exhibit a variety of bioactivities including antioxidation, neuroprotection, and anti-inflammation; however, the impact of CA on subarachnoid hemorrhage (SAH) has never been elucidated. The current study was undertaken to explore the role of CA in early brain injury (EBI) secondary to SAH and the underlying mechanisms. Adult male Sprague-Dawley rats were perforated to mimic a clinical aneurysm with SAH. CA or vehicle was administered intravenously immediately after the SAH occurred. Mortality, SAH grade, neurologic function scores, brain water content, Evans blue extravasation, and the levels of reactive oxygen species (ROS) levels in the ipsilateral cortex were determined 24 h after the SAH occurred. Western blot, immunofluorescence, Fluoro-Jade C (FJC) and TUNEL staining were also performed. Our results showed that CA decreased ROS levels, alleviated brain edema and blood-brain barrier permeability, reduced neuronal cell death, and promoted neurologic function improvement. To probe into the potential mechanisms. We showed that CA increased SIRT1, MnSOD, and Bcl-2 expression, as well as decreased p66shc, Bax, and cleaved caspase-3 expression. Interestingly, sirtinol, a selective inhibitor of SIRT1, abolished the anti-apoptotic effects of CA. Taken together, these data revealed that CA has a neuroprotective role in EBI secondary to SAH. The potential mechanism may involve suppression of neuronal apoptosis through the SIRT1/p66shc signaling pathway. CA may provide a promising therapeutic regimen for management of SAH