Inhibition of lysine-specific demethylase 1 enhances the sensitivity of the chemotherapeutic drug doxorubicin in gastric cancer cell.

AIM: Lysine-Specific Demethylase 1 (LSD1) inhibitors have been developed and reached the clinic, but its effect in combination with cytotoxic chemotherapy is unclear. Here, we investigated the anti-tumor effect of LSD1 inhibitor GSK-LSD1 and its anti-tumor effect with the DNA damage drug doxorubicin (DOX) in gastric cancer (GC) cells. METHODS: Cells were treated with different concentrations of GSK-LSD1 to examine the anti-tumor effect versus cell viability by MTT and cell cycle arrest by flow cytometry. To explore whether LSD1 inhibitors can increase the anti-tumor effect of DNA damage drugs, cells were treated with DOX for 48 h after pretreatment with GSK-LSD1 for 48 h. Cell viability was detected by MTT and apoptosis-related proteins were examined by Western blot. Furthermore, anti-tumor efficacy of combination GSK-LSD1 with DOX was also measured in MGC-803 xenografts model in nude mice. RESULTS: The results showed that LSD1 was highly expressed in GC cell lines. Inhibition of LSD1 has a weak effect on cell viability and cell cycle. Moreover, LSD1 inhibitors pretreatment could significantly increase the anti-tumor effect of DOX. Further study found that inhibition of LSD1 can significantly enhance DOX-induced the apoptosis, accompanied by down-regulation of antiapoptotic Bcl-2 expression and up-regulation of proapoptotic Bax expression. We also confirmed that inhibition of LSD1 can sensitize the anti-tumor effect of DOX in vivo. CONCLUSION: Our findings suggest that the LSD1 inhibitor GSK-LSD1 has a weak inhibitory effect on the viability and cell cycle of GC cells, but can enhance the sensitivity of DOX.

Clinical outcomes of revision with retrograde intermedullary nailing for failed plating of distal femoral fractures: a retrospective study.

PURPOSE: To assess the feasibility and effectiveness of retrograde intramedullary nail (RIN) revision surgeries for locking compression plate (LCP) failure in distal femoral fractures. METHODS: This retrospective study included 13 patients who suffered from metalwork failures after they initially underwent open reduction and LCP fixation. In patients who eventually underwent RIN revision from January 2014 to December 2016, range of motion (ROM) and Hospital for Special Surgery (HSS) scores obtained before surgery and at the final follow-up time were analysed. RESULTS: The average operative time was 155 minutes (range, 120-210 minutes), and the average blood loss volume was 650 ml (range, 200-1350 ml). There were two cases of complications (15.38%): one was calf muscle vein thrombosis, and the other was a superficial infection. No deep tissue infection or deep vein thrombosis was observed post-operatively. The average follow-up time was 16 months (range, 12-24 months). All fractures healed in a mean of 6.5 months (range, 4-12 months), and one patient underwent an additional bone graft surgery that did not involve a bone graft during the RIN revision operation (this eventually healed at 12 months post-operatively). The mean ROM before the operation was 86.92 ± 12.34°. At the final follow-up, the mean ROM was 112.69 ± 9.27°. There was a significant difference between pre-operative and post-operative ROM (P < 0.01). The mean HSS score improved significantly from 38.85 ± 9.62 points pre-operatively to 79.62 ± 5.42 points post-operatively. There was a significant difference between pre-operative and post-operative HSS scores (P < 0.01). CONCLUSIONS: RIN revision surgery achieved excellent clinical results in patients with LCP failure.

Identification and characterization of stearoyl-CoA desaturase in Toxoplasma gondii.

Few information of the function of stearoyl-coenzyme A (CoA) desaturase (SCD) in apicomplaxan parasite has been obtained. In this study, we retrieved a putative fatty acyl-CoA desaturase (TGGT1_238950) by a protein alignment with Plasmodium falciparum SCD in ToxoDB. A typical Δ9-desaturase domain was revealed in this protein. The putative desaturase was tagged with HA endogenously in Toxoplasma gondii, and the endoplasmic reticulum localization of the putative desaturase was revealed, which was consistent with the fatty acid desaturases in other organisms. Therefore, the TGGT1_238950 was designated T. gondii SCD. Based on CRISPR/Cas9 gene editing technology, SCD conditional knockout mutants in the T. gondii TATi strain were obtained. The growth in vitro and pathogenicity in mice of the mutants suggested that SCD might be dispensable for tachyzoite growth and proliferation. The SCD-overexpressing line was constructed to further explore SCD function. The portion of palmitoleic acid and oleic acid were increased in SCD-overexpressing parasites, compared with the RH parental strain, indicating that T. gondii indeed is competent for unsaturated fatty acid synthesis. The SCD-overexpressing tachyzoites propagated slower than the parental strain, with a decreased invasion capability and weaker pathogenicity in mice. The TgIF2α phosphorylation and the expression changes of several genes demonstrated that ER stress was triggered in the SCD-overexpressing parasites, which were more apt toward autophagy and apoptosis. The function of unsaturated fatty acid synthesis of TgSCD was consistent with our hypothesis. On the other hand, SCD might also be involved in tachyzoite autophagy and apoptosis.

MicroRNA-223 inhibits lipopolysaccharide-induced inflammatory response by directly targeting Irak1 in the nucleus pulposus cells of intervertebral disc.

This study was aimed to research the effect of miR-223 on the inflammatory responses induced by lipopolysaccharide (LPS) in nucleus pulposus (NP) cells of rat intervertebral disc. Isolated rat NP cells were induced by LPS. Reverse transcriptase quantitative real-time polymerase chain reaction was used to detect gene expression. To detect protein expression, Western blot and enzyme-linked immunosorbent assay experiments were applied. The putative targeting relationship between miR-223 and Irak1 was determined using dual-luciferase reporter gene assay. We found that miR-223 was downregulated in LPS-induced NP cells. MiR-223 upregulated the expression of extracellular matrix-related genes (Aggrecan and Collagen II). Matrix degrading enzymes (ADAMTS4, ADAMTS5, MMP3 and MMP13), NO reaction-associated proteins (PGE2, COX-2 and INOS) and the expression of nuclear factor (NF)-κB signaling-related proteins were downregulated after miR-233 overexpression. In addition, luciferase reporter assays demonstrated that miR-223 directly targeted Irak1. MiR-223 overexpression could inhibit NF-κB signaling by targeting Irak1, and finally suppress the LPS-induced inflammation in NP cells. © 2018 IUBMB Life, 70(6):479-490, 2018.

Moderate selenium dosing inhibited chromium (VI) toxicity in chicken liver.

This study aimed to clarify the effect of selenium (Se) on chromium (VI) [Cr(VI)]-induced damage in chicken liver. A total of 105 chickens were randomly divided into seven groups of 15. Group I received deionized water; group II received Cr(VI) (7.83 mg/kg/d) alone; and other groups orally received both Cr(VI) (7.83 mg/kg/d) and Se of different doses (0.14, 0.29, 0.57, 1.14, and 2.28 mg/kg/d). The levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), Ca2+ -ATPase, and mitochondrial membrane potential (MMP) were measured. Results showed that Cr(VI) increased MDA content and decreased GSH content, T-SOD activity, Ca2+ -ATPase activity, and MMP level. Meanwhile, Se co-treatment (0.14, 0.29, and 0.57 mg/kg/d) increased the viability of the above indicators compared with Cr(VI)-treatment alone. In addition, histopathologic examination revealed that Cr(VI) can cause liver damage, whereas Se supplementation of moderate dose inhibited this damage. This study confirmed that Se exerted protective effect against Cr(VI)-induced liver damage.

Sterculic Acid and Its Analogues Are Potent Inhibitors of Toxoplasma gondii.

Toxoplasmosis is a serious disease caused by Toxoplasma gondii, one of the most widespread parasites in the world. Lipid metabolism is important in the intracellular stage of T. gondii. Stearoyl-CoA desaturase (SCD), a key enzyme for the synthesis of unsaturated fatty acid is predicted to exist in T. gondii. Sterculic acid has been shown to specifically inhibit SCD activity. Here, we examined whether sterculic acid and its methyl ester analogues exhibit anti-T. gondii effects in vitro. T. gondii-infected Vero cells were disintegrated at 36 hr because of the propagation and egress of intracellular tachyzoites. All test compounds inhibited tachyzoite propagation and egress, reducing the number of ruptured Vero cells by the parasites. Sterculic acid and the methyl esters also inhibited replication of intracellular tachyzoites in HFF cells. Among the test compounds, sterculic acid showed the most potent activity against T. gondii, with an EC50 value of 36.2 µM, compared with EC50 values of 248-428 µM for the methyl esters. Our study demonstrated that sterculic acid and its analogues are effective in inhibition of T. gondii growth in vitro, suggesting that these compounds or analogues targeting SCD could be effective agents for the treatment of toxoplasmosis.

Angiotensin-(1-7) treatment mitigates right ventricular fibrosis as a distinctive feature of diabetic cardiomyopathy.

In diabetic patients, left ventricular (LV) remodeling is highly prevalent; however, little is known about the impact of diabetes on right ventricular (RV) structure and function. We recently found that overexpression of angiotensin (ANG)-converting enzyme 2 (ACE2), which metabolizes ANG-II to ANG-(1-7) and ANG-I to ANG-(1-9), may improve LV remodeling in diabetic cardiomyopathy (DCM). Here, we aimed to assess whether LV remodeling and dysfunction are paralleled by RV alterations and the effects of ANG-(1-7) on RV remodeling in DCM. After 12 wk of diabetes induced by a single intraperitoneal injection of streptozotocin, rats were treated with saline, ANG-(1-7), perindopril, ANG-(1-7) plus perindopril, ANG-(1-7) plus Mas receptor antagonist A779, or ANG-(1-7) plus ANG-II type 2 receptor antagonist PD123319 for 4 wk. RV remodeling in diabetic rats was indicated by fibrosis of the RV free wall in the absence of hypertrophy and apoptosis. Treatment with ANG-(1-7) prevented diabetes-induced RV fibrosis and dysfunction. ANG-(1-7) (800 ng·kg(-1)·min(-1)) was superior to perindopril in improving RV fibrosis. The major mechanisms involved a complex interaction of ANG-II type 2 and Mas receptors for subsequent downregulation of ACE expression and activity and ANG-II type 1 receptor expression, as well as upregulation of ACE2 expression and activity and the expression of ANG-II type 2 receptor and sarco(endo)plasmic reticulum Ca(2+)-ATPase. Thus RV fibrosis and dysfunction plays a central role in DCM, and ANG-(1-7) mitigates diabetes-induced RV alterations.

Van der Waals coefficients beyond the classical shell model.

Van der Waals (vdW) coefficients can be accurately generated and understood by modelling the dynamic multipole polarizability of each interacting object. Accurate static polarizabilities are the key to accurate dynamic polarizabilities and vdW coefficients. In this work, we present and study in detail a hollow-sphere model for the dynamic multipole polarizability proposed recently by two of the present authors (JT and JPP) to simulate the vdW coefficients for inhomogeneous systems that allow for a cavity. The inputs to this model are the accurate static multipole polarizabilities and the electron density. A simplification of the full hollow-sphere model, the single-frequency approximation (SFA), circumvents the need for a detailed electron density and for a double numerical integration over space. We find that the hollow-sphere model in SFA is not only accurate for nanoclusters and cage molecules (e.g., fullerenes) but also yields vdW coefficients among atoms, fullerenes, and small clusters in good agreement with expensive time-dependent density functional calculations. However, the classical shell model (CSM), which inputs the static dipole polarizabilities and estimates the static higher-order multipole polarizabilities therefrom, is accurate for the higher-order vdW coefficients only when the interacting objects are large. For the lowest-order vdW coefficient C6, SFA and CSM are exactly the same. The higher-order (C8 and C10) terms of the vdW expansion can be almost as important as the C6 term in molecular crystals. Application to a variety of clusters shows that there is strong non-additivity of the long-range vdW interactions between nanoclusters.

MIC3, a novel cross-protective antigen expressed in Toxoplasma gondii and Neospora caninum.

Microneme protein 3 (MIC3) is an important adhesion molecule expressed by Toxoplasma gondii and Neospora caninum that plays a crucial role in invasion. In our study, we found that recombinant TgMIC3 (rTgMIC3) was recognized by both T. gondii-reactive sera and hyper-immune serum against N. caninum. Polyclonal antibodies against TgMIC3 reacted with N. caninum by western blot and immunofluorescence assay (IFA). These results indicate that MIC3 is a novel cross-reactive antigen expressed in N. caninum and T. gondii. To evaluate the immune-protective effect of TgMIC3, we created the eukaryotic expression vector pcDNA3.1-TgMIC3, transfected this vector into HEK293T cells by lipofection, and evaluated TgMIC3 expression in HEK293T cells using western blot and IFA. Then, groups of BALB/c mice were immunized with recombinant TgMIC3 protein, pcDNA3.1-TgMIC3, or two-vaccine immunization. The mice were challenged with T. gondii RH or N. caninum Nc-1 tachyzoites 14 days after the final immunization. The survival time of T. gondii-infected mice was recorded, and the parasite burden in the brain of N. caninum-infected mice 30 days post-infection was measured using real-time PCR. The results demonstrated that mice immunized with TgMIC3-based vaccines elicited high antibody titers. After parasitic challenge, mice immunized with pcDNA-TgMIC3 exhibited prolonged survival when infected with T. gondii tachyzoites and a lower parasitic burden in the brains of mice challenged with N. caninum tachyzoites. These results demonstrate that TgMIC3 is a cross-protective antigen expressed in T. gondii and N. caninum and could elicit some protection against toxoplasmosis and neosporosis.

Improved synthesis and biological evaluation of Tc-99m radiolabeled AMO for miRNA imaging in tumor xenografts.

MicroRNAs (miRNAs) have been considered as important biomarkers for malignant tumors. In this study, we introduced an improved (99m)Tc labeling method for noninvasive visualization of overexpressed miRNAs in tumor-bearing mice. Anti-miRNA-21 oligonucleotide (AMO) with partial 2'-O-methyl and phosphorothioate modification was designed and chemically synthesized. After conjugated with NHS-MAG3, AMO was labeled with (99m)Tc. Optimization was made to shorten reaction time and to improve labeling efficiency. Labeling efficiency was 97%, and specific activity was 2.78 MBq/ng. During 12 h, (99m)Tc-AMO showed no significant degradation by gel electrophoresis. Its radiochemical purity was stable, between 95.8% and 99.1%. Further, (99m)Tc-AMO decreased the level of miR-21 and increased the expression of PTEN protein at cellular level, shown by qRT-PCR and Western blot. Fluorescent protein labeled AMO displayed specific distribution and good stability in tumor cells. After the administration in tumor-bearing mice, (99m)Tc-AMO showed more radioactive uptake in the miR-21 over-expressed tumors than scramble control. Biodistribution results further proved the significant difference of tumor uptake between (99m)Tc-AMO and (99m)Tc-control. Therefore, this study presents an improved method with shorten time to prepare a (99m)Tc radiolabeled AMO. In addition, it supports the role of (99m)Tc-AMO for noninvasive visualization of miR-21 in malignant tumors.

Angiotensin-(1-7) dose-dependently inhibits atherosclerotic lesion formation and enhances plaque stability by targeting vascular cells.

OBJECTIVE: To test the hypothesis that chronic infusion of angiotensin-(1-7) [Ang-(1-7)] may dose-dependently inhibit atherosclerotic lesion formation by targeting vascular smooth muscle cells and a large dose of Ang-(1-7) may stabilize mature plaque by targeting macrophages. APPROACH AND RESULTS: In vivo, the effects of Ang-(1-7) on atherogenesis and plaque stability were observed in ApoE(-/-) mice fed a high-fat diet and chronic angiotensin II infusion. In vitro, the effects of Ang-(1-7) on vascular smooth muscle cells' proliferation and migration, and macrophage inflammatory cytokines were examined. Ang-(1-7) dose-dependently attenuated early atherosclerotic lesions and inhibited vascular smooth muscle cells' proliferation and migration via suppressing extracellular regulated protein kinase/P38 mitogen-activated protein kinase and janus kinase/signal transducers and activators of transcription activities and enhancing smooth muscle 22α and angiotensin II type 2 receptor expression. Ang-(1-7) treatment resulted in high contents of collagen and vascular smooth muscle cells, and low contents of macrophages and lipids in carotid mature plaques. Ang-(1-7) lowered the expression levels of proinflammatory cytokines and activities of matrix metalloproteinases in mature plaques. CONCLUSIONS: Ang-(1-7) treatment inhibits early atherosclerotic lesions and increases plaque stability in ApoE(-/-) mice, thus providing a novel and promising approach to the treatment of atherosclerosis.

Study on the Influence of Metal Substrates on Protective Performance of the Coating by EIS.

The degradation process of a red iron oxide epoxy coating on three kinds of metals under a periodic cycling exposure to 3.5 wt% NaCl solution (45 °C 12 h + 25 °C 12 h) was comparatively studied using electrochemical impedance spectroscopy (EIS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD) methods. The influence of the metal substrates (carbon steel, brass, and Al alloy) on the protection performance of the coating was analyzed using variations in the electrochemical and chemical parameters. The failure criteria of the coating were discussed. The results show that the coating on the three substrates presents different failure times, with the coating on steel presenting the shortest time and the coating on Al alloy the longest time. The characteristics of metal substrates and their corrosion products influence the coating failure behavior. The corrosion products with loose and hygroscopic properties of steel and brass have promoting effects on the diffusion of water through the coating. The passive film of the Al alloy substrate and the formation of salt film containing Cl- have corrosion-inhibiting effects on the substrate. Evaluation of the coating performance by |Z|0.01Hz should consider the characteristics of the metal substrates.

Density functionals that recognize covalent, metallic, and weak bonds.

Computationally efficient semilocal approximations of density functional theory at the level of the local spin density approximation (LSDA) or generalized gradient approximation (GGA) poorly describe weak interactions. We show improved descriptions for weak bonds (without loss of accuracy for strong ones) from a newly developed semilocal meta-GGA (MGGA), by applying it to molecules, surfaces, and solids. We argue that this improvement comes from using the right MGGA dimensionless ingredient to recognize all types of orbital overlap.

Enhanced tumor inhibiting effect of 131I-BDI-1-based radioimmunotherapy and cytosine deaminase gene therapy modulated by a radio-sensitive promoter in nude mice bearing bladder cancer.

Radioimmunotherapy (RIT) has great potential in cancer therapy. However, its efficacy in numerous tumors is restricted due to myelotoxicity, thereby limiting the dose of radionuclide. To increase tumor radiosensitivity, we incorporated the recombinant lentivirus into the EJ cells (bladder cancer [BC] cells), and examined the combined anti-tumor effects of RIT with 131I-BDI-1(131I-monoclonal antibody against human BC-1) and gene therapy (GT). The recombinant lentivirus was constructed and packed. The animal xenograft model was built and when the tumor reached about 0.5 cm in diameter, the mice were randomly separated into four groups: (1) RIT + GT: the xenografts were continuously incorporated with the recombinant lentivirus for two days. And 7.4 MBq 131I-BDI-1 was IV-injected, and 10 mg prodrug 5-fluorocytosine (FC) was IV-injected for 7 days, (2) RIT: same dose of 131I-BDI-1 as the previous group mice, (3) GT: same as the first group, except no 131I-BDI-1, and (4) Untreated. Compute tumor volumes in all groups. After 28 days the mice were euthanized and the tumors were extracted and weighed, and the inhibition rate was computed. The RIT + GT mice, followed by the RIT mice, exhibited markedly slower tumor growth, compared to the control mice. The tumor size was comparable between the GT and control mice. The tumor inhibition rates after 28 days of incubation were 42.85 ± 0.23%, 27.92 ± 0.21% and 0.57 ± 0.11% for the four groups, respectively. In conclusion, RIT, combined with GT, suppressed tumor development more effectively than RIT or GT alone. This data highlights the potent additive effect of radioimmune and gene therapeutic interventions against cancer.

Graphene oxide-assisted optimized narrow-thermal-cycling amplification for accurate detection of Salmonella spp.

Salmonella is a rod-shaped, Gram-negative zoonotic pathogen that poses a serious global socioeconomic and public health threat. Rapid and accurate detection of Salmonella spp. is critical for effective control of its infection. In this study, an accurate, sensitive and specific graphene oxide-assisted accelerated strand exchange amplification (GO-ASEA) method for rapid detection of Salmonella spp. was developed and validated. The detection limit of the GO-ASEA method was 8.6 × 101 fg µL-1 of Salmonella genomic DNA or 1 × 101 CFU g-1 of Salmonella in spiked chicken faeces free of pre-enrichment. And the GO-ASEA method could specifically detect Salmonella spp. without cross-reactivity with other enteric pathogens. In addition, the novel method achieved Salmonella detection within 30 min and was validated using 209 clinical samples, showing its good clinical applicability. Therefore, the GO-ASEA method is a new optional tool for the rapid detection of pathogenic microorganisms, which is ideal for food safety monitoring and high-throughput detection.

Public health preparedness for the world's largest mass gathering: 2010 World Exposition in Shanghai, China.

The 2010 World Exposition in Shanghai China (Expo) was the largest mass gathering in world history, attracting a record 72 million visitors. More than 190 countries participated in the Expo, along with more than 50 international organizations. The 2010 Expo was six months in duration (May 1 through October 30, 2010), and the size of the venue site comprised 5.28 square kilometers. Great challenges were imposed on the public health system in Shanghai due to the high number and density of visitors, long duration of the event, and other risk factors such as high temperatures, typhoon, etc. As the major metropolitan public health agency in Shanghai, the Shanghai Municipal Center for Disease Control and Prevention (SCDC) implemented a series of actions in preparing for, and responding to, the potential health impact of the world's largest mass gathering to date, which included partnerships for capacity building, enhancement of internal organizational structure, risk assessment, strengthened surveillance, disaster planning and exercises, laboratory management, vaccination campaign, health education, health intervention, risk communication and mass media surveillance, and technical support for health inspection. The clear-cut organizational structures and job responsibilities, as well as comprehensive operational and scientific preparations, were key elements to ensure the success of the 2010 World Exposition.

Ponicidin Treatment Improved the Cell Proliferation, Differentiation, and Calcium Mineralization on the Osteoblast-Like MG-63 Cells.

Osteoporosis is a general bone-related ailment characterized by reduced bone density and quality, elevated bone fragility, and fractures. It was reported that both aged men and women has an increased risks of osteoporosis. The current research work focused to unveil the beneficial roles of ponicidin treatment in the proliferation and calcium deposition on the osteoblast-like MG-63 cells. The effect of 5 and 10 µg/ml of ponicidin on the cell proliferation was assessed. The viability of ponicidin-supplemented MG-63 cells was inspected by MTT test. The contents of osteocalcin, collagen, and ALP activity in the ponicidin administered cells were assessed by kits. The level of calcium mineralization was examined by ARS staining technique. The ponicidin treatment remarkably improved the proliferation of MG-63 cells. The ponicidin did not affect the MG-63 cells viability but promoted its viability 24- and 48-h treatment. The contents of osteocalcin, collagen, and ALP activity in the 5 and 10 µg/ml of ponicidin-supplemented MG-63 cells were found increased than the control cells. The ponicidin also increased the level of calcium deposition in MG-63 cells, which is assessed by ARS staining. In conclusion, it was clear that ponicidin improved the proliferation and calcium mineralization in a MG-63 cells. Therefore, it was clear that ponicidin has helpful roles on the new bone development as a hopeful therapeutic candidate to treat the bone-related disease like osteoporosis.

Meta-analysis of aldehyde dehydrogenase 2 gene polymorphism and Alzheimer's disease in East Asians.

BACKGROUND: The association of genetic polymorphism of mitochondrial aldehyde dehydrogenase 2 (ALDH2) and Alzheimer's disease (AD) has been controversial and has been investigated only in several small-sample studies. In the present study, we performed a meta-analysis to evaluate the cross-sectional association of ALDH2 variants and AD risk in East Asian populations. METHODS: Trials were retrieved through MEDLINE, EMBASE, J-STAGE and the China National Knowledge Internet databases (from January 1, 1994 to November 1, 2010) without any restriction on language. Data were abstracted by a standardized protocol. RESULTS: We found four studies of 821AD patients and 1380 healthy controls that qualified for the analysis. The variant ALDH2 genotype GA/AA was not associated with increased AD risk (odds ratio (OR) = 1.35; 95% confidence interval (CI) = 0.75-2.42; p = 0.32), even after stratification for the status of apolipoprotein E epsilon 4 allele. However, in the subgroup analyses, the association was significant for men (OR = 1.72; 95% CI = 1.10-2.67; p = 0.02). CONCLUSIONS: This study adds to the evidence that ALDH2 GA/AA genotype increases the risk of AD among East Asian men, although the effect size is moderate.

Efficacy and safety of intensive insulin therapy for critically ill neurologic patients: a meta-analysis.

BACKGROUND: Whether intensive insulin therapy (IIT) may improve clinical outcomes for patients admitted to intensive care units, especially critically ill neurologic patients, is still debated. In the present study, we performed a meta-analysis of literature comparing the efficacy and safety of IIT and conventional insulin therapy (CIT) for critically ill neurologic patients in terms of mortality, infection rate, neurologic outcome, and hypoglycemia. METHODS: We searched for published reports of studies of randomized control trials (up to March 10, 2011) of patients admitted to neurologic intensive care units and investigated an IIT (target of blood glucose control <120 mg/dL) with a control of CIT. Data were abstracted by a standardized protocol. RESULTS: We retrieved reports of five studies involving 924 patients. The risk of mortality, infection rate, and neurologic outcome did not differ with IIT or CIT. However, the incidence of hypoglycemic episodes was significantly higher with IIT than CIT (78.8% vs. 48.9%), with a relative risk of 2.62 (95% confidence interval [CI]: 1.07-6.43; p < 0.04). CONCLUSIONS: As compared with CIT, IIT may not benefit critically ill neurologic patients in terms of mortality, infection rate, or neurologic outcome and in fact may be associated with increased hypoglycemic complications. Therefore, IIT cannot be recommended over conventional control for critical neurologic disease, but further study is warranted.