Efficacy and safety of venetoclax in patients with relapsed/refractory multiple myeloma: a meta-analysis.

BACKGROUND: Venetoclax is clinically active in treating relapsed/refractory multiple myeloma (RRMM). This study evaluated the efficacy and safety of venetoclax or venetoclax with other agents in treating RRMM. METHODS: PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched. We included studies investigating the efficacy and safety of venetoclax or venetoclax with other agents in treating RRMM. Overall response rates (ORR), stringent complete response rates (sCR), complete response rates (CR), very good partial response rates (VGPR), partial response rates (PR), stable disease (SD), progressive disease (PD) and adverse events were synthesized using either a random-effects model or a fixed-effects model. RESULTS: A total of 7 clinical trials with 482 patients with RRMM were included. Concerning venetoclax with other agents, the pooled ORR, sCR, CR, VGPR, PR, SD, and PD were 0.76 (95% CIs: 0.62, 0.87), 0.11 (95% CIs: 0.04, 0.21), 0.18 (95% CIs: 0.11, 0.26), 0.16 (95% CIs: 0.12, 0.25), 0.29 (95% CIs: 0.25, 0.34), 0.07 (95% CIs: 0.05, 0.10), and 0.11 (95% CIs: 0.04, 0.23). The overall rate of adverse events ≥ Grade 3 was 0.84 (95% CIs: 0.77, 0.91). The most common non-hematologic adverse events were nausea, diarrhea, fatigue, back pain, and vomiting; hematologic adverse events included thrombocytopenia, neutropenia, anemia, leukopenia, and lymphopenia. CONCLUSIONS: This study indicates that venetoclax alone or in combination with other agents reveals favorable treatment responses and acceptable adverse events in treating RRMM.

Load Effect of Automated Truck Platooning on Highway Bridges and Loading Strategy.

Automated truck platooning (ATP) has gained growing attention due to its advantage in reducing fuel consumption and carbon emissions. However, it poses serious challenges to highway bridges due to the load effect of multiple closely spaced heavy-duty trucks on the bridge. In China, ATP also has great application prospects in the massive and ever-increasing highway freight market. Therefore, the load effects of ATP on bridges need to be thoroughly investigated. In this study, typical Chinese highway bridges and trucks were adopted. ATP load models were designed according to the current Chinese road traffic regulations. The load effects of ATP on highway bridges were calculated using the influence line method and evaluated based on the Chinese bridge design specifications. Results show that the load effect of ATP on bridges increases with the increase in the gross vehicle mass and the truck platooning size but decreases with the increasing inter-truck spacing and the critical wheelbase. The Grade-I (best quality standard) highway bridges are generally capable of withstanding the ATP loads, while caution should be exercised for other bridges. Strategies for preventing serious adverse impacts of ATP load on highway bridges are proposed.

Therapeutic Effects of Hydrogen Sulfide in Treating Delayed Encephalopathy After Acute Carbon Monoxide Poisoning.

Carbon monoxide (CO) poisoning is one of the most common diseases induced by CO injury. More than a half of the survivors still likely to have cognitive dysfunction, which is delayed encephalopathy after acute CO poisoning. There is no other effective treatment for delayed encephalopathy after acute CO poisoning except hyperbaric oxygen. Hydrogen sulfide is a novel signal molecule for the central nervous system regulation and plays a role of neural protection in many diseases. H2S has the inhibitory effects on oxidative stress and apoptosis to protect against oxidative damage of nerve. A CO-poisoning rat model was established to detect the effect of H2S on delayed encephalopathy after acute CO poisoning. Spatial learning and memory was tested by Morris water maze. Nissl staining and terminal deoxynucleotidyl transferase-mediated nick end labeling assay were used to examine apoptosis induced by CO poisoning in the brain. Then, the protein levels of proinflammatory cytokines and the indicators of oxidative damage were measured. We found that H2S significantly improved cognitive function, reduced apoptosis and the inflammatory response, and decreased the oxidative damage induced by CO poisoning in rats. These results suggest that H2S may be a novel specific and effective treatment of delayed encephalopathy of CO poisoning.

[Effects of food waste biogas residue composting on soil aggregates and its organic matter content in relocation site]. / åŽ¨ä½™åžƒåœ¾æ²¼æ¸£å †è‚¥å¯¹æ¬è¿åœ°åœŸå£¤å›¢èšä½“åŠå ¶æœ‰æœºè´¨å«é‡çš„å½±å“.

Understanding the effects of food waste biogas residue composting and chemical amendments on soil aggregates composition of different particle sizes, stability, and organic matter distribution in relocation sites could provide primary data for improving soil quality and land utilization of food waste biogas residue composting. We analyzed the characteristics of soil aggregates distribution, stability of aggregates, and organic matter content in different particle sizes under treatments with different application amounts of food waste biogas residue composting, chemical amendments (ß-cyclodextrin, calcium sulfate and ferric oxide were mixed at a mass ratio of 1:1:1), and control (100% soil). The results showed that 20% (soil: biogas residue composting=8:2) and 30% (soil: biogas residue composting =7:3) biogas residue composting significantly decreased the micro-aggregates content with the particle size of <0.106 mm and increased the large aggregates content with the particle size of 0.5-1.0 mm. All treatments significantly increased large aggregates content with the particle size of ≥2.0 mm, soil aggregate structure content, and mean weight diameter, but reduced the percentage of aggregate destruction. Among all the treatments, the effect of mixes application of 20% biogas residue composting and chemical amendments was the best. Biogas residue composting treatments significantly affected the distribution of organic matter in soil aggregates, with the strongest effect under 30% biogas residue composting treatment. Biogas residue composting treatments significantly increased soil organic matter content in all aggregates, with the maximal increase of organic matter content in soil micro-aggregates with the particle size of 0.106-0.25 mm. In conclusion, biogas residue composting could increase organic matter content of soil aggregates in different particle sizes, promote the formation of large soil aggregates, and improve the stability of aggregation. Specifically, the mixed application of biogas residue composting and chemical amendments performed better on soil improvement in relocation site.

In Situ Precision Cell Electrospinning as an Efficient Stem Cell Delivery Approach for Cutaneous Wound Healing.

Mesenchymal stem cell (MSC) therapies have been brought forward as a promising treatment modality for cutaneous wound healing. However, current approaches for stem cell delivery have many drawbacks, such as lack of targetability and cell loss, leading to poor efficacy of stem cell therapy. To overcome these problems, in the present study, an in situ cell electrospinning system is developed as an attractive approach for stem cell delivery. MSCs have a high cell viability of over 90% even with a high applied voltage of 15 kV post-cell electrospinning process. In addition, cell electrospinning does not show any negative effect on the surface marker expression and differentiation capacity of MSCs. In vivo studies demonstrate that in situ cell electrospinning treatment can promote cutaneous wound healing through direct deposition of bioactive fish gelatin fibers and MSCs onto wound sites, leading to a synergic therapeutic effect. The approach enhances extracellular matrix remodeling by increasing collagen deposition, promotes angiogenesis by increasing the expression of vascular endothelial growth factor (VEGF) and forming small blood vessels, and dramatically reduces the expression of interleukin-6 (IL-6) during wound healing. The use of in situ cell electrospinning system potentially provides a rapid, no touch, personalized treatment for cutaneous wound healing.

The complete mitochondrial genome of Rhinogobius maculagenys (Gobiidae:Gobionellinae).

The complete mitochondrial genome of Rhinogobius maculagenys Wu et al., (Perciformes,Gobiidae) was sequenced and annotated in this study. The circular mitogenome is 16,500 bp long and consists of 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes and two main non-coding regions (a putative control region and an L-strand replication origin). The overall base composition is 27.5% A, 25.5% T, 16.9% G, and 30.1% C. The gene order and composition are similar to those of other Gobionellinae species. Phylogenetic analysis revealed that R. maculagenys is closely related to Rhinogobius shennongensis in both the maximum likelihood tree and the Bayesian inference tree. The complete mitogenome of R. maculagenys will serve as a valuable resource for future studies on evolution, taxonomy, and genetic conservation of Rhinogobius.

Losartan and pioglitazone ameliorate nephropathy in experimental metabolic syndrome rats.

It is well known that metabolic syndrome (MS) is a risk factor for proteinuria and chronic kidney disease. Losartan (angiotensin II receptor blocker, ARB) and pioglitazone (peroxisome proliferator-activated receptor-γ, PPARγ agonist) have been shown to confer renoprotection. However, to date, whether or not an ARB and a PPARγ agonist have synergistic renoprotective effects remains controversial. Thus, the present study was designed to evaluate a combined treatment with losartan and pioglitazone in Sprague-Dawley rats fed with a high-fat, high-salt (HFS) diet and 20% sucrose solution for 16 weeks, an animal model of MS accompanying with renal lesions. Losartan, pioglitazone, and their combination were orally administered in the MS rats from 8 weeks to the end of this study. At 16 weeks, the MS rats showed the elevation in systolic blood pressure (SBP), urinary albumin excretion (UAE), and glomerulosclerosis (GS) score, but creatinine clearance, urinary protein excretion, and score of tubulointerstitial damage were not affected. Renal vascular endothelial growth factor (VEGF) protein level, mRNA and protein expression, which were respectively measured by enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analysis, were obviously decreased in the MS rats. Treatment with the combination of losartan and pioglitazone provided synergistic effects in reducing the SBP, UAE, and GS score when compared with monotherapy. These effects were not associated with ameliorated the downregulation of renal VEGF expression. Our data suggest that combined treatment with losartan and pioglitazone may offer additional advantages in treating MS nephropathy.

Diversity patterns and drivers of soil microbial communities in urban and suburban park soils of Shanghai, China.

BACKGROUND: The rapid expansion of urbanization leads to significant losses of soil ecological functions. Microbes directly participate in key soil processes and play crucial roles in maintaining soil functions. However, we still have a limited understanding of underlying mechanisms shaping microbial communities and the interactions among microbial taxa in park soils. METHODS: In this study, the community variations of bacteria and fungi in urban and suburban park soils were investigated in Shanghai, China. Real-time PCR and high-throughput Illumina sequencing were used to examine the microbial abundance and community composition, respectively. RESULTS: The results showed that soil molecular biomass and fungal abundance in urban park soils were significantly higher than those in suburban park soils, while no significant difference was observed in the bacterial abundance between urban and suburban park soils. The alpha diversity of soil microbes in urban and suburban park soils was similar to each other, except for Chao1 index of fungal communities. The results of similarity analysis (ANOSIM) revealed remarkable differences in the composition of bacterial and fungal communities between urban and suburban park soils. Specifically, park soils in urban areas were enriched with the phyla Methylomirabilota and Verrucomicrobiota, while the relative abundance of Gemmatimonadota was higher in suburban park soils. Moreover, the fungal class Eurotiomycetes was also enriched in urban park soils. Compared with suburban park soils, nodes and average paths of the bacterial and fungal networks were higher in urban park soils, but the number of module hubs and connectors of the bacterial networks and negative interactions among bacterial taxa were lower. Compared with suburban park soils, Acidobacteriota bacterium and Mortierellomycota fungus played more important roles in the ecological networks of urban park soils. Soil available zinc (Zn), available nitrogen (N), pH, and total potassium (K) significantly affected fungal community composition in park soils in Shanghai. Soil available Zn was also the most important factor affecting the bacterial community composition in this study. CONCLUSION: There were significant differences in the soil molecular biomass, fungal abundance, and the community composition and co-occurrence relations of both soil bacterial and fungal communities between urban and suburban park soils. Soil available Zn played an important part in shaping the structures of both the bacterial and fungal communities in park soils in Shanghai.

Analysis of the Effect of Proton-Pump Inhibitors on the Course of COVID-19.

OBJECTIVE: This study is to evaluate the effect of proton-pump inhibitors on the course of COVID-19. METHODS: Clinical data of moderate COVID-19 patients admitted to the Shanghai Public Health Clinical Center for treatment from January 20, 2020, to March 16, 2020, were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton-pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by Cox proportional hazards (PH) regression models and the propensity score matching method. RESULTS: A total of 154 patients with moderate COVID-19 were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton-pump inhibitor group, and 119 patients (77.3%) in the control group. In the proton-pump inhibitor group and the control group, the duration of the SARS-CoV-2 clearance was 7 days (95% CI, 6-9) and 7 days (95% CI, 6-11), and the duration of the hospital stay was 21 days (95% CI, 16-25) and 20 days (95% CI, 15-26), respectively. There was no significant difference between the both groups in the cumulative incidence of the SARS-CoV-2 clearance and the discharge, and the same results were obtained after the propensity score matching, all P > 0.05. There was no significant association between the use of proton-pump inhibitors and the duration of SARS-CoV-2 clearance, according to univariate analysis (HR, 1.309; 95% CI, 0.893-1.918) and multivariate analysis (HR, 1.575; 95% CI, 0.993-2.499). There was no significant association between the use of proton-pump inhibitors and the duration of hospital stay for COVID-19, according to univariate analysis (HR, 1.044; 95% CI, 0.714-1.528) and multivariate analysis (HR, 1.064; 95% CI, 0.651-1.740). CONCLUSION: The use of proton-pump inhibitors has no effect on prolonging or shortening the course of adults hospitalized with COVID-19.

Decitabine inhibits the proliferation of human T-cell acute lymphoblastic leukemia molt4 cells and promotes apoptosis partly by regulating the PI3K/AKT/mTOR pathway.

T cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematological cancer; however, there is a lack of effective chemotherapeutic or targeted drugs for the treatment of T-ALL. Decitabine is a DNA demethylation agent but it has not been used for T-ALL treatment. Therefore, the present study aimed to assess the inhibitory effect of decitabine on T-ALL molt4 cells and determine its regulatory role in the PI3K/AKT/mTOR pathway. Molt4 cells were stimulated with decitabine in vitro, after which cell proliferation, apoptosis and cell cycle analyses were performed to assess cell viability. Subcellular morphology was observed using transmission electron microscopy. Expression levels of phosphate and tension homology (PTEN), genes involved in the PI3K/AKT/mTOR pathway and the corresponding downstream genes were analyzed using reverse transcription-quantitative PCR and western blotting. The results showed that decitabine induced apoptosis, inhibited proliferation and arrested molt4 cells in the G2 phase. Following decitabine intervention, an increase in the number of lipid droplets, autophagosomes and mitochondrial damage was observed. At concentrations of 1 and 10 µM, decitabine downregulated the expression of PI3K, AKT, mTOR, P70S6 and eukaryotic initiating factor 4E-binding protein 1, which in turn upregulated PTEN expression; however, 50 µM decitabine downregulated PTEN levels. Overall, these results demonstrated that decitabine reduced the viability of molt4 cells partly by inhibiting the PI3K/AKT/mTOR pathway via PTEN, especially at low decitabine concentrations.

The effect of rat nerve growth factor combined with vitamin B on peripheral neuropathy in multiple myeloma patients.

Background: Peripheral neuropathy can induce marked disability and negative effects on quality of life and is the most common therapy-related complication in multiple myeloma patients treated with bortezomib. Currently, there is no useful method to prevent or treat it. So, it is necessary to study the clinical efficacy of rat nerve growth factor combined with vitamin B for the treatment of peripheral neuropathy in multiple myeloma patients. Methods: Sixty multiple myeloma patients who developed peripheral neuropathy after bortezomib-based chemotherapy in Jiaxing First Hospital from October 2015 to May 2018 were randomly divided into treatment and control groups. Changes in serum NGF level and electromyograms before and after treatment were analyzed, and the effects were evaluated via a FACT/GOG-Ntx questionnaire score. Results: After treatment, the NGF level in the treatment group (13.2 ± 3.73 pg/ml) was higher than that in the control group (9.22 ± 2.93 pg/ml, P < 0.05). Improvements in the electromyograms were more pronounced in treatment group than those in the control group, with statistical significance. The FACT/GOG-Ntx questionnaire scores, both in the treatment group and the control group, were decreased (4.00 ± 1.58 vs. 5.20 ± 2.33; P < 0.05), and the alleviation of the symptoms in the treatment group were more obvious. Conclusion: Rat nerve growth factor combined with vitamin B is a safe and effective method for treating peripheral neuropathy in multiple myeloma patients.

Characterization of a 4 lncRNAs-based prognostic risk scoring system in adults with acute myeloid leukemia.

PURPOSE: The study aims to develop a prognostic scoring system based on prognostic lncRNAs for acute myeloid leukemia (AML). METHODS: Based on lncRNA expression profiles downloaded from The Cancer Genome Atlas (TCGA), differentially expressed long noncoding RNAs (DELs) between good prognosis and bad prognosis samples were screened, from which prognosis-related lncRNAs were selected using uni-variate and multi-variate Cox regression analysis. Based on the expression profiles of these signature prognosis-related lncRNAs, a risk scoring system was developed and applied to a training set and validated on a testing set. With sample-matched mRNAs of the signature lncRNAs, lncRNA-mRNA networks were built, followed by function analysis for the mRNAs in these networks. RESULT: Total 66 DELs were identified between good prognosis and bad prognosis samples. Among these DELs, LINC01003, CTD-2234N14, RP1-137K24, and RP11-834C111 were found to be independent predictors of prognosis. A risk scoring system based on the expressions of the 4 signature lncRNAs was developed. Kaplan-Meier survival analysis found that the risk score system could classify patients into high-risk and low-risk groups with significantly different survival outcomes. Function analysis showed that the mRNAs in these lncRNA-mRNA networks were significantly linked to mTOR signaling pathway, apoptosis, Fc epsilon RI signaling pathway, B cell receptor signaling pathway, natural killer cell mediated cytotoxicity, and T cell receptor signaling pathway. CONCLUSION: This study suggested a promising 4 prognostic lncRNAs-based risk scoring system in AML. These 4 lncRNAs may play roles in regulating prognosis partly via mTOR signaling pathway, apoptosis, and some immune-related pathways.

RNA-seq Profiling Showed Divergent Carbohydrate-Active Enzymes (CAZymes) Expression Patterns in Lentinula edodes at Brown Film Formation Stage Under Blue Light Induction.

Lentinula edodes (shiitake mushroom) is one of the most important edible mushrooms worldwide. The L. edodes cultivation cycle includes a unique developing stage called brown film formation that directly affects the development of primordium and the quality of fruiting body. Brown film formation is induced by light, especially blue light. To promote our understanding of the role of blue light in brown film formation mechanisms of L. edodes, we used RNA-seq and compared the transcriptomes of L. edodes grown under blue light and in dark, and validated the expression profiles using qRT-PCR. Blue light stimulated the formation of brown film and increased the content of polysaccharides in L. edodes. Blue light also promoted L. edodes to absorb more polysaccharides by enhancing the activities of enzymes. Among the 730 differentially expressed genes (DEGs), 433 genes were up-regulated and 297 were down-regulated. Most of the DEGs were in the oxidoreductase activity group. Pentose and glucuronic acid conversion and starch and sucrose metabolism were the most important pathways in the formation of brown film. A total of 79 genes of DEGs were identified as genes encoding carbohydrate-active enzymes (CAZymes). Fifty-one of the CAZymes genes were up-regulated, suggesting that CAZymes play important roles in brown film formation to provide sufficient nutrition for L. edodes. The results will facilitate future functional investigations of the genes involved in the developmental control of L. edodes.

Theaflavin attenuates cerebral ischemia/reperfusion injury by abolishing miRNA­128­3p­mediated Nrf2 inhibition and reducing oxidative stress.

Theaflavin has been proven to own strong antioxidative capacity; however, the molecular mechanism underlying its protective effect against cerebral ischemia­reperfusion (I/R) injury remains unclear. Therefore, the present study was designed to elucidate the neuroprotective effects of theaflavin on cerebral I/R injury and its underlying molecular mechanisms. To investigate the effects of theaflavin on neurological function, neurogenesis, and oxidative stress, experiments were performed using a cerebral I/R injury rat model, and neural stem cells (NSCs) were subjected to oxygen­glucose deprivation and reoxygenation (OGD/R). Further, the expression profiles of miRNA­128­3p and the regulatory function of nuclear factor (erythroid­derived 2)­related factor 2 (Nrf2) were evaluated in these models. We found that theaflavin treatment significantly reduced infarct volume and neuronal injury, and thus improved the impaired memory and learning ability. Furthermore, theaflavin treatment significantly enhanced the increase in NSC proliferation, reduction in the apoptotic rate and inhibition of oxidative stress. Mechanistically, theaflavin targeted miRNA­128­3p and further activated the Nrf2 pathway to reduce oxidative stress. In summary, theaflavin has a strong ability to attenuate cerebral I/R injury through miRNA­128­3p­mediated recovery of the impaired antioxidant defense system, which suggests that it could be a potential drug candidate for ischemic stroke.

Watershed prioritization in the upper Han River basin for soil and water conservation in the South-to-North Water Transfer Project (middle route) of China.

Watershed prioritization with the objective of identifying critical areas to undertake soil and water conservation measures was conducted in the upper Han River basin, the water source area of approximately 95,000 km2 for the middle route of China's South-to-North Water Transfer Project. Based on the estimated soil erosion intensity in uplands and clustering analysis of measured nutrient concentrations in rivers, the basin was grouped into very-high-, high-, moderate-, and low-priority regions for water and soil conservation, respectively. The results indicated that soil erosion was primarily controlled by topography, and nutrients in rivers were associated with land use and land cover in uplands. Also, there was large spatial disparity between soil erosion intensity in the uplands and nutrient concentrations in the rivers across the basin. Analysis was then performed to prioritize the basin by the integration of the soil erosion intensity and water quality on a GIS platform in order to identify critical areas for water and soil conservation in the basin. The identified high-priority regions which occupy 5.74% of the drainage areas need immediate attention for soil and water conservation treatments, of which 5.28% is critical for soil erosion prevention and 0.46% for water conservation. Understandings of the basin environment and pollutant loading with spatial explicit are critical to the soil and water resource conservation for the interbasin water transfer project.

A novel scoring system for acute myeloid leukemia risk assessment based on the expression levels of six genes.

Acute myeloid leukemia (AML) is the most common type of acute leukemia and is a heterogeneous clonal disorder. At present, the pathogenesis of AML and potential methods to effectively prevent AML have become areas of interest in research. In the present study, two messenger ribonucleic acid sequencing datasets of patients with AML were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus databases. The differentially expressed genes (DEGs) of the poor and good prognosis groups were screened using the Linear Models for Microarray Data package, and the prognosis­related genes were screened using univariate Cox regression analysis. A total of 206 significant DEGs were identified. Following univariate and multivariate Cox regression analysis, 14 genes significantly associated with prognosis were screened and six of these genes, including triggering receptor expressed on myeloid cells 2 (TREML2), cysteine­glutamate transporter (SLC7A11), NACHT, LRR, and PYD domains­containing protein 2 (NLRP2), DNA damage­inducible transcript 4 protein (DDIT4), lymphocyte­specific protein 1 (LSP1) and C­type lectin domain family 11 member A (CLEC11A), were used to construct model equations for risk assessment. The prognostic scoring system was used to evaluate risk for each patient, and the results showed that patients in the low­risk group had a longer survival time, compared with those in the high­risk group (P=9.59e­06 for the training dataset and P=0.00543 for the validation dataset). A total of eight main Kyoto Encyclopedia of Genes and Genomes pathways were identified, the top three of which were hematopoietic cell lineage, focal adhesion, and regulation of actin cytoskeleton. Taken together, the results showed that the scoring system established in the present study was credible and that the six genes were identified, which were significantly associated with the risk assessment of AML, offer potential as prognostic biomarkers. These findings may provide clues for further clarifying the pathogenesis of AML.

Mortality and Outcome Comparison Between Brain Tissue Oxygen Combined with Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy and Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy in Traumatic Brain Injury: A Meta-Analysis.

BACKGROUND: The combination of brain tissue oxygen and standard intracranial pressure (ICP)/cerebral perfusion pressure (CPP)-guided therapy is thought to improve traumatic brain injury (TBI) prognosis compared with standard ICP/CPP-guided therapy. However, related results of previous observational studies and recently published cohort studies and randomized controlled trials (RCTs) remain controversial. The objective of this study was to compare the effect of the combined therapy with that of standard ICP/CPP-guided therapy on mortality rate, favorable outcome, ICP/CPP, and length of stay (LOS). METHODS: We systematically searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science in July 2016 for studies comparing the combined therapy and standard ICP/CPP-guided therapy. Random-effect and fixed-effect models were used for pooled analyses. RESULTS: After screening 362 studies, 8 cohort studies and 1 RCT were included. Primary outcomes were mortality and favorable outcome. The overall mortality risk ratio showed no obvious advantages between the 2 groups (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.54-1.06) and discharge mortality (RR, 1.01; 95% CI, 0.80-1.26) and 3-month mortality (RR, 0.77; 95% CI, 0.53-1.12). Compared with the ICP/CPP group, the combined group was more likely to achieve better outcome during the 6 months after TBI (RR, 1.26; 95% CI, 1.04-1.52) or exactly at 6 months (RR, 1.34; 95% CI, 1.07-1.68), whereas ICP (standardized mean difference [SMD], -0.19; 95% CI, -0.43 to 0.05), CPP (SMD, 0.13; 95% CI, -0.09 to 0.35), and LOS (SMD, 0.13; 95% CI, -0.11 to 0.37) showed no obvious differences. CONCLUSIONS: Compared with standard ICP/CPP-guided therapy, brain tissue oxygen combined with ICP/CPP-guided therapy improved long-term outcomes without any effects on mortality, ICP/CPP, or LOS.

Towards dropout training for convolutional neural networks.

Recently, dropout has seen increasing use in deep learning. For deep convolutional neural networks, dropout is known to work well in fully-connected layers. However, its effect in convolutional and pooling layers is still not clear. This paper demonstrates that max-pooling dropout is equivalent to randomly picking activation based on a multinomial distribution at training time. In light of this insight, we advocate employing our proposed probabilistic weighted pooling, instead of commonly used max-pooling, to act as model averaging at test time. Empirical evidence validates the superiority of probabilistic weighted pooling. We also empirically show that the effect of convolutional dropout is not trivial, despite the dramatically reduced possibility of over-fitting due to the convolutional architecture. Elaborately designing dropout training simultaneously in max-pooling and fully-connected layers, we achieve state-of-the-art performance on MNIST, and very competitive results on CIFAR-10 and CIFAR-100, relative to other approaches without data augmentation. Finally, we compare max-pooling dropout and stochastic pooling, both of which introduce stochasticity based on multinomial distributions at pooling stage.

Combination therapy with losartan and pioglitazone additively reduces renal oxidative and nitrative stress induced by chronic high fat, sucrose, and sodium intake.

We recently showed that combination therapy with losartan and pioglitazone provided synergistic effects compared with monotherapy in improving lesions of renal structure and function in Sprague-Dawley rats fed with a high-fat, high-sodium diet and 20% sucrose solution. This study was designed to explore the underlying mechanisms of additive renoprotection provided by combination therapy. Losartan, pioglitazone, and their combination were orally administered for 8 weeks. The increased level of renal malondialdehyde and expression of nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) and nitrotyrosine as well as the decreased total superoxide dismutase activity and copper, zinc-superoxide dismutase expression were tangible evidence for the presence of oxidative and nitrative stress in the kidney of model rats. Treatment with both drugs, individually and in combination, improved these abnormal changes. Combination therapy showed synergistic effects in reducing malondialdehyde level, p47(phox), and nitrotyrosine expression to almost the normal level compared with monotherapy. All these results suggest that the additive renoprotection provided by combination therapy might be attributed to a further reduction of oxidative and nitrative stress.