Surface Ammonium Ions Assisted Decoration of Monodisperse Cobalt Nanoparticles on Molybdenum Oxide Films as Efficient Electrocatalysts for Hydrogen Evolution Reaction.

The high expense associated with electrocatalysts poses a challenge to the advancement of a hydrogen-based energy economy. The utilization of nonprecious metal-based electrocatalysts that are easily prepared and cost-effective is imperative for the future sustainability of a hydrogen society. The semiconductive MoO3-x has been identified as a promising nonprecious electrocatalyst for the hydrogen evolution reaction (HER). Nevertheless, enhancing its relatively low electrocatalytic activity toward HER remains a top priority. This study illustrates the manipulation of surface ammonium ions (NH4+) to produce uniform and distinct cobalt nanoparticles (Co NPs) on active MoO3-x supports, resulting in a more effective heterostructured composite electrocatalyst for HER. The presence of NH4+ ions in the MoO3-x film was extensively examined using infrared spectroscopy, X-ray photoelectron spectroscopy, and UV-visible colorimetric techniques. Additionally, the firmly attached NH4+ ions were employed as binding sites to precipitate Co-containing complex ions. Due to the monolayer-like adsorption of NH4+ ions, only a small quantity of Co precipitate was formed, which was subsequently electrochemically transformed into Co atoms that diffused and created well-separated uniform metallic Co nanoparticles (with an average size of less than 10 nm) on the MoO3-x film. The resulting heterostructure displays a 4.5-fold increase in current density for HER compared to the MoO3-x electrocatalyst through electrochemical assessments. The enhanced catalytic activity was ascribed to the optimized adsorption/desorption of the species involved in water reduction at the heterointerfaces and improved charge transfer rates. These nanoheterostructures hold great promise for a variety of applications in heterogeneous electrocatalysis, while the novel approach could potentially direct the creation of more heterostructures.

Application of thromboelastography to predict the severity of bleeding after chimeric antigen receptor (CAR)-T cell therapy in patients with hematological malignancy.

OBJECTIVES: We aim to analyze the predictive value of thromboelastography on bleeding severity of patients with chimeric antigen receptor (CAR)-T cell therapy. METHODS: A total of 80 patients with refractory/relapsed hematological malignancy were enrolled and divided into two groups: the severe bleeding group and the non-severe bleeding group. The thromboelastography data was collected on the day of CAR-T infusion and the 3rd, 7th, 10th, 13th, 17th, and 20th day after CAR-T cell infusion. RESULTS: The patients of the severe bleeding group had lower platelet (p < .007), maximum amplitude (p = .002), coagulation index (p = .005), and longer coagulation time (p = .019). Increasing trend in reaction time and coagulation time and decreasing trend in Alpha, maximum amplitude, and coagulation index on Days 0-10, opposite on Days 10-20. Univariate logistic regression analysis and multivariable logistic regression analysis showed maximum amplitude on the 3rd day after CAR-T cell infusion (MA3) (OR = 0.9; 95% CI = 0.84-0.95; p < .001) and cytokine release syndrome grade (OR = 2.57; 95% CI = 1.35-5.32; p = .006) were significantly associated with high bleeding severity. CONCLUSIONS: Thromboelastography was considered to be a good predictor of bleeding severity.

Visible-Light-Enhanced Hydrogen Evolution through Anodic Furfural Electro-Oxidation Using Nickel Atomically Dispersed Copper Nanoparticles.

A novel copper nanoparticle variant, denoted as Cu98Ni2 NPs, which incorporate Ni atoms in an atomically dispersed manner, has been successfully synthesized via a straightforward one-pot electrochemical codeposition process. These nanoparticles were subsequently employed as an anode to facilitate the oxidation of furfural, leading to the production of hydrogen gas. Voltammetric measurements revealed that the inclusion of trace amounts of Ni atoms in the nanoparticles resulted in a pronounced synergistic electronic effect between Cu and Ni. Consequently, a 43% increase in current density at 0.1 V was observed in comparison to pure Cu NPs. Importantly, when the Cu98Ni2 NPs were irradiated with visible light, a remarkable current density enhancement factor of 505% at 0.1 V was achieved relative to that of pure Cu NPs in the absence of light. This enhancement can be attributed to localized surface plasmon resonance induced by visible light, which triggers photothermal and photoelectric effects. These effects collectively contribute to the significant overall improvement in the electrocatalytic oxidation of furfural, leading to enhanced hydrogen evolution.

Causal relationship between gut microbiota and diabetic nephropathy: A bidirectional mendelian randomization study.

In this study, we summarized the key findings and potential implications of association studies investigating the relationship between gut microbiota composition and risks for Diabetic nephropathy (DN). We used Mendelian randomization (MR) analysis to explore the relationship between gut microbiota and DN using two different publicly available DN databases. The results were also summarized using five mainstream MR analysis methods. We controlled for various possible biases in the results. The results showed that specific bacterial genera were associated with increased or decreased risk of DN. These associations can be attributed to a variety of factors, including metabolites produced by certain bacteria. Most of our findings are consistent with the existing research findings, but there are still some differences with the existing results. In addition, we also pointed out that some microbiota that may be associated with DN but remain unnoticed can bring new research directions. Our work made use of MR, a reliable technique for examining causal correlations using genetic data investigating potential processes, carrying out longitudinal studies, looking into intervention options, and using a multi-omics approach may be future research avenues. Further, our findings also point to a few unexplored possible study paths for DN in the future. These initiatives may improve our reconciliation of the internal relationships between the gut microbiota and DN and pave the way for more precise prevention and treatment methods. However, it is also critical to recognize any potential restrictions, such as those caused by sample size, population variety, and analytical techniques.

Uridine phosphorylase-1 promotes cell viability and cell-cycle progression in human epidermal keratinocytes via the glycolytic pathway.

Glycolysis is vital for the excessive proliferation of keratinocytes in psoriasis, and uridine phosphorylase-1 (UPP1) functions as an enhancer of cancer cell proliferation. However, little is known about whether UPP1 promotes keratinocyte proliferation and accelerates psoriasis development. This study revealed that UPP1 facilitates cell viability and cell-cycle progression in human epidermal keratinocytes (HEKs) by modulating the glycolytic pathway. Bioinformatics analysis of UPP1 gene expression and its correlation with the Reactome revealed that UPP1 mRNA expression, cell-cycle progression, the interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway and glycolysis were positively associated with psoriasis. Cell proliferation, the cell cycle and glycolysis were evaluated after UPP1 was silenced or overexpressed. The results showed that UPP1 overexpression increased cell proliferation, cell-cycle progression and glycolysis, which was contrary to the effects of UPP1 silencing. However, the STAT3 inhibitor diminished UPP1 expression because STAT3 can bind to the UPP1 promoter. In conclusion, UPP1 was significantly activated by the IL-6/STAT3 pathway and could modulate glycolysis to regulate cell proliferation and cell-cycle progression in keratinocytes during the development of psoriasis.

Plasmon-enhanced photocatalysis using gold nanoparticles encapsulated in nanoscale molybdenum oxide shell.

Using solar energy to enhance the transformation rate of organic molecules is a promising strategy to advance chemical synthesis and environmental remediation. Plasmonic nanoparticles responsive to sunlight show great promise in the catalysis of chemical reactions. In this work, we used a straightforward wet-chemistry method to synthesize plasmonic octahedral gold nanoparticles (NPs) coated with thin molybdenum oxide (MoO3-x), Au@MoO3-xNPs, which exhibited strong surface plasmon resonance in a broad wavelength range. The synthesized Au@MoO3-xNPs were characterized by UV-vis, SEM, TEM, EDS, XPS, and the electrochemical technique of cyclic voltammetry (CV). The catalytic performance of Au@MoO3-xNPs under visible light irradiation was investigated using the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) as a model reaction. The presence of a thin capping layer of MoO3-xon our Au NPs contributed to the broadening of their range of absorption of visible light, resulting in a stronger intra-particle plasmonic resonance and the modulation of surface energy and electronic state. Accordingly, the kinetics of plasmon photocatalytic transformation of 4-NP to 4-AP was significantly accelerated (by a factor of 8.1) under visible light, compared to uncapped Au NPs in the dark. Our as-synthesized Au@MoO3-xNPs is an example that the range of plasmonic wavelengths of NPs can be effectively broadened by coating them with another plasmon-active (semiconducting) material, which substantially improves their plasmonic photocatalytic performance. Meanwhile, the synthesized Au@MoO3-xNPs can be used to accelerate the transformation of organic molecules under visible light irradiation.

Optical coherence tomography for in vivo longitudinal monitoring of artificial dermal scaffold.

OBJECTIVES: Artificial dermal scaffold (ADS) has undergone rapid development and been increasingly used for treating skin wound in clinics due to its good biocompatibility, controllable degradation, and low risk of disease infection. To obtain good treatment efficacy, ADS needs to be monitored longitudinally during the treatment process. For example, scaffold-tissue fit, cell in-growth, vascular regeneration, and scaffold degradation are the key properties to be inspected. However, to date, there are no effective, real-time, and noninvasive techniques to meet the requirement of the scaffold monitoring above. MATERIALS AND METHODS: In this study, we propose to use optical coherence tomography (OCT) to monitor ADS in vivo through three-dimensional imaging. A swept source OCT system with a handheld probe was developed for in vivo skin imaging. Moreover, a cell in-growth, vascular regeneration, and scaffold degradation rate (IRDR) was defined with the volume reduction rate of the scaffold's collagen sponge layer. To measure the IRDR, a semiautomatic image segmentation algorithm was designed based on U-Net to segment the collagen sponge layer of the scaffold from OCT images. RESULTS: The results show that the scaffold-tissue fit can be clearly visualized under OCT imaging. The IRDR can be computed based on the volume of the segmented collagen sponge layer. It is observed that the IRDR appeared to a linear function of the time and in addition, the IRDR varied among different skin parts. CONCLUSION: Overall, it can be concluded that OCT has a good potential to monitor ADS in vivo. This can help guide the clinicians to control the treatment with ADS to improve the therapy.

Involvement of microRNAs and their potential diagnostic, therapeutic, and prognostic role in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 85%-90% of primary liver cancer. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting the 3'UTR of mRNA. Abnormal expression and regulation of miRNAs are involved in the occurrence and progression of HCC, and miRNAs can also play a role in the diagnosis and treatment of HCC as oncogenes or tumor suppressors. METHODS: In the past decades, a large number of studies have shown that miRNAs play an essential regulatory role in HCC and have potential as biomarkers for HCC. We reviewed the literature to summarize these studies. RESULTS: By reviewing the literature, we retrospected the roles of miRNAs in the development, diagnosis, treatment, and prognosis of HCC, and put forward prospects for the further research on miRNAs in the precision treatment of HCC. CONCLUSION: MicroRNAs are important regulators and biomarkers in the occurrence, progression, outcome, and treatment of HCC, and can provide new targets and strategies for improving the therapeutic effect of HCC.

Evaluating Ciliary Body Damage Induced by Blunt Low Speed Impact Using Finite Element Simulation.

PURPOSE: To evaluate the ciliary body mechanical load during low speed impact using finite element method to explain the mechanism of the cause of angle recession and cyclodialysis cleft. METHODS: Optical coherence tomography images were obtained to assess the patient's ciliary body angle recession. A finite element eye model was established based on Virginia Tech eye model with the consideration of dynamic impact of a projectile striking an eye. The mechanical properties of the ocular tissues were obtained from literatures. The stress and strain were evaluated. RESULTS: The stress distribution of the eye was calculated. The stress concentration at zonules was observed after 0.75 ms of the impact. The maximum stress at the cornea reached 3.8 MPa. The maximum stress at ciliary body was 57 KPa, which has high probability to cause ciliary body injury. The maximum stress at zonules was 0.98 MPa. The lateral expansion also reduces the forces transmitted along the sclera to the rear part of the eye. CONCLUSIONS: The eye under frontal impact will result in lateral expansion, which increase the stretch force of the lens, zonules and ciliary body. This mechanism can be seen as the protection for retina. The boundary of ciliary body is the most vulnerable position, where angle recession and cyclodialyses cleft will occur before retina damage occurrence. TRANSLATIONAL RELEVANCE: The finite element model explains the blunt low speed impact induced ciliary body related injuries, which enables us to assess the ocular injury for low energy impact and better diagnosis and treatment in clinics.

Suppression of lncRNA HOTAIR alleviates RCC angiogenesis through regulating miR-126/EGFL7 axis.

Renal cell carcinoma (RCC) has the highest mortality rate among urological cancers and tumor angiogenesis that plays a critical role in RCC progress. Epidermal growth factor-like domain multiple 7 (EGFL7) has been recently identified as a regulator in RCC tumor angiogenesis and progression. Long noncoding RNA (LncRNA) HOTAIR has been considered as a pro-oncogene in multiple cancers, but its precise mechanism of tumor angiogenesis has rarely been reported. MicroRNA-126 (miR-126) functions as a tumor suppressor in RCC. However, the underlying tumor angiogenesis mechanism of HOTAIR/miR-126 axis in RCC has not been studied. The proliferation, migration, angiogenesis, and expression of EGFL7 and related proteins in extracellular signal-regulated kinase (ERK)/activators of transcription 3 (STAT3) signal pathway were determined to examine the effect and mechanism of HOTAIR and miR-126 on RCC progress. The regulatory relationship of HOTAIR and miR-126, as well as miR-126 and EGFL7 were tested using dual-luciferase reporter assay. Aenograft RCC mice model was used to examine the effect of HOTAIR on RCC tumor growth and metastasis in vivo. HOTAIR knockdown and miR-126 overexpression suppressed the proliferation, migration, and angiogenesis of RCC cells. HOTAIR regulated EGFL7 expression by competitively binding to miR-126. Knockdown of HOTAIR significantly suppressed the RCC tumor progression and lung metastasis in vivo. These findings suggest that lncRNA HOTAIR regulate RCC angiogenesis through miR-126/EGFL7 axis and provide a new perspective on the molecular pathways of angiogenesis in RCC development, which might be potential therapeutic targets for RCC treatment.

Pyrroloquinoline quinone promotes mitochondrial biogenesis in rotenone-induced Parkinson's disease model via AMPK activation.

Mitochondrial dysfunction is considered to be one of the important pathogenesis in Parkinson's disease (PD). We previously showed that pyrroloquinoline quinone (PQQ) could protect SH-SY5Y cells and dopaminergic neurons from cytotoxicity and prevent mitochondrial dysfunction in rotenone-induced PD models. In the present study we investigated the mechanisms underlying the protective effects of PQQ in a mouse PD model, which was established by intraperitoneal injection of rotenone (3 mg·kg-1·d-1, ip) for 3 weeks. Meanwhile the mice were treated with PQQ (0.8, 4, 20 mg·kg-1·d-1, ip) right after rotenone injection for 3 weeks. We showed that PQQ treatment dose-dependently alleviated the locomotor deficits and nigral dopaminergic neuron loss in PD mice. Furthermore, PQQ treatment significantly diminished the reduction of mitochondria number and their pathological change in the midbrain. PQQ dose-dependently blocked rotenone-caused reduction in the expression of PGC-1α and TFAM, two key activators of mitochondrial gene transcription, in the midbrain. In rotenone-injured human neuroblastoma SH-SY5Y cells, PTMScan Direct analysis revealed that treatment with PQQ (100 µM) differentially regulated protein phosphorylation; the differentially expressed phosphorylated proteins included the signaling pathways related with adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway. We conducted Western blot analysis and confirmed that AMPK was activated by PQQ both in PD mice and in rotenone-injured SH-SY5Y cells. Pretreatment with AMPK inhibitor dorsomorphin (4 µM) significantly attenuated the protective effect and mitochondrial biogenesis by PQQ treatment in rotenone-injured SH-SY5Y cells. Taken together, PQQ promotes mitochondrial biogenesis in rotenone-injured mice and SH-SY5Y cells via activation of AMPK signaling pathway.

Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence.

Long noncoding RNAs (lncRNAs) function through a diverse array of mechanisms that are not presently fully understood. Here, we sought to find lncRNAs differentially regulated in cancer cells resistant to either TNF-related apoptosis-inducing ligand (TRAIL) or the Mcl-1 inhibitor UMI-77, agents that act through the extrinsic and intrinsic apoptotic pathways, respectively. This work identified a commonly up-regulated lncRNA, ovarian adenocarcinoma-amplified lncRNA (OVAAL), that conferred apoptotic resistance in multiple cancer types. Analysis of clinical samples revealed OVAAL expression was significantly increased in colorectal cancers and melanoma in comparison to the corresponding normal tissues. Functional investigations showed that OVAAL depletion significantly inhibited cancer cell proliferation and retarded tumor xenograft growth. Mechanically, OVAAL physically interacted with serine/threonine-protein kinase 3 (STK3), which, in turn, enhanced the binding between STK3 and Raf-1. The ternary complex OVAAL/STK3/Raf-1 enhanced the activation of the RAF protooncogene serine/threonine-protein kinase (RAF)/mitogen-activated protein kinase kinase 1 (MEK)/ERK signaling cascade, thus promoting c-Myc-mediated cell proliferation and Mcl-1-mediated cell survival. On the other hand, depletion of OVAAL triggered cellular senescence through polypyrimidine tract-binding protein 1 (PTBP1)-mediated p27 expression, which was regulated by competitive binding between OVAAL and p27 mRNA to PTBP1. Additionally, c-Myc was demonstrated to drive OVAAL transcription, indicating a positive feedback loop between c-Myc and OVAAL in controlling tumor growth. Taken together, these results reveal that OVAAL contributes to the survival of cancer cells through dual mechanisms controlling RAF/MEK/ERK signaling and p27-mediated cell senescence.

Bidentatide, a Novel Plant Peptide Derived from Achyranthes bidentata Blume: Isolation, Characterization, and Neuroprotection through Inhibition of NR2B-Containing NMDA Receptors.

Increasing attention is being focused on the use of polypeptide-based N-methyl-d-aspartate (NMDA) receptor antagonists for the treatment of nervous system disorders. In our study on Achyranthes bidentata Blume, we identified an NMDA receptor subtype 2B (NR2B) antagonist that exerts distinct neuroprotective actions. This antagonist is a 33 amino acid peptide, named bidentatide, which contains three disulfide bridges that form a cysteine knot motif. We determined the neuroactive potential of bidentatide by evaluating its in vitro effects against NMDA-mediated excitotoxicity. The results showed that pretreating primary cultured hippocampal neurons with bidentatide prevented NMDA-induced cell death and apoptosis via multiple mechanisms that involved intracellular Ca2+ inhibition, NMDA current inhibition, and apoptosis-related protein expression regulation. These mechanisms were all dependent on bidentatide-induced inhibitory regulation of NR2B-containing NMDA receptors; thus, bidentatide may contribute to the development of neuroprotective agents that would likely possess the high selectivity and safety profiles inherent in peptide drugs.

Clinical efficacy and safety of aidi injection combination with vinorelbine and cisplatin for advanced non-small-cell lung carcinoma: A systematic review and meta-analysis of 54 randomized controlled trials.

The Aidi injection contains multiple active ingredients, including astragaloside (Re, Rb1, and Rg1), ginsenoside, cantharidin, elentheroside E, and syringin, and it is administered with vinorelbine and cisplatin (NP) to treat non-small-cell lung carcinoma (NSCLC). In this study, we performed a systematic review and meta-analysis to determine the clinical efficacy and safety of the Aidi injection with NP, and the optimal threshold and treatment regimen to produce the desired responses. We collected all studies regarding the Aidi injection with NP for NSCLC from Chinese and English databases (up to April 2019). Risk of methodological bias was evaluated for each study. Data for analysis were extracted using a standard data extraction form. Evidence quality was assessed following the Grading of Recommendations Assessment, Development and Evaluation approach. We included 54 trials containing 4,053 patients for analysis. Combining the Aidi injection with NP significantly increased the objective response rate (odds ratio [OR], 1.32; confidence interval [CI], 1.23, 1.42), disease control rate (OR, 1.14; CI, 1.11, 1.18), and quality of life (OR, 1.80; CI, 1.61, 1.98), with decreased risks of myelosuppression, neutropenia, thrombocytopenia, anemia, gastrointestinal reaction, and liver dysfunction. For patients with a Karnofsky Performance Status score of ≥60, the Aidi injection (50 mL/day, two weeks/cycle, with two to three cycles) treatment with vinorelbine (25 mg/m2) and cisplatin (30-35 mg/m2 or 40-50 mg/m2) might be the optimal regimen for producing the desired tumor response and achieving a good safety level. Most results were robust, and their quality was moderate. The results suggest that administration of the Aidi injection and concomitant NP is beneficial to NSCLC, and provide evidence for the optimal threshold and treatment regimen that may improve tumor response with a good safety level.

Pyrroloquinoline Quinone Inhibits Rotenone-Induced Microglia Inflammation by Enhancing Autophagy.

Neuroinflammation is a feature common to neurodegenerative diseases, such as Parkinson's disease (PD), which might be responsive to therapeutic intervention. Rotenone has been widely used to establish PD models by inducing mitochondrial dysfunction and inflammation. Our previous studies have reported that pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor, could prevent mitochondrial dysfunction in rotenone induced PD models by regulating mitochondrial functions. In the present study, we aimed to investigate the effect of PQQ on neuroinflammation and the mechanism involved. BV2 microglia cells were pre-treated with PQQ followed by rotenone incubation. The data showed that PQQ did not affect the cell viability of BV2 cells treated with rotenone, while the conditioned medium (CM) of BV2 cells pre-treated with PQQ significantly increased cell viability of SH-SY5Y cells. In rotenone-treated BV2 cells, PQQ dose-dependently decreased lactate dehydrogenase (LDH) release and suppressed the up-regulation of pro-inflammation factors, such as interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) in the cultured media, as well as nitric oxide (NO) release induced by rotenone. PQQ pretreatment also increased the ratio of LC3-II/LC3-I and expression of Atg5 in BV2 cells stimulated with rotenone. Additionally, the autophagosome observed by transmission electron microscopy (TEM) and co-localization of mitochondria with lysosomes indicated that mitophagy was induced by PQQ in rotenone-injured BV2 cells, and the PINK1/parkin mediated mitophagy pathway was regulated by PQQ. Further, autophagy inhibitor, 3-methyladenine (3-MA), partially abolished the neuroprotective effect of PQQ and attenuated the inhibition of inflammation with PQQ pretreatment. Taken together, our data extend our understanding of the neuroprotective effect of PQQ against rotenone-induced injury and provide evidence that autophagy enhancement might be a novel therapeutic strategy for PD treatment.

FAST1 promotes the migration and invasion of colorectal cancer cells.

BACKGROUND: The forkhead activin signal transducer 1 (FAST1) is involved in several oncogenic signaling pathways and its abnormal expression has been discovered in some cancers. Yet the role of FAST1 in colorectal cancer (CRC) remains largely unclear. Therefore, the goal of this study was to explore the function of FAST1 in CRC. METHODS: In this study, we analyzed FAST1 expression and its relationship with clinicopathological parameters and prognostic significance in CRC via immunohistochemistry analysis. The effects and mechanisms of FAST1 on cell proliferation, migration and invasion were explored in vitro and in vivo. RESULTS: We found that increased FAST1 as an independent prognostic factor was positively associated with TNM stage and pathological grade in CRC. FAST1 overexpression promoted the CRC cell proliferation, migration and invasion in vivo. Furthermore, mechanistic studies implicated that FAST1 enhanced the pulmonary metastasis of CRC cells through down-regulating E-cadherin levels. CONCLUSIONS: In summary, FAST1 was significantly associated with CRC progression and could serve as an independent prognostic factor. FAST1 may be potential therapeutic target for CRC patients.

Effectiveness and safety of chemotherapy with cytokine-induced killer cells in non-small cell lung cancer: A systematic review and meta-analysis of 32 randomized controlled trials.

BACKGROUND AIMS: Cytokine-induced killer (CIK) cells are the most commonly used cellular immunotherapy for multiple tumors. To further confirm whether chemotherapy with CIK cells improves clinical effectiveness and to reveal its optimal use in non-small cell lung cancer (NSCLC), we systematically reevaluated all relevant studies. METHODS: We collected all studies about chemotherapy with CIK cells for NSCLC from the Medline, Embase, Web of Science, China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Data, China Biological Medicine Database (CBM), Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and U.S. clinical trials. We evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (RCTs) (version 5.1.0), extracted the data using a standard data extraction form, synthesized the data using meta-analysis and finally rated the evidence quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Thirty-two RCTs with 2250 patients were included, and most trials had unclear risk of bias. The merged risk ratios values and their 95% confidence intervals of meta-analysis for objective response rate, disease control rate, 1- and 2-year overall survival rates, 1- and 2-year progression-free survival rates were as following: 1.45 (1.31-1.61), 1.26 (1.16-.37), 1.42 (1.23-1.63), 2.06 (1.36-3.12), 1.93 (1.38-2.69) and 3.30 (1.13-9.67). Compared with chemotherapy alone, all differences were statistically significant. CIK cells could increase the CD3+ T cells, CD3+ CD4+ T cells, NK cells and the ratio of CD4+/CD8+ T cells. The chemotherapy with CIK cells had a lower risk of hematotoxicity, gastrointestinal toxicity, liver injury and a higher fever than that of chemotherapy alone. The evidence quality was "moderate" to "very low." CONCLUSIONS: The available moderate evidences indicate that chemotherapy with CIK cells, especially autologous CIK cells, can significantly improve the tumor responses, 1- and 2-year overall and progression-free survival rates in patients with advanced NSCLC. This treatment does have a high risk of fever. The optimal use may be treatment with one or two cycles and in combination with vinorelbine and cisplatin, paclitaxel and cisplatin, or docetaxel and cisplatin.

Analysis of biological functional networks during sciatic nerve repair and regeneration.

Peripheral nerve injury is a common disease with a low recovery rate. A better understanding of the molecular changes underlying peripheral nerve injury and regeneration may contribute to the development of novel therapies for the treatment of peripheral nerve injury. In the current study, we analyzed differentially expressed genes in rat sciatic nerve stumps at 1, 4, 7, and 14 days post nerve crush and built biological functional networks at each time point. Our outcomes suggested that "Neurological Disease" involved networks were significant at 1 day post nerve crush, "Cellular Assembly and Organization" involved networks were important at 4 and 7 days post nerve crush, while "Tissue Morphology" involved networks were important at 14 days post nerve crush. We also investigated the temporal expression patterns as well as central genes of these critical networks. Taken together, our study revealed genetic networks and gene-gene interactions in the injured nerve stumps and thus might enhance our understanding of peripheral nerve regeneration.

Transcriptional Profiling at High Temporal Resolution Reveals Robust Immune/Inflammatory Responses during Rat Sciatic Nerve Recovery.

After peripheral nerve injury, immune/inflammatory responses are triggered, which are critical for nerve regeneration. Despite their importance, the underlying molecular changes in immune/inflammatory responses remain largely unknown. In this study, we systematically analyzed differentially expressed genes in immune/inflammatory-related pathways at high temporal resolution and experimentally validated gene expression changes with RT-PCR following sciatic nerve crush in rats. We found that immune/inflammatory reactions not only occur in the acute injury but also remained activated over two weeks after injury. Detailed bioinformatic studies suggested that multiple immune/inflammatory pathways, including agranulocyte adhesion and diapedesis, granulocyte adhesion and diapedesis, IL-6 signaling, and IL-10 signaling, were sustained activated during nerve degeneration and regeneration. Our current study expands our understanding of the molecular basis of altered immune/inflammatory-related pathways following injury and thus might offer the possibility of targeting related molecules as therapeutic intervention for peripheral nerve regeneration.

Development of dietary soluble fibres by enzymatic synthesis and assessment of their digestibility in in vitro, animal and randomised clinical trial models.

The aim was to develop novel fibres by enzymatic synthesis, to determine their total dietary fibre by AOAC method 2009.01 and to estimate their potential digestibility and assess their digestibility in vivo using glycaemic and insulinaemic responses as markers in mice and randomised clinical trial models. We found that fibre candidates to which α-(1,2) branching was added were resistant to digestion in the mouse model, depending on the amount of branching. These results show that in vivo models are needed to reliably assess the digestibility of α-glycosidic-linked oligomeric dietary fibre candidates, possibly due to absence of brush border α-glucosidase activity in the current in vitro assessment. α-(1,3)-linked and α-(1,6)-linked glucose oligomers were completely digested in humans and mice. In conclusion, it is possible to develop dietary soluble fibres by enzymatic synthesis. Adding α-(1,2) branching increases their resistance to digestion in vivo and can thus improve their suitability as potential fibre candidates. Clinical Trial Registry: ClinicalTrials.gov, NCT02701270.