ChemMORT: an automatic ADMET optimization platform using deep learning and multi-objective particle swarm optimization.

Drug discovery and development constitute a laborious and costly undertaking. The success of a drug hinges not only good efficacy but also acceptable absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties. Overall, up to 50% of drug development failures have been contributed from undesirable ADMET profiles. As a multiple parameter objective, the optimization of the ADMET properties is extremely challenging owing to the vast chemical space and limited human expert knowledge. In this study, a freely available platform called Chemical Molecular Optimization, Representation and Translation (ChemMORT) is developed for the optimization of multiple ADMET endpoints without the loss of potency (https://cadd.nscc-tj.cn/deploy/chemmort/). ChemMORT contains three modules: Simplified Molecular Input Line Entry System (SMILES) Encoder, Descriptor Decoder and Molecular Optimizer. The SMILES Encoder can generate the molecular representation with a 512-dimensional vector, and the Descriptor Decoder is able to translate the above representation to the corresponding molecular structure with high accuracy. Based on reversible molecular representation and particle swarm optimization strategy, the Molecular Optimizer can be used to effectively optimize undesirable ADMET properties without the loss of bioactivity, which essentially accomplishes the design of inverse QSAR. The constrained multi-objective optimization of the poly (ADP-ribose) polymerase-1 inhibitor is provided as the case to explore the utility of ChemMORT.

Experimental demonstration of deterministic quantum search for multiple marked states without adjusting the oracle.

Grover's search algorithm is a well-known quantum algorithm that has been extensively studied and improved to increase its success rate and enhance its flexibility. However, most improved search algorithms require an adjustment of the oracle, which may not be feasible in practical problem-solving scenarios. In this work, we report an experimental demonstration of a deterministic quantum search for multiple marked states without adjusting the oracle. A linear optical setup is designed to search for two marked states, one in a 16-state database with an initial equal-superposition state and the other in an 8-state database with different initial nonequal-superposition states. The evolution of the probability of finding each state in the database is also measured and displayed. Our experimental results agree well with the theoretical predictions, thereby proving the feasibility of the search protocol and the implementation scheme. This work is a pioneering experimental demonstration of deterministic quantum search for multiple marked states without adjusting the oracle.

Enantioselective Csp3-Csp3 formation by nickel-catalyzed enantioconvergent cross-electrophile alkyl-alkyl coupling of unactivated alkyl halides.

The pervasive occurrence of saturated stereogenic carbon centers in pharmaceuticals, agrochemicals, functional organic materials, and natural products has stimulated great efforts toward the construction of such saturated carbon centers. We report a reaction mode for the enantioselective construction of alkyl-alkyl bond to access saturated stereogenic carbon centers by asymmetric reductive cross-coupling between different alkyl electrophiles in good yields with great levels of enantioselectivity. This reaction mode uses only alkyl electrophiles for enantioselective Csp3-Csp3 bond-formation, rendering reductive alkyl-alkyl cross-coupling as an alternative to traditional alkyl-alkyl cross-coupling reactions between alkyl nucleophiles and alkyl electrophiles to access saturated stereogenic carbon centers without the use of organometallic reagents. The reaction displays a broad scope for two alkyl electrophiles with good functional group tolerance. Mechanistic studies reveal that the reaction undergoes a single electron transfer that enabled the reductive coupling pathway to form the alkyl-alkyl bond.

Ligand-enabled Ni-catalysed enantioconvergent intermolecular Alkyl-Alkyl cross-coupling between distinct Alkyl halides.

α-Tertiary aliphatic amides are key elements in organic molecules, which are abundantly present in natural products, pharmaceuticals, agrochemicals, and functional organic materials. Enantioconvergent alkyl-alkyl bond-forming process is one of the most straightforward and efficient, yet highly challenging ways to build such stereogenic carbon centers. Herein, we report an enantioselective alkyl-alkyl cross-coupling between two different alkyl electrophiles to access α-tertiary aliphatic amides. With a newly-developed chiral tridentate ligand, two distinct alkyl halides were successfully cross-coupled together to forge an alkyl-alkyl bond enantioselectively under reductive conditions. Mechanistic investigations reveal that one alkyl halides exclusively undergo oxidative addition with nickel versus in-situ formation of alkyl zinc reagents from the other alkyl halides, rendering formal reductive alkyl-alkyl cross-coupling from easily available alkyl electrophiles without preformation of organometallic reagents.

Ligand-Controlled Nickel-Catalyzed Regiodivergent Cross-Electrophile Alkyl-Alkyl Couplings of Alkyl Halides.

Functionalizing specific positions on a saturated alkyl molecule is a key challenge in synthetic chemistry. Herein, a ligand-controlled regiodivergent alkylations of alkyl bromides at different positions by Ni-catalyzed alkyl-alkyl cross-electrophile coupling with the second alkyl bromides has been developed. The reaction undergoes site-selective isomerization on one alkyl bromides in a controlled manner, providing switchable access to diverse alkylated structures at different sites of alkyl bromides. The reaction occurs at three similar positions with excellent chemo- and regioselectivity, representing a remarkable ligand tuned reactivity between alkyl-alkyl cross-coupling and nickel migration along the hydrocarbon side chain. This reaction offers a catalytic platform to diverse saturated architectures by alkyl-alkyl bond-formation from identical starting materials.

A real-time pluripotency reporter for the long-term and real-time monitoring of pluripotency changes in induced pluripotent stem cells.

To master the technology of reprogramming mouse somatic cells to induced pluripotent stem cells (iPSCs), which will lay a good foundation for setting up a technology platform on reprogramming human cancer cells into iPSCs. Mouse iPSCs (i.e., Oct4-GFP miPSCs) was successfully generated from mouse embryonic fibroblasts (MEFs) harboring Oct4-EGFP transgene by introducing four factors, Oct4, Sox2, c-Myc and Klf4, under mESC (Murine embryonic stem cells) culture conditions. Oct4-GFP miPSCs were similar to mESCs in morphology, proliferation, mESC-specific surface antigens and gene expression. Additionally, Oct4-GFP miPSCs could be cultured in suspension to form embryoid bodies (EBs) and differentiate into cell types of the three germ layers in vitro. Moreover, Oct4-GFP miPSCs could develop to teratoma and chimera in vivo. Unlike cell cycle distribution of MEFs, Oct4-GFP miPSCs are similar to mESCs in the cell cycle structure which consists of higher S phase and lower G1 phase. More importantly, our data demonstrated that MEFs harboring Oct4-EGFP transgene did not express GFP, until they were reprogrammed to the pluripotent stage (iPSCs), while the GFP expression was progressively lost when these pluripotent Oct4-GFP miPSCs exposed to EB-mediated differentiation conditions, suggesting the pluripotency of Oct4-GFP miPSCs can be real-time monitored over long periods of time via GFP assay. Altogether, our findings demonstrate that Oct4-GFP miPSC line is successfully established, which will lay a solid foundation for setting up a technology platform on reprogramming cancer cells into iPSCs. Furthermore, this pluripotency reporter system permits the long-term real-time monitoring of pluripotency changes in a live single-cell, and its progeny.

Using resting thalamic connectivity to identify the relationship between Eysenck personality traits and intelligence in healthy adults.

Personality refers to a set of relatively stable psychological characteristics of individuals and has been associated with intelligence. It is well known that the thalamus plays an important role in cognitive processes and personality traits, but the relationship between personality traits, thalamic function, and intelligence has rarely been directly explored. Hence, we investigated the relationship between Eysenck personality traits, resting-state functional connectivity (rsFC) of the thalamus, and intelligence in a large sample of healthy adults (N = 176). We found that the trait of psychoticism was negatively associated with intelligence. The high intelligence group showed significantly lower psychoticism and demonstrated enhanced thalamic connectivity to the amygdala, inferior parietal lobules, pallidum, medial superior/middle frontal gyrus, and precuneus. Furthermore, a mediation analysis indicated that the FC between the left thalamus and left amygdala significantly mediated the correlation between psychoticism and full IQ (FIQ). These findings suggest that intelligent people may be less prone to psychoticism. Meanwhile, thalamic rsFC may reflect individual differences in intelligence and play a key role in the relationship between personality traits and intellectual abilities.

Liver-specific over-expression of Cripto-1 in transgenic mice promotes hepatocyte proliferation and deregulated expression of hepatocarcinogenesis-related genes and signaling pathways.

In this study, we investigated the role of embryonic gene Cripto-1 (CR-1) in hepatocellular carcinoma (HCC) using hepatocyte-specific CR-1-overexpressing transgenic mice. The expression of truncated 1.7-kb CR-1 transcript (SF-CR-1) was significantly higher than the full-length 2.0-kb CR-1 transcript (FL-CR-1) in a majority of HCC tissues and cell lines. Moreover, CR-1 mRNA and protein levels were significantly higher in HCC tissues than adjacent normal liver tissues. Hepatocyte-specific over-expression of CR-1 in transgenic mice enhanced hepatocyte proliferation after 2/3 partial hepatectomy (2/3 PHx). CR-1 over-expression significantly increased in vivo xenograft tumor growth of HCC cells in nude mice and in vitro HCC cell proliferation, migration, and invasion. CR-1 over-expression in the transgenic mouse livers deregulated HCC-related signaling pathways such as AKT, Wnt/ß-catenin, Stat3, MAPK/ERK, JNK, TGF-ß and Notch, as well as expression of HCC-related genes such as CD5L, S100A8, S100A9, Timd4, Orm2, Orm3, PDK4, DMBT1, G0S2, Plk2, Plk3, Gsta1 and Gsta2. However, histological signs of precancerous lesions, hepatocyte dysplasia or HCC formation were not observed in the livers of 3-, 6- or 8-month-old hepatocyte-specific CR-1-overexpressing transgenic mice. These findings demonstrate that liver-specific CR-1 overexpression in transgenic mice deregulates signaling pathways and genes associated with HCC.

MST4 negatively regulates the EMT, invasion and metastasis of HCC cells by inactivating PI3K/AKT/Snail1 axis.

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has a poor prognosis due to the high incidence of invasion and metastasis-related progression. However, the underlying mechanism remains elusive, and valuable biomarkers for predicting invasion, metastasis, and poor prognosis of HCC patients are still lacking. Methods: Immunohistochemistry (IHC) was performed on HCC tissues (n = 325), and the correlations between MST4 expression of the clinical HCC tissues, the clinicopathologic features, and survival were further evaluated. The effects of MST4 on HCC cell migratory and invasive properties in vitro were evaluated by Transwell and Boyden assays. The intrahepatic metastasis mouse model was established to evaluate the HCC metastasis in vivo. The PI3K inhibitor, LY294002, and a specific siRNA against Snail1 were used to investigate the roles of PI3K/AKT pathway and Snail1 in MST4-regulated EMT, migration, and invasion of HCC cells, respectively. Results: In this study, by comprehensively analyzing our clinical data, we discovered that low MST4 expression is highly associated with the advanced progression of HCC and serves as a prognostic biomarker for HCC patients of clinical-stage III-IV. Functional studies indicate that MST4 inactivation induces epithelial-to-mesenchymal transition (EMT) of HCC cells, promotes their migratory and invasive potential in vitro, and facilitates their intrahepatic metastasis in vivo, whereas MST4 overexpression exhibits the opposite phenotypes. Mechanistically, MST4 inactivation elevates the expression and nuclear translocation of Snail1, a key EMT transcription factor (EMT-TF), through the PI3K/AKT signaling pathway, thus inducing the EMT phenotype of HCC cells, and enhancing their invasive and metastatic potential. Moreover, a negative correlation between MST4 and p-AKT, Snail1, and Ki67 and a positive correlation between MST4 and E-cadherin were determined in clinical HCC samples. Conclusions: Our findings indicate that MST4 suppresses EMT, invasion, and metastasis of HCC cells by modulating the PI3K/AKT/Snail1 axis, suggesting that MST4 may be a potential prognostic biomarker for aggressive and metastatic HCC.

The Yunnan national medicine Maytenus compound inhibits the proliferation of hepatocellular carcinoma (HCC) by suppressing the activation of the EGFR-PI3K-AKT signaling pathway.

Objective: To investigate the effects of Maytenus compound on the proliferation of hepatocellular carcinoma (HCC) cells in vitro and in vivo and to explore the underlying mechanism. Methods: The half maximal inhibitory concentration (IC50) values of Maytenus compound in HepG2 and BEL-7402 cells were determined by the MTS assay. HepG2 and BEL-7402 cells were treated with different concentrations of Maytenus compound. MTS assays, colony formation assays and cell cycle analyses were performed to clarify the inhibitory effect of Maytenus compound on the proliferation of HepG2 and BEL-7402 cells in vitro. After subcutaneous injection of HepG2 cells, nude mice were randomly divided into a vehicle control group and a drug intervention group, which were intragastrically administered ddH2O or Maytenus compound, respectively. The inhibitory effect of Maytenus compound on the proliferation of HepG2 cells in vivo was analyzed using subcutaneous tumor growth curves, tumor weight, the tumor growth inhibition rate and the immunohistochemical detection of BrdU-labeled cells in S phase. The organ toxicity of Maytenus compound was initially evaluated by comparing the weight difference and organ index of the two groups of nude mice. The main proteins in the EGFR-PI3K-AKT signaling pathway were detected by Western blot after Maytenus compound intervention in vivo and in vitro. Results: Maytenus compound showed favorable antiproliferation activity against HepG2 and BEL-7402 cells with IC50 values of 79.42±11.71 µg/mL and 78.48±8.87 µg/mL, respectively. MTS assays, colony formation assays and cell cycle analyses showed that Maytenus compound at different concentration gradients within the IC50 concentration range significantly suppressed the proliferation of HepG2 and BEL-7402 cells in vitro and inhibited cell cycle progression from G1 to S phase. Additionally, Maytenus compound, at an oral dose of 2.45 g/kg, dramatically inhibited, without obvious organ toxicity, the proliferation of subcutaneous tumors formed by HepG2 cells in nude mice. In addition, the tumor growth inhibition rate for Maytenus compound was 66.94%. Furthermore, Maytenus compound inhibited the proliferation of liver orthotopic transplantation tumors in nude mice. Western blot analysis showed that Maytenus compound significantly downregulated the expression of p-EGFR, p-PI3K, and p-AKT and upregulated the expression of p-FOXO3a, p27, and p21 in vivo and in vitro. Conclusion: Maytenus compound significantly inhibited the proliferation of HCC cells in vitro and in vivo. The downregulation of the EGFR-PI3K-AKT signaling pathway and subsequent inhibition of cell cycle progression from G1 to S phase is one of the possible mechanisms. Maytenus compound has a high tumor growth inhibition rate and has no obvious organ toxicity, which may make it a potential anti-HCC drug, but the results from this study need to be confirmed by further clinical trials in HCC patients.

Correlates of intelligence via resting-state functional connectivity of the amygdala in healthy adults.

Intelligence is a form of advanced cognition that includes reasoning, problem solving, pattern recognition, and establishing relationships among items. The amygdala plays an important role in cognitive processing, but the relationship between amygdalar function and intelligence has rarely been explored directly. Here, we investigated the relationship between resting-state functional connectivity (RSFC) of the amygdala and intelligence test performance in a large sample of healthy adults (N = 197). We found that two pairs of RSFCs were significantly increased in the high IQ group compared with that of the general IQ group. One of these RSFCs consisted of the right amygdala and the right superior parietal lobule, whereas the other RSFC consisted of the right amygdala and the left middle cingulum. In addition, we found that the brain regions in which the strength of RSFC significantly correlated with full IQ (FIQ) were mainly distributed in the parietal and limbic lobes. What's more, a further mediation analysis indicated that the functional connectivity of the right amygdala and the right superior parietal lobule significantly mediated the correlation between comprehension and object assembly, whereas the functional connectivity of the right amygdala and the left middle cingulum mediated the association between similarities and digit symbol. These findings suggest that amygdalar RSFC may reflect individual differences in intelligence and mediate specific relationships among different intellectual abilities.

MST4 inhibits human hepatocellular carcinoma cell proliferation and induces cell cycle arrest via suppression of PI3K/AKT pathway.

Objective: MST4 has exhibited functions in regulating cell polarity, Golgi apparatus, cell migration, and cancer. Mechanistically, it affects the activity of p-ERK, Hippo-YAP pathway and autophagy. The aim of this study is to further examine the functions of MST4 in hepatocellular carcinoma (HCC) and the underlying mechanism. Methods: The expression level of MST4 in HCC and noncancer adjacent liver tissues was determined by qRT-PCR and immunohistochemistry staining. Wild-type MST4 (MST4) and a dominant-negative mutant of MST4 (dnMST4) were overexpressed in HCC cell lines, respectively. CCK-8 assay, EdU incorporation assay, and soft agar assay were used to determine cell proliferation in vitro. The xenograft mouse model was employed to determine HCC cell growth in vivo. Cell cycle analysis was performed by PI staining and flow cytometry. The expression of key members in PI3K/AKT pathway was detected by Western blot analysis. Results: In our study, we reported new evidence that MST4 was frequently down-regulated in HCC tissues. Gain-of-function and loss-of-function experiments demonstrated that MST4 negatively regulated in vitro HCC cell proliferation. Additionally, MST4 overexpression suppressed Bel-7404 cell tumor growth in nude mice. Further experiments revealed that the growth-inhibitory effect of MST4 overexpression was partly due to a G1-phase cell cycle arrest. Importantly, mechanistic investigations suggested that dnMST4 significantly elevated the phosphorylation levels of key members of PI3K/AKT pathway, and the selective PI3K inhibitor LY294002 can reverse the proliferation-promoting effect of dnMST4. Conclusions: Overall, our results provide a new insight into the clinical significance, functions and molecular mechanism of MST4 in HCC, suggesting that MST4 might have a potential therapeutic value in the HCC clinical treatment.

Loss of PDK4 expression promotes proliferation, tumorigenicity, motility and invasion of hepatocellular carcinoma cells.

Although the roles and underlying mechanisms of other PDK family members (i.e., PDK1, PDK2 and PDK3) in tumor progression have been extensively investigated and are well understood, the functions and underlying molecular mechanisms of pyruvate dehydrogenase kinase 4 (PDK4) in the tumorigenesis and progression of various cancers [including hepatocellular carcinoma (HCC)] remain largely unknown. In this study, we examined the expression profile of PDK4 in HCC clinical tissue specimens and the roles of PDK4 in the proliferation, tumorigenicity, motility and invasion of HCC cells. The immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) results revealed that PDK4 was significantly downregulated in the cohort of HCC clinical specimens. Additionally, PDK4 protein was found in both the nucleus and cytoplasm of HCC cells based on an immunofluorescence (ICC) assay, and PDK4 protein was also found in the nucleus and cytoplasm of cancer cells contained in HCC clinical specimens based on IHC. The CCK-8 assay and cell colony formation assay demonstrated that stable depletion of endogenous PDK4 by lentivirus-mediated RNA interference (RNAi) markedly promoted the proliferation of HCC cell lines (i.e., BEL-7402 and BEL-7404 cells) in vitro, while PDK4 silencing significantly enhanced the tumorigenic ability of BEL-7404 cells in vivo. In addition to enhance proliferation and tumorigenesis induced by PDK4 silencing, additional studies demonstrated that knockdown of PDK4 led to increase migration and invasion of BEL-7402 and BEL-7404 cells in vitro. Taken together, these findings suggest that the loss of PDK4 expression contributes to HCC malignant progression.

miR-26a promotes hepatocellular carcinoma invasion and metastasis by inhibiting PTEN and inhibits cell growth by repressing EZH2.

A previous study revealed that therapeutic miR-26a delivery suppresses tumorigenesis in a murine liver cancer model, whereas we found that forced miR-26a expression increased hepatocellular carcinoma (HCC) cell migration and invasion, which prompted us to characterize the causes and mechanisms underlying enhanced invasion due to ectopic miR-26a expression. Gain-of-function and loss-of-function experiments demonstrated that miR-26a promoted migration and invasion of BEL-7402 and HepG2 cells in vitro and positively modulated matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, and MMP-10 expression. In addition, exogenous miR-26a expression significantly enhanced the metastatic ability of HepG2 cells in vivo. miR-26a negatively regulated in vitro proliferation of HCC cells, and miR-26a overexpression suppressed HepG2 cell tumor growth in nude mice. Further studies revealed that miR-26a inhibited cell growth by repressing the methyltransferase EZH2 and promoted cell migration and invasion by inhibiting the phosphatase PTEN. Furthermore, PTEN expression negatively correlated with miR-26a expression in HCC specimens from patients with and without metastasis. Thus, our findings suggest for the first time that miR-26a promotes invasion/metastasis by inhibiting PTEN and inhibits cell proliferation by repressing EZH2 in HCC. More importantly, our data also suggest caution if miR-26a is used as a target for cancer therapy in the future.

Direct conversion of pig fibroblasts to chondrocyte-like cells by c-Myc.

Unexpectedly, we found that c-Myc-expressing porcine embryonic fibroblasts (PEFs) subcutaneously implanted into nude mice formed cartilage-like tissues in vivo, while previous studies revealed the direct conversion of mouse and human somatic cells into chondrocytes by the combined use of several defined factors, including c-Myc, which prompted us to explore whether PEFs can be reprogrammed to become pig induced chondrocyte-like cells (piCLCs) via ectopic expression of c-Myc alone. In this study, c-Myc-expressing PEFs, designated piCLCs, which exhibited a significantly enhanced proliferation ability in vitro, displayed a chondrogenic phenotypes in vitro, as shown by the cell morphology, toluidine blue staining, alcian blue staining and chondrocyte marker gene expression. Additionally, piCLCs with a polygonal chondrocyte-like morphology were readily and efficiently converted from PEFs by enforced c-Myc expression within 10 days, while piCLCs maintained the chondrocytic phenotype and normal karyotype during long-term subculture. piCLC-derived single clones with a chondrogenic phenotype in vitro exhibited homogeneity in cell morphology and staining intensity compared with mixed piCLCs. Although the mixtures of cartilaginous tissues and tumorous tissues accounted for ~12% (6/51) of all xenografts (51), piCLCs generated stable, homogenous, hyaline cartilage-like tissues without tumour formation at 45 out of the 51 injected sites when subcutaneously injected into nude mice. The hyaline cartilage-like tissues remained for at least 16 weeks. Taken together, these findings demonstrate for the first time the direct induction of chondrocyte-like cells from PEFs with only c-Myc.

The effects of bisphosphonates on osteoporotic patients after lumbar fusion: a meta-analysis.

PURPOSE: We conducted a meta-analysis of controlled clinical trials to evaluate the efficacy of bisphosphonates in lumbar fusion. INTRODUCTION: Bisphosphonates reduce bone resorption and remodeling by osteoclast activity inhibition, inactivation, and apoptosis. However, it remains controversial whether bisphosphonate therapy affects spinal fusion. METHODS: We searched MEDLINE, Cochrane CENTRAL, ScienceDirect, EMBASE, and Google Scholar to identify studies reporting the effects of bisphosphonates on osteoporotic patients after lumbar fusion. Secondary sources were identified from the references of the included literature. Pooled data were analyzed using RevMan 5.1. RESULTS: Seven studies met the inclusion criteria. There were significant differences in solid intervertebral fusion (RD=0.07, 95% CI: -0.00 to 0.15, P=0.05), subsequent VCFs (RD=-0.21, 95% CI: -0.30 to -0.12, P<0.00001), pedicle screw loosening (RD=-0.17, 95% CI: -0.28 to -0.05, P=0.006), and cage subsidence (RD=-0.25, 95% CI: -0.42 to -0.07, P=0.005) between two groups. No significant differences between two groups were found regarding implant fixation failure (RD=-0.06, 95% CI: -0.22 to 0.10, P=0.48). CONCLUSION: This meta-analysis showed that bisphosphonates may increase solid intervertebral fusion and decrease subsequent VCFs, pedicle screw loosening, and cage subsidence.

[Effect of surgical intervention time on the recovery of nerve function in acute spinal cord injury: a Meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of different operation time for acute spinal cord injury(SCI) based on systematic review. METHODS: PubMed database, EMBASE database, Cochrane Library, ISI Web of knowledge, CBM database, VIP database, CNKI database and Wanfang database were searched from their start year up to February 2017 for relevant randomized clinical trials on the treatment of acute spinal cord injury with different intervention times. RESULTS: Four randomized clinical trials of total 156 cases were included. Early surgical intervention for the patients with incomplete spinal cord injury can improve the ASIA motor function score [MD=3.29, 95%CI(-7.90, 14.49), P=0.56] and overall Frankel score[OR=7.65, 95%CI(2.69, 21.74), P=0.000 1]. There was no significant difference in the improvement of the overall Frankel score[OR=4.88, 95%CI(0.74, 32.09), P=0.10] for the patients with complete spinal cord injury between the early surgery and delayed surgery group. There was no significant difference in hospitalization time[MD=-3.4, 95%CI(-8.12, 1.32), P=0.16], death rate [OR=1.07, 95%CI(0.21, 5.56), P=0.93]and incidence of decubitus[OR=1.07, 95%CI(0.17, 6.69), P=0.94] between the early surgery and delayed surgery group. CONCLUSIONS: Early surgical intervention can promote the nerve function recovery after spinal cord injury, whithout further incidence of complications, but random control trails with higher quality are still required for this conclusion.

Intermolecular σ-Bond Cross-Exchange Reaction between Cyclopropenones and (Benzo)silacyclobutanes: Straightforward Access towards Sila(benzo)cycloheptenones.

Described herein is the first intermolecular σ-bond exchange reaction between the C-C bond of cyclopropenones and C-Si bond of (benzo)silacyclobutanes and it proceeds smoothly by treatment with either 1 mol % of a palladium or 2 mol % of a nickel catalyst. This reaction constitutes an unprecedented route for the synthesis of various sila(benzo)suberones. And it is also the first example of a σ-bond exchange reaction involving cyclopropenones.

Biomechanical effects of different vertebral heights after augmentation of osteoporotic vertebral compression fracture: a three-dimensional finite element analysis.

BACKGROUND: Clinical results have shown that different vertebral heights have been restored post-augmentation of osteoporotic vertebral compression fractures (OVCFs) and the treatment results are consistent. However, no significant results regarding biomechanical effects post-augmentation have been found with different types of vertebral deformity or vertebral heights by biomechanical analysis. Therefore, the present study aimed to investigate the biomechanical effects between different vertebral heights of OVCFs before and after augmentation using three-dimensional finite element analysis. METHODS: Four patients with OVCFs of T12 underwent computed tomography (CT) of the T11-L1 levels. The CT images were reconstructed as simulated three-dimensional finite-element models of the T11-L1 levels (before and after the T12 vertebra was augmented with cement). Four different kinds of vertebral height models included Genant semi-quantitative grades 0, 1, 2, and 3, which simulated unilateral augmentation. These models were assumed to represent vertical compression and flexion, left flexion, and right flexion loads, and the von Mises stresses of the T12 vertebral body were assessed under different vertebral heights before and after bone cement augmentation. RESULTS: Data showed that the von Mises stresses significantly increased under four loads of OVCFs of the T12 vertebral body before the operation from grade 0 to grade 3 vertebral heights. The maximum stress of grade 3 vertebral height pre-augmentation was produced at approximately 200%, and at more than 200% for grade 0. The von Mises stresses were significantly different between different vertebral heights preoperatively. The von Mises stresses of the T12 vertebral body significantly decreased in four different loads and at different vertebral body heights (grades 0-3) after augmentation. There was no significant difference between the von Mises stresses of grade 0, 1, and 3 vertebral heights postoperatively. The von Mises stress significantly decreased between pre-augmentation and post-augmentation in T12 OVCF models of grade 0-3 vertebral heights. CONCLUSION: Vertebral augmentation can sufficiently reduce von Mises stresses at different heights of OVCFs of the vertebral body, although this technique does not completely restore vertebral height to the anatomical criteria.

Transanal Tube for the Prevention of Anastomotic Leakage After Rectal Cancer Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Transanal tubes (TTs) have been used to prevent and reduce anastomotic leakage after rectal cancer surgery. The aim of this review was to investigate the efficacy and safety of the TT. METHODS: A systematic literature search was performed to identify randomized controlled trials and controlled clinical trials assessing the clinical efficacy and safety of TTs in rectal cancer surgery. RESULTS: Seven trials with 1609 participants were included. The TT group had a lower anastomotic leakage rate than the non-transanal tube group [RR 0.38; 95 % confidence interval (CI) 0.25-0.58; P < 0.0001], as well as a lower reoperation rate (RR 0.31; 95 % CI 0.19-0.53; P < 0.0001) and a shorter hospital stay (mean = -2.59 days; 95 % CI -3.69 to -1.49; P < 0.0001). There were no significant differences in mortality between the two groups. CONCLUSION: TT use in rectal cancer surgery is likely to be an effective and safe method of preventing and reducing anastomotic leakage and is associated with a decreased risk of reoperation and faster recovery.