Novel lignans from Zanthoxylum nitidum and antiproliferation activity of sesaminone in osimertinib-resistant non-small cell lung cancer cells.

Seven previously undescribed tetrahydrofuran lignans with different configurations and unusual isopentenyl substitutions, nitidumlignans D-J (corresponding to compounds 1, 2, 4, 6, 7, 9 and 10), along with 14 known lignans, were isolated from Zanthoxylum nitidum. Notably, compound 4 is an uncommon naturally occurring furan-core lignan derived from tetrahydrofuran aromatization. The antiproliferation activity of the isolated compounds (1-21) was determined in various human cancer cell lines. The structure-activity study revealed that the steric positioning and chirality of the lignans exert important effects on their activity and selectivity. In particular, compound 3 (sesaminone) exhibited potent antiproliferative activity in cancer cells, including acquired osimertinib-resistant non-small-cell lung cancer (HCC827-osi) cells. Compound 3 also inhibited colony formation and induced the apoptotic death of HCC827-osi cells. The underlying molecular mechanisms revealed that 3 downregulated the activation of the c-Met/JAK1/STAT3 and PI3K/AKT/mTOR signaling pathways in the HCC827-osi cells. In addition, the combination of 3 and osimertinib exhibited synergistic effects on the antiproliferative activity against HCC827-osi cells. Overall, these findings inform the structure elucidation of novel lignans isolated from Z. nitidum, and sesaminone was identified as a potential compound for exerting antiproliferative effects on osimertinib-resistant lung cancer cells.

Four New Sesquiterpenoids from Zanthoxylum nitidum.

Zanthoxylum nitidum (Roxb.) DC., is one of Guangxi's characteristic national medicines, and is the classic Laoban medicine of Yao people "Ru Shan Hu" and Zhuang medicine "Liang Bei Zhen". It has been used as an anti-inflammatory, analgesic and haemostatic medicine for thousands of years. In this study, four new sesquiterpenoids (1-4), along with six previously described coumarins (5-10), were isolated from 95 % EtOH extract of Zanthoxylum nitidum. Comprehensive spectroscopic analyses (NMR and HR-ESI-MS) were used to elucidate the structures of these isolates. The absolute configurations of nitidumine A-D (1-4) were established by electronic circular dichroism (ECD). Their cytotoxicity of all the isolates against five cancer cell lines (T24, HeLa, MGC-803, A549, and HepG2) was evaluated by MTT experiment and found not to be cytotoxicity.

Diagnosis and surgical treatment of primary isolated aggressive lumbar myeloid sarcoma: a rare case report and review of the literatures.

BACKGROUND: Myeloid sarcoma is a rare, extramedullary, solid tumor derived from immature myeloid cell precursors. It is most frequently accompanied by acute myelogenous leukemia, though infrequently found in non-acute myelogenous leukemia patients. The tumor may involve any part of the body, but the lumbar spine is seldom involved. The present case study aims to understand the diagnosis and surgical treatment of a rare primary isolated myeloid sarcoma of the lumbar spine causing aggressive spinal cord compression in a non-acute myelogenous leukemia patient. CASE PRESENTATION: A 29-year-old man complained of an aggressive radiating pain to the lower extremities and moderate dysuria with a Visual Analogue Scale score that gradually increased from 3 to 8. Lumbar enhanced magnetic resonance imaging and computed tomography revealed a lumbar canal lesion at lumbar spine L2 to L4 with spinal cord compression. A whole body bone scan with fused single photon emission computed tomography/computed tomography demonstrated abnormal 99mTc-methylene diphosphonate accumulation in the L3 lamina and spinous process. No evidence of infection or hematology disease was observed in laboratory tests. Due to rapid progression of the symptoms and lack of a clear diagnosis, decompression surgery was performed immediately. During the operation, an approximately 6.0 × 2.5 × 1.2 cm monolithic, fusiform, soft mass in the epidural space and associated lesion tissues were completely resected. The radiating pain was relieved immediately and the dysuria disappeared within 1 week. Intraoperative pathological frozen section analysis revealed a hematopoietic malignant tumor and postoperative immunohistochemistry examination confirmed the diagnosis of myeloid sarcoma. CONCLUSIONS: The primary isolated aggressive lumbar myeloid sarcoma is rarely seen, the specific symptoms and related medical history are unclear. Surgery and hematological treatment are effective for understanding and recognizing this rare tumor.

Clinical and radiological subsequent fractures after vertebral augmentation for treating osteoporotic vertebral compression fractures: a meta-analysis.

PURPOSE: This study aimed to identify all relevant randomized controlled trials (RCT) and prospective non-RCTs to further investigate whether percutaneous vertebral augmentation (PVA) was associated with clinical and radiological subsequent fractures on unoperated levels. METHODS: We systematically searched PubMed, EMBASE, Cochrane library, Google Scholar, web of science, and ClinicalTrial.gov from the establishment of the database to January 2020. All eligible studies comparing subsequent fractures after PVA with those after conservative treatment (CT) were incorporated. The pooled risk ratio (RR) with its 95% confidence intervals (95% CIs) was used. Heterogeneity, sensitivity, and publication bias analyses were performed. RESULTS: In all, 32 studies were included in the study: 82/512 patients (16.02%) and 58/433 patients (13.39%) had clinical subsequent fractures in the PVA group and CT group, respectively. No significant differences were observed between the two groups [RR = 1.22, 95% CI 0.70-2.12, P = 0.49]. Further, 175/837 patients (20.91%) in the PVA group and 160/828 patients (19.32%) in the CT group had radiological subsequent fractures. No significant difference was observed between groups [RR = 0.91, 95% CI 0.71-2.12, P = 1.16]. Further, no statistical difference was observed on subgroup analysis between RCTs and non-RCTs or PVP and PKP. CONCLUSION: Our systematic review revealed that subsequent fractures on unoperated levels were not associated with PVA, regardless of whether they were clinical or radiological subsequent fractures.

Comparison of clinical outcomes of expansive open-door laminoplasty with unilateral or bilateral fixation and fusion for treating cervical spondylotic myelopathy: a multi-center prospective study.

BACKGROUND: The present study evaluated the clinical outcomes and safety of expansive open-door laminoplasty, when securing with C4 - C6 lateral mass screw and fusion. METHODS: A total of 110 patients with cervical spondylotic myelopathy (CSM) were enrolled. There were 88 male and 22 female, with mean age at 60.55 ± 10.95 years. All of the patients underwent expansive open-door laminoplasty with unilateral or bilateral C4-6 lateral mass screws fixation and fusion. Clinical data, including age, gender, operation-related information, pre- and post-operation Japanese Orthopedic Association (JOA) scores, and cervical curvatures were collected. RESULTS: The mean follow-up time of the cohort was 13.61 ± 9.53 months. Among the 110 patients, 33 of them were allocated to Unilateral group, and 77 of them were in Bilateral group. The mean JOA score of the 110 patients before surgery was 10.07 ± 2.39, and the score was improved significantly to 12.85 ± 2.45 after surgery. There were no reported cases of neurological deterioration or symptom worsening. Patients in both the Unilateral group and Bilateral groups had significant improvement of JOA scores. Among all patients, the most frequently observed complications were axial symptoms (n = 7). The average preoperative cervical curvature among all patients was 15.17 ± 5.26, and the post-surgery curvature was 14.41 ± 4.29. Similar observations were found between Unilateral and Bilateral groups. CONCLUSION: The modified surgical approach provided satisfactory clinical outcome in patients with CSM. The unilateral and bilateral fixation appeared to provide similar outcomes, in terms of cervical curvature maintenance and improvement of clinical symptoms. However, the examination of the exact differences between the two fixation methods await further biomechanical studies.

Preoperative Alfa-Fetoprotein and Fibrinogen Predict Hepatocellular Carcinoma Recurrence After Liver Transplantation Regardless of the Milan Criteria: Model Development with External Validation.

BACKGROUND/AIMS: Patient selection is critically important in improving the outcomes of liver transplantation for hepatocellular carcinoma. The aim of the current study was to identify biochemical measures that could affect patient prognosis after liver transplantation. METHODS: A total of 119 patients receiving liver transplantation for hepatocellular carcinoma were used to construct a model for predicting recurrence. The results were validated using an independent sample of 109 patients from independent hospitals. All subjects in both cohorts met the Hangzhou criteria. RESULTS: Analysis of the discovery cohort revealed an association of recurrence with preoperative fibrinogen and AFP levels. A mathematical model was developed for predicting probability of recurrence within 5 years: Y = logit(P) = -4.595 + 0.824 ×fibrinogen concentration (g/L) + 0.641 × AFP score (1 for AFP<=20ng/ml, 2 for 20 400ng/ml). At a cutoff score of -0.85, the area under the curve (AUC) was 0.819 in predicting recurrence (vs. 0.655 when using the Milan criteria). In the validation cohort, this model had reasonable performance in predicting 5-year overall survival (68.8% vs. 28.1% in using the -0.85 cutoff, p< 0.001) and disease-free survival (65.7% vs. 25.9%, p< 0.001). The sensitivity and specificity were 77.0% and 62.5%, respectively. The AUC of this newly developed model was similar to that with the Milan criteria (0.698 vs. 0.678). Surprisingly, the DFS in patients with score <= -0.85 under this model but not meeting the Milan criteria was similar to that in patients meeting the Milan criteria (53.8% vs. 60.0%, p=0.380). CONCLUSIONS: Preoperative AFP and fibrinogen are useful in predicting recurrence of hepatocellular carcinoma after liver transplantation.

Imbalance of intestinal immune function in piglets infected by porcine circovirus type 2 during the fetal period.

Porcine circovirus type 2- (PCV2-) associated reproductive disorders and enteritis have commonly been observed on PCV2-contaminated pig farms in recent years. In order to investigate disorders of intestinal immunity in piglets infected by PCV2 during the fetal period, 9 PCV2b-infected piglets and 6 non-infected piglets at one day of age were selected and euthanised prior to suckling. Samples of mesenteric lymph nodes (MLNs) and duodena were collected to investigate factors related to intestinal immunity and to detect lymphocytic apoptosis. The results indicated that there were no significant changes in the levels of IL-2, IL-10 and transforming growth factor-ß (TGF-ß) in the PCV2b-infected piglets but IFN-γ levels were significantly lower (P < 0.01) and IL-4 levels were significantly higher (P < 0.05) in infected piglets than in the controls. Furthermore, lymphocytic apoptosis increased in PCV2b-infected piglets and CD4+ to CD8+ ratios were lower in these piglets than in the controls. These findings suggest vertical transmission of PCV2b to fetuses, leading to an imbalance of intestinal immune function in piglets.

Serum DLK1 is a potential prognostic biomarker in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death in developing countries, especially in East Asia and South Africa, and the identification of new biomarkers for early diagnosis and prognosis is needed. Delta-like 1 homologue (Drosophila) (DLK1) is expressed in malignancies and promotes cancer cell stemness and tumourigenicity, which makes this molecule a potential target for therapies directed against cancer stem/progenitor cells. Here, we aimed to assess the predictive value of DLK1 as a diagnostic and prognostic biomarker in HCC. With this purpose, serum DLK1 levels were detected using an enzyme-linked immunosorbent assay (ELISA) in serum specimens from 397 HCC patients, 114 healthy individuals, 43 patients with chronic hepatitis B virus (HBV) infection and 24 cirrhotic liver patients with HBV infection, and the correlation between DLK1 levels and clinical features was evaluated. Our data showed that the serum DLK1 level was significantly higher in HCC patients than in healthy individuals or patients with chronic HBV infection (HBV carriers) (P < 0.05). Moreover, the serum DLK1 levels were positively correlated with tumour size and α-fetoprotein (AFP) levels, but not with gender, age, histological grade, HBV infection, intrahepatic metastasis or cirrhosis in HCC patients. Kaplan-Meier analysis indicated that higher DLK1 levels were associated with shorter survival in HCC patients. These results suggest that the serum levels of DLK1 may serve as a prognostic biomarker for HCC patients.

Fucoidan from Ascophyllum nodosum and Undaria pinnatifida attenuate SARS-CoV-2 infection in vitro and in vivo by suppressing ACE2 and alleviating inflammation.

The global healthcare challenge posed by COVID-19 necessitates the continuous exploration for novel antiviral agents. Fucoidans have demonstrated antiviral activity. However, the underlying structure-activity mechanism responsible for the inhibitory activity of fucoidans from Ascophyllum nodosum (FUCA) and Undaria pinnatifida (FUCU) against SARS-CoV-2 remains unclear. FUCA was characterized as a homopolymer with a backbone structure of repeating (1 â†’ 3) and (1 â†’ 4) linked α-l-fucopyranose residues, whereas FUCU was a heteropolysaccharide composed of Fuc1-3Gal1-6 repeats. Furthermore, FUCA demonstrated significantly higher anti-SARS-CoV-2 activity than FUCU (EC50: 48.66 vs 69.52 µg/mL), suggesting the degree of branching rather than sulfate content affected the antiviral activity. Additionally, FUCA exhibited a dose-dependent inhibitory effect on ACE2, surpassing the inhibitory activity of FUCU. In vitro, both FUCA and FUCU treatments downregulated the expression of pro-inflammatory cytokines (IL-6, IFN-α, IFN-γ, and TNF-α) and anti-inflammatory cytokines (IL-10 and IFN-ß) induced by viral infection. In hamsters, FUCA demonstrated greater effectiveness in attenuating lung and gastrointestinal injury and reducing ACE2 expression, compared to FUCU. Analysis of the 16S rRNA gene sequencing revealed that only FUCU partially alleviated the gut microbiota dysbiosis caused by SARS-CoV-2. Consequently, our study provides a scientific basis for considering fucoidans as poteintial prophylactic food components against SARS-CoV-2.

Quantitative proteomic analysis identifies CPNE3 as a novel metastasis-promoting gene in NSCLC.

To discover metastasis-associated proteins within cancer cells, we used the isobaric tags for relative and absolute quantitation (iTRAQ) approach combined with nano liquid chromatography-tandem mass spectrometry (NanoLC-MS/MS) analysis to identify proteins that were differentially expressed between lung adenocarcinoma cancer cell lines SPC-A-1sci cells with high metastatic potential and parent SPC-A-1 cells with low metastatic potential. By employing biological and technical replicates, we identified 5818 nonredundant proteins and quantified 5443 proteins, 256 of which were differentially expressed in the two cell lines. Through si-RNA-mediated functional screens, Myosin heavy chain 9 (MYH9) and Copine III (CPNE3) were indicated as positively correlating with the migration and invasion properties of SPC-A1sci cells, and the same function of CPNE3 was confirmed in another lung cancer cell line, H1299. Furthermore, overexpressing CPNE3 promoted nonsmall-cell lung cancer (NSCLC) cell line (SPC-A-1 and XL-2) migration and invasion in vitro. Moreover, the targeted knock-down of CPNE3 inhibited the in vivo metastatic abilities of H1299 cells in mouse models. Lastly, immunohistochemistry revealed that the CPNE3 expression level was positively correlated with the clinical stage and TNM classification in NSCLC patients. Taken together, our results indicate that CPNE3 could play a critical role in NSCLC metastasis.

Structurally diverse isobutylamides from Zanthoxylum nitidum.

Five pairs of new racemic alkamides (1a/1b and 4a/4b-7a/7b) and two new achiral derivatives (2-3), as well as five known ones (8-12), were purified from the 95% EtOH extract of Zanthoxylum nitidum. Their structures were elucidated based on spectroscopic analyses (NMR and HR-ESI-MS), electronic circular dichroism (ECD) and NMR calculations. The enantiomeric separation was successfully achieved by chiral-phase HPLC-ECD measurements. Among all the isolates, compounds 2, 3, and 10 showed inhibitory effects against five human cancer cell lines, with IC50 values in range of 18.51-48.03 µM.

Undescribed isoquinolines from Zanthoxylum nitidum and their antiproliferative effects against human cancer cell lines.

Eleven previously undescribed alkaloids, including three pairs of enantiomers nitidumalkaloids A-C, a pair of scalemic mixtures nitidumalkaloid D and three optically pure or achiral alkaloids, nitidumalkaloids E-G, along with 20 known alkaloids, were isolated from an ethanolic extract of the whole Zanthoxylum nitidum (Roxb.) DC plant. The chemical structures of the alkaloids were elucidated using a combination of comprehensive nuclear magnetic resonance (NMR) and high-resolution electro-spray ionization mass spectrometry (HR-ESI-MS) analyses. The configuration of the stereogenic centers of all undescribed compounds was precisely established based on single-crystal X-ray diffraction and electronic circular dichroism (ECD) calculations. Racemic mixtures of nitidumalkaloids A-D were purified, and their enantiomers were analyzed via chiral-phase high-performance liquid chromatography with electrochemical detection measurements (HPLC-ECD). Twelve compounds exhibited significant antiproliferative activities against a panel of cancer cell lines. Further studies were designed to investigate the underlying molecular mechanism of (1'S, 6R)-nitidumalkaloid B, which was the most active antiproliferative agent against human cancer A549 cells. G2/M cell cycle arrest, induction of apoptosis, and suppression of the Wnt/ß-catenin signaling pathway were in part associated with the antiproliferative activity of (1'S, 6R)-nitidumalkaloid B. Moreover, (1'S, 6R)-nitidumalkaloid B inhibited cell migration by downregulating the epithelial-mesenchymal transition process in A549 cells. These data suggest that the antiproliferation activity of (1'S, 6R)-nitidumalkaloid B was correlated with the stereoselectivity of the stereoisomers, and (1'S, 6R)-nitidumalkaloid B was prioritized as a potential leading compound for the management of aggressive human non-small-cell lung cancer (NSCLC) from natural products.

Clinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinoma.

BACKGROUND: Although Dickkopf-1 (DKK1) is known to be a negative regulator of the Wnt/ß-catenin pathway, it has been recently found to be upregulated in cancers. AIMS: We investigated the clinical and prognostic significance of both serum and transcript DKK1 and its functional roles in human hepatocellular carcinoma (HCC). METHODS: We evaluated the expression level of DKK1 in both tissue and serum samples from patients with HCC using GeneChip microarray and real-time-quantitative PCR and sandwich ELISA system respectively. The clinicopathological and prognostic significance of serum and tissue DKK1 levels was examined. Functional characterization of DKK1 with regard to cell migration, invasion and tumour growth was performed. RESULTS: Both DKK1 transcript and serum protein were upregulated in a stepwise manner in human HCCs. Its transcript levels were associated with more aggressive tumour behaviour, in terms of venous invasion (P = 0.003), advanced tumour stage (P = 0.003). DKK1 transcript correlated with shorter overall (P = 0.006) and disease-free survival (P = 0.012), and higher serum DKK1 levels correlated with shorter disease-free survival (P = 0.046). Knockdown of DKK1 significantly reduced both migratory and invasive abilities of HCC cells, whereas overexpression of DKK1 enhanced the tumour formation efficiency and tumour growth in vivo. CONCLUSIONS: Serum and tissue DKK1 levels increased in a stepwise manner in multistep hepatocarcinogenesis and had prognostic significance. DKK1 plays a functional role in cell migration, invasion and tumour growth.

[Biomechanical effect on adjacent vertebra after percutaneous kyphoplasty with cement leakage into disc: a finite element analysis of thoracolumbar osteoporotic vertebral compression fracture].

OBJECTIVE: To explore the biomechanical effects on adjacent vertebra of thoracolumbar osteoporotic vertebral compression fracture (OVCF) after percutaneous kyphoplasty (PKP) with cement leakage into the disc by using finite element analysis. METHODS: T10-L2 segment data were obtained from computed tomography (CT) scans of an elder female with single T12 OVCF undergoing a cement leakage into the T12-L1 disc after PKP. A three-dimensional finite element Model of thoracolumbar spine (T10-L2) was built in the Mimics and the ABAQUS software. The stress on annulus fiber, nucleus pulposus, endplate and facet joints under axial pressure (0.3, 1.0, 4.0 MPa) were analyzed. RESULTS: The 3D finite element after percutaneous kyphoplasty (PKP) with cement leakage into the disc may be strongly related with the changes of biomechanical effects on adjacent vertebra of thoracolumbar OVCF. Models of thoracolumbar OVCF before and after PVP with a cement leakage into the T12-L1 disc were successfully established. The stresses increased with a rising axial pressure in the model of cement leakage into the disc after PVP, the stress augmentation scope on adjacent end plates(T11 low plate & L1 top plate) and intervertebral disc (T11-12 & T12-L1) increased. The maximal Von Mises stress on adjacent vertebra (T11 & L1) increased while but the maximal Von Mises stress on end vertebra (T10 & L2) decreased. CONCLUSION: Postoperative adjacent vertebral fracture.

Development and Validation of Computerized Adaptive Assessment Tools for the Measurement of Posttraumatic Stress Disorder Among US Military Veterans.

Importance: Veterans from recent and past conflicts have high rates of posttraumatic stress disorder (PTSD). Adaptive testing strategies can increase accuracy of diagnostic screening and symptom severity measurement while decreasing patient and clinician burden. Objective: To develop and validate a computerized adaptive diagnostic (CAD) screener and computerized adaptive test (CAT) for PTSD symptom severity. Design, Setting, and Participants: A diagnostic study of measure development and validation was conducted at a Veterans Health Administration facility. A total of 713 US military veterans were included. The study was conducted from April 25, 2017, to November 10, 2019. Main Outcomes and Measures: The participants completed a PTSD-symptom questionnaire from the item bank and provided responses on the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (PCL-5). A subsample of 304 participants were interviewed using the Clinician-Administered Scale for PTSD for DSM-5. Results: Of the 713 participants, 585 were men; mean (SD) age was 52.8 (15.0) years. The CAD-PTSD reproduced the Clinician-Administered Scale for PTSD for DSM-5 PTSD diagnosis with high sensitivity and specificity as evidenced by an area under the curve of 0.91 (95% CI, 0.87-0.95). The CAT-PTSD demonstrated convergent validity with the PCL-5 (r = 0.88) and also tracked PTSD diagnosis (area under the curve = 0.85; 95% CI, 0.79-0.89). The CAT-PTSD reproduced the final 203-item bank score with a correlation of r = 0.95 with a mean of only 10 adaptively administered items, a 95% reduction in patient burden. Conclusions and Relevance: Using a maximum of only 6 items, the CAD-PTSD developed in this study was shown to have excellent diagnostic screening accuracy. Similarly, using a mean of 10 items, the CAT-PTSD provided valid severity ratings with excellent convergent validity with an extant scale containing twice the number of items. The 10-item CAT-PTSD also outperformed the 20-item PCL-5 in terms of diagnostic accuracy. The results suggest that scalable, valid, and rapid PTSD diagnostic screening and severity measurement are possible.

Mesoporous Co3O4 and Au/Co3O4 catalysts for low-temperature oxidation of trace ethylene.

Low-temperature catalysts of mesoporous Co(3)O(4) and Au/Co(3)O(4) with high catalytic activities for the trace ethylene oxidation at 0 degrees C are reported in this paper. The catalysts were prepared by using the nanocasting method, and the mesostructure was replicated from three-dimensional (3D) cubic KIT-6 silicas. High resolution transmission electron microscopy (HRTEM) studies revealed that {110} facets were the exposed active surfaces in the mesoporous Co(3)O(4), whereas the Co(3)O(4) nanosheets prepared by the precipitation method exhibited the most exposed {112} facets. We found that the mesoporous Co(3)O(4) was significantly more active for ethylene oxidation than the Co(3)O(4) nanosheets. The results indicated that the crystal facet {110} of Co(3)O(4) played an essential role in determining its catalytic oxidation performance. The synthesized Au/Co(3)O(4) materials, in which the gold nanoparticles were assembled into the pore walls of the Co(3)O(4) mesoporous support, exhibited stable, highly dispersed, and exposed gold sites. Gold nanoparticles present on Co(3)O(4) readily produced surface-active oxygen species and promoted ethylene oxidation to achieve a 76% conversion at 0 degrees C, which is the highest conversion reported yet.

[Three-dimensional finite element model of thoracolumbar spine with osteoporotic vertebral compression fracture].

OBJECTIVE: To build a three-dimensional finite element model of thoracolumbar spine with osteoporotic vertebral compression fracture (OVCF) and analyze its biomechanical change. METHODS: The T10-L2 segment data were obtained from computed tomography (CT) scans of an elderly female with a single T12 OVCF. A three-dimensional finite element model of thoracolumbar spine was constructed with the MIMICS and ABAQUS software. The model was composed of bony vertebrae, articulating facets, intervertebral disc and associated ligaments. The basic stress analysis of T10-L2 motion segment was made for different material properties of bone, ligaments and facet joints contacting frictional property. The stress on the annulus fiber, nucleus pulposus, endplate and facet joints under axial pressure (0.3 MPa, 1.0 MPa, 4.0 MPa) were analyzed. RESULTS: A three-dimensional finite element model of human T12-L2 motion segment had 617468 elements. And the stress was higher in vertebral body than posterior structure. The distribution of pressure stresses in intervertebral disc was asymmetrical. The stress increased with a rising axial pressure. CONCLUSION: 3D finite element model of thoracolumbar OVCF and adjacent segments are successfully established. The results of stress analysis are both feasible and reliable.

Identification of carboxypeptidase of glutamate like-B as a candidate suppressor in cell growth and metastasis in human hepatocellular carcinoma.

PURPOSE: We have previously done large-scale cDNA transfection screening on human hepatocellular carcinoma (HCC) cells and have identified 3,806 cDNA genes that possess the ability of either stimulating or inhibiting cell growth. In this study, we characterized one of these growth suppressor genes, carboxypeptidase of glutamate like-B (CPGL-B), in HCC. EXPERIMENTAL DESIGN: Semiquantitative reverse-transcription PCR was used to examine the expression levels of CPGL-B. The cellular localization and functions of CPGL-B were investigated by enforced expression of CPGL-B in HCC cells. RESULTS: From our previous cDNA transfection screening, we identified a gene named CPGL and its isoform, CPGL-B. With computational analysis, CPGL was located at chromosome 18q22.3 and was a homologue of peptidase family M20. CPGL was expressed in all adult and fetal tissues, whereas its isoform, CPGL-B, lacking exons 3 and 4, was expressed in all fetal tissues but only in liver and placenta of adult tissues. In HCC, CPGL-B was frequently underexpressed (35 of 90, 38.9%) in tumorous tissues compared with the corresponding nontumorous livers. Intriguingly, the underexpression was significantly associated with the presence of venous invasion (P=0.018) and tumor microsatellite formation (P=0.004). Stable transfection of CPGL-B in SMMC7721 HCC cells showed significant inhibition in cell viability, colony formation, cell invasion, and tumor formation in nude mice. CPGL-B also down-regulated CXCR3, matrix metalloproteinase 11, and CD44s, which are involved in cell growth and cell migration. CONCLUSIONS: These findings suggest that the frequent underexpression of CPGL-B may be associated with cell growth and metastasis of HCC.

Anterior vs conventional approach right hepatic resection for large hepatocellular carcinoma: A systematic review and meta-analysis.

AIM: To compare the clinical outcomes of right hepatectomy for large hepatocellular carcinoma via the anterior and conventional approach. METHODS: We comprehensively performed an electronic search of PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) or controlled clinical trials (CCTs) published between January 2000 and May 2017 concerning the anterior approach (AA) and the conventional approach (CA) to right hepatectomy. Studies that met the inclusion criteria were included, and their outcome analyses were further assessed using a fixed or random effects model. RESULTS: This analysis included 2297 patients enrolled in 16 studies (3 RCTs and 13 CTTs). Intraoperative blood loss [weighted mean difference = -255.21; 95% confidence interval (95%CI): -371.3 to -139.12; P < 0.0001], intraoperative blood transfusion [odds ratio (OR) = 0.42; 95%CI: 0.29-0.61; P < 0.0001], mortality (OR = 0.59; 95%CI: 0.38-0.92; P = 0.02), morbidity (OR = 0.77; 95%CI: 0.62-0.95; P = 0.01), and recurrence rate (OR = 0.62; 95%CI: 0.47-0.83; P = 0.001) were significantly reduced in the AA group. Patients in the AA group had better overall survival (hazard ratio [HR] = 0.71; 95%CI: 0.50-1.00; P = 0.05) and disease-free survival (HR = 0.67; 95%CI: 0.58-0.79; P < 0.0001) than those in the CA group. CONCLUSION: The AA is safe and effective for right hepatectomy for large hepatocellular carcinoma and could accelerate postoperative recovery and achieve better survival outcomes than the CA.

The transcription factor Ikaros inhibits cell proliferation by downregulating ANXA4 expression in hepatocellular carcinoma.

The occurrence and progression of hepatocellular carcinoma (HCC) are affected by complicated signal transduction factors. Our previous study identified Ikaros as a novel reactivated therapeutic target that acts as a transcriptional repressor and reactivates anticancer mechanisms in HCC therapy. Annexin A4 (ANXA4) is a member of the Annexin family that plays an essential role in several cancers, but it has not been investigated in HCC proliferation. Using cDNA microarrays, ANXA4 was shown to be associated with Ikaros in Ikaros-overexpressing cells. The aim of this work was to characterize the relationship between Ikaros and ANXA4 and the role of ANXA4 in HCC. The effect of Ikaros on ANXA4 was analyzed in HCC cell lines and HCC patient samples, and functional recovery experiments were performed between Ikaros and ANXA4. Furthermore, the effect of ANXA4 on cell proliferation in vitro was analyzed by MTT and colony formation assays in HCC cells. We used a subcutaneous xenograft model to elucidate the role of ANXA4 in vivo. We found that ANXA4 overexpression promotes HCC cell proliferation, but Ikaros can inhibit ANXA4 expression by repressing its promoter activity. Moreover, we demonstrated that downregulated expression of ANXA4 inhibited HCC cell proliferation and tumorigenesis in vitro and in vivo. Our findings indicate that ANXA4 may be a critical factor in HCC tumorigenesis. Ikaros is an attractive inhibitor of ANXA4 and may function as an anticancer agent in HCC.