The Combination of Preoperative Nutritional Risk Screening-2002 and Neutrophil-to-Lymphocyte Ratio is a Useful Prognostic Marker in Patients with Esophageal Squamous Cell Carcinoma.

The aim of this study was to investigate the prognostic values of a novel evaluated system, named the CONN (combination of Nutritional Risk Screening 2002 [NRS-2002] and neutrophil-to-lymphocyte ratio [NLR]), in patients with esophageal squamous cell carcinoma (ESCC) by curative esophagectomy. A total of 278 patients with ESCC receiving standard curative esophagectomy were retrospectively analyzed. The CONN was calculated by combined NRS-2002 and NLR according to the corresponding cutoff values: patients with both elevated NRS-2002 (≥3.0) and NLR (≥3.0) were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. In our univariate analysis, the following factors were significantly associated with poor PFS and OS: T stage, N stage, TNM stage, NLR, NRS-2002 and CONN (all P < 0.05). Furthermore, multivariate Cox regression analysis showed that N stage (P = 0.039), NRS-2002 (P = 0.041) and CONN (P = 0.001) were independent prognostic factors for PFS. While T stage (P = 0.017), N stage (P = 0.048), NLR (P = 0.021), NRS-2002 (P = 0.001) and CONN (P = 0.001) were independent prognostic factors for OS. In conclusion, CONN was an independent prognostic marker for survival prediction in patients with ESCC receiving surgery.

Partial splenic embolization of patients with hypersplenism by transradial or transfemoral approach: a prospective randomized controlled trial.

BACKGROUND: Partial splenic artery embolization (PSE) is an effective treatment modality for patients with hypersplenism. It is less invasive and has a quicker recovery compared with surgical procedures. PSE is usually performed using a femoral artery approach that requires bedrest for a few hours, which is rarely the case for transradial PSE. PURPOSE: To compare the transradial and transfemoral approaches for embolization of spleen in patients with hypersplenism. MATERIAL AND METHODS: In all, 84 patients with hypersplenism who required PSE were recruited. They were randomly divided into two groups on the basis of the procedure followed: the transradial approach (R-PSE, n = 39) or transfemoral approach (F-PSE, n = 45). Technical success, puncture rate, total procedure time, X-ray exposure time, length of stay in hospital (LOS), and complications of the two groups were recorded. RESULTS: The procedure time, X-ray exposure time, and LOS were found to be lower in the R-PSE group than in the F-PSE. However, this difference was not statistically significant. CONCLUSION: The transradial artery approach for PSE in patients with hypersplenism is feasible with no major complications as compared to the femoral approach.

Establishing assistant diagnosis models of solitary pulmonary nodules based on intelligent algorithms.

AIMS: This study aimed to establish an auxiliary diagnosis model for solitary pulmonary nodules (SPNs) and evaluate its test efficacy. METHODS: Three hundred thirty-two pathologically diagnosed SPN patients (186 malignant, 146 benign) were collected as subjects. The serum levels of 8 types of markers and 9 computed tomography (CT) imaging features of each patient were treated as independent variables. The corresponding pathological classification results (fungal inflammation, tuberculosis and tuberculoma, inflammatory pseudotumor, tumor middle differentiation, cancer) of quantized patients were treated as dependent variables. A 17-to-1 mathematical auxiliary SPN diagnosis model was established using a back propagation (BP) algorithm and a support vector machine (SVM) algorithm. A 40-case test set was used to estimate the effect. RESULTS: Two different auxiliary SPN diagnosis models were successfully established. The diagnostic accuracy, sensitivity and specificity of the BP algorithm diagnosis model were 60%, 68% and 46.7%, respectively, and those of the SVM algorithm model were 80%, 85.7% and 66.7%, respectively. CONCLUSION: The accuracy, sensitivity and specificity of the SVM diagnostic model were relatively high, indicating that the model has important reference value for determining the degree of SPN differentiation and is suitable for the auxiliary diagnosis of benign and malignant SPN.

Study on the Function of Tumor Necrosis Factor α Before and After Mutation in Hepatitis B.

BACKGROUND/AIMS: To explore the cause of functional changes of TNF-α in removing hepatitis B virus (HBV) through the structural changes of each site in TNF-α before and after mutation. METHODOLOGY: Three typical mutant sites (TNF-α-308G/A, 857C/T and 863C/A of TNF-α) were chosen and methods like ab initio modeling was adopted for 3D modeling of TNF-α before and after mutation. The structural changes were also analyzed. Then structural changes and functional changes were brought together for comparison to infer the root cause of the changes. RESULTS: Mutation of TNF-α-308G/A led to the production of multiple helical structures and that of 863C/A caused the production of one helical structure in its adjacent region. Mutation of 857C/T, however, did not cause the change in the basic structure of TNF-α. CONCLUSIONS: The helical structure of TNF-α may have a positive effect on the removal of hepatitis B virus.

Clinical Outcomes and Prognostic Factors of Salvage Treatment for Local Lymph Node Recurrence After Radical Resection of Oesophageal Carcinoma.

BACKGROUND: There are no standard therapeutic strategies for local lymph node (LN) recurrence after radical resection of oesophageal squamous cell carcinoma (ESCC), and prognostic risk factors remain controversial. We assessed clinical outcomes and prognostic factors of chemoradiotherapy (CRT) or radiotherapy (RT) for LN recurrence of ESCC after curative resection. METHODS: A total of 117 ESCC patients with LN recurrence after radical resection receiving salvage treatment at our hospital were retrospectively reviewed from 2014 to 2017. Overall survival (OS) was estimated using the Kaplan-Meier method; clinical characteristics were assessed using the Log rank test in the univariate analysis. Multivariate prognostic analysis was performed using the Cox proportional hazard model. RESULTS: With a median follow-up of 19 months, the 1-, 2- and 3-year OS rates were 75.2%, 40.2% and 27.4%, respectively. The median survival time (MST) was 19.0 months. On univariate analysis for OS, pathological TNM stage, number of LN metastasis, LN maximum (Max) diameter, salvage treatment mode and tumor response were significantly associated with OS (P = 0.0074, P = 0.015, P = 0.0011, P = 0.028, P < 0.000, respectively). On multivariate analysis, tumor response [Response vs No-response hazard ratio (HR), 2.43; 95% confidence interval (CI), 1.53-3.90, P < 0.000] and LN Max diameter (≤28 mm vs >28 mm HR, 2.07; 95% CI, 1.33-3.32, P = 0.012) were independent prognostic factors. CONCLUSION: Salvage CRT or RT was safe and effective for treating LN recurrence after radical resection in ESCC. Patients with the small LN Max diameter (≤28 mm) and obtained response after salvage therapy appeared to achieve long-term OS.

Arterial instillation of rapamycin in treatment of rabbit hepatic xenograft tumors and its effects on VEGF, iNOS, HIF-1α, Bcl-2, Bax expression and microvessel density.

Hepatocellular carcinoma is one of the leading causes of malignant tumor related death word wide with poor prognosis. Chemotherapy and TACE are main treatment methods for advanced stage cases. Rapamycin, a macrolide compound that initially used to coat coronary stents, can inhibit the growth of a variety of cancer cells especially hepatocellular carcinoma. Twenty-four healthy adult New Zealand white rabbits underwent CT-guided puncture to prepare a model of VX2 liver xenograft tumor. The rabbits were randomly divided into four groups with six in each group and received the following treatments: APR-TACE1: arterial perfusion of high-dose rapamycin combined with TACE; APR-TACE2: arterial perfusion of low-dose rapamycin combined with TACE; TACE: TACE alone; and IVR-TACE: intravenous injection of rapamycin combined with TACE. Two weeks after TACE treatment, the rabbits received CT scan and DSA angiography examination, and then killed by air embolism. The non-necrotic region and surrounding tissues were obtained from the peripheral tumor for iNOS, HIF-1α, VEGF, Bcl-2, and Bax protein expression analysis. Protein expression of iNOS, HIF-1α, VEGF, and Bcl-2 in APR-TACE1 were significantly lower than those in groups APR-TACE2, TACE, and IVR-TACE (p < 0.05). iNOS, HIF-1α, and VEGF in APR-TACE2 were lower than those in TACE (p < 0.05). iNOS and VEGF in APR-TACE2 were significantly lower than those in IVR-TACE (p < 0.05). iNOS in IVR-TACE was significantly lower than that in TACE (p < 0.05). The expression levels of Bcl-2 and Bax were statistically significant between APR-TACE2 and TACE (p < 0.05). The MVD of the tumor tissue in APR-TACE1 was lower than that of groups APR-TACE2, TACE, IVR-TACE with statistical difference (p < 0.05). However, MVD of APR-TACE2 was lower than that of groups TACE, IVR-TACE with significant statistical difference (p < 0.05). Arterial instillation of rapamycin+TACE in treatment of rabbit hepatic xenograft tumors can reduce tumor neovascularization and inhibit iNOS, HIF-1α, VEGF, Bcl-2, and Bax protein expression.

Cyclic loading test study on a new cast-in-situ insulated sandwich concrete wall.

Insulated sandwich concrete panel (ISCP) is widely used because of its high thermal insulation efficiency and low construction cost. Aiming at improving traditional ISCP, a new cast-in-situ concrete wall structure made of ISCP is proposed, which is composed of thin-walled cold-formed steels, slant steel wire connectors, steel wire meshes, concrete layers, expanded polystyrene sheets and reinforced concrete embedded columns. In order to assess the hysteretic properties of the new insulated sandwich concrete wall and the influence of various parameters, low-frequency horizontal cyclic load tests were carried out on seven full-scale specimens of new type cast-in-situ insulated sandwich concrete wall. The specimens were compared and analyzed with respect to failure mode, bearing capacity, ductility, degradation characteristics and energy dissipation capacity. The results show that the final failure pattern of the specimen is two main diagonal cracks intersecting each other; the bearing capacity is greatly affected by concrete thickness and axial compression ratio, regardless of concrete strength. Brittle failure is typically observed when the steel wire spacing is large, while ductility is pronounced when the concrete layer thickness is small and the concrete strength is low; the smaller the thickness of concrete layer, the faster the stiffness degrades. The wall structure shows a better energy dissipation performance with a smaller steel wire spacing, lower concrete strength and smaller axial compression ratio.

Nomogram-Integrated C-Reactive Protein/Albumin Ratio Predicts Efficacy And Prognosis In Patients With Thoracic Esophageal Squamous Cell Carcinoma Receiving Chemoradiotherapy.

OBJECTIVE: To investigate the therapeutic effect and survival outcome using nomogram by incorporating significant inflammatory markers in patients with thoracic esophageal squamous cell carcinoma (ESCC) who received chemoradiotherapy (CRT) or single radiotherapy (RT). METHOD: A total of 266 patients diagnosed with thoracic ESCC receiving standard curative RT only or concurrent CRT were retrospectively analysed. The patients were grouped for statistical analysis depending on the median values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and C-reactive protein/albumin (CRP/Alb) ratio. The therapeutic effect was analysed by univariate and multivariate logistic analyses. The survival prognosis was estimated by univariate and multivariate Cox analyses. At last, the nomogram was developed by incorporating the significant inflammatory markers and clinicopathological parameters, and the predictive value was verified by calibration curve, concordance index (C-index) and decision curve. RESULTS: The treatment responses were highly associated with clinical stage, tumor location, NLR, PLR and CRP/Alb ratio (all P<0.05) by univariate logistic analysis. However, in the multivariate logistic analysis, the results showed that only CRP/Alb ratio (P=0.000) and TNM stage (P=0.008) were independent risk parameters for tumour response. In addition, NLR, PLR, CRP/Alb ratio, age and TNM stage were significantly associated with OS by the univariate Cox analysis (all P<0.05). Furthermore, the multivariate Cox analysis showed that only CRP/Alb ratio (P=0.000), TNM stage (P=0.000) and age (P=0.001) were considered independent prognostic factors for OS. Finally, the calibration curves of nomogram were highly consistent with actual observation for the therapeutic effect and prognosis, and the decision curve analysis showed more potential of clinical benefit of the nomogram compared with TNM staging system. CONCLUSION: This research found that nomogram-integrated CRP/Alb ratio was promising as a predictive model for the therapeutic effect and survival outcome in patients with thoracic ESCC receiving CRT or single RT.

TGFß-induced degradation of TRAF3 in mesenchymal progenitor cells causes age-related osteoporosis.

Inflammaging induces osteoporosis by promoting bone destruction and inhibiting bone formation. TRAF3 limits bone destruction by inhibiting RANKL-induced NF-κB signaling in osteoclast precursors. However, the role of TRAF3 in mesenchymal progenitor cells (MPCs) is unknown. Mice with TRAF3 deleted in MPCs develop early onset osteoporosis due to reduced bone formation and enhanced bone destruction. In young mice TRAF3 prevents ß-catenin degradation in MPCs and maintains osteoblast formation. However, TRAF3 protein levels decrease in murine and human bone samples during aging when TGFß1 is released from resorbing bone. TGFß1 induces degradation of TRAF3 in murine MPCs and inhibits osteoblast formation through GSK-3ß-mediated degradation of ß-catenin. Thus, TRAF3 positively regulates MPC differentiation into osteoblasts. TRAF3 deletion in MPCs activated NF-κB RelA and RelB to promote RANKL expression and enhance bone destruction. We conclude that pharmacologic stabilization of TRAF3 during aging could treat/prevent age-related osteoporosis by inhibiting bone destruction and promoting bone formation.

Arterial Infusion of Rapamycin in the Treatment of Rabbit Hepatocellular Carcinoma to Improve the Effect of TACE.

BACKGROUND: Hepatocellular carcinoma is one of the leading causes of cancer-related death. Hepatic transcatheter arterial chemo-embolization (TACE) is commonly used clinically for advanced hepatocellular carcinoma treatment. AIM: The aim of this study was to evaluate whether arterial infusion of rapamycin can improve the effect of TACE in treatment of rabbit hepatocellular carcinoma. MATERIAL AND METHODS: Eighteen healthy New Zealand white rabbits weighing 2.6 ± 0.3 kg were used in a standardised hepatocellular carcinoma model and randomly divided into three groups of 6 rabbits. Group A: the rabbits were treated with rapamycin and TACE by administering arterial perfusion of 2 mg/kg rapamycin + 1 mg/kg epirubicin, 0.2 mg/kg mitomycin, and lipiodol emulsion embolization. Group B: rapamycin was reduced to 1 mg/kg. And for Group C, the rabbits received only TACE treatment. 14 days post operation, CT scan and digital subtraction angiography (DSA) was performed to examine TACE efficacy. The rabbits were killed by air embolism and the expression of HIF-1a, VEGF, iNOS, and CD34 were measured in an immunohistochemical assay of thetumor tissue. RESULTS: HIF-1a, VEGF and iNOS protein expression in Group A was significantly lower than that of Group B and Group C (P<0.05). The tumor MVD in group C was significantly higher than that of group A and group B (P<0.05); and the tumor MVD of group B was significantly higher than group A (P<0.05). CONCLUSION: Arterial infusion of rapamycin combined with TACE can improve treatment efficacy by decreasing HIF-1a, VEGF, iNOS and CD34 expression.

TNF Induction of NF-κB RelB Enhances RANKL-Induced Osteoclastogenesis by Promoting Inflammatory Macrophage Differentiation but also Limits It through Suppression of NFATc1 Expression.

TNF induces bone loss in common bone diseases by promoting osteoclast formation directly and indirectly, but it also limits osteoclast formation by inducing expression of NF-κB p100. Osteoclast precursors (OCPs) are derived from M1 (inflammatory) and M2 (resident) macrophages. However, it is not known if TNF stimulates or limits osteoclast formation through regulation of M1 or M2 differentiation or if RelB, a partner of p100, is involved. To investigate these questions, we treated bone marrow cells (BMCs) with M-CSF alone or in combination with TNF to enrich for OCPs, which we called M-OCPs and T-OCPs, respectively. We found that TNF switched CD11b+F4/80+ M-OCPs from Ly6C-Gr1- M2 to Ly6C+Gr1-CD11c+ and Ly6C-Gr1-CD11c+ M1 cells. RANKL induced osteoclast formation from both Ly6C+Gr1- and Ly6C-Gr1- T-OCPs, but only from Ly6C+Gr1- M-OCPs, which formed significantly fewer osteoclasts than T-OCPs. Importantly, Ly6C+Gr1- cells from both M- and T-OCPs have increased expression of the M1 marker genes, iNOS, TNF, IL-1ß and TGFß1, compared to Ly6C-Gr1- cells, and Ly6C-Gr1- cells from T-OCPs also have increased expression of iNOS and TGFß1 compared to cells from M-OCPs. Both RANKL and TNF increased RelB mRNA expression. TNF significantly increased RelB protein levels, but RANKL did not because it also induced RelB proteasomal degradation. TNF inhibited RANKL-induced NFATc1 mRNA expression and osteoclast formation from M-OCPs, but not from T-OCPs, and it did not induce Ly6C+Gr1-CD11c+ or Ly6C-Gr1-CD11c+ M1 macrophages from RelB-/- BMCs. Furthermore, overexpression of RelB in M-OCPs reduced RANKL-induced osteoclast formation and NFATc1 mRNA expression, but it increased TNF-induced OC formation without affecting NFATc1 levels. Thus, TNF induction of RelB directly mediates terminal osteoclast differentiation independent of NFATc1 and limits RANKL-induced osteoclastogenesis by inhibiting NFATc1 activation. However, the dominant role of TNF is to expand the OCP pool by switching the differentiation of M-CSF-induced M2 to M1 macrophages with enhanced osteoclast forming potential. Strategies to degrade RelB could prevent TNF-induced M2/M1 switching and reduce osteoclast formation.

Roles of noncoding RNAs in metastasis of nonsmall cell lung cancer: A mini review.

Recent advances in genome-wide sequencing and gene expression profiling technologies has facilitated the discovery of a huge amount of long noncoding RNA (lncRNA) transcripts. In general, these lncRNAs have been reported to participate in multiple biological processes and human diseases through transcriptional, posttranscriptional and epigenetic pathway. Furthermore, emerging evidence has suggested that dysregulation of lncRNA contributes to the development and progression of human malignancies, notably lung cancer, which is one of the leading causes of cancer-related death. In this review, we will summarize the functions of lncRNAs from recent reports in human nonsmall cell lung cancer (NSCLC) research, especially in the metastasis of NSCLC, and highlight the future opportunities and challenges in diagnostics and therapy of NSCLC patients.

Optimization modeling of single-chain antibody against hepatoma based on similarity algorithm.

The purposes was to establish optimal modeling of single-chain antibody molecules based on similarity algorithm and seek the connecting peptides that had the minimal effect on the structure and bioactivity of the variable region of heavy chain (VH) and that of light chain (VL) in a single-chain antibody against liver cancer. After the Linker with different lengths (n=0~7) had been added into single chain fragment variable (ScFv), modeling of the overall sequences of VH, VL and ScFv were conducted respectively. Meanwhile, the peptide chain structure of (Gly4Ser)n was adopted for the connecting peptide. Then the spatial spherical shell layer alignment algorithm based on spherical polar coordinates was utilized for comparing the structural similarity of VH and VL before and after adding connecting peptide. Equally, in order to determine the stability of VH and VL, MATLAB was applied for analysis of the fore and aft distances and the diffusion radius. Indirect ELISA method was used to detect single-chain antibody immunological activity of Linker with different lengths. The MTT assay was utilized for the examination of the inhibition rate of single-chain antibody with different lengths of Linker to liver cancer cell. When n=4, the structural similarity between VH together with VL and their original ones was the highest. When n=3, the influence of connecting peptide on the stability of VH and VL was minimum. When n>3, the fore and aft distances changed little due to the increase and fold of the length of peptide chain. The results of ELISA detection showed that when n=4, affinity of single chain antibody to liver cancer cells was much higher. The MTT test also indicated that when n=4, the inhibition rate of the connecting peptide on hepatoma carcinoma cell reached the highest, and that came second when n=3. When n=4, the structural stability and biological functions of anti-hepatoma single-chain antibody were both favorable. This study has provided a basis for the design and construction of single-chain antibody.

Clinical observation of three dimensional conformal radiotherapy with tamoxifen in treatment of postoperative malignant glioma.

OBJECTIVE: To evaluate the efficacy and adverse effects of three dimensional conformal radiotherapy (3D-CRT) with tamoxifen in treating patients with postoperative malignant glioma. PATIENTS AND METHODS: 60 patients of postoperative malignant glioma were randomly assigned into two groups, 30 patients were treated with 3D-CRT plus tamoxifen (treatment group), and the other 30 patients with 3D-CRT plus temozolomide (control group). All patients were radiated by 6MV X-ray, 2.0 Gy per fraction, once daily, with a total dose (DT) of 56~60 Gy. Tamoxifen was delivered at 60 mg /m2/d, temozolomide was given at 75 mg/m2/d. All patients were treated with concurrent radiotherapy. RESULTS: One, 2, 3 year survival rates of treatment and control group were 63.3%, 30.0%, 23.0% and 70.0%, 33.3%, 26.7%, respectively (χ2=0.01, 0.23, 0.09, P>0.05). The rate of thromboembolism in treatment group was 6.7%. CONCLUSION: Therapeutic efficacy of two groups was similar, but it was more cost- effective in treatment group, and toxicity did not increase.

NF-κB RelB negatively regulates osteoblast differentiation and bone formation.

RelA-mediated NF-κB canonical signaling promotes mesenchymal progenitor cell (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and thus negatively regulates bone formation. Previous studies suggest that NF-κB RelB may also negatively regulate bone formation through noncanonical signaling, but they involved a complex knockout mouse model, and the molecular mechanisms involved were not investigated. Here, we report that RelB(-/-) mice develop age-related increased trabecular bone mass associated with increased bone formation. RelB(-/-) bone marrow stromal cells expanded faster in vitro and have enhanced OB differentiation associated with increased expression of the osteoblastogenic transcription factor, Runt-related transcription factor 2 (Runx2). In addition, RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly, RelB(-/-) bone-derived MPCs formed bone more rapidly than wild-type cells after they were injected into a murine tibial bone defect model. Our findings indicate that RelB negatively regulates bone mass as mice age and limits bone formation in healing bone defects, suggesting that inhibition of RelB could reduce age-related bone loss and enhance bone repair.

Phase II study on breast conservative surgery plus chemo- and radiotherapy in treating Chinese patients with early staged breast cancer.

PURPOSE: To evaluate the efficacy of conservative surgery plus chemo-, radio-therapy in treating patients with early stage breast cancer. PATIENTS AND METHODS: Eligible patients were treated by postoperative chemotherapy as well as whole-breast irradiation with tumor bed boost. Postoperative radiotherapy consisted of 6 MV whole breast linear accelerator irradiation with two tangential half fields to a total dose of 45~50 Gy, followed by 10~15 MeVß boost irradiation to tumor bed for 10~20 Gy, total dose 56~66 Gy. RESULTS: Fifty-two patients were enrolled. Overall 1-, 2- and 3 year survival rates were 98.1%, 92.3%, and 90.4%, respectively, with a local recurrence rate of 5.77%. Cosmetic results were evaluated as good by doctors in 90.4% of patients. CONCLUSIONS: Breast conservative surgery combined with chemo- radio-therapy could be a treatment option for Chinese patients with early stage breast cancer.