Objective To investigate the local-regional recurrence in thoracic esophageal cancer after radical surgery including two-field lymph node dissection and provide evidence for postoperative radiotherapy. Methods We reviewed local-regional recurrence for 134 cases with esophageal squamous cell carcinoma after radical surgery from 2004 to 2009. Results In 134 cases, lymph node metastasis rate,anastomosis recurrence rate and tumor bed recurrence rate was 94. 0%, 9. 7% and 3.7%, respectively. As to the 126 cases with lymph node metastasis, significant difference was detected between mediastinal metastasis, supraclavicular metastasis and abdominal lymph node metastasis (80. 2%, 43.7% and 13.5%,respectively, χ2= 113. 15, P = 0. 000). Furthermore, the relative metastasis rate in upper mediastinum,middle mediastinum and the lower mediastinum was 73.8%, 39.7% and 1.6%, respectively, the difference was statistically significant ( χ2 = 139. 11, P = 0. 000 ). Significant difference was identified between right and left supraclavicular lymph node metastasis (31.7% vs 16. 7%, χ2= 7. 81, P = 0. 005 ).To confirm the analysis above,lymph node metastasis rate of left recurrent laryngeal nerve nodes, (including region 1L, 2L, 4L and 5) ,right recurrent laryngeal nerve nodes, azygos nodes, subcarinal nodes, and 2R region was 38.9%, 43.7%, 15.1%, 34.1% and 25.4%, respectively. Conclusions The main characteristics of local-regional recurrence may be lymph node metastasis for esophageal squamous cell carcinoma after radical surgery. On the contrary, tumor bed recurrence is rare. Dangerous regions include supraclavicular nodes, recurrent laryngeal nerve nodes, azygos nodes as well as subcarinal nodes.

A novel method of feature extraction from protein primary structure has been proposed and applied to classify the protein homodimer, homotrimer, homotetramer and homohexamer, i. e. one protein sequence can be represented by a feature vector composed of amino acid compositions and a set of weighted auto-correlation function factors of amino acid residue index. As a result, high classification accuracies are obtained. For example, with the same support vector machine (SVM), the total accuracies of QIANA, AIANB, MEEJ, ROBB and SNEP sets based on this novel feature extraction method are 77.63, 77.16, 76.46, 76.70 and 75.06% respectively in Jackknife test, which are 6.39, 5.92, 5.22, 5.46 and 3.82 percent points respectively higher than that of COMP set based on the conventional method composed of amino acid compositions. With the same QIANA set, the total accuracy of SVM is 77.63%, which is 16.29 percent points higher than that of covariant discriminant algorithm. These results show: (1) The novel feature extraction method is effective and feasible, and the feature vectors based on this method may contain more protein quaternary structure information and appear to capture essential information about the composition and hydrophobicity of residues in the surface patches buried in the interfaces of associated subunits; (2) SVM can be referred as a powerful computational tool for classifying the homo-oligomers of proteins.
Algorithms ; Amino Acid Sequence ; Artificial Intelligence ; Cluster Analysis ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Proteins ; chemistry ; classification ; Sequence Analysis, Protein ; methods

Objective To investigate the clinical effect of induction chemotherapy plus concurrent radiochemotherapy in the treatment of locally advanced non-small cell lung cancer (NSCLC) through a meta-analysis.Methods CBM, CNKI, Cochrane Library, PubMed, and EMbase were searched for the articles on comparison between induction chemotherapy plus concurrent radiochemotherapy and concurrent radiochemotherapy for patients with locally advanced NSCLC.According to the inclusion and exclusion criteria, the data on short-term outcome and survival were collected.A Meta-analysis was performed to evaluate the clinical effect of induction chemotherapy followed by concurrent radiochemotherapy.Results A total of 5 articles were included, which involved 845 patients.The results showed that the short-term outcome and the 2-and 3-year survival rates were similar between patients receiving induction chemotherapy plus concurrent radiochemotherapy and those receiving concurrent radiochemotherapy ( OR=0.875, 95% CI 0.507-1.510, P=0.631;HR=0.770, 95% CI 0.515-1.151, P=0.203;HR=0.809, 95% CI 0.559-1.172, P=0.262), but the patients receiving induction chemotherapy plus concurrent radiochemotherapy showed a significantly higher incidence rate of grade ≥ 3 leukopenia than those receiving concurrent radiochemotherapy alone ( OR=0.637, 95% CI 0.435-0.931, P=0.020).Conclusions Induction chemotherapy plus concurrent radiochemotherapy shows no significant advantages over concurrent radiochemotherapy alone in the short-term outcome and 2-and 3-year survival rates, but it significantly increases myelosuppression.Since there are few studies involving a limited number of cases included in this analysis, more multicenter randomized trials are needed to provide more detailed data and further clarify the clinical value of induction chemotherapy plus concurrent radiochemotherapy.

Objective To examine the effects of different pre-treatment nutritional status and inflammatory markers on acute adverse reactions in esophageal cancer patients during concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy.Methods The acute adverse reactions of 338 eligible esophageal cancer patients who received concurrent IMRT and chemotherapy in our hospital from 2006 to 2014 were reviewed.The effects of different pre-treatment nutritional status, such as body mass index level (BMI), albumin level (ALB), total lymphocyte count (TLC), the presence or absence of anemia, and inflammatory indicators including neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), on acute adverse reactions in the patients were examined.Data were analyzed using the chi-square test with continuity correction and logistic regression analysis.Results The incidence rate of malnutrition in the patients based on their nutritional status was 5.62%-54.14%.The incidence rate of grade≥2 acute radiation esophagitis (RE) was significantly higher in the low ALB group than in the normal ALB group (P=0.000).The incidence rate of adverse reactions in the hematologic system increased as TLC decreased (P=0.006), but the incidence rate of acute radiation pneumonitis (RP) was reduced as TLC decreased (P=0.001).In addition, the incidence rate of grade ≥2 acute RE was significantly higher in the anemia group than in the non-anemia group.Inflammatory marker analysis demonstrated that the incidence rate of acute RE was significantly higher in the high NLR group and high PLR group than in the low NLR group and low PLR group (P=0.000 and P=0.024, respectively).Logistic regression analysis of nutritional status and inflammatory markers showed that TLC was an independent risk factor for acute adverse reactions in the hematologic system (P=0.001), and ALB and PLR were independent risk factors for acute RE (P=0.017 and P=0.011,respectively).Conclusions Nutritional status and inflammatory markers are associated with concurrent chemoradiotherapy-induced acute adverse reactions in esophageal carcinoma patients, and hence may be valuable indicators of acute adverse reactions during treatment.In addition, nutritional treatment and support care should be actively provided to the patients to prevent the development of acute adverse reactions during treatment.

Aim To investigate the effects of Naotai formula extract(NTE)on the expression of heme oxygenase-1(HO-1) and hephaestin(Heph) in hippocampus of rats after cerebral ischemia/reperfusion by Keap1-Nrf2/ARE signaling pathway.Methods Eighty rats were randomly divided into five groups as follows: sham operation group(Sham), cerebral ischemia/reperfusion group(I/R), low dose group of NTE(4.5 g·kg-1), middle dose group of NTE (9 g·kg-1) and high dose group of NTE(18 g·kg-1).Rats were pretreated by intragastric administration for three consecutive days, and then subjected to middle cerebral artery occlusion (MCAO) 2 hours before reperfusion.The rats were administered with intragastric administration for two days.After cerebral ischemia reperfusion 72 hours, the behavioral activity of rats was recorded by Zea Longa neurological score, and the infarct volume was measured by TTC staining.The expressions of Nrf2, HO-1 and Heph in hippocampus of cerebral ischemia reperfusion rats were observed by real-time quantitative PCR and Western blot, respectively.Results Compared with model group, the neurobehavioral scores significantly decreased in NTE high-dose and middle-dose groups (P<0.01);the infarct volume of NTE groups markedly decreased (P<0.01);the expression of HO-1 mRNA apparently increased (P<0.05) in NTE groups;the expression of Heph mRNA significantly increased in NTE middle-dose and high-dose groups (P<0.05);the expression of Nrf2 and Heph protein evidently increased in the NTE middle and high dose groups (P<0.05, P<0.01);and the expression of HO-1 protein also increased in NTE groups(P<0.01).Conclusions Naotai formula can relieve cerebral ischemia-reperfusion injury.The mechanism might be associated with activating Keap1-Nrf2/ARE signaling pathways, promoting HO-1 generation, advancing the expression of Heph, and then reducing brain iron deposition, to achieve the protection of neurons after cerebral ischemia-reperfusion.

OBJECTIVETo investigate the effects of HIF-1α on adhesion and invasion of human nasopharyngeal carcinoma CNE-1 cells under hypoxia and underlying molecular mechanisms.

METHODSCoCl₂was used to mimic tumor hypoxic microenvironment. mRNA and protein expressions of HIF-1α, E-cadherin and CXCR4 in CNE-1 cells at different hypoxic time phases were detected by RT-PCR and ELISA respectively. The influences of silencing HIF-1α using RNA interference on E-cadherin and CXCR4 expressions were evaluated. Adhesion test Transwell invasion test were used to evaluate the effects of HIF-1α gene silencing on cell adhesion and invasion.

RESULTSUnder hypoxia, HIF-1α mRNA expression in CNE-1 cells was stable, but its protein expression increased obviously (P<0.05). Both mRNA and protein expressions of E-cadherin were decreased significantly with prolonged hypoxia, while mRNA and protein expressions of CXCR4 increased significantly (P<0.05). After silencing HIF-1α gene, expression of E-cadherin protein was up-regulated, but with down-regulated expression of CXCR4 protein, with a decrease significantly in adhesion rate or invasive cell number of CNE-1 cells (P<0.05).

CONCLUSIONSHypoxia can increase HIF-1α protein expression in nasopharyngeal carcinoma cell line CNE-1. Silencing HIF-1α by RNA interference can reduce inhesion and invasion abilities of CNE-1 cells, which may be mediated by down-regulating E-cadherin expression and up-regulating CXCR4 expression.

Cadherins ; genetics ; metabolism ; Carcinoma ; Cell Hypoxia ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Nasopharyngeal Neoplasms ; genetics ; pathology ; RNA Interference ; RNA, Messenger ; Receptors, CXCR4 ; genetics ; metabolism

OBJECTIVETo explore the expression of hypoxia inducible factor-1α(HIF-1α) in esophageal squamous cell carcinoma and its correlation with clinicopathological features.

METHODSOriginal literatures in foreign languages regarding correlation between HIF-1α and esophageal squamous cell carcinoma were identified from Cochrane Library, PubMed, EMbase database, and Chinese original literatures were from CBM, CNKI. All analyses were performed by Stata 11.0 software. Histological grade, degree of differentiation, T stage, lymph node metastasis, tumor stage, lymphatic invasion and vascular invasion were analyzed using pooled odds ratio (OR) with 95% confidence interval (CI).

RESULTSA total of 14 studies including 1 121 patients were enrolled in this meta analysis. Comparing with normal tissue, the expression of HIF-1α in esophageal squamous cell carcinoma was significantly enhanced (OR = 0.088, 95% CI: 0.061-0.129, P = 0.000); HIF-1α was significantly associated with T stage and lymph node metastasis (OR = 0.421, 95% CI: 0.222-0.798, P = 0.008; OR = 0.387, 95% CI: 0.207-0.725, P = 0.003). High expression of HIF-1α was correlated with an increased depth of tumor invasion, more lymph node metastasis and advanced tumor stage, whereas there was no relation to the degree of differentiation, histological grade, tumor stage, lymphatic invasion and vascular invasion.

CONCLUSIONSHigh expression of HIF-1α protein correlates with an increased risk of esophageal squamous cell carcinoma. HIF-1α may be an indicator for T stage, lymph node metastasis and tumor stage, but further studies are needed.

Biomarkers, Tumor ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Confidence Intervals ; Esophageal Neoplasms ; metabolism ; pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Lymphatic Metastasis ; Odds Ratio

Objective: To study the mechanism of action of Danggui Shaoyao San (DSS) in the treatment of Alzheimer'sdisease (AD) from a systematic network level using network pharmacology. Methods: The active ingredients of DSS intreating AD was screened from the Traditional Chinese Medicine System Pharmacology Database (TCSMP), and thedrugs-targets-disease network was built. Target organ localization network, GO analysis and Pathway enrichmentanalysis were used for bioinformatics analysis. Results: 51 kinds of DSS active ingredients were screened by networkpharmacology, showing 377 predicted targets of active compounds. Among them, 197 targets were associated with AD, and the pharmacodynamic targets of DSS active compounds were highly enriched with AD-related signals. The pathwaywas closely related to the reduction of Aβ aggregation and inhibition of tau hyperphosphorylation and biological processessuch as anti-inflammatory and anti-apoptosis, and the mRNA expression of the targeted gene was mainly enriched in theliver, heart, and brain. Conclusion: DSS active compounds interact with multiple targets in multiple ways in a synergisticmanner, mainly to produce important therapeutic effects on AD with anti-inflammatory, anti-apoptotic, enhancingmetabolism and immune system.

postoperative pathological examination results and radiotherapy toxicities. Results All the 45 patients completed preoperative concurrent chemoradiotherapy and surgery, with two cycles of chemotherapy in 39 patients and one cycle in 6 patients. The rates of R0resection and pathological complete response(pCR) were 95.6%(43/45)and 22.2%(10/45), respectively. There were 10(22.2%), 17(37.8%), 15 (33.3%),and 3(6.7%)patients with tumor regression grades 0,1,2,3,respectively. The rate of lymph node metastasis was 37.8%(17/45),and the lymph node ratio was 4.33%(46/1 062). The postoperative pathological examination showed that T and N downstaging after surgery was observed in 24 and 26 patients, respectively;the proportions of patients with T3-T4tumors and positive lymph nodes after surgery declined by 51.1%(P=0.000)and 42.2%(P=0.000), respectively. The overall incidence of radiation esophagitis/gastritis was 44.4%(20/45), and the incidence rates of grade 1, 2, and 3 radiation esophagitis/gastritis were 18%,22%,and 4%,respectively. The incidence of acute radiation pneumonitis was 6.7%(3/45), all in grades 1 and 2. There was one perioperative treatment-related death. Conclusions Two cycles of XELOX chemotherapy combined with concurrent 45 Gy radiotherapy before surgery in patients with locally advanced Siewert type Ⅱ and Ⅲ AEG can achieve a relatively high pCR rate,effectively reduce the lymph node metastasis rate, achieve downstaging, and increase R0resection rate. This regimen has many good advantages,including low incidence of acute toxicities,good tolerability,and acceptable rate of perioperative treatment-related deaths. The target volume delineation involving metastatic lymph nodes is feasible.

Objective To analyze the clinical efficacy,toxicity and survival prognosis of patients diagnosed with Siewert type Ⅱ and Ⅲ locally advanced adenocarcinoma of esophagogastric junction (AEG) undergoing preoperative involved-field irradiation with concurrent chemotherapy. Methods A total of 45 cases were recruited in this prospective clinical trial. Prior to surgery, patients received 2 cycles of chemotherapy with XELOX and concurrent radiotherapy ( a total of 45 Gy in 25 fractions,5 times weekly). After 6-8 weeks,they underwent surgical resection. After the surgery,patients received 6 cycles of adjuvant chemotherapy. The completion of preoperative neoadjuvant chemoradiotherapy, postoperative pathological status,TNM down-staging effect and adverse reactions were observed. Kaplan-Meier method was applied to estimate survival analysis. Results All 45 patients completed preoperative neoadjuvant chemoradiotherapy. Among them, 39 patients completed 2 cycles of chemotherapy, and 6 patients completed 1 cycle of chemotherapy. The median time of surgical interval was 6 weeks. The R0resection rate was 96%.The pathological complete response (pCR) rate was 22%. The TNM down-staging rate was 69%.The incidence of acute radiation-induced esophagitis or gastritis was 44% and the incidence of radiation-induced pneumonitis was 7%. The incidence of grade 1-3 leukocytopenia,thrombocytopenia and neutropenia was 78%,47% and 44%,respectively. In terms of gastrointestinal reactions,the incidence of nausea,vomiting and loss of appetite was 62%,24% and 71%,respectively. No hematologic or nonhematologic adverse effects was observed at grade 4 or 5.The median follow-up time was 30 months. 11 patients died of cancer,1 patient was treatment-related death in the perioperative period and 1 patient died of pneumonia. The 1-,2-and 3-year progression-free survival (PFS) rates were 90%,70% and 67%,respectively. The 1-,2-and 3-year overall survival rates were 95%,80% and 75%,respectively. The 1-,2-and 3-year local control rates were 95%,84% and 84%, respectively. The 1-, 2-and 3-year distant metastasis rates were 7%, 25% and 25%, respectively. Conclusions Preoperative involved-field irradiation with concurrent chemotherapy yields relatively high clinical efficacy and is well tolerated by patients with Siewert typeⅡandⅢlocally advanced AEG.Patients are recommended to receive 4 cycles of adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery.