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Objective: This study aimed to construct a new staging system for patients with esophageal squamous cell carcinoma (ESCC) based on combined pathological TNM (pTNM) stage, radiomics, and proteomics., Methods: This study collected patients with radiomics and pTNM stage (Cohort 1, n = 786), among whom 103 patients also had proteomic data (Cohort 2, n = 103). The Cox regression model with the least absolute shrinkage and selection operator, and the Cox proportional hazards model were used to construct a nomogram and predictive models. Concordance index (C-index) and the integrated area under the time-dependent receiver operating characteristic (ROC) curve (IAUC) were used to evaluate the predictive models. The corresponding staging systems were further assessed using Kaplan-Meier survival curves., Results: For Cohort 1, the RadpTNM4c staging systems, constructed based on combined pTNM stage and radiomic features, outperformed the pTNM4c stage in both the training dataset 1 (Train1; IAUC 0.711 vs. 0.706, p < 0.001) and the validation dataset 1 (Valid1; IAUC 0.695 vs. 0.659, p < 0.001; C-index 0.703 vs. 0.674, p = 0.029). For Cohort 2, the ProtRadpTNM2c staging system, constructed based on combined pTNM stage, radiomics, and proteomics, outperformed the pTNM2c stage in both the Train2 (IAUC 0.777 vs. 0.610, p < 0.001; C-index 0.898 vs. 0.608, p < 0.001) and Valid2 (IAUC 0.746 vs. 0.608, p < 0.001; C-index 0.889 vs. 0.641, p = 0.009) datasets., Conclusions: The ProtRadpTNM2c staging system, based on combined pTNM stage, radiomic, and proteomic features, improves the predictive performance of the classical pTNM staging system., (© 2022. Society of Surgical Oncology.)

This study investigates patient appointment scheduling and examination room assignment problems involving patients who undergo ultrasound examination with considerations of multiple examination rooms, multiple types of patients, multiple body parts to be examined, and special restrictions. Following are the recommended time intervals based on the findings of three scenarios in this study: In Scenario 1, the time interval recommended for patients' arrival at the radiology department on the day of the examination is 18 min. In Scenario 2, it is best to assign patients to examination rooms based on weighted cumulative examination points. In Scenario 3, we recommend that three outpatients come to the radiology department every 18 min to undergo ultrasound examinations; the number of inpatients and emergency patients arriving for ultrasound examination is consistent with the original time interval distribution. Simulation optimization may provide solutions to the problems of appointment scheduling and examination room assignment problems to balance the workload of radiological technologists, maintain high equipment utilization rates, and reduce waiting times for patients undergoing ultrasound examination.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 10 9 /L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Ma, Yu, Ouyang, Luo, Pei, Xu, Hu, Mo, Xu, Lan, Shen, Shou, Qian, Feng, Zhao, Jiang, Hu, Zhang, Qian, Wu, Wu, Qiu, Li, Lang, Chen, Chen, Guo, Cao, Jiang, Xia, Le, Zhao, Huang, Zhang, Lv, Hua, Hong, Zheng, Wang, Hu, Chen, Zhang, Tao, Xie, Kuang, Luo, Su, Guo, Wu, Jiang, Zhang, Zhang, Chen, Xu, Guo, Tu, Hu, Yan, Yao, Lou, Jin and the APL Cooperative Group of Zhejiang Province.)

Objective: To investigate the role of microRNA-582-5p (miR-582-5p) on osteosarcoma (OS) cell behaviors and provide potential therapeutic targets for OS., Materials and Methods: Expression levels of miR-582-5p in OS cell lines and normal cell lines were measured by quantitative real-time PCR. Cell proliferation, migration and invasion capacities were assessed by cell counting kit-8 assay, wound-healing assay, and transwell invasion assay, respectively. Downstream target of miR-582-5p was confirmed by Luciferase activity reporter assay and Western blotting assay., Results: MiR-582-5p expression was downregulated in OS cell lines compared with normal cell lines. Overexpression of miR-582-5p inhibits OS cell proliferation, migration, and invasion capacities. Neuro-oncological ventral antigen 1 (NOVA1) was chosen as target gene of miR-582-5p by bioinformatics analysis and Luciferase reporter assay. Moreover, overexpression of NOVA1 could impair tumor suppression role of miR-582-5p on OS cell behaviors., Conclusions: MiR-582-5p exerts tumor-suppressive role on OS cell behaviors via targeting NOVA1 in vitro, which will help us to understand the mechanisms underlying OS progression.

Objective: To study the characteristics and clinical significance of pulmonary function test and kerbs von den lungen 6 (KL-6) in anti-synthetase syndrome related interstitial lung disease (ASSD-ILD) and idiopathic pulmonary fibrosis (IPF). Methods: The clinical data of 43 patients with ASSD-ILD (ASSD-ILD group) from May 2015 to May 2017 were collected retrospectively, including 12 males and 31 females, and 34 patients with IPF (IPF group) treated in the First Affiliated Hospital of Zhengzhou University during the same period, including 28 males and 6 females, were also included. The basic information, and the value of pulmonary function test [pulmonary function parameters included the forced vital capacity expressed as percent predicted (FVC%pred), the forced expiratory volume in 1 second expressed as percent predicted (FEV(1)%pred), the ratio of FVC to FEV(1) (FVC/FEV(1)), the peak expiratory flow expressed as percent predicted (PEF%pred), the forced expiratory flow at 25%, 50%, 75% of FVC as percent predicted (FEF(25)%pred, FEF(50)%pred, and FEF(75)%pred), the maximum mid-expiratory flow as percent predicted (MMEF% pred), and the diffusing capacity for carbon monoxide as percent predicted (DLCO% pred)], and serum KL-6 level in ASSD-ILD and IPF were compared. Results: The FEV(1)%pred, FEF(50)%pred, FEF(75)%pred, and MMEF%pred values in ASSD-ILD group were significantly lower than those in IPF group (all P< 0.05), while the FVC% pred, FVC/FEV(1), PEF% pred, FEF(25)%pred, and DLCO% pred values in ASSD-ILD group had no significant difference compared with IPF group (all P> 0.05). There was no significant difference in serum KL-6 level between ASSD-ILD group and IPF group [(1 169±911) vs (1 210±908) U/ml, t =0.62, P =0.463]. Follow-up analysis showed that the serum KL-6 level of ASSD-ILD patients who died within two years was significantly higher than that of survivors [(2 060±1 168) vs (1 042±858) U/ml, t =2.93, P =0.041]. The serum KL-6 level of patients who died within two years of IPF patients was also significantly higher than that of patients who survived [(1 767±865) vs (1 089±894) U/ml, t =2.53, P =0.026]. The serum KL-6 level in ASSD-ILD group was negatively correlated with FVC%pred ( r =-0.43, P =0.004), FEV(1)%pred ( r =-0.39, P =0.010) and DLCO% pred ( r =-0.41, P =0.006). There was no correlation between serum KL-6 level and pulmonary function test indexes in IPF group (all P> 0.05). Conclusions: There is difference in pulmonary function test between ASSD-ILD patients and IPF patients. High serum KL-6 level will be predictive of poor prognosis.

Background: Chylothorax after esophagectomy is uncommon but potentially fatal. We performed a retrospective study to assess the effect of olive oil administered orally before surgery on reducing chylothorax in patients who underwent minimal invasive esophagectomy., Methods: Between May 2013 and December 2016, patients with esophageal squamous cell cancer who underwent minimal invasive esophagectomy were screened. Patients in the investigational group were preoperatively administered olive oil orally 8 hours before surgery, and patients in the control arm received no olive oil. We used a propensity score matching model to derive 1:1 cohorts. Statistical analysis was performed by using the t test or χ 2 or Fisher's exact test., Results: The propensity score matching model finally selected 384 of 425 patients, with 192 patients in each group. The patient characteristics were balanced. Oral olive oil was well tolerated. The thoracic duct identification rate was higher in the investigational group (100% versus 45.31%, χ 2  = 141.78, p < 0.01). The investigational group was associated with a reduced incidence of ligation (7.81% versus 18.22%, χ 2  = 8.03, p = 0.003). The incidence of chylothorax was significantly reduced in the investigational group compared with that of the control group (0% versus 3.12%, χ 2  = 4.23, p = 0.03)., Conclusions: Preoperative administration of olive oil is a simple and safe method to minimize chylothorax complicating minimal invasive esophagectomy., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Nasopharyngeal carcinoma is the most common head and neck tumor in Southern China and Southeast Asia, presenting high rates of local invasion and early distant metastasis. Abnormally expressed miR-99a has been discovered in many tumors, and it is involved in nasopharyngeal carcinoma as well. This study aims to explore the molecular mechanisms of miR-99a and mTOR in regulating nasopharyngeal carcinoma., Patients and Methods: MiR-99a expression in nasopharyngeal carcinoma cells was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was performed for accessing cell proliferative capacity. Dual-Luciferase reporter gene assay was employed to verify the combination between miR-99a and mTOR., Results: We found that miR-99a was downregulated while mTOR was upregulated in nasopharyngeal carcinoma cell lines CNE1 and SUNE1. Low expression of miR-99a or high expression of mTOR predicted poor prognosis of nasopharyngeal carcinoma. MiR-99a overexpression inhibited the proliferation of CNE1 and SUNE1 cells through targeting mTOR., Conclusions: We provided evidence that miR-99a inhibits NPC cell proliferative ability by inhibiting mTOR. The newly identified miR-99a/mTOR axis provides novel insight into the pathogenesis of NPC and represents a potential therapeutic target for NPC.

Background: To compare overall survival in patients with clinical T1-3N0-1 thoracic esophageal squamous cell carcinoma treated with surgery or definitive chemoradiation therapy (CRT)., Methods: We used propensity-score matching to derive 1:1 cohorts of surgery versus definitive CRT. Statistical analysis was performed using χ 2 or Fisher's exact tests. Survival functions were estimated using Kaplan-Meier survival plots, and survival distributions were compared using log-rank tests. Cox proportional hazards modeling was used to analyze the factors affecting overall survival., Results: A total of 334 patients treated with surgery and 252 treated with definitive CRT were included. 129 (38.6%) of 334 patients had recurrence after surgery versus 118 (46.8%) of 252 after definitive CRT. Before matching, the median overall survival were 39.5 months (95% CI, 28.8-50.2) and 23.5 months (95% CI, 18.5-28.5) (P < 0.001) in the surgery and definitive CRT group, respectively. After matching (112 patients in each treatment group), median overall survival was 43.6 months (95% CI, 28.1-59.1) with surgery versus 19.3 months (95% CI, 14.4-24.2) with CRT (P < 0.001)., Conclusions: In this retrospective analysis, surgery was associated with better overall survival compared with definitive CRT., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

As a severe photoreceptor-degenerative disease, retinitis pigmentosa (RP) is currently incurable and eventually leads to partial or complete blindness. (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TIM) is a novel antioxidant isolated from the plant of Alpinia katsumadai Hayata, with protective effects on photoreceptor cells against lipoteichoic acid-induced damage through inhibiting oxidative stress. The present study was to further demonstrate whether TIM could ameliorate retinal degeneration of Pde6b rd10 (rd10) mice, a mouse model of RP. rd10 mice were treated with TIM by intraperitoneal injection daily from postnatal Day 10 (P10) to P26. Retinal function was tested by electroretinography. Histology was evaluated by toluidine blue staining and TUNEL assay. Oxidative stress markers were measured by ELISA. Immunohistochemistry, real-time PCR, and western blotting were applied to explore the protective mechanism. Results showed TIM significantly improved the retinal function and decreased photoreceptor cell apoptosis in rd10 mice through reducing oxidative stress. For the first time, this study demonstrated the protective effects of TIM against retinal degeneration in rd10 mice, providing scientific rationale to use TIM treating the RP.

Multiple myeloma (MM) is a cancer that occurs in plasma cells, which fall under the category of white blood cells that are in charge of antibody production. According to previous studies, microRNA-497 (miR-497) functions as a tumor suppressor in several types of cancer, including gastric cancer and colorectal cancer. Therefore, the present study aims to investigate the effects of miR-497 on cellular function of human MM cells through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway by targeting Raf-1. The differentially expressed genes and miRs in MM, and the relationship between the miR and gene were verified. It was found that Raf-1 was a target gene of miR-497. The data obtained from MM tissues showed increased Raf-1 level and decreased miR-497 level. MM cells were treated with mimic, inhibitor and siRNA in order to evaluate the role of miR-497, Raf-1 and MAPK/ERK in MM. The expression pattern of miR-497, Raf-1, ERK1/2, survivin, B-cell lymphoma-2 (Bcl-2) and BCL2-Associated X (Bax) as well as the extent of ERK1/2 phosphorylation were determined. Retored miR-497 and si-Raf-1 resulted in increases in the Bax expression and cell apoptosis and decreases in the expressions of Raf-1, MEK-2, survivin, Bcl-2, along with the extent of ERK1/2 phosphorylation. In addition, the biological function evaluations of MM cells revealed that miR-497 mimic or si-Raf-1 led to suppression in cell proliferation, invasion and migration. In conclusion, our results have demonstrated that miR-497 targets Raf-1 in order to inhibit the progression of MM by blocking the MAPK/ERK signaling pathway.

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.

MicroRNA (miR)-9 has been demonstrated to regulate the radiosensitivity of tumor cells. In the present study, the mechanism by which miR-9 modulates the sensitivity of nasopharyngeal carcinoma (NPC) cells to ultraviolet (UV) radiation was investigated. The results demonstrated that exposure of NPC cells to UV light resulted in a significant increase in the expression of miR-9, and that CNE2 cells overexpressing miR-9 exhibited reduced levels of DNA damage and increased levels of total glutathione upon UV exposure. Accordingly, the inhibition of the expression of miR-9 promoted UV-induced DNA damage and apoptosis. Although miR-9 inhibited the expression of E-cadherin in the CNE2 cells and increased their resistance to UV radiation, the use of small interfering RNA to inhibit the expression of E-cadherin was not sufficient to decrease the radiosensitivity of the NPC cells. These data demonstrated that miR-9 did not modulate the sensitivity of the CNE2 cells to UV radiation through E-cadherin, but suggested that miR-9 regulated radiosensitivity through its effects on glutathione. These findings suggest that miR-9 may be a potential target for modulating the radiosensitivity of NPC cells.

The lipocalin proteins (lipocalins) are a large family of small proteins characterized by low sequence similarity and highly conserved crystal structures. Lipocalins have been found to play important roles in many human diseases. For this reason, a systemic analysis of the molecular properties of human lipocalins is essential. In this study, human lipocalins were found to contain four structurally conserved regions (SCRs) and could be divided into two subgroups. A human lipocalin protein-protein interaction network (PPIN) was constructed and integrated with their expression data in esophageal carcinoma. Many lipocalins showed obvious co-expression patterns in esophageal carcinoma. Their subcellular distributions also suggested these lipocalins may transfer signals from the extracellular space to the nucleus using the pathway-like paths. These analyses also expanded our knowledge about this human ancient protein family in the background of esophageal carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) has the highest mortality rates in China. The 5-year survival rate of ESCC remains dismal despite improvements in treatments such as surgical resection and adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. The aim of the present study, therefore, was to develop an immunohistochemistry-based prognostic model to improve clinical risk assessment for patients with ESCC., Methods: We developed a molecular prognostic model based on the combined expression of axis of epidermal growth factor receptor (EGFR), phosphorylated Specificity protein 1 (p-Sp1), and Fascin proteins. The presence of this prognostic model and associated clinical outcomes were analyzed for 130 formalin-fixed, paraffin-embedded esophageal curative resection specimens (generation dataset) and validated using an independent cohort of 185 specimens (validation dataset)., Results: The expression of these three genes at the protein level was used to build a molecular prognostic model that was highly predictive of ESCC survival in both generation and validation datasets (P = 0.001). Regression analysis showed that this molecular prognostic model was strongly and independently predictive of overall survival (hazard ratio = 2.358 [95% CI, 1.391-3.996], P = 0.001 in generation dataset; hazard ratio = 1.990 [95% CI, 1.256-3.154], P = 0.003 in validation dataset). Furthermore, the predictive ability of these 3 biomarkers in combination was more robust than that of each individual biomarker., Conclusions: This technically simple immunohistochemistry-based molecular model accurately predicts ESCC patient survival and thus could serve as a complement to current clinical risk stratification approaches.

Focal distribution of microvascular and lymphatic vessels is a critical issue in cancer, and is measured by tissue microarray (TMA) construction from paraffin-embedded surgically obtained tissues, a process that may not accurately reflect true focal distribution. The aim of this study was to assess the concordance of microvascular density (MVD) and lymphatic vessel density (LVD) in TMAs with corresponding whole sections, and to correlate the MVD or LVD with clinicopathological parameters in 124 cases of esophageal squamous cell carcinoma (ESCC). MVD, determined by CD105 immunohistochemistry of whole sections, was strongly associated with lymph node metastasis (p=0.000) and pTNM stage (p=0.001). Kaplan-Meier survival analysis showed that increasing CD105 microvessel count correlated with decreasing survival (p<0.001). The same result was acquired when MVD was calculated from tissue microarrays. Analysis of continuous data showed a highly significant correlation between whole sections and TMA data (Pearson r=0.522, p<0.001). Increasing LVD, as determined by D2-40 immunohistochemistry of whole sections, correlated with decreasing survival, but this relationship was undetectable using TMAs. In conclusion, we demonstrate that for the selected endothelial markers, TMAs can provide a realistic and reliable estimate of the extent of MVD, but not LVD in ESCC samples., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Background: According to the hygiene hypothesis, bacterial infections during early life contribute to a reduced incidence of asthma in animals. However, the effects of microbial products at a safe dose and within a rational time course on the prevention of allergic rhinitis (AR) have been inconclusive. This study investigated the immunomodulatory effects of oral administration of a bacterial extract, OM-85 Broncho-Vaxom (BV), with a low dose and general time course, which is currently used for respiratory infections in humans, on AR inflammation in mice., Methods: We developed a mouse model of ovalbumin (OVA)-induced AR allergic inflammation in the nose mucosa of mice. Low doses of OM-85 BV were orally administered for 3 months (long term) before sensitization. We evaluated nasal symptoms, pathology in the nose, inflammatory cells, and the levels of T helper 1 (Th1)/Th2 cytokines in the nasal lavage fluids, and the serum levels of specific IgE and IgG1. We also observed enhanced effects of OM-85 BV with 1 month (short term) of treatment., Results: We found that long-term pretreatment with OM-85 BV protected the mice from the majority of allergy-specific symptoms; specifically, OM-85 BV suppressed nasal symptoms, inhibited eosinophil infiltration in the nose, inhibited inflammatory infiltrates and the Th2 response by reducing cytokines (IL-4, IL-5, or IL-13) in the nasal lavage fluids, and reduced IgE and IgG1 levels. Furthermore, short-term treatment with OM-85 BV decreased the levels of Th2 cytokines and IgE., Conclusion: Taken together, our data suggested that OM-85 BV is a low-cost alternative candidate to prevent AR with simple oral administration.

NGAL (neutrophil gelatinase-associated lipocalin) is a novel cancer-related protein involves multiple functions in many cancers and other diseases. We previously overexpressed NGAL to analyze its role in esophageal squamous cell carcinoma (ESCC). In this study, a protein-protein interaction (PPI) was constructed and the shortest paths from NGAL to transcription factors in the network were analyzed. We found 28 shortest paths from NGAL to RELA, most of them obeying the principle of extracellular to cytoplasm, then nucleus. These shortest paths were also prioritized according to their normalized intensity from the microarray by the order of interaction cascades. A systems approach was developed in this study by linking differentially expressed genes with publicly available PPI data, Gene Ontology and subcellular localizaton for the integrated analyses. These shortest paths from NGAL to DEG transcription factors or other transcription factors in the PPI network provide important clues for future experimental identification of new pathways.

Objectives: Esophageal squamous cell carcinoma (ESCC) is one of the most frequent causes of cancer death worldwide and effective diagnosis is needed. We assessed the diagnostic potential of an autoantibody panel that may benefit early diagnosis., Methods: We analyzed data for patients with ESCC and normal controls in a test cohort and a validation cohort. Autoantibody levels were measured against a panel of six tumor-associated antigens (p53, NY-ESO-1, matrix metalloproteinase-7 (MMP-7), heat shock protein 70 (Hsp70), peroxiredoxin VI (Prx VI), and BMI1 polycomb ring finger oncogene (Bmi-1)) by enzyme-linked immunosorbent assay., Results: We assessed serum autoantibodies in 513 participants: 388 with ESCC and 125 normal controls. The validation cohort comprised 371 participants: 237 with ESCC, and 134 normal controls. Autoantibodies to at least 1 of 6 antigens demonstrated a sensitivity/specificity of 57% (95% confidence interval (CI): 52-62%)/95% (95% CI: 89-98%) and 51% (95% CI: 45-57%)/96% (95% CI: 91-99%) in the test and validation cohorts, respectively. Measurement of the autoantibody panel could differentiate early-stage ESCC patients from normal controls (sensitivity 45% (95% CI: 32-59%) and specificity 95% (95% CI: 89-98%) in the test cohort; 46% (95% CI: 35-58%) and 96% (95% CI: 91-99%) in the validation cohort). In either cohort, no significant differences were seen when patients were subdivided by age, gender, smoking status, size of tumor, site of tumor, depth of tumor invasion, histological grade, lymph node status, TNM stage, or early-stage and late-stage groups., Conclusions: Measurement of an autoantibody response to multiple tumor-associated antigens in an optimized panel assay, to help discriminate early-stage ESCC patients from normal controls, may aid in early detection of ESCC.

Objective: To explore the anatomic features of mesoesophagus in combined thoracoscopic and laparoscopic esophagectomy with three-fields lymphadenectomy., Methods: Clinical data of 67 patients undergoing thoracoscopic and laparoscopic esophagectomy with three-fields lymphadenectomy from July 2011 to September 2012 were analyzed retrospectively. All the patients underwent three-fields lymphadenectomy. Proper surgical planes were selected according to anatomy of mesoesophagus. Thoracoscopic surgical space was bounded on azygotic vein and divided into upper and low esophageal triangle. Pancreas was the key anatomical mark for laparoscopic gastric dissection, and peripancreatic space was the natural laparoscopic surgical plane. Prevertebral fascia was bottom surface of neck dissection and carotid sheath was the boundary of two sides., Results: The median operative time was 251.6 min (range, 220 to 320 min). The median operative blood loss was 105.6 ml (range, 40 to 320 ml). The median number of lymph nodes dissected was 29.1 (range, 13 to 46, totally 1949). There was no perioperative death. Sixty-six patients were followed up with a mean follow-up time of 8.2 months (range, 2 to 14 months). Postoperative complications included reflux esophagitis in 10 and anastomotic stenosis in 3 cases., Conclusion: It is safe and more radical for minimally invasive esophagectomy that overall concept of minimally invasive anatomy of mesoesophagus is applied to identify the anatomic plane and landmark during operation.

Objective: To investigate the effects of down-regulated miR-9 expression on ultraviolet rays (UV)-induced reactive oxygen species (ROS) damage in nasopharyngeal carcinoma (NPC) cells., Methods: The NPC cells were transfected with inhibitors of miR-9 by lipofectamine to decrease the expression of miR-9, and the cells transfected with inhibitor control as the control. ROS levels following UV exposure were examined with DCF-DA method and the concentration of glutathione was analyzed via the benzoic acid method; DNA damage and apoptosis also were evaluated., Results: There was significant difference in ROS levels between miR-9 expression-inhibited cells and control cells (26 895 ± 218 vs 15 765 ± 927, t = 39.754, P < 0.001), and also there were significant differences in DNA damage rates (28.0% ± 10.0% vs 23.6% ± 9.2%) and in apoptosis rates (8.0% ± 0.9% vs 4.5% ± 0.8%) following UV exposure between two groups of cells. The miR-9 expression-inhibited cells showed lower level (1.87 ± 0.15) µmol/L of glutathione compared with the control cells (9.85 ± 0.15) µmol/L (t = -48.832, P < 0.001)., Conclusion: Inhibition of miR-9 expression promoted UV-induced ROS damage in nasopharyngeal carcinoma cells.

Endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2), a new splicing variant of VEGFR-2, was shown to be the first endogenous specific inhibitor of lymphatic vessel growth. The expression of esVEGFR-2 and its clinicopathological roles in esophageal squamous cell carcinoma (ESCC) are unclear. In this article, quantitative RT-PCR was employed to detect the mRNA levels of esVEGFR-2 and VEGF-C in 90 paired primary ESCC tissues, along with immunohistochemical staining to measure esVEGFR-2 protein in 182 ESCC primary tissues. Correlations between esVEGFR-2 expression and clinicopathological features were also analyzed. Compared with the corresponding non-neoplastic esophageal mucosa tissues, the mRNA level of esVEGFR-2 was decreased, whereas the mRNA level of VEGF-C was increased in ESCCs. Downregulation of esVEGFR-2 mRNA level was significantly correlated with pTNM stages (χ(2) = 7.790, p=0.02). Immunohistochemical staining of esVEGFR-2 was inclined to be reduced in ESCC tissues; lower esVEGFR-2 protein expression was related to better prognosis (χ(2) = 6.366, p=0.012), whereas higher esVEGFR-2 protein accumulation in ESCC tissues was an independent prognostic factor for poor survival of patients (hazard ratio, 1.606; 95% confidence interval, 1.042-2.476; p=0.032). Taken together, altered expression of esVEGFR-2 is correlated with progression of ESCC. esVEGFR-2 might serve as a new independent prognostic marker for ESCC patients.

This study was aimed to explore the expression and significance of DNMT1 gene in bone marrow of patients with acute myelogenous leukemia (AML). The expression of DNMT1 gene was detected by real-time PCR in 30 healthy people and 126 AML patients. The results showed that the expression level of DNMT1 gene was lower in the 30 healthy people and was higher in AML patients. There was a marked decline in the expression level of DNMT1 gene after complete remission (CR) as compared with the initial treatment. The expression level of DNMT1 gene did not correlated with age, sex and the clinical characteristics at initial diagnosis such as white blood cell count and chromosomal karyotype in AML patients. The CR rate in AML patients with low expression level of DNMT1 gene was lower than that in those with high expression level. It is concluded that bone marrow DNMT1 gene level may play an important role in AML pathogenesis and can serve as an index in evaluating AML prognosis.

Objective: To investigate the clinical effect of chronic myelocytic leukemia (CML) patients treated with imatinib (IM) and interferon (IFN)-α., Methods: One hundred and fifty five CML patients at chronic phase were included in the study. All patients were divided into two groups according to treatment regimen: IM + IFN group and IM group. Complete cytogenetic response (CCyR) rate, major molecular response (MMR) rate, complete molecular response (CMR) rate, overall survival (OS) and progression free survival (PFS) were observed and compared in both groups., Results: The CCyR rate was higher in the IM + IFN group than that in the IM group at 6 months (60.6% vs 41.6%, P < 0.05), but no difference was observed later on. The MMR + CMR rate was higher in the IM + IFN group than that in the IM group at 6 months and 12 months (71.2% vs 34.8%, 77.3% vs 52.8%, respectively, P < 0.05), but no difference after that. After stratification according to Sokal risk, the CCyR rate of low- and intermediate-risk patients was higher in the IM + IFN group than that in the IM group at 6 months (77.8% vs 52.6%, 75.0% vs 46.7%, P < 0.05), but not from 12 months on; the MMR + CMR rate of low- and intermediate-risk patients was higher in the IM + IFN group than that in the IM group at 6 months and 12 months (85.2% vs 36.8%, 90.0% vs 36.7%, P < 0.05; 88.9% vs 57.9%, 90.0% vs 56.7%, P < 0.05), but not from 24 months on. There was no significant difference in high-risk patients. OS in IM and IM + IFN group at 6, 12, 24 and 36 months was 100%, 100%, 96.8% and 90.0%, and 100%, 100%, 97.9% and 93.1%, respectively. PFS in IM and IM + IFN group at 6, 12, 24 and 36 months was 97.8%, 95.5%, 91.9% and 85.5%, and 98.5%, 95.5%, 91.5% and 86.2%, respectively. There was no significant difference in OS (u = 0.427, P = 0.514) or PFS (u = 0.556, P = 0.456). The side effects in both groups included pancytopenia, edema, weight gain, ostalgia, rash and muscle spasm. In addition, patients in the IM + IFN group suffered from flu-like symptoms, impaired liver function, abnormal thyroid function and extremity sensory disturbance. It seemed that grade III or IV pancytopenia occurred more commonly in the patients in the IM + IFN group, however, there was no statistically significance., Conclusions: The response to IM + IFN is more rapid than that to IM alone, especially for the low- and intermediate-risk patients. It seems no benefit of the addition of IFN to treatment of high-risk patients. During the period of 36 months, survival rate in the IM + IFN group is not higher than that in IM group, and it is possible to increase the side effects of pharmaceutical drugs.

Objective: To explore the effects of beta-elemene combined with aclarubicin on the induction of HL-60 cell apoptosis and its mechanisms in antileukemia therapy., Methods: HL-60 cells were treated for 20 hours with different dose of aclarubicin (0.05, 0.10, 0.25 microg/ml) or with different concentrations of beta-elemene (10, 20, 40 microg/ml) in the presence or absence of aclarubicin (0.10 microg/m). The apoptotic rate was analyzed by flow cytometry (FCM), the productions of PGE2 in culture supernatants was detected by competitive ELISA and the expressions of COX-2 and NF-kappaB activity in HL-60 cells by Western blot., Results: Lower concentration of aclarubicin (0.05, 0.10 microg/ml) didn't affect apoptotic rate, and COX-2, NF-kappa B and PGE2 expression on HL-60 cells. Combined treatment of beta-elemene and aclarubicin (0.10 microg/ml) enhanced the apoptotic effect and down-regulated COX-2, NF-kappaB and PGE2 expressions. There was a positive correlation between the effects and beta-elemene concentrations., Conclusion: beta-elemene enhances aclarubicin-mediated apoptotic effect, down-regulation of COX-2 and their inducing products PGE2 in HL-60 cells by suppressing activitation of NF-kappaB.