Prognosis and influencing factors analysis of patients with initially resectable gastric cancer liver metastasis who were treated by different modalities: a nationwide, multicenter clinical study / 中华消化外科杂志

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Prognostic value of a predictive model comprising preoperative inflammatory response and nutritional indexes in patients with gastric cancer / 中华胃肠外科杂志

Objective: To investigate the prognostic value of preoperative inflammatory and nutritional condition detection in the postoperative survival, and establish a prognostic model for predicting the survival of patients with gastric cancer. Methods: The clinicopathological data of 1123 patients with gastric cancer who had undergone radical gastrectomy in Tianjin Medical University Cancer Institute & Hospital from January 2005 to December 2014 were retrospectively analyzed. Patients with history of other malignancy, with history of gastrectomy, who had received preoperative treatment, who died during the initial hospital stay or first postoperative month, and missing clinical and pathological information were excluded. Cox univariate and multivariate analyses were used to identify independent clinicopathological factors associated with the survival of these gastric cancer patients. Cox univariate analysis was used to identify preoperative inflammatory and nutritional indexes related to the survival of patients with gastric cancer after radical gastrectomy. Moreover, the Cox proportional regression model for multivariate survival analysis (forward stepwise regression method based on maximum likelihood estimation) was used. The independent clinicopathological factors that affect survival were incorporated into the following three new prognostic models: (1) an inflammatory model: significant preoperative inflammatory indexes identified through clinical and univariate analysis; (2) a nutritional model: significant preoperative nutritional indexes identified through clinical and univariate analysis; and (3) combined inflammatory/nutritional model: significant preoperative inflammatory and nutritional indexes identified through clinical and univariate analysis. A model that comprised only pT and pN stages in tumor TNM staging was used as a control model. The integrated area under the receiver operating characteristic curve (iAUC) and C-index were used to evaluate the discrimination of the model. Model fitting was evaluated by Akaike information criterion analysis. Calibration curves were used to assess agreement between the predicted probabilities and actual probabilities at 3-year or 5-year overall survival (OS). Results: The study cohort comprised 1 123 patients with gastric cancer. The mean age was 58.9±11.6 years, and 783 were males. According to univariate analysis, age, surgical procedure, extent of lymph node dissection, tumor location, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and nerve invasion were associated with 5-year OS after radical gastrectomy for gastric cancer (all P<0.050). Multivariate analysis further identified age (HR: 1.18, 95%CI: 1.03-1.36, P=0.019), maximum tumor size (HR: 1.19, 95%CI: 1.03-1.38, P=0.022), number of examined lymph nodes (HR: 0.79, 95%CI: 0.68-0.92, P=0.003), pT stage (HR: 1.40, 95%CI: 1.26-1.55, P<0.001) and pN stage (HR: 1.28, 95%CI: 1.21-1.35, P<0.001) as independent prognostic factors for OS of gastric cancer patients. Additionally, according to univariate survival analysis, the preoperative inflammatory markers of neutrophil count, percentage of neutrophils, neutrophil/lymphocyte ratio, platelet/neutrophil ratio and preoperative nutritional indicators of serum albumin and body mass index were potential prognostic factors for gastric cancer (all P<0.05). On the basis of the above results, three models for prediction of prognosis were constructed. Variables included in the three models are as follows. (1) Inflammatory model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, and neutrophil-lymphocyte ratio; (2) nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and serum albumin; and (3) combined inflammatory/nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, neutrophil-lymphocyte ratio, and serum albumin. We found that the predictive accuracy of the combined inflammatory/nutritional model, which incorporates both inflammatory indicators and nutrition indicators (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.698),was superior to that of the inflammation model (iAUC: 0.662, 95% CI: 0.673-0.706;C-index: 0.675), nutritional model (iAUC: 0.666, 95% CI: 0.642-0.698, C-index: 0.672), and TNM staging control model (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.658). Furthermore, the combined inflammatory/nutritional model had better fitting performance (AIC: 10 762) than the inflammatory model (AIC: 10 834), nutritional model (AIC: 10 810), and TNM staging control model (AIC: 10 974). Conclusions: Preoperative percentage of neutrophils, NLR, and BMI have predictive value for the prognosis of gastric cancer patients. The inflammatory / nutritional model can be used to predict the survival and prognosis of gastric cancer patients on an individualized basis.

Modified Linggui Zhugan Decoction () Ameliorates Glycolipid Metabolism and Inflammation via PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α Signaling Pathways in Obese Type 2 Diabetic Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects of modified Linggui Zhugan Decoction (, MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus (T2DM) rats.@*METHODS@#Fifty Sprague-Dawley rats were randomly divided into 5 groups by a random number table, including normal, obese T2DM (ob-T2DM), MLZD low-dose [MLDZ-L, 4.625 g/(kg·d)], MLZD middle-dose [MLD-M, 9.25 g/(kg·d) ] and MLZD high-dose [MLD-H, 18.5 g/(kg·d)] groups, 10 rats in each group. After 4-week intervention, blood samples and liver, pancreas, muscle tissues were collected to assess the insulin resistance (IR), blood lipid, adipokines and inflammation cytokines. The alteration of phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or Akt)/the mammalian target of rapamycin (mTOR)-ribosome protein subunit 6 kinase 1 (S6K1 )/AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α) pathways were also studied.@*RESULTS@#MLZD dose-dependently reduced fasting blood glucose, fasting insulin, homeostasis model of assessment for IR index and increased insulin sensitive index compared with ob-T2DM rats (P<0.05). Similarly, total cholesterol, triglyceride, low-density lipoprotein cholesterol and free fatty acids were also decreased compared with ob-T2DM rats after 4-week treatment (P<0.05 or P<0.01). Improvements in adipokines and inflammatory cytokines were observed with a raised level of adiponectin and a reduced level of leptin, resistin, tumor necrosis factor-α and interleukin-6 (P<0.05 or P<0.01). MLZD regulated the PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α pathways and restored the tissue structure of liver and pancreas (P<0.05 or P<0.01).@*CONCLUSIONS@#MLZD ameliorated glycolipid metabolism and inflammation, which may be attributed to the regulation of PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α pathways.

Experimental Study on Effect of Modified Guilu Erxianjiao Decoction Combined with Cisplatin on Resistance-related Genes and IL-7-mediated Wnt/β-catenin Signaling Pathway in Mice with Lewis Lung Cancer / 中国实验方剂学杂志

Objective:To observe the effect of modified Guilu Erxianjiao decoction combined with cisplatin on the immune function， resistance-related genes and interleukin-7（IL-7）-mediated Wnt/<italic>β</italic>-serial protein（<italic>β</italic>-catenin）signaling pathway in Lewis lung cancer mice by establishing a mouse model of Lewis lung cancer with deficiency of both Qi and Yin. And the anti-cancer mechanism of modified Guilu Erxianjiao decoction was clarified， so as to provide a basis for its clinical application. Method:A Lewis lung cancer mouse model （type of deficiency of both Qi and Yin） was established. Mice were divided into a normal group （no modeling）， a model group （saline solution）， a cisplatin group （cisplatin， 2 mg·kg^-1）， a traditional Chinese medicine （TCM） group （modified Guilu Erxianjiao decoction， 19.63 g·kg^-1·d^-1）， and a combined group （modified Guilu Erxianjiao decoction， 19.63 g·kg^-1·d^-1 + cisplatin， 2 mg·kg^-1）. The 10 mice in each group were administered separately for 21 days of intervention. The general conditions and organ indexes of mice were observed， and tumor inhibition rate was calculated. CD4⁺CD25⁺ regulatory T cell （CD4⁺CD25⁺ Treg） were detected by flow cytometry， the IL-7 level of cytokines in serum was detected by enzyme linked immunosorbent assay（ELISA）， and real-time quantitative polymerase chain reaction（Real-time PCR） was used to detect the gene expression level of drug resistance-related genes P-glycoprotein（P-gp）， and multidrug resistance protein1（MRP1）in tumor tissues. The protein expression of Wnt/<italic>β</italic>-serial protein（<italic>β</italic>-catenin）signaling pathway in tumor tissues were detected by Western blot. Result:In the TCM group and the combined group， the food intake increased， the mental state was better， the response was sensitive， and the body weight increased. Compared with the cisplatin group， the thymus index and spleen index in the combined group were significantly increased （<italic>P</italic><0.01）， and the tumor inhibition rate of the combined group was significantly increased （<italic>P</italic><0.01）. Compared with the cisplatin group， the percentage of CD4⁺CD25⁺Treg/CD4⁺ in the TCM group and the combined group was significantly reduced （<italic>P</italic><0.01）， and IL-7 in the TCM group and the combined group was significantly increased （<italic>P</italic><0.01）. Compared with the cisplatin group， the expressions of P-gp and MRP1 genes in the TCM group and the combined group were significantly reduced （<italic>P</italic><0.05， <italic>P</italic><0.01）， and the protein expressions of secretory glycoprotein1（Wnt1）and <italic>β</italic>-serial protein（<italic>β</italic>-catenin）in the TCM group and the combined group were significantly reduced （<italic>P</italic><0.01）. Conclusion:The combined use of modified Guilu Erxianjiao decoction and cisplatin can significantly inhibit the growth of tumors in mice with Lewis lung cancer， and its mechanism of action may be related to the efficacy of m odified Guilu Erxianjiao decoction in relieving the body's immunosuppressive state， promoting the body to produce IL-7， regulating IL-7-mediated Wnt/<italic>β</italic>-catenin signaling pathway and reducing the expression of resistance-related genes in lung cancer tissues.

Clinical and radiological results of thoracic and lumbar fracture and dislocation treated with posterior transforaminal decompression and interbody fusion / 中国骨伤

OBJECTIVE@#To evaluate the clinical and radiological results of patients with thoracic and lumbar fracture and dislocation treated by posterior transforaminal decompression and interbody fusion.@*METHODS@#From June 2010 to June 2017, posterior transforaminal decompression, interbody fusion combined with pedicle screw fixation were performed in 21 patients with thoracic and lumbar fracture and dislocation. Their clinical and radiological data were collected and retrospectively analyzed, including 15 males and 6 females, aged from 25 to 58 years with an average of 45 years old. According to the criterion of American Spinal Injury(ASIA), preoperative neurological function was graded A in 3 cases, B in 7 cases, C in 6 cases, D in 4 cases and E in 1 case. Operative time and intraoperative blood loss and correlative complications were recorded. And VAS score, ODI and Cobb angle were evaluated before and after surgery. The improvement of neurological function was also analyzed at the final follow-up. Intervertebral bony fusion was observed during the follow-up by CT three-dimensional reconstruction.@*RESULTS@#The operative time was 150 to 240 min with an average of (192±47) min. The intraoperative blood loss was 380 to 750 ml with an average of(603±120) ml. Dura sac tearing and cerebral fluid leakage occurred in 3 cases and were repaired during operation; superficial wound infection occurred in 1 case, and got healing after dressing change. The postoperative follow-up duration was 24 to 45 months with an average of(37.0±9.5) months. VAS score was improved from preoperative 8.9±0.4 to immediately postoperative 4.2±1.3(<0.05). At the final follow-up, VAS score decreased further to 3.6±0.8. ODI was decreased from preoperative (95.30±3.52)% to (32.51±6.30)% at the final follow-up (<0.05). Cobb angle was corrected from preoperative (21.2±8.8)° to immediately postoperative(2.3±3.1)° (<0.05). At the final follow-up, Cobb angle was (3.2±2.5)°, showing no significant difference with immediately postoperative value. The neurological function was grade A in 3 cases, B in 3 cases, C in 5 cases, D in 6 cases and E in 4 cases at the final follow-up. All the patients got solid intervertebral bone fusion in 8 to 13 months after operation, with an average fusion time of (10.3±2.5) months.@*CONCLUSIONS@#For the patients with thoracic and lumbar fracture and dislocation mainly involving intervertebral disc and endplate plane, posterior transforaminal decompression and interbody fusion not only is less invasive, but also can effectively reconstruct spinal three column and obtain good biomechanical stability. And, it is beneficial for the good recovery of neurological function.

Research advances of EDIL3 in tumor / 国际肿瘤学杂志

Epidermal growth factor (EGF)-like repeat and discoidin Ⅰ-like domain 3 (EDIL3)is a extracellular matrix protein that produced and secreted by endothelial cells and plays important roles in embry-onic development,angiogenesis,and limit inflammation. Several recent studies indicate that EDIL3 is aberrant-ly expressed in pancreatic cancer,liver cancer,colorectal cancer,lung cancer and breast cancer,which is as-sociated with cell proliferation,apoptosis,invasion,metastasis,and angiogenesis. EDIL3 is widely participated in the regulating tumor initiation,progression and metastasis,and its abnormal expression is expected to provide a new method for diagnosis and therapy of cancers.

Research advances of EDIL3 in tumor / 国际肿瘤学杂志

Epidermal growth factor (EGF)-like repeat and discoidin Ⅰ-like domain 3 (EDIL3) is a extracellular matrix protein that produced and secreted by endothelial cells and plays important roles in embryonic development, angiogenesis, and limit inflammation. Several recent studies indicate that EDIL3 is aberrantly expressed in pancreatic cancer, liver cancer, colorectal cancer, lung cancer and breast cancer, which is associated with cell proliferation, apoptosis, invasion, metastasis, and angiogenesis. EDIL3 is widely participated in the regulating tumor initiation, progression and metastasis, and its abnormal expression is expected to provide a new method for diagnosis and therapy of cancers.

Influence of acute high altitude exposure and short-term acclimation on platelet-associated parameters in healthy young man / 解放军医学杂志

Objective To explore the effect of high altitude exposure and short-term acclimation on the platelet-associated parameters by studying the changes of platelet-associated parameters in healthy young man.Methods Four hundred and sixtytwo young men were recruited from Chengdu (the elevation of 500m) during Jun.2012 to Aug.2013 according to the inclusion and exclusion criteria,of which 193 had been living in Chengdu (plain group),and 269 flew from Chengdu to Lhasa (3700m) in 2 hours,and then 147 of them were exposed in the high altitude for 1 day (acute high altitude exposure group),and another 122 for 7 days (short-term acclimation group).The demographic data were collected and the blood routine and platelet-associated parameters were measured of all the participants,and then the information collected were compared between the 3 groups.Results Compared to the plain group,the platelet count (PLT),platelet distribution width (PDW) and plateletcrit (PCT) reduced and the mean platelet volume (MPV) increased significantly (P＜0.05) in the acute high altitude exposure group;while all the indexes in short-term acclimation group returned to approach the levels in the plain group,but statistical differences still existed in PLT,PDW and PCT (P＜0.05).The platelet activating factor (PAF) and epinephrine (Epi) decreased markedly in acute high altitude exposure group than in plain group (P＜0.05);while in short-term acclimation group,the PAF returned to approach the level in plain group,and the Epi was further down (P＜0.05).In addition,no marked difference of 5-HT level was observed in the 3 groups (P＞0.05).Pearson correlation analysis indicated that high altitude-induced reduction of oxygen saturation (SpO2) was positively related to the changes of PLT.Conclusions Acute high altitude exposure may reduce PLT,PDW and PCT levels,but elevate MPV and enhance the platelet activity.The reduction of SpO2 might be associated with the changes of PLT,PDW and PCT.Platelet-associated parameters may be recovered to normal with a compensatory effect after short-term acclimation.

Analysis of lymph node metastasis pattern in gastric cancer patients at stage pN1 / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the lymph node metastasis pattern in pN1 stage gastric cancer patients and to analyze its risk factors.</p><p><b>METHODS</b>Clinicopathological data of 219 patients who underwent radical gastrectomy and were confirmed as pN1 stage gastric cancer between January 2013 and March 2016 were reviewed. All the patients underwent D2 or extended D2(D2+) lymphadenectomy. The overall metastatic rate was calculated. The risk factors associated with lymph node metastasis were analyzed. The pattern of skip lymph node metastasis and clinicopathological factors related to skip metastasis were analyzed.</p><p><b>RESULTS</b>Among 219 patients, 119 patients had only one metastatic lymph node, and 100 patients had two metastatic lymph nodes. The relatively higher sites of lymph node metastasis were station No.3[29.2%(64/219)], No.6[18.3%(40/219)] and No.4[11.4%(25/219)]. Compared to patients with tumor diameter ≤5 cm, metastatic rates of station No.3[39.4% (39/99) vs. 20.8%(25/120), P=0.003], No.4[16.2%(16/99) vs. 7.5%(9/120), P=0.045] and No.8[16.2%(16/99) vs. 6.7%(8/120), P=0.025] were significantly higher in those with tumor diameter >5 cm. Skip lymph node metastasis was detected in 56 cases(25.6%) and skip lymph node metastatic rate was significantly higher in patients with tumor diameter >5 cm [34.3%(34/99) vs. 18.3%(22/120), P=0.007]. Logistic regression analysis showed that the tumor size was an independent risk factor for the skip lymph node metastasis in pN1 stage gastric cancer (OR=1.982, 95%CI: 0.978 to 3.921, P=0.033).</p><p><b>CONCLUSIONS</b>The perigastric station No1 lymph node is the main site of early lymph node metastasis of pN1 stage gastric cancer. General pattern of lymph node metastasis is from proximus to distance, while quite a lot of skip lymph node metastases are observed. Tumor size is an important factor affecting the lymph node metastasis and bigger tumor may result in skip lymph node metastasis easily.</p>

Analysis of clinicopathological characteristics and prognosis on 42 patients with primary gastric adenosquamous cell carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics, diagnosis, treatment and prognosis of patients with primary gastric adenosquamous cell carcinoma.</p><p><b>METHODS</b>A total of 5 562 patients with gastric neoplasm were admitted in Tianjin Medical University Cancer Institute and Hospital from January 2001 to January 2011. Among them 42 patients were diagnosed as primary gastric adenosquamous cell carcinoma, accounting for 0.76% of all the patients. The clinicopathological and follow-up data of these 42 patients with primary gastric adenosquamous cell carcinoma were retrospectively analyzed, and Cox proportional hazard model was used to analyze the prognostic factors of gastric adenocarcinoma squamous cell carcinoma.</p><p><b>RESULTS</b>Among above 42 patients, 32 were male and 10 were female, with a male-to-female ratio of 3.2/1.0 and the average age was 63 years (range: 46 to 77 years). Five patients (11.9%) were confirmed as adenosquamous cell carcinoma by preoperative pathological examination, while other 37 patients were diagnosed as adenocarcinoma preoperatively. According to the 7th edition AJCC TNM classification system for gastric adenocarcinoma, 5 patients (11.9%) were in stage II(, 30 patients (71.4%) in stage III( and 7 patients (16.7%) in stage IIII(. The maximum tumor diameter was > 5 cm in 18 patients (42.9%). Borrmann type III(-IIII( was found in 29 patients (69.0%), and poorly differentiated (or undifferentiated) tumor was found in 32 patients (76.2%). Radical operations were performed in 31 patients (73.8%), the reasons of non radical operations included infiltration of pancreas in 3 patients, infiltration of radices mesocili transvers in 1 patient and classification of stage IIII( in 7 patients. Lymph node dissection was performed in 37 patients, 83.8% of them (31/37) was found with lymphatic metastases. Twenty-five patients received adjuvant chemotherapy except for 7 patients in stage IIII( and 10 patients who refused adjuvant chemotherapy. All the patients had an average survival time of 36.4 months and median survival time of 28.0 months, and the overall 1-, 3- and 5-year survival rates were 82.2%, 42.3% and 18.2% respectively. Univariate analysis revealed that tumor size (χ=4.039, P=0.044), Borrmann type (χ=18.728, P=0.000), tumor differentiation (χ=19.612, P=0.000), radical gastectomy (χ=41.452, P=0.000), lymph node metastasis (χ=9.689, P=0.002) and clinical stage (χ=26.277, P=0.000) were associated with postoperative survival. Multivariate analysis revealed that tumor differentiation (HR=10.560, 95%CI:2.263-49.281, P=0.003), radical gastrectomy (HR=4.309, 95%CI:1.311-14.168, P=0.016) and clinical stage (HR=2.392, 95%CI:1.022-5.600, P=0.044) were independent prognosis factors.</p><p><b>CONCLUSIONS</b>Primary gastric adenosquamous cell carcinoma is rare with poor prognosis. Radical gastrectomy is recommended. Tumor differentiation, radical gastrectomy and clinical stage are important indicators to evaluate prognosis of primary gastric adenosquamous cell carcinoma.</p>

Clinical observation of capecitabine monotherapy or combination regimen in the treatment of advanced breast cancer / 中国生化药物杂志

Objective To explore the clinical effect and safety of patients with advanced breast cancer with capecitabine and gemcitabine combined with capecitabine treatment scheme. Methods 82 cases of patients with advanced breast cancer received treatment in our hospital from February 2014 to March 2016 were randomly selected and were randomly divided into control group and study group, 41 cases in each group.The control group using capecitabine monotherapy, the study group used capecitabine combined with docetaxel treatment. The therapeutic effects, safety and adverse reactions of the two groups were compared. Results The effective rate of treatment in the study group was 56.48 %, significantly better than that in the control group(34.28 %), the difference was statistically significant, The incidence of complications after treatment in the control group was 40.22 %, significantly higher than that in the study group (18.04 %), and the difference was statistically significant (P<0.05). Conclusion Capecitabine combined with docetaxel in the treatment of advanced breast cancer has good effect and low incidence of adverse reactions. It is worthy of recommendation and Application.

Clinical observation of capecitabine monotherapy or combination regimen in the treatment of advanced breast cancer / 中国生化药物杂志

Objective To explore the clinical effect and safety of patients with advanced breast cancer with capecitabine and gemcitabine combined with capecitabine treatment scheme. Methods 82 cases of patients with advanced breast cancer received treatment in our hospital from February 2014 to March 2016 were randomly selected and were randomly divided into control group and study group, 41 cases in each group.The control group using capecitabine monotherapy, the study group used capecitabine combined with docetaxel treatment. The therapeutic effects, safety and adverse reactions of the two groups were compared. Results The effective rate of treatment in the study group was 56.48 %, significantly better than that in the control group(34.28 %), the difference was statistically significant, The incidence of complications after treatment in the control group was 40.22 %, significantly higher than that in the study group (18.04 %), and the difference was statistically significant (P<0.05). Conclusion Capecitabine combined with docetaxel in the treatment of advanced breast cancer has good effect and low incidence of adverse reactions. It is worthy of recommendation and Application.

Analysis of risk factors for No.11p lymph node metastasis in advanced gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the risk factors for No.11p lymph node metastasis in advanced gastric cancer.</p><p><b>METHODS</b>A retrospective analysis was executed of the clinical data of 204 patients who were subject to advanced gastric cancer and accepted radical gastrectomy in Tianjin Cancer Hospital from January 2007 to December of 2011. All of the patients were diagnosed as gastric adenocarcinoma and received No.11p lymph node dissection. The general information of the patients and the number of dissected and positive lymph nodes were recorded in detail. Univariate and multivariate analysis of clinicopathological factors influencing No.11p lymph metastasis were performed by chi-square test and binary Logistiic Discussion, respectively.</p><p><b>RESULTS</b>The No.11p lymph node metastasis rate is 14.3%(29/204) in the 204 patients. The univariate analysis showed that No.11p lymph metastasis was correlated with diameter of tumor, depth of invasion (T stage), lymph node metastasis (N stage) and TNM stage (χ(2)=5.106, χ(2)=5.368, χ(2)=25.911, P<0.05). The association between the metastasis of the regional lymph nodes No.1, No. 3, No. 4sb, No. 5, No. 7, No. 9 and No.11p was significant (χ(2)=4.228, χ(2)=10.655, χ(2)=17.954, χ(2)=11.087, χ(2)=15.142, χ(2)=16.727, all P<0.05). Multivariate analysis confirmed that lymph node N3 stage(OR=4.791, 95% CI:2.056-11.167), No.4sb(OR=3.498, 95% CI:1.157-10.578) and No.9(OR=4.006, 95% CI:1.359-11.805) were three independent risk factors of No.11p lymph node metastasis(all P<0.05).</p><p><b>CONCLUSION</b>The No.11p lymph node dissection in radical gastrectomy conventionally is reasonable and necessary. Lymph node N3 stage and the metastasis of regional lymph No.4sb and No.9 are independent risk factors of the metastasis of No.11p lymph node.</p>

Research progress on STMN1 and gastric cancer / 中国肿瘤临床

STMN1 is a microtubule-destabilizing protein that regulates cell cycle by phosphorylation and dephosphorylation. It plays an important role in the proliferation and differentiation of cells, in addition to the tumorigenesis. This protein is highly expressed in a wide variety of human cancers, including leukemia and multiple types of solid tumors. The relationship between STMN1 and gastric cancer has recently been investigated. Studying STMN1 in gastric cancer is important. A number of studies have suggested that overex-pression of STMN1 can affect the therapeutic response of docetaxel, an anti-microtubule drug. This review summarizes the role of ST-MN1 in gastric carcinogenesis, development, prognosis, and treatment. The relationship between STMN1 and clinical pathology and its regulation pathways is also investigated.

Interference of DEHP on the key genes of glucose and lipid metabolism in HepG2 cells / 中国职业医学

OBJECTIVE: To investigate the effects of di-( 2-ethylhexyl) phthalate( DEHP) on the expression of the key genes involved in glucose and lipid metabolism,and explore the toxicity of DEHP on the glucose and lipid metabolism in HepG2 cells cultured in vitro. METHODS: HepG2 cells in logarithmic growth phase were divided into DEHP exposure group and control group. The exposure group was exposed to DEHP with different final concentrations( 5,10,50,100,500 and1 000 μmol / L),and the control group was exposed to dimethyl sulfoxide of corresponding concentrations. After 24 hours of DEHP exposure,real-time fluorescence quantitative polymerase chain reaction( Q-PCR) was applied to detect the level of mRNA transcription of peroxisome proliferators-activated receptor α( PPARα), which is an endogenous marker indicating the success of DEHP exposure. In addition,the level of mRNA transcription of key genes involved in glucose and lipid metabolism were also measured by Q-PCR,including glucose-6-phosphatase( G-6-Pase),phosphoenolpyruvate carboxykinase( PEPCK),stearoyl-coenzyme A desaturase 1( SCD1),fatty acid synthase,sterol regulatory elementbinding protein 1c and acetyl Co A carboxylase 1. P ≤0. 008 was considered as statistical significance. RESULTS: After DEHP exposure,the mRNA transcription level of PPARα was significantly elevated in all exposure groups( P < 0. 008)except for 5 μmol / L DEHP exposure group,which indicated the successful establishment of DEHP exposure model. The mRNA transcription level of G-6-Pase was significantly increased in 100 and 500 μmol / L DEHP exposure groups( P ≤0. 008) when compared with the controls; the PEPCK mRNA transcription level of showed no significant differences between the 6 DEHP exposure groups and their corresponding control groups( P > 0. 008). The mRNA transcription level of SCD1 was significantly down-regulated in 100 μmol / L DEHP exposure group( P < 0. 008) when compared with its control. The mRNA transcription level of other key genes involved in the lipid metabolism were not significantly altered after DEHP exposure( P > 0. 008). CONCLUSION: The effect of DEHP on glucose metabolism was mainly manifested by promoting G-6-Pase gene expression,which is the rate-limiting enzyme for gluconeogenesis. The effect of DEHP on the lipid metabolism of HepG2 cells was limited.

Research progress on the role of hedgehog signaling pathway in gastric cancer / 中国肿瘤临床

Hedgehog (Hh) signaling pathway is critical during embryonic development. Recent studies have shown that Hh sig-naling plays an important role in oncogenesis and development of many malignant tumors. In particular, activation of the Hh signaling pathway is implicated in the aggressiveness and progression of gastric cancer. This review provides an overview of the research prog-ress on the role of Hh pathway in gastric cancer. Investigation of this pathway may reveal a novel target for gastric cancer therapy.

Effects of linggui zhugan decoction combined calorie restriction on the insulin resistance of model rats and mechanisms research / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effects of Linggui Zhugan Decoction (LZD) combined calorie restriction on fasting plasma glucose (FPG), the insulin resistance (IR), and the peroxisome proliferator-activated receptor gamma (PPAR-gamma) of IR model rats.</p><p><b>METHODS</b>Totally 48 male Wistar rats were randomly divided into the control group, the model group, the calorie restriction group, and the TCM + calorie restriction group, 12 in each group. Ordinary forage was given to those in the control group, and high fat diet was fed to those in the rest 3 groups for 12 weeks to establish the IR model. After successful modeling, rats in the control group and the model group were continually fed with the original farage for 4 days. The normal saline at the daily dose of 20 mL/kg was given to them by gastrogavage. The normal saline at the daily dose of 20 mL/kg was given to rats in the calorie restriction group by gastrogavage after 4-day calorie restriction. LZD at the daily dose of 20 mL/kg was given to rats in the TCM +calorie restriction group by gastrogavage after 4-day calorie restriction. The body weight, FPG, serum fasting insulin (FINS), insulin resistance index (IRI), and the protein expression of PPAR-y in the omental adipose tissue were compared.</p><p><b>RESULTS</b>After 4-day calorie restriction, the body weight obviously decreased in the calorie restriction group and the TCM +calorie restriction group, when compared with the model group (P <0.01). There was no statistical difference between the former two groups (P >0.05). The FINS and IRI obviously decreased in the calorie restriction group (P <0.01, P <0.05). The FPG, FINS, and IRI significantly decreased in the TCM + calorie restriction group (P <0. 05, P <0.01). The protein expression of PPAR-gamma obviously decreased in the calorie restriction group and the TCM + calorie restriction group (P <0.01).The phlegm dampness state was alleviated, with more significant effects shown in the TCM + calorie restriction group.</p><p><b>CONCLUSIONS</b>LZD combined calorie restriction could reduce the body weight, FPG, and IRI of IR rats. Besides, it showed better effects than calorie restriction alone. Its effects in improving IR might be correlated with inhibiting the activities of PPAR-gamma. Meanwhile, it might play a role in inhibiting the differentiation of fat cells.</p>

The effect of Doppler ultrasound,X-ray mammography and MRI in early diagnosis and differential for breast cancer / 中国基层医药

Objective To explore the applicated value of Doppler ultrasound,X-ray mammography and MRI in early diagnosis and differential for breast cancer.Methods 182 cases examine femaled patients,which were hospitalized to breast lumps as the object of study,they were confirmed by Doppler ultrasound,X-ray mammography and MRI three checks.Caccording to the patient after surgery,the pathology results were used to diagonosed the value of the three detection methods.Results 182 patients with breast cancer and 143 cases(78.7％),benign tumors and 39cases(21.3％),the sensitivity of MRI was significantly higher than the other two,three associated with the accuracy of the examination results was significantly higher than that of each individual(P ＜0.05),the difference was statistically significant.Conclusion Doppler ultrasound,X-ray mammography and MRI are used in breast cancer in the early diagnosis,which have their own advantages,the combination can increase the accuracy to a certain extent.

Prognosis analysis of 310 patients with pathological stage pN3 gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics and prognostic factors of patients with pathological stage pN3 gastric cancer.</p><p><b>METHODS</b>A retrospective study of 310 patients with histologically confirmed pN3 stage gastric cancer undergoing radical gastrectomy from January 2000 to December 2006 in our department was performed. The Kaplan-Meier method was used to analyze the survival. Log-rank test and Cox regression model were carried out for univariate and multivariate analyses.</p><p><b>RESULTS</b>All the patients were followed up for 2 to 103 (mean 35.7) months. The overall 5-year survival rate was 14.6%. There were 201 cases with stage pN3a and 109 cases with stage pN3b, and the 5-year survival rates were 16.8% and 10.3% respectively (P=0.013). Univariate analysis showed that tumor location, Borrmann type, depth of tumor invasion, surgical method, metastatic lymph node ratio, and pN stage were associated with postoperative survival (all P<0.05). The multivariate analysis revealed that depth of tumor invasion, surgical method and metastatic lymph node ratio were independent prognostic factors, while the pN stage was not. The difference of 5-year survival rate between pN3a and pN3b subgroups was significant in pT4a patients (16.1% vs. 12.8%, P=0.001), while such difference was not significant in pT4b patients (8.6% vs. 3.1%, P=0.137).</p><p><b>CONCLUSIONS</b>Prognosis of patients with pN3 stage gastric cancer after radical resection is poor. Depth of tumor invasion and surgical method are independent prognostic factors for pN3 stage gastric cancer. Metastatic lymph node ratio is valuable to predict the prognosis of pN3 stage patients. The pN3 staging of the 7th UICC provides a more accurate prediction of prognosis.</p>

Role of poly (ADP-ribose) polymerase 1 on DNA methylation variation induced by B(a)P in human bronchial epithelial cell / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate DNA methylation variation in human cells induces by B(a)P, and to explore the role of PARP1 during this process.</p><p><b>METHODS</b>The changes of DNA methylation of 16HBE and its PARP1-deficient cells exposed to B(a)P (1.0, 2.0, 5.0, 10.0, 15.0, 30.0 µmol/L) were investigated by immunofluorescence and high performance capillary electrophoresis, and simultaneously, the expression level of PARP 1 and DNMT 1 were monitored dynamically.</p><p><b>RESULTS</b>The percentage of methylated DNA of overall genome (mCpG%) in 16HBE and 16HBE-shPARP1 cells were separately (4.04 ± 0.08)% and (9.69 ± 0.50)%. After being treated by 5-DAC for 72 hours, mCpG% decreased to (3.15 ± 0.14)% and (6.07 ± 0.54)%. After both being exposed to B(a)P for 72 hours, the mCpG% in 16HBE group (ascending rank) were separately (5.10 ± 0.13), (4.25 ± 0.10), (3.91 ± 0.10), (4.23 ± 0.27), (3.70 ± 0.15), (3.08 ± 0.07); while the figures in 16HBE-shPARP1 group (ascending rank) were respectively (10.63 ± 0.60), (13.08 ± 0.68), (9.75 ± 0.55), (7.32 ± 0.67), (6.90 ± 0.49) and (6.27 ± 0.21). The difference of the results was statistically significant (F values were 61.67 and 60.91, P < 0.01). For 16HBE group, expression of PARP 1 and DNMT 1 were 141.0%, 158.0%, 167.0%, 239.0%, 149.0%, 82.9% and 108.0%, 117.0%, 125.0%, 162.0%, 275.0%, 233.0% comparing with the control group, whose difference also has statistical significance (t values were 11.45, 17.32, 32.24, 33.44, 20.21 and 9.87, P < 0.01). For 16HBE-shPARP1 group, expression of PARP 1 and DNMT 1 were 169.0%, 217.0%, 259.0%, 323.0%, 321.0%, 256.0% and 86.0%, 135.0%, 151.0%, 180.0%, 229.0%, 186.0% comparing with the control group, with statistical significance (t values were 9.06, 15.92, 22.68, 26.23, 37.19 and 21.15, P < 0.01). When the dose of B(a)P reached 5.0 µmol/L, the mRNA expression of DNMT 1 in 16HBE group (ascending rank) were 125.0%, 162.0%, 275.0%, 233.0% times of it in control group, with statistical significance (t values were 12.74, 24.92, 55.11, 59.07, P < 0.01); while the dose of B(a)P reached 2.0 µmol/L, the mRNA expression of DNMT 1 in 16HBE-shPARP1 group were 135.0%, 151.0%, 180.0%, 229.0%, 186.0% of the results in control group, and the differences were statistically significant (t values were 23.82, 40.17, 32.69, 74.85, 46.76, P < 0.01).</p><p><b>CONCLUSION</b>The hypomethylation of 16HBE cells induced by B(a)P might be one important molecular phenomenon in its malignant transformation process. It suggests that PARP1 could regulate DNA methylation by inhibiting the enzyme activity of DNMT1, and this effect could be alleviated by PARP1-deficiency.</p>