Objective To analyze the clinicopathological characteristics and prognosis of different subtypes of breast cancer patients with bone metastasis.Methods For this study, we recruited 300 primary breast cancer patients with bone metastasis treated at the Department of Oncology, the First Affiliated Hospital of Xi`an Jiaotong University, between September 1, 2007 and September 1, 2011.We also retrospectively analyzed their clinical and follow-up data.Results The percentage of Luminal A, Luminal B, human epidermal growth factor receptor-2 (HER-2) overexpression and triple negative subtypes in all the bone metastatic breast cancer patients was 59.0％, 16.0％, 13.7％ and 11.3％, respectively.Age, tumor size and histologic grade significantly differed among the four subtypes (P<0.05).However, there were no significant differences in menopausal status, lymph node metastasis, histological type or lymphovascular invasion among different subtypes (P>0.05).The median survival time of Luminal A breast cancer patients with bone metastasis was 28.6 months, longer than Luminal B (26.9 months), HER-2 overexpression (20.9 months) and triple negative breast cancer patients (12.0 months) with bone metastasis.The overall survival significantly differed among the patients with four subtypes of breast cancer.Conclusion Different subtypes of breast cancer patients with bone metastasis have different clinical characteristics and prognosis.Luminal A breast cancer patients with bone metastasis have better prognosis whereas triple negative subtype has poorer prognosis.

Aim To investigate the effects of metformin on phospho-signal transducers and activators of transcription 3(p-STAT3) expression in the spinal dorsal horn in rats with bone cancer pain(BCP).Methods Healthy female SD rats weighing 200~220 g were randomly divided into four groups(n=12 each): Sham+NS, Sham+Metformin, BCP+NS, BCP+Metformin groups.Normal saline or metformin(200 mg·kg-1) was given intraperitoneally once a day at 7~14 day after surgery in four groups.Mechanical withdrawal threshold(MWT) was measured on-1, 3, 5, 7, 10, 12, 14 day after BCP.The L4-6 segments of spinal cords were used to detect the expression of p-STAT3 by Western blot and immunohistochemical staining technique after the behavioral test was completed on day 14.Results Intraperitoneal injection of metformin reversed hyperalgesia and suppressed the expression of p-STAT3 in BCP rats.Conclusion Metformin can attenuate BCP by inhibiting the expression of p-STAT3 in the spinal dorsal horn.

Objective:To observe and analyze the function of intestinal barrier in patients with pouchitis, and to explore the role of nucleotide oligomerization domain 2 (NOD2) in ileal pouchitis, so as to provide new ideas for the pathogenesis of pouchitis.Methods:From January 2011 to December 2016, the clinical pathological data of patients with ileal pouch-anal anastomosis who underwent pouch mucosa biopsy at the Endoscopy Center of General Hospital of Tianjin Medical University were retrospectively analyzed. According to the disease activity index of pouchitis, patients were divided into pouchitis group (20 cases) and non-pouchitis group (30 cases). In addition, UC patients who did not undergo surgery were selected as the control group (10 cases). The intestinal structure of patients of the pouchitis group and non-pouchitis group was observed under transmission electron microscope. The positive expression rates of occludin, alpha human defensin and NOD2 in the control group, non-pouchitis group and pouchitis group were detected and calculated by immunohistochemistry. Levene test, independent sample t test and Spearman correlation analysis were used for statistical analysis. Results:Under the transmission electron microscope, the tight junction epithelial structure and microvilli of intestinal mucosal of patients in the pouchitis group were severely injured. The results of immunohistochemistry showed that the positive expression rates of occludin, alpha human defensin and NOD2 in the intestinal mucosa of patients in the pouchitis group were all lower than those of the control group and non-pouchitis groups ((19.3±0.4)% vs. (84.0±0.3)% and (77.9±0.5)%; (60.0±1.3)% vs. (85.0±0.1)% and (77.3±0.4)%; (46.1±1.6)% vs. (72.0±0.7)% and (60.7±0.5)%), and the differences were statistically significant ( t=-8.451, -7.514, -3.943, -2.970, -5.115 and -2.982, all P<0.05). The correlation analysis showed that the expression level of NOD2 was positively correlated with occludin and alpha human defensin ( r=0.671 and 0.628, both P<0.01). Conclusions:Intestinal barrier function is impaired in patients with ileal pouchitis, and NOD2-related intestinal barrier injury may play an important role in the pathogenesis of ileal pouchitis.

Nonalcoholic fatty liver disease(NAFLD)has become the most common liver disease in the world and is an important risk factor for the progression to hepatocellular carcinoma.However,the pathogenesis of NAFLD remains unclear,and there is still a lack of specific treatment measures.Sterol regulatory element-binding proteins(SREBP)are an important nuclear transcription factor,which mainly maintains the balance of lipid metabolism inside the body by activating the genes associated with the synthesis and uptake of cholesterol,fatty acids,and triglycerides,and therefore,SREBP are a target for the treatment of metabolic diseases.This article reviews the latest advances in SREBP in the pathogenesis of NAFLD and the latest evidence of SREBP-targeted therapy for NAFLD.It is worth noting that recent studies have shown that SREBP inhibition can cause liver injury together with autophagy damage.Therefore,excessive inhibition of lipogenesis may exert a counterproductive effect on the treatment of NAFLD.In conclusion,SREBP is a promising therapeutic target for NAFLD;the molecular mechanism of SREBP in lipid metabolism is regulated by many factors,and these factors are being deeply explored and analyzed,which has an important clinical significance for the treatment of NAFLD.

OBJECTIVE:To provide reference for guarantee the supply of short-landed drugs.METHODS:A questionnaire survey was conducted to investigate the drug shortage in 40 medical institutions in China.Based on the survey data,the econometric model was built to analyze the reasons for drug shortage in medical institutions.RESULTS:40 questionnaires were issued and 26 valid questionnaires were collected with effective recovery rate of 65.0％.The institutions surveyed received 87 samples of short-landed drugs,involving 33 drugs;82.8％ of short-landed drug samples were in short supply for more than 3 months,and even 21.8％ short-landed drug samples were in short supply for more than 12 months.The common reasons for drug shortage mainly included:not entering the provincial bidding directory;adopting the government pricing method;being redistribution system;not establishing provincial normal reserve mechanism.In addition to common reasons,there were some personality reasons for drug shortage based on the necessity of clinical needs,drug attributes and drug price.CONCLUSIONS:There are many reasons for the shortage of drugs in medical institutions.There are both common causes and personality reasons.It is necessary to solve many problems of drug shortage from the source,and it needs many policies and systems to cooperate with them.

Acute kidney injury (AKI) is a common clinical critical illness, and ischemic kidney injury is the main type. The mortality rate of ischemic kidney injury is high, because the efficacy of treatment is limited due to symptomatic and supportive treatment. Establishing a reliable animal model of ischemic AKI is an important prerequisite for conducting research on physiological, pathological and pharmacological researches, so as to explore effective prevention methods and strategies. In recent years, the establishment methods of animal models of ischemic AKI have been continuously improved. The article summarizes the common methods and model characteristics of animal models of ischemic AKI in order to provide a reference for researchers to choose a reasonable modeling method.

Objective To investigate the effect of long?term exposure of nitrogen dioxide on the incidence of hypertension. Methods From March to December 2009, 37 386 eligible residents from four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) were enrolled in a follow?up study by using the random cluster sampling method. Demographic characteristics, lifestyle, history of diseases, and self?report situation of hypertension were collected by using questionnaire. Based on the average annual concentration of NO2 during the period from the cohort to the onset of hypertension as an estimate of exposure, the effect of NO2 exposure on hypertension was analyzed by employing Cox proportional hazards model. The interactions between NO2 exposure and different characteristics (age, sex, body mass index, smoking, alcohol consumption, education, economy, exercise, and fruit intake) were also examined. Results The baseline age of residents was (43.74±13.78) years, and the body mass index (BMI) was (22.56±2.92) kg/m2. During an average follow?up time of 11.40 years, 2 619 (7.0%) new cases of hypertension were reported. The overall mean environmental pollution levels during the study period for the entire cohort was (40.74±17.07) μg/m3. After adjusting for age, sex, BMI, family history of hypertension, socio?economic information, and lifestyle, the hazard ratio (HR) of incident hypertension with a 10 μg/m3 increase of NO2 was 1.21 (95%CI:1.18-1.25). Compared with residents aged 60 years and over ( HR=1.19, 95%CI : 1.14-1.26), former and current smoking ( HR=1.20, 95%CI : 1.14-1.25), and high?frequency fruit consumption ( HR=1.17, 95%CI :1.13-1.21), residents younger than 60 years ( HR=1.28, 95%CI : 1.25-1.32), non?smoker ( HR=1.23, 95%CI :1.19-1.27), and low?frequency fruit consumption ( HR=1.27, 95%CI : 1.20-1.35) had stronger interaction effect with NO2 (all P values for interaction<0.05). Conclusion NO2 exposure may lead to the onset of hypertension, which has a stronger effect on people younger than 60 years old, without smoking history and with low?frequency fruit consumption.

Objective To investigate the effect of long?term exposure of nitrogen dioxide on the incidence of hypertension. Methods From March to December 2009, 37 386 eligible residents from four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) were enrolled in a follow?up study by using the random cluster sampling method. Demographic characteristics, lifestyle, history of diseases, and self?report situation of hypertension were collected by using questionnaire. Based on the average annual concentration of NO2 during the period from the cohort to the onset of hypertension as an estimate of exposure, the effect of NO2 exposure on hypertension was analyzed by employing Cox proportional hazards model. The interactions between NO2 exposure and different characteristics (age, sex, body mass index, smoking, alcohol consumption, education, economy, exercise, and fruit intake) were also examined. Results The baseline age of residents was (43.74±13.78) years, and the body mass index (BMI) was (22.56±2.92) kg/m2. During an average follow?up time of 11.40 years, 2 619 (7.0%) new cases of hypertension were reported. The overall mean environmental pollution levels during the study period for the entire cohort was (40.74±17.07) μg/m3. After adjusting for age, sex, BMI, family history of hypertension, socio?economic information, and lifestyle, the hazard ratio (HR) of incident hypertension with a 10 μg/m3 increase of NO2 was 1.21 (95%CI:1.18-1.25). Compared with residents aged 60 years and over ( HR=1.19, 95%CI : 1.14-1.26), former and current smoking ( HR=1.20, 95%CI : 1.14-1.25), and high?frequency fruit consumption ( HR=1.17, 95%CI :1.13-1.21), residents younger than 60 years ( HR=1.28, 95%CI : 1.25-1.32), non?smoker ( HR=1.23, 95%CI :1.19-1.27), and low?frequency fruit consumption ( HR=1.27, 95%CI : 1.20-1.35) had stronger interaction effect with NO2 (all P values for interaction<0.05). Conclusion NO2 exposure may lead to the onset of hypertension, which has a stronger effect on people younger than 60 years old, without smoking history and with low?frequency fruit consumption.

This article reviews the demand, development process, aid types, effects, and existing problems of decision aids for colorectal cancer. The aim is to provide reference for the development of convenient and efficient decision aids for colorectal cancer diagnosis and treatment in China, and to improve the quality of treatment decisions for colorectal cancer patients.

Purpose: Numerous studies have shown that the frequency of myeloid-derived suppressor cells (MDSCs) is associated with tumor progression, metastasis, and recurrence. Chemokine (C-C motif) ligand 3 (CCL3) may be secreted by tumor cells and attract MDSCs into the tumor microenvironment. In the present study, we aimed to explore the molecular mechanisms whereby CCL3 is involved in the interaction of breast cancer cells and MDSCs. Methods: The expression of CCL3 and its receptors was investigated using real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The cell counting Kit-8, wound healing, and transwell assays were performed to study cell growth, migration, and invasion. Cell cycling, apoptosis, and the frequency of MDSCs were investigated through flow cytometry. Transwell assays were used for co-culture and chemotaxis detection. Markers of the epithelial-mesenchymal transition (EMT) were determined with western blotting. The role of CCL3 in vivo was studied via tumor xenograft experiments. Results: CCL3 promoted cell proliferation, migration, invasion, and cycling, and inhibited apoptosis of breast cancer cells in vitro. Blocking CCL3 in vivo inhibited tumor growth and metastases. The frequency of MDSCs in patients with breast cancer was higher than that in healthy donors. Additionally, MDSCs might be recruited by CCL3. Co-culture with MDSCs activated the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway and promoted the EMT in breast cancer cells, and their proliferation, migration, and invasion significantly increased. These changes were not observed when breast cancer cells with CCL3 knockdown were co-cultured with MDSCs. Conclusion CCL3 promoted the growth of breast cancer cells, and MDSCs recruited by CCL3 interacted with these cells and then activated the PI3K-Akt-mTOR pathway, which led to EMT and promoted the migration and invasion of the cells.