Objective To explore the clinical significance of Ezrin and β?catenin in breast cancer. Methods Immunohistochemical staining method was adopted to detect Ezrin and β?catenin protein expression level in 145 cases of breast cancer tissues,and their correlation with clinical data and prognosis of breast cancer was analyzed. Results Ezrin was expressed in 70 cases(48.3%),β?catenin was expressed in 82 cases (56.6%),and there was significantly negative correlation(r=0.267,P=0.001). The higher histologic grade of breast cancer,the higher expres?sion level of Ezrin(P=0.007),and the lower expression level of β?catenin(P<0.001). Ezrin expression level was increased significantly(P=0.027),but β?catenin expression level was reduced significantly(P=0.011)in lymph node positive breast cancer tissue. Ezrin expression was sig?nificantly correlated with shorter overall survival(P=0.004)and disease free survival(P=0.017)of breast cancer patients,but β?catenin expres?sion was significantly correlated with longer overall survival(P<0.001)and disease free survival(P=0.001)of breast cancer patients. However , Ezrin and β?catenin were not the independent risk factors of breast cancer patients as determined by multivariate Cox regression. Conclusion Ez?rin was significantly negative correlated with β?catenin in breast cancer. They play a role in the progression and poor prognosis of breast cancer , which can be used as breast cancer treatment targets.

Objective To evaluate the expression and relationship of miR-100 and FZD-8, one of the major compo?nents of Wnt signaling pathway, and the correlation of their expressions with lymph node metastasis in patients with breast cancer. Methods The expression of miR-100 was determined in 50 samples of human breast cancer tissues and adjacent normal tissues by in situ hybridization. The correlation of miR-100 expression with lymph node metastasis was analyzed by Mann-Whitney U test. The expression of FZD-8 was measured in 50 samples of human breast cancer tissues and adjacent normal tissues by immunohistochemistry. The correlation of the miR-100 expression with the protein expression of FZD-8 was evaluated by Pearson rank analysis. Results The expression of miR-100 was significantly lower in human breast can?cer tissues than that in adjacent normal breast tissues [2.00 (1.00, 3.00) vs. 6.00 (3.50, 8.00)]. The miR-100 expression was lower in patients with lymph node metastasis than that in patients without lymph node metastasis [1.50 (1.00, 2.75) vs. 3.00 (2.00, 4.00)]. The expression of FZD-8 was significantly higher in human breast cancer tissues than that in adjacent normal breast tissues [8.00 (6.00, 9.00) vs. 6.00 (3.75, 9.00)]. The miR-100 expression was negatively correlated with the FZD-8 pro?tein expression in human breast cancer tissues (rs=-0.592, P<0.001). Conclusion The miR-100, as an anti-metastasis-miRNA, may involve in the metastasis of breast cancer, which may be related with the regulation of the expression of FZD-8.

Objective To investigate the relationship between Ezrin expression and subcellular localization of E?cadherin(E?cad),and explore the clinical significance of this relationship to pathological features such as lymph nodes metastasis in breast cancer. Methods Ninety four cases of breast cancer tissue samples with lymph node metastasis were collected. The expression of Ezrin and E?cad was detected by immunohistochemi?cal method. Results The positive rates of and E?cad and Ezrin were respectively 45.7%and 58.5%in 94 nodes positive breast cancer,containing membranal expression of E?cad(E?cadm)in 20 cases and cytoplasmic expression of E?cad(E?cadc)in 23 cases;the frequency of E?cadc positive staining was significantly higher in Ezrin(+)tissues than that in Ezrin(-)tissues(P=0.025);E?cad expression level was significantly lower in TNMⅡ?Ⅲstage cases(P=0.001),and Ezrin expression(P=0.036)and E?cadc(P=0.013)was significantly increased in bigger cases;com?pared with E?cad(+),Ezrin(-),E?cadm tissues,the number of lymph node metastasis in E?cad(-)(P=0.011),Ezrin(+)(P=0.002),E?cadc (P=0.020)tissues were increased significantly;in the order of E?cad(+)/Ezrin(-),E?cad(-)/Ezrin(-),E?cad(+)/Ezrin(+),and E?cad(-)/Ezrin(+),the number of lymph node metastasis was increased significantly(P<0.001);similarly,in the order of E?cadm/Ezrin(-),E?cadc/Ezrin(-),E?cadm/Ezrin(+),and E?cadc/Ezrin(+),the number of lymph node metastasis was increased significantly(P=0.007). Conclusion Ezrin may regulate the subcellular localization of E?cad in metastatic breast cancer ,which may affect the course of breast cancer and promote the metastasis of lymph nodes.

Objective To study the preventive effect ofω-6 soybean oil fatty emulsion on gastric ulcer caused by acetic acid in rat model, and investigate its mechanisms. Methods Thirty healthy rats were randomly and equally assigned to the following 3 groups:sham operation,gastric ulcer,andω-6 Soybean oil fatty emulsion group.The model was induced by acetic acid. Five days after the model was established successfully,rats in ω-6 soybean oil group received the treatment by tail intravenous injection with the dose of 10 mL.kg-1 .d-1 ,the sham operation group and gastric ulcer group were given the same dose of 0.9%sodium chloride solution.The rats were sacrificed at 10th day after the treatment.The pathological changes of rat gastric ulcer tissue were observed by HE staining, and the concentration of gastric acid was detected by acid-base neutralization method,as well as the activity of pepsin was detected by colorimetry.Serum NO concentration was detected with nitrate reductive enzymatic method, and the expression of EGFR in gastric mucosal was detected with immunohistochemical method. Results Gastric ulcer area inω-6 soybean oil fatty emulsion group (5.67±2.32 mm2) was significantly lower than that in gastric ulcer group(8.68±1.98 mm2). The concentration of gastric acid (1.70±0.53 mmol.L-1), activity of pepsin(23.12±6.97 U) and NO level (64.62±13.86μmol.L-1 ) inω-6 soybean oil fatty emulsion group were much lower than those in the model control group.While the expression of EGFR in gastric ulcer tissue was increased after treatment withω-6 soybean oil fatty emulsion. Conclusion ω-6 soybean oil fatty emulsion exerts significant promotion effect on the healing of gastric ulcer,and its mechanism might be related to inhibiting the level of gastric acid, pepsin and NO, while improving the protective effect of EGFR on gastric mucosa.

Objective To investigate the correlationship between DNMT3a, DNMT3b protein expressions and the state of promoter methylation of ERα gene and ERα protein expression in the development of sporadic breast cancer. Methods A total of 180 patients with sporadic breast cancer and 30 patients with breast fibroadenoma were included in this study. The expressions of DNMT3a and DNMT3b protein were detected by immunohistochemical method. The state of promoter methylation of ERα gene was detected by methylation specific PCR in 97 patients with sporadic breast cancer. Results There were no significant differences in positive expression rates of DNMT3a and DNMT3b protein between breast fibroadenoma and breast cancer. There were higher expression levels of DNMT3a and DNMT3b in breast cancer patient of Ⅲ～Ⅳstages than those of Ⅰ～Ⅱstages. The expression of DNMT3a was significantly higher in patients with lymph node metastasis than that of patients without lymph node metastasis (P＜0.05). Of 97 cases of breast cancer patients, ERα gene promoter methylation occurred in 39 cases (40.2%). The positive expression of DNMT3a protein was positively correlated with the ERα gene methylation (rS=0.250). The DNMT3a protein expression showed a significant influence to the overall survival (OS) in patients of breast cancer (P=0.035), no significant influence to the disease-free survival (DFS) (P=0.064). DNMT3b protein expression showed no significant influence to OS and DFS of patients with breast cancer (P=0.914 and 0.961). Conclusion The positive expressions of DNMT3a and DNMT3b are correlated with the invasion, metastasis and poor prognosis of sporadic breast cancer. DNMT3a was positively correlated with the state of ERα gene promoter methylation. The inhibition of DNMT3a and DNMT3b may have advantages in the prevention and treatment of sporadic breast cancer.

Objective to investigate the protective effect of omega-3 fish oil fat emulsion on cyclophosphamide-induced gastric mucosal injury in mice. Methods Forty-five kunming mice were randomly divided into three groups as control,model,and omega-3 fish oil fat emulsion group(with 15 mice in each group). Mice of the two experiment groups were administrated with cyclophosphamide i.p. for 2 days to establish the damage model. then mice in omega-3 fish oil fat emulsion group received omega-3 fish oil fat emulsion at a dose of 15 mL/kg daily for 14 days. Meanwhile,the ani-mals in control group and model group were intravenously administered with the same volume of saline. the weight and food intake of the mice in each group were assessed daily. Five mice in each group were respectively sacrificed at day 1,day 7,day 14 after intravenous injection. Morphology of gastric mucosa was observed by HE staining and the activities of SOD and MAO in gastric mucosa were measured respectively by xanthine oxida-tion and ultraviolet spectrophotometry methods. Results Compared with the model group,the general status,nutritional status and the injury in stomach mucosa in omega-3 fish oil fat emulsion group were significantly improved. After 14 day′s treatment,the activities of SOD and MAO in gas-tric mucosa of mice in omega-3 fish oil fat emulsion group were significantly increased(P < 0.05)compared with model group. Conclusion omega-3 fish oil fat emulsion has a significant protective effect on the cyclophosphamide induced injury in gastric mucosa of mice,which may be related to the upregulation of MAO and SOD.

PURPOSE: Fanconi anemia complementation group F (FANCF) is a key factor to maintaining the function of Fanconi anaemia/BRCA (FA/BRCA) pathway, a DNA-damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. In the present study, we evaluated the chemosensitization effect of FANCF in breast cancer cells. METHODS: We performed specific knockdown of the endogenous FANCF in breast cancer cells by transfecting the cells with an FANCF short hairpin RNA (shRNA) vector. Cell viability was measured with a Cell Counting Kit-8, and DNA damage was assessed with the alkaline comet assay. The apoptosis, cell cycle, and drug accumulation were measured by flow cytometric analysis. Protein expression levels were determined by Western blot analysis, using specific antibodies. RESULTS: The analyses of two breast cancer cell lines (MCF-7 and MDA-MB-435S) demonstrated that the FANCF shRNA could effectively block the FA/BRCA pathway through the inhibition of Fanconi anemia complementation group D2 ubiquitination. Moreover, FANCF silencing potentiated the sensitivity of cells to mitomycin C (MMC), where combined FANCF shRNA/MMC treatment inhibited cell proliferation, induced S-phase arrest, apoptosis, and DNA fragmentation, and reduced the mitochondrial membrane potential, compared with MMC treatment alone. CONCLUSION: Taken together, this study demonstrates that the inhibition of FANCF by its shRNA leads to a synergistic enhancement of MMC cytotoxicity in breast cancer cells. These results suggest that the inhibition of the FA/BRCA pathway is a useful adjunct to cytotoxic chemotherapy for the treatment of breast cancer.
Apoptosis ; Blotting, Western ; Breast ; Breast Neoplasms ; Cell Count ; Cell Cycle ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Comet Assay ; Complement System Proteins ; DNA Damage ; DNA Fragmentation ; Fanconi Anemia ; Fanconi Anemia Complementation Group F Protein ; Membrane Potential, Mitochondrial ; Mitomycin ; RNA, Small Interfering ; Ubiquitin ; Ubiquitination

Background/Aims: The utility of Baveno-VII criteria of clinically significant portal hypertension (CSPH) to predict decompensation in compensated advanced chronic liver disease (cACLD) patient needs validation. We aim to validate the performance of CSPH criteria to predict the risk of decompensation in an international real-world cohort of cACLD patients. Methods: cACLD patients were stratified into three categories (CSPH excluded, grey zone, and CSPH). The risks of decompensation across different CSPH categories were estimated using competing risk regression for clustered data, with death and hepatocellular carcinoma as competing events. The performance of “treating definite CSPH” strategy to prevent decompensation using non-selective beta-blocker (NSBB) was compared against other strategies in decision curve analysis. Results: One thousand one hundred fifty-nine cACLD patients (36.8% had CSPH) were included; 7.2% experienced decompensation over a median follow-up of 40 months. Non-invasive assessment of CSPH predicts a 5-fold higher risk of liver decompensation in cACLD patients (subdistribution hazard ratio, 5.5; 95% confidence interval, 4.0–7.4). “Probable CSPH” is suboptimal to predict decompensation risk in cACLD patients. CSPH exclusion criteria reliably exclude cACLD patients at risk of decompensation, regardless of etiology. Among the grey zone, the decompensation risk was negligible among viral-related cACLD, but was substantially higher among the non-viral cACLD group. Decision curve analysis showed that “treating definite CSPH” strategy is superior to “treating all varices” or “treating probable CSPH” strategy to prevent decompensation using NSBB. Conclusions Non-invasive assessment of CSPH may stratify decompensation risk and the need for NSBB in cACLD patients.

Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug conjugates (ADCs), with the core benefits of enhanced cellular permeability and improved drug selectivity. Two drugs are now approved for market by US Food and Drug Administration (FDA), and in the last two years, the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer, coronavirus disease 2019 (COVID-19), metabolic diseases, and so on. The therapeutic benefits of PDCs are significant, but poor stability, low bioactivity, long research and development time, and slow clinical development process as therapeutic agents of PDC, how can we design PDCs more effectively and what is the future direction of PDCs? This review summarises the components and functions of PDCs for therapeutic, from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability, targeting, and stability of the various components of PDCs. This holds great promise for the future of PDCs, such as bicyclic peptide‒toxin coupling or supramolecular nanostructures for peptide-conjugated drugs. The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised. The way is shown for future PDC development.

This article proposes a novel occupational practice model implied from the native concept of Taiji Diagram. Four elements of Taiji Diagram, namely Yang-fish, Yin-fish, Yin-fish-eye and Yang-fish-eye, are matched to the elements of occupational practice, namely person, environment, economic condition and mental condition, respectively. The interaction between persons and their environment can be thought as the interaction between Yin and Yang, and the balance would be focused on. Some different ideas may be brought from this model, such as Appropriate Challenge, Appropriate Empowerment.