Objective : To explore the role of semaphoring 6d(SEMA6D) in the malignant progression of triple-negative breast cancer(TNBC). Methods : Bioinformatics and Immunohistochemistry(IHC) were used to analyze the expression level of SEMA6D in TNBC and paracancer non-tumor tissues and its relationship with patients′ clinicopathological features. MDA-MB-231 cell line stably knocking down the expression of SEMA6D was constructed, and the effects of SEMA6D on migration and invasion of TNBC cells were investigated by Wound-healing assays and Transwell assays. cBioPortal and GEPIA2 databases were used to screen out the gene negatively associated with it, namely aurora kinase A(AURKA). Bioinformatics and IHC were used to analyze the expression level of AURKA in TNBC and paracancer non-tumor tissues and its relationship with patients' clinicopathological features. Western blot assay was used to analyze the expression of AURKA and the effect of epithelial-mesenchymal transition(EMT) makers Claudin-1, N-cadherin and Vimentin after knocking downSEMA6D. Results: Bioinformatics analysis and IHC results showed that the expression of SEMA6D in TNBC tissues was significantly lower than that in paracancer non-tumor tissues(bothP<0.05). The expression of AURKA in TNBC tissues was significantly higher than that in paracancer non-tumor tissues(bothP<0.05), SEMA6D and AURKA were significantly negatively correlated in TNBC(P<0.01). Both low expression of SEMA6D and high expression of AURKA were positively correlated with tumor size, tumor histological grade, clinical stage and lymph node metastasis in TNBC patients(allP<0.05). The knockdown ofSEMA6Dsignificantly promoted the migration and invasion ability of TNBC cells(bothP<0.01). Western blot results showed that the knockdown ofSEMA6Dupregulated AURKA expression, promoted the expression of N-cadherin and Vimentin, and inhibited the expression of Claudin-1 in tumor cells. Conclusion Down-regulation of SEMA6D expression in TNBC may be involved in the malignant progression of TNBC through up-regulation of AURKA expression and promotion of EMT.

Purpose To explore the expression of autoph-agy-related 7(ATG7)in breast cancer and its effect on the breast cancer development.Methods Immunohistochemistry(IHC)was used to detect ATG7 protein expression in breast cancer tissues and the relationship between ATG7 and clinico-pathological features was analyzed.ShRNA was used to interfere with the expression of ATG7 in breast cancer cell line MCF-7.Puromycin was used to screen for stably transfected cells and Western blot was used to detect transfection efficiency.The effect of ATG7 knockdown cells on proliferation ability was de-tected by CCK8 and clone formation experiments.The effect of ATG7 knockdown cells on tumorigenicity in vivo was detected by subcutaneous tumor formation experiment in nude mice.Results IHC showed that ATG7 expression in breast cancer tissues was mainly localized in cytoplasm,and its expression was significant-ly correlated with tumor size and Ki67 expression(P＜0.05).ATG7-shRNA significantly interfered with ATG7 expression in breast cancer cells MCF-7.CCK8 and clone formation experi-ments showed that ATG7 knockdown promoted the cell prolifera-tion compared with the control group.The experiment of subcu-taneous tumor formation in nude mice showed that the tumor for-mation ability of mice was significantly increased after ATG7 knockdown compared with the control group.Conclusion ATG7 may inhibit the proliferation capacity of breast cancer and could be a potential target for breast cancer therapy.

Purpose To investigate the expression differ-ence of p16 in lung gland precursor lesions and lung adenocarci-noma and its correlation with HPV infection.Method The ex-pression of p16 in the tissues of 30 cases of pulmonary atypical adenomatous hyperplasia(AAH),40 cases of adenocarcinoma in situ(AIS),33 cases of microinvasive adenocarcinoma(MIA),and 45 cases of invasive adenocarcinoma(IAC)mainly of the acinar type was detected by immunohistochemical(IHC)method,and the relationship between p16 expression and the clinicopathological characteristics of the patients was analyzed.The PCR was used to detect HPV infection in IAC,and the cor-relation between p16 expression and HPV infection was ana-lyzed.Results The results of IHC showed that the expression of p16 protein was positively correlated with the precursors of lung glands and the histological grade of lung adenocarcinoma(P＜0.05).Compared with non-infiltrating components,the expression of p16 protein in MIA and IAC infiltrating compo-nents was significantly increased(P＜0.05).The PCR results showed that the positive detection rate of HPV DNA in the high expression group of p16 was significantly higher than that in the low expression group of IAC(P＜0.05).Conclusion The ex-pression of p16 protein is significantly correlated with the malig-nant progression of lung adenocarcinoma,which may be an ideal molecular marker to accurately identify the infiltrating compo-nents of lung adenocarcinoma.High expression of p16 in IAC may suggest HPV infection.

Purpose To explore the association of RIPK1 expression and Miller-Payne score after neoadjuvant therapy and its effect on chemotherapy sensitivity in breast cancer.Methods Immunohistochemistry(IHC)was used to detect RIPK1 in paraffin samples from breast cancer.Western blot was used to detect the expression of RIPK1 in different breast cancer cell lines,knockdown cell lines were constructed.CCK-8,clone for-mation experiment and flow cytometry were used to detect the effect of knockdown RIPK1 on the sensitivity of cells to chemo-therapy.Results The IHC results showed that the high expres-sion rate of RIPK1 was 69.0％(20/29)in the resistant group and 42.9％(15/35)in the sensitive group,and the expression of RIPK1 was significantly correlated with the Miller-Payne score(P=0.037).Western blot assay showed that the expression levels of RIPK1 were different in different cell lines,RIPK1 knockdown cell lines were constructed and induced apoptosis u-sing different concentrations of drugs.CCK-8,clone formation experiment and flow cytometry showed that knockdown of RIPK1 could decrease the cell survival rate,increase the apoptosis rate and decrease the colony formation rate compared with the control group.Conclusion Knockdown of RIPK1 promotes chemother-apy sensitivity of breast cancer cells.

Purpose To investigate the expression differ-ence of p16 in lung gland precursor lesions and lung adenocarci-noma and its correlation with HPV infection.Method The ex-pression of p16 in the tissues of 30 cases of pulmonary atypical adenomatous hyperplasia(AAH),40 cases of adenocarcinoma in situ(AIS),33 cases of microinvasive adenocarcinoma(MIA),and 45 cases of invasive adenocarcinoma(IAC)mainly of the acinar type was detected by immunohistochemical(IHC)method,and the relationship between p16 expression and the clinicopathological characteristics of the patients was analyzed.The PCR was used to detect HPV infection in IAC,and the cor-relation between p16 expression and HPV infection was ana-lyzed.Results The results of IHC showed that the expression of p16 protein was positively correlated with the precursors of lung glands and the histological grade of lung adenocarcinoma(P＜0.05).Compared with non-infiltrating components,the expression of p16 protein in MIA and IAC infiltrating compo-nents was significantly increased(P＜0.05).The PCR results showed that the positive detection rate of HPV DNA in the high expression group of p16 was significantly higher than that in the low expression group of IAC(P＜0.05).Conclusion The ex-pression of p16 protein is significantly correlated with the malig-nant progression of lung adenocarcinoma,which may be an ideal molecular marker to accurately identify the infiltrating compo-nents of lung adenocarcinoma.High expression of p16 in IAC may suggest HPV infection.

Purpose To explore the association of RIPK1 expression and Miller-Payne score after neoadjuvant therapy and its effect on chemotherapy sensitivity in breast cancer.Methods Immunohistochemistry(IHC)was used to detect RIPK1 in paraffin samples from breast cancer.Western blot was used to detect the expression of RIPK1 in different breast cancer cell lines,knockdown cell lines were constructed.CCK-8,clone for-mation experiment and flow cytometry were used to detect the effect of knockdown RIPK1 on the sensitivity of cells to chemo-therapy.Results The IHC results showed that the high expres-sion rate of RIPK1 was 69.0％(20/29)in the resistant group and 42.9％(15/35)in the sensitive group,and the expression of RIPK1 was significantly correlated with the Miller-Payne score(P=0.037).Western blot assay showed that the expression levels of RIPK1 were different in different cell lines,RIPK1 knockdown cell lines were constructed and induced apoptosis u-sing different concentrations of drugs.CCK-8,clone formation experiment and flow cytometry showed that knockdown of RIPK1 could decrease the cell survival rate,increase the apoptosis rate and decrease the colony formation rate compared with the control group.Conclusion Knockdown of RIPK1 promotes chemother-apy sensitivity of breast cancer cells.

N6-methyladenosine(m6A)represents one of the most abundant modifications in eukaryotes RNA.M6A modification is catalyzed and modified by m6A methyltransferases and demethylases.The fates of m6A-modified mRNAs rely on the functions of distinct"reader"proteins that recognize them,which may affect the splicing,processing,translation or degradation of the target mRNAs.Methyltransferase-like 3(METTL3)is a catalytic core component of m6A methyltransferase compound,whose abnormal expression could lead to disordered m6A modifications and further influence the proliferation,invasion,migration and drug resistance of tumor cells.As the functions of METTL3 have been explored in depth,METTL3 inhibitors have become research hotspots.Therefore,this review focus on the different target molecules and downstream signaling pathways affected by METTL3 with the assistance of different readers in the tumorigenesis and progression of urologic tumors,and summarizes the research progress of METTL3 inhibitors,in the hope to provide insights for the prevention,diagnosis and treatment of tumors.

Objective:To observe the effects of intervention based on self-regulation mode on illness perception, medical coping styles and quality of life of patients with psoriasis.Methods:Eighty patients with psoriasis from February 2018 to August 2019 in Qinhuangdao First Hospital were selected and divided into two groups by random digits table method, 40 patients in each group. The control group was given routine intervention, and the experimental group was given intervention based on self-regulation mode. The Illness Perception Questionnaire-Revised (IPQ-R) scores, Medical Coping Modes Questionnaire (MCMQ) scores, dermatologylifequalityindex (DLQI) scores and compliance of the two groups were compared before and after intervention.Results:There was no significant difference in the score of IPQ-R, MCMQ, DLQI before intervention between the two groups( P>0.05). After intervention, scores of symptoms, disease perception and causes of the disease in IPQ-R were (7.24±0.75), (162.34±20.35), (76.23±8.65) points in the experimental group and (6.08±0.72), (123.26±18.57), (52.79±7.84) points in the control group, there were significant differences between the two groups ( t values were 7.057, 8.972, 12.699, P<0.01). In the MCMQ, facing score,avoidance score and yielding score were (25.67±2.83), (12.26±1.84), (9.12±1.24) points in the experimental group, (21.76±3.89), (14.35±2.48), (10.45±1.68) points in the control group, there were significant differences between the two groups ( t values were 5.141, -4.280, -4.028, P<0.01). The DLQI scores of experimental group were significantly higher than those of control group ( t values were 2.648-8.244, P<0.05 or 0.01), and compliance of experimental group (97.5%, 39/40) was significantly better than control group (80.00%, 32/40) with statistically significant( Z value was 40.000, P<0.01). Conclusions:Intervention based on self-regulation mode can effectively reduce negative emotions of patients with psoriasis, increase their illness perception and compliance, improve their medical coping styles, self-management ability and quality of life, with positive application value.

Primary biliary cholangitis (PBC) is an autoimmune liver disease, mainly characterized by chronic progressive cholestasis. The root cause of PBC is the loss of immune tolerance to autoantigen E2 subunit of pyruvate dehydrogenase (PDC-E2). The unique immunobiological characteristics of intrahepatic bile duct epithelial cells make it an active participant in the pathogenesis of PBC. In recent years, the detection rate of PBC has been increasing year by year, but the clinical situation of ursodeoxycholic acid monotherapy has not changed. Therefore, an in-depth understanding of the immune pathogenesis of PBC will help clinicians better prevent and treat diseases.