ObjectiveTo investigate the mechanism of topical treatment of allergic contact dermatitis （ACD） mice with Portulacae Herba based on the nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/nuclear factor-κB （NF-κB） signaling pathway. MethodsA total of 70 6-week-old specific pathogen free （SPF） female Kunming mice were adaptively fed for 1 week and randomly divided into blank group， model group， compound dexamethasone acetate cream group （2.075×10^-2 g·g^-1）， blank matrix cream group， low-dose Portulacae Herba cream group （0.1 g·g^-1）， high-dose Portulacae Herba cream group （0.2 g·g^-1）， and Portulacae Herba + inhibitor group （0.2 g·g^-1 + 30 mg·kg^-1 ML385）， with 10 mice in each group. One day before the experiment， the mice were shaved on the neck and back. Except for the blank group， the mice in the other groups were treated with 2，4-dinitrochlorobenzene （DNCB） to establish an ACD model. After respective administration， the skin lesion of the mice was scored， and the histopathological changes of the skin were stained with hematoxylin-eosin （HE）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， reactive oxygen species （ROS）， superoxide dismutase （SOD） activity， and malondialdehyde （MDA） in serum of mice. The expression of Nrf2/HO-1/NF-κB signaling pathway-related proteins in mouse skin tissue was detected by immunohistochemistry （IHC）， Western blot， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， the mice in the model group had an increased skin lesion score （P<0.01）， severe pathological damage to skin tissue， increased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and decreased content of SOD （P<0.01）. In addition， the mRNA and protein expression levels of Nrf2， HO-1， and nuclear factor-κB inhibitor α （IκBα） in skin tissue were up-regulated （P<0.01）， while the protein expression levels of phosphorylated （p）-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.01）. Compared with the model group and the blank matrix cream group， the mice treated with Portulacae Herba had a decreased skin lesion score （P<0.01）， reduced pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and increased content of SOD （P<0.01）. Additionally， the mRNA and protein expression levels of Nrf2， HO-1， and IκBα in skin tissue were down-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were up-regulated （P<0.05，P<0.01）. Compared with the Portulacae Herba + inhibitor group， the high-dose Portulacae Herba cream group had a decreased skin lesion score （P<0.01）， alleviated pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in the serum of mice （P<0.05，P<0.01）， and increased content of SOD （P<0.01）. The protein expression levels of Nrf2， HO-1， and IκBα and the mRNA expression of Nrf2 and HO-1 in skin tissue were up-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.05）. ConclusionPortulacae Herba can improve DNCB-induced ACD skin damage in mice by regulating the Nrf2/HO-1/NF-κB signaling pathway.

Individuals with breast cancer susceptibility genes(BRCA) germline mutations have a significantly increased lifetime risk for breast cancer, BRCA-mutant cancer cells have abnormal homologous recombination repair of DNA.Inhibition of Poly (ADP-ribose) polymerase (PARP) has shown marked benefit for breast cancer with homologous recombination deficiency, whether driven by defects in BRCA1, BRCA2, or other pathway components. Currently, under U. S.Food and Drug Administration approval of PARP inhibitor on ovarian cancer, clinical trials for PARP inhibitor are being conducted to assess whether PARP inhibitor as monotherapy or in combination with other drugs could benefit more breast cancer patients. Besides the studies of PARP inhibitor as monotherapy in breast cancer patients, researches in investigating platinum-PARP inhibitor combination in BRCA mutated breast cancer or triple negative breast cancer were conducted. In addition, many studies of immunotherapy combined with PARP inhibitor in breast cancer are ongoing. However, resistance to PARP inhibitors and the toxicity of the drugs remain challenges. This review will discuss the utility and unsolved problems of PARP inhibitor in breast cancer as well as the potential future directions.

Objective To explore the clinical significance and treatment regimen of sentinel lymph node(SLN) micrometastases and isolated tumor cell metastasis in breast cancer.Methods Ninety-seven breast cancer patients with sentinel lymph node micrometastases or isolated tumor cell metastasis from January 2013 to December 2015 were retrospectively studied.The patients were assigned to axillary lymph node dissection group (ALND,41 cases) and non axillary lymph node dissection group(non-ALND,56 cases) according to the final surgery mode to the axilla.Disease-free survival(DFS) and overall survival (OS) were compared between the two groups.Results Neither clinico-pathological factors,such as age,tumor size,grade,ER/PR status,HER-2 gene expression,Ki-67 expression and the size of the SLN metastasis,nor the treatment,such as breast surgery,postoperative adjuvant chemotherapy,radiotherapy and hormone therapy were found statistically different between the two groups (P ＞ 0.05).There were 96 patients evaluable with a median follow up of 24 months.The DFS of the ALND and non-ALND group was 97.5％ and 96.6％ (P ＞ 0.05),and the OS was 100％ and 98.2％ (P ＞ 0.05) respectively with no difference between the two groups.There were 2 ispilateral axillary recurrence in the non-ALND group and non in the ALND group.Conclusion Axillary lymph node dissection may be omitted for the breast cancer patients with sentinel lymph node micrometastases and isolated tumor cell metastases.But the postoperative adjuvant systemic treatment should be emphasized.

Objective To explore and evaluate the model of antiretroviral treatment that oriented to the medical needs of people living with HIV/AIDS (HIV/AIDS),based on the local prevalence of HIV/AIDS.Methods A total of 268 HIV/AIDS were selected the CDC of 13 administrative district in Wuhan from 2012 to 2013 and 275 HIV/AIDS were selected in the hospitals of 13 administrative district in Wuhan from 2013 to 2014.The antiretroviral effect of the two groups was compared and the related factors were analyzed.Results An antiretroviral treatment network that oriented to the medical needs of HIV/AIDS was developed.Data showed that the adherence of patients was better than that when the treatment was carried out at the CDC offices and the status of immuno-recovery on HIV/AIDS was more effective than the hospital-based treatment (P＜0.05).Data from multivariable logistic regression analysis showed that different patterns did play different roles on the effects of treatment.Conclusions The mode of antiretroviral treatment that oriented to the medical needs of HIV/AIDS could effectively improve the adherence and outcomes of treatment.We believe this model could also be adopted elsewhere.

OBJECTIVETo analyze the relationship between the expression level of Ki67 and clinicopathological features in breast cancer.

METHODSData of 918 female patients with invasive ductal breast carcinoma treated in the Cancer Hospital, Chinese Academy of Medical Sciences from Jan. to Dec. 2010 were analyzed retrospectively. The correlation of Ki67 expression and other clinicopathological features in the breast cancer was analyzed.

RESULTSAmong the 918 cases, the Ki67 index was 0.9% to 95% (mean value 27.8%). Taking the Ki67 index 14% as the boundary to divide the patients into two subgroups, 263 cases (28.6%) were ≤ 14%, and 655 cases (71.4%) were >14%. There were significant differences between the Ki67 expression and age, tumor size, axillary lymph nodes status, histological grade and the expressions of C-erbB-2, estrogen receptor (ER) and progesterone receptor (PR) (P < 0.05 for all). All the Ki67 indexes of Ki67 expression in luminal B (30.44%), HER-2 overexpression (36.77%) and triple negative (47.40%) subtypes were significantly higher than that in the luminal A subtype (21.36%)(P < 0.01). The expression level of Ki67 in triple-negative subtype (47.40%) was significantly higher than that in the non-triple-negative subtype (24.79%)(P < 0.001).

CONCLUSIONSKi67 index is significantly correlated with the age, tumor TNM stage, axillary lymph node status, histological grading, ER status, PR status and HER-2 status. A high expression level of Ki67 is a poor prognostic factor for breast cancer. The expression level of Ki67 should be detected routinely and it may become a useful prognostic marker in the treatment of breast cancer.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Female ; Humans ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Young Adult

Objective To study the co-effects of methylene blue(MB) and exposure with the cold light source on cell DNA damage, and to explore the mechanism involved. Methods The alkaline single cell gel electrophoresis was used to determine cell DNA damage. Apoptosis of the cells was determined by flow cytometry analysis using Annexin V-FITC/PI staining. DCFH-DA probe was used to determine endocellular Reactive Oxygen Species (ROS). Results The levels of DNA damage in the SGC7901 adenocarcinoma cells treated with methylene blue in the light were significantly increased compared to that of control ( F = 8.39, P＜0.05 ). The DNA damage levels were related to the length of time of light exposure, and the damage was recovered to a certain level after light withdrew. Cell apoptosis ( x2=7.71,P ＜0.05)and endocellular ROS level (F = 34.11, P＜0.01＝ increased significantly in the exposure group. Conclusions Methylene blue chromoendoscopy can induce DNA damage and cell apoptosis, and the mechanism may be associated with ROS produced by the photochemical reaction.

Objective To evaluate the accuracy of core needle biopsy (CNB) in diagnosing breast masses and its coherence with immunohistochemical (IHC) examination results of estrogen receptor (ER), progesterone receptor (PR) and Her2 protein between pre-and post-chemotherapy in invasive breast cancer. Methods The results of 516 CNB cases from June, 2005 to April, 2008 were analyzed retrospectively. The pathological examination was performed by two pathologists independently. Results 484 cases of malignant tumor, carcinoma in situ and phyllodes tumor were found in this group with the sensitivity of 96.7%. Sixteen cases of false negative (3. 3% ) were demonstrated by surgical biopsy. The accurate rate of CNB was not influenced by the maximum diameter of masses ( P = O. 423 ). The agreement rate of IHC results of ER, PgR and Her2 between pre- and post-chemotherapy were 90. 3%, 76. 8% and 82.5%, respectively. Conclusion CNB is a useful diagnostic method with a satisfactory accuracy in any size of breast masses. Given the histological heterogeneity of invasive breast cancer and the influence of ehemotherapy, the coherence of prechemotherapy IHC for ER, PgR and Her2 is not optimal with that of post-chemotherapy.

Objective To evaluate the localized biopsy of nonpalpable breast lesions (NPBLs) and its role in the early diagnosis and treatment of breast cancer. Methods One hundred and fifty-eight NPBLs from a series of 141 women detected by mammography were resected with wire localization technique. Results Forty-two lesions (26.6%, 42/158) in 42 patients were diagnosed with malignant result, including 12(28.6%) patients with stage 0 breast cancer, 24(57.1%) with stageⅠ, 2(4.8%) with stage Ⅱ and 4(9.5%) with stage Ⅲ disease according to American Joint Committee on Cancer (AJCC) staging system(the 6th edition). The contralateral axillary lymph nodes metastasis were found in only one (2.4%) patient with stage Ⅲ disease and the other forty-one patients remained free of recurrent disease at a median follow-up of 31 months.Conclusion The results showed that the most nonpalpable breast cancers detected by mammography were early-stage breast cancers and had good prognosis. The NPBLs should get a localized biopsy in order to facilitate the early diagnosis and treatment of nonpalpable breast cancers.

OBJECTIVETo investigate the expression of extracellular signal-regulated kinase (ERK) and its relationship with clinicopathological characteristics of breast cancer as well as the effect of preoperative chemotherapy on ERK expression.

METHODSExpression of ERK-1 and ERK-2 protein was examined by Western blot in the breast cancer and normal breast (control) tissue of 48 patients, of whom 8 had received preoperative chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR), with distribution of ERKs protein detected by immunohistochemical method.

RESULTSExpression of ERK-1 and ERK-2 protein was increased in tumor specimen as compared with control tissue (P < 0.01). A positive correlation was observed between ERK-1 and ERK-2 (r = 0.457, P < 0.01). Protein level of ERK-1 and ERK-2 was higher in stage III patients than in stage I and stage II patients (P < 0.05). Expression of both ERK-1 and ERK-2 in the carcinoma tissue was decreased in patients who had received preoperative chemotherapy of 5'-DFUR. ERK-1 and ERK-2 proteins were mainly located in the cytoplasm.

CONCLUSIONThe hyperexpression of ERK may play an important role in the initiation and development of human breast cancer. Preoperative chemotherapy of 5'-DFUR is able to partially inhibit ERK expression.

Antimetabolites, Antineoplastic ; therapeutic use ; Breast Neoplasms ; classification ; drug therapy ; enzymology ; pathology ; Female ; Floxuridine ; therapeutic use ; Humans ; Mitogen-Activated Protein Kinase 1 ; biosynthesis ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases ; biosynthesis ; Neoplasm Staging

Objective To evaluate breast imaging reporting and data system (BI-RADS) in categorization and biopsy of nonpalpable breast lesions (NPBLs). MethodsOne hundred and sixty-two NPBLs from 144 female patients detected by mammography were retrospectively categorized according to BI-RADS. All the lesions finally got histopathological diagnosis by wire-localization biopsy. Results There were 46 malignant lesions, with the positive predictive value for cancer of 28.4% (46/162). The cases of BI-RADS 2-5 lesions were 11, 55, 77, and 19 after categorization according to the BI-RADS, and the positive predictive value of each category for cancer was 0% (0/11),3.6% (2/55),37.7% (29/77),78.9% (15/19) respectively. ConclusionBI-RADS categorization improves the diagnostic specificity of nonpalpable breast lesions and helps decision-making for biopsy. It is suggested that NPBLs on category of BI-RADS 4 or 5 should undergo biopsy.