Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.

Objective: To explore the influencing factors for the primary and secondary school students with abnormal angle of trunk rotation for the prevention. Methods: The students of Grade Four to Nine in Jiashan County of Zhejiang Province were selected by cluster sampling method. A self-designed questionnaire was used to collect social demographic data, diet behaviors, physical activities, reading and writing habits. The angle of trunk rotation was measured by scoliometer. Logistic regression model was used to investigate the influencing factors for abnormal angle of trunk rotation. Results: This study included 2 942 schoolchildren, with 1 582 ( 53.78% ) boys and 1 360 ( 46.23% ) girls. The incidence rate of abnormal angle of trunk rotation was 7.82%. The incidence rate of abnormal angle of trunk rotation in girls was 10.74%, which was higher than 5.31% in boys ( P<0.05 ). Grade ( OR=1.485, 95%CI: 1.058-2.085 ), gender ( OR=2.084, 95%CI: 1.536-2.828 ), frequency of eating fresh vegetables in the past week ( OR=0.749, 95%CI: 0.633-0.887 ) and watching electronic screen in the dark ( OR=1.188, 95%CI: 1.002-1.408 ) were the influencing factors for abnormal angle of trunk rotation in primary and secondary school students. Grade ( OR=2.664, 95%CI: 1.481-4.791 ) and watching electronic screen in the dark ( OR=1.325, 95%CI: 1.030-1.704 ) were influencing factors for abnormal angle of trunk rotation in boys. Frequency of eating fresh vegetables in the past week ( OR=0.714, 95%CI: 0.574-0.887 ) and uncorrected eyesight less than 5.0 ( OR=1.795, 95%CI: 1.164-2.767 ) were influencing factors for abnormal angle of trunk rotation in girls. Conclusion The abnormal angle of trunk rotation in primary and secondary school students is related to gender, grade, reading and writing behaviors as well as diets; and the influencing factors are different in male and female students.

OBJECTIVE: To explore the correlation of EB virus infection with the prognosis of B-ALL children. METHODS: The peripheral blood of children with newly diagnosed B-ALL admitted in Children's Hospital of Chongqing Medical University from January 2012 to December 2017 were collected, and the EBV DNA in plasma was detected by real-time quantitative PCR. The clinical data of B-ALL children were collected and the correlation of EBV infection with the prognosis of B-ALL children was analyzed. RESULTS: Among 162 B-ALL children, the EBV infection rate was 41.36%. Univariate analysis showed that the B-ALL children with EBV infection had the poor prognosis and higher risk of shorter survival time, as compared with B-ALL children without EBV infection (HR=2.373, 95% CI: 1.129-4.987) (P＜0.05), the multivariate analysis showed that the result was consistent with result of univariate analysis indicating that EBV infection was an independent predictor for poor prognosis of B-ALL children. CONCLUSION The EBV infection may play an important role in the occurrence and progression of B-ALL and is an independent predictor for poor prognosis, therefore the detection of EBV DNA in plasma of B-ALL children possesses an important significance for evaluation of B-ALL children's prognosis.
B-Lymphocytes ; Child ; DNA, Viral ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis

Background: The long-term predicted value of microvolt T-wave alternans (MTWA) for ventricular tachyarrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains unclear. Our study explored the characteristics of MTWA and its prognostic value when combined with an electrophysiologic study (EPS) in patients with ARVC. Methods: All patients underwent non-invasive MTWA examination with modified moving average (MMA) analysis and an EPS. A positive event was defined as the first occurrence of sudden cardiac death, documented sustained ventricular tachycardia (VT), ventricular fibrillation, or the administration of appropriate implantable cardioverter defibrillator therapy including shock or antitachycardia pacing. Results: Thirty-five patients with ARVC (age 38.6 ± 11.0 years; 28 males) with preserved left ventricular (LV) function were recruited. The maximal TWA value (MaxValt) was 17.0 (11.0–27.0) μV. Sustained VT was induced in 22 patients by the EPS. During a median follow-up of 99.9 ± 7.7 months, 15 patients had positive clinical events. When inducible VT was combined with the MaxValt, the area under the curve improved from 0.739 to 0.797. The receiver operating characteristic curve showed that a MaxValt of 23.5 μV was the optimal cutoff value to identify positive events. The multivariate Cox regression model for survival showed that MTWA (MaxValt, hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01–1.11; P = 0.01) and inducible VT (HR, 5.98; 95% CI, 1.33–26.8; P = 0.01) independently predicted positive events in patients with ARVC. Conclusions MTWA assessment with MMA analysis complemented by an EPS might provide improved prognostic ability in patients with ARVC with preserved LV function during long-term follow-up.

Objective:To observe effect of Zeqi Tang in intervening mice with orthotopic lung cancer model, in order to observe its anti-tumor mechanism. Method:An in situ mouse model of non-small cell lung cancer was established through intrapulmonary injection with 1×10⁵ LLC-luc cells. The model mice were intragastrically administered with Zeqi Tang(0.171 g·mL^-1) or normal saline for 35 days. Appearance (spirit, hair, appetite, sleep), survival period and Zeqi Tang anti-tumor effect were observed, weekly vital imaging was performed to detect the fluorescence signal in the lungs of mice. Flow cytometry was used to detect the NK cell content in the spleen of the model mice. CD107α was used to detect the degranulation of NK cells in the spleen of mice after administration of Zeqi Tang. Kromasil 100 5 C₁₈ column was used and eluted with acetonitrile-0.025%phosphoric acid in a gradient mode, with flow rate at 1.0 mL·min^-1, column temperature at 35℃ and detection wavelength of 265 nm, as to establish the fingerprint of Zeqi Tang. The fingerprints of 10 batches of samples was evaluated by using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System Software (2012 Edition) recommended by the Chinese Pharmacopoeia Commission, in order to complete the quality control of Zeqi Tang. Result:Zeqi Tang could significantly inhibit the lung fluorescence signal of lung cancer in situ model mice and prolong the survival of mice(P<0.05, P<0.01). After the intervention with Zeqi Tang, the NK cells in the tumors increased significantly(P<0.01), and the degranulation of CD107α also increased significantly(P<0.01). Moreover, the HPLC-DAD fingerprint of Zeqi Tang showed a significant increase in the fingerprint similarity of 10 batches of lacquer soup aqueous extract. Moreover, the HPLC-DAD fingerprint of Zeqi Tang showed that the fingerprint similarity of 10 batches of lacquer soup aqueous extract was ≥ 0.9, indicating that small differences between the batches. Conclusion:Zeqi Tang may enhance the tumor growth and prolong the survival period of mice by up-regulating the number of NK cells in mice and enhancing their degranulation function. The evaluation of similarity of HPLC fingerprint of Zeqi Tang reflects the quality of lacquer soup to a certain extent, and can provide reference for further study.

Early diagnoses and treatment methods are being constantly improved, but cancer metastasis remains a main cause of mortality in malignant tumor patients. Lung is thought to be the organ most prone to distal metastasis among malignant tumors due to its unique physiological and pathological character. Tumor lung metastasis is unpredictable and may result in irreversible damages. Presently, no exact mechanism or specific targeting therapies are found. Depending on the unique theory system-treatment based on symptom differentiation, traditional Chinese medicine has made significant progress on controlling tumor lung metastasis, but its application methods and mechanism still need further study and exploration. More appropriate and idealized animal models are required as a studying medium. Therefore, the establishment of animal models to simulate lung metastasis of cancer patients has become the key to the study of tumor lung metastasis. In order to produce a better platform for investigating the pathogenesis, underlying mechanism, early diagnosis and therapeutics for tumor lung metastasis, and to provide reference for the selection and establishment of mouse lung metastasis model, this article would introduce the implementation, application and estimation of several common methods (tail vein injection, mammary fat pad orthotopic injection, tibia injection, tissue orthotopic implantation, transgenic mice and so on). Meanwhile, the development of mouse lung metastasis model still needs expanding of thoughts, rational and flexible utilization of existing models, and interdisciplinary cooperation to establish preferable animal models and make results more reliable.

Lung cancer is a common malignancy with a high morbidity and high mortality. Although chemoradiotherapy is still the main therapy, the side effects caused by radiotherapy and chemotherapy cannot be ignored. There is an urgent need to find a targeted anti-cancer compound with a low toxicity and strong effect. Therefore, a large number of natural product-derived compounds have received increasing attention for their anti-cancer effect. They are diverse in structure, rich in variety but simpler in composition than natural plants, with a clear efficacy. This facilitates research, and the enriched ingredients have stronger pharmacological effect and clinical efficacy than natural plants. Quinonoids are natural bioactive molecules that widely exist in more than 100 species of higher and lower plants, including naphthoquinones, phenanthrenequinones, benzoquinones and pyrenes. Most of them have anti-tumor effect. They are applied and studied in many cancers, especially lung cancer; and the mechanism of action involves multiple pathways, which play a role in promoting apoptosis, inhibiting proliferation, inducing autophagy, inhibiting angiogenesis and cell invasion and migration. When they are used in combination with other drugs, there is also an anti-tumor effect. With the development of researches, many synthetic quinonoid derivatives with similar structures also increase the diversity of anti-cancer steroids, and quinonoids have broad application prospects in lung cancer. On the basis of a large amount of literature, this article reviews current studies on the molecular mechanisms of antitumor activity of quinonoids, summarizes the common research targets with different effect, and analyzes the relationship between the pharmacological effects and anti-lung cancer effects of quinonoids, and proposes the direction of further research, so as to provide the reference for the follow-up research and development of other quinonoids.

The diagnosis and treatment methods for cancer are being improved continually, but the mortality of cancer still remains high. At present, the academic circle has realized deficiency of existing treatment ideas, and the concept of cancer cells has been gradually changed from "extremely extinct" to "peaceful coexistence". The concept of "survival with tumors" is universally accepted in the cancer academia. The tumor microenvironment is the place where tumor cells survive and develop. Therefore, regulation of the tumor microenvironment has become an important new strategy for tumor treatment. Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells that have immunosuppressive properties on T cells in the tumor microenvironment and play an important role in tumor immune escape. Now, therapy with MDSCs in the tumor microenvironment as the treatment targets also provides new ideas for the tumor treatment. As MDSCs subpopulations are similar with neutrophils and monocytes, they can be divided into two major subtypes:granulocyte-like myeloid-derived suppressor cells (G-MDSCs) and monocyte-myeloid-derived suppressor cells(M-MDSCs). But how to differ these two subtypes from neutrophils and monocytes. What are the differences in the functional characteristics of different subtypes of MDSCs. How do they accumulate, differentiate, and exert immunosuppressive effects through different pathways. Traditional Chinese medicine(TCM) has always been good at modulating the body's microenvironment. More and more researches have shown that, the recruitment, amplification and activation of MDSCs can be effectively inhibited by TCM compound and its active ingredients, providing scientific basis for Chinese medicine targeting MDSCs in the tumor microenvironment. However, which specific pathways could regulate G-MDSCs or M-MDSCs is still in need of further studies. Most previous literature focus on the overall level of MDSCs, while the this paper would be based on the specific subpopulations of MDSCs to clarify the biological characteristics of these two subtypes of MDSCs, so as to achieve more precise targeted therapy in the tumor microenvironment.

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions: Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.
Antineoplastic Combined Chemotherapy Protocols ; Bortezomib/therapeutic use* ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Multiple Myeloma/therapy* ; Retrospective Studies ; Stem Cell Transplantation ; Transplantation, Autologous ; Treatment Outcome