1.Survival Analysis on Patients with Malignant Cancers in Nanhui District of Shanghai from 2002 to 2004
Yifei FU ; Yun PENG ; Meiyu ZHANG
Chinese Journal of Prevention and Control of Chronic Diseases 2006;0(01):-
Objective To investigate the survival rates of main malignant tumors in Nanhui district. Methods Total 5 783 cases, registered as new cases with malignant neoplasm from 2002 to 2004 in Nanhui, were followed up. Data was studied by survival analysis with SPSS 13.0 of life table and Kaplan -Meier. Results The average annual crude incidence of malignant tumors was 267.57 / 100 000, the World standardized incidence rate of 209.98 / 100 000. Cancer Incidence in the top five ranks followed by lung, liver, stomach, colon and esophageal cancer, the incidence was 43.06 / 100 000, 28.65 / 100 000, 26.82 / 100 000, 18.63 / 100 000 and 9.57 / 100 000, respectively. The difference of the survival rates between the top five cancers was remarkable. Survival rates of cancers among males from the lowest to the highest were liver, lung, esophagus, stomach and intestines. Survival rates of cancers among females from the lowest to the highest were of liver, lung, esophagus, stomach, intestines, cervical and breast. The male or female main cancer's relative survival rate droped along with the age rising. Conclusion The survival status was better in the patients with intestine cancers and female patients with breast cancer, but worse in patients with liver, ung and esophageal cancer.
2.Progress in mechanism of tumor-derived exosomes on myeloid-derived suppressor cells
Mengyu ZHANG ; Jie SHEN ; Meiyu PENG
Chinese Journal of Microbiology and Immunology 2022;42(11):912-916
Myeloid-derived suppressor cells (MDSCs) play an important immunosuppressive role in the tumor microenvironment. Tumor cells can regulate the immunosuppressive function of MDSCs in the tumor microenvironment through exosomes, thereby affecting the development of tumors. Tumor-derived exosomes (TEXs) promote the development of MDSCs and improve their immunosuppressive function in the tumor microenvironment mainly by participating in the processes such as intercellular information exchange and information transmission. Moreover, the miRNAs in TEXs will also be transferred to recipient cells to inhibit the immunosuppressive function of MDSCs by inducing the negative regulation of target genes. This review summarized the progress in the mechanism of TEXs on MDSCs.
3.Effect of acupuncture on TGF-β1/Smads pathway in mice with airway remodeling mic.
Huihui LIU ; Jiayi LIU ; Meiyu PENG ; Yuhui LI ; Chunqiao LI
Journal of Southern Medical University 2018;38(11):1372-1377
OBJECTIVE:
To investigate the effect of acupuncture on TGF-β1/Smads signaling pathway in the lung tissue of mice with airway remodeling.
METHODS:
Thirty specific pathogen-free mice were randomly divided into blank group, model group and acupuncture group (=10). Mouse models of asthma were established in the model group and the acupuncture group, and the mice in the latter group received 7 acupuncture therapies (at bilateral Fei Shu, Da Zhui and Zu Sanli, 20 min each time) every other day, starting on the 10th day after the modeling. At 24 h after the last acupuncture, the mice were subjected to inhalation of 1% OVA for 3 days, and 24 h after the last challenge, the mice were given methacholine chloride (Mch) inhalation at different concentrations for measurement of lung resistance using a noninvasive stroke volume meter. HE staining was used to observe the pathological changes in the lung tissues, and TGF-β1 levels in the the bronchoalveolar lavage fluid (BALF) and serum were detected using ELISA; Western blotting was used to detect the differential protein expressions in the airway smooth muscles between the two groups. The airway smooth muscle cells were isolated from the mice in the acupuncture group and treated with a TGF- β1 inhibitor (LY2157299), and the relative expressions of type-Ⅰ and Smads proteins were detected using Western blotting.
RESULTS:
The mice in the model showed obvious tracheal fistula with airway pathologies including lumen narrowing, bronchial mucosa thickening, dissociation of the epithelial cells, and thickening of the alveolar septum and airway smooth muscles. These pathological changes were obviously milder in the acupuncture group. The asthmatic mice exhibited significantly increased lung resistance in positive correlation with Mch concentration. Serum TGF-β1 level was significantly elevated in asthmatic mice ( < 0.05); TGF-β1 levels in the serum and BALF were significantly lower in the acupuncture group than in the model group ( < 0.05). In the model group, the expressions of -SMA, TGF-β1 and Smads in the airway smooth muscles were significantly higher than those in the other two groups (both < 0.05). In cultured airway smooth muscle cells, the expressions of type-Ⅰ and Smads were significantly higher in cells treated with LY2157299 than in the control cells (>0.05).
CONCLUSIONS
Acupuncture can inhibit airway remodeling by inhibiting the expression of airway TGF-β1 and down-regulating the expression of Smads and -SMA to reduce airway inflammatory response. Airway expressions of type-Ⅰ and Smads proteins remain high after inhibiting TGF-β1. Acupuncture may control asthma progression through the TGF-β1/Smads pathway.
Acupuncture Points
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Acupuncture Therapy
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Airway Remodeling
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Airway Resistance
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Animals
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Asthma
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metabolism
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pathology
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therapy
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Bronchi
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pathology
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Disease Progression
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Lung
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metabolism
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physiopathology
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Mice
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Muscle, Smooth
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Random Allocation
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Smad Proteins
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analysis
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metabolism
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Transforming Growth Factor beta1
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analysis
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metabolism
4.Effect of bovine lactoferrin supplementation on intestinal inflammatory factor expression in premature rats model of necrotizing enterocolitis
Xiangyong KONG ; Lu ZHUANG ; Meiyu WANG ; Shan ZHANG ; Jianru PENG ; Zhichun FENG
Chinese Journal of Applied Clinical Pediatrics 2020;35(2):151-155
Objective:To investigate the protective effects of bovine lactoferrin (bLF) supplementation on intestinal mucosal tissue and its influence on of inflammatory factors in the premature rats model of necrotizing enterocolitis(NEC), and to provide the theoretical basis for prevention of NEC by bLF supplementation.Methods:Premature SD rats were randomly divided into 4 groups, 25 cases in each group.Control group: oral feeding; model group : oral feeding with lipopolysaccharides(LPS) gavage + hypoxic stimulation; high dose bLF intervention group: daily bLF (7 g/L) + oral feeding with LPS gavage + hypoxic stimulation; low dose bLF intervention group: daily bLF (2 g/L) + oral feeding with LPS gavage + hypoxic stimulation.Histopathological analysis was performed by HE staining.The expression levels of interleukin-1β(IL-1β)and interleukin-6(IL-6)in intestinal mucosa were detected by enzyme linked immunosorbent assay (ELISA).Results:(1) Morphological observation: the intestinal wall of model group was thin, and there were different degrees of pneumoconiosis and effusion in intestinal cavity.Under the microscopy, it could be observed that the intestinal tissue necrosis was serious, the intestinal villi fell off, glands arranged disorderly, epithelial edema was significant, the lamina propria and submucosa had severely edema and were separated, and there were a large number of inflammatory cells infiltrated.The above-mentioned manifestations were alleviated in the high-dose and low-dose bLF intervention groups, and no significant abnormalities were found in the control group.(2) The expression of IL-1β and IL-6 in intestinal tissue: the tissue concentration of IL-1β and IL-6 in the model group rats [(380.89±20.25) ng/L, (485.12±31.44) ng/L]were significantly higher than those in the control group[(270.69±45.58) ng/L, (212.62±89.46) ng/L]( q =9.785, 14.030, all P<0.01). The expression of IL-1β and IL-6 in mucosal tissue of ileum was significantly inhibited in hypoxic and LPS-stimulated rats fed with bLF(IL-1β: q=9.105, 8.761, all P<0.01; IL-6: q=8.175, 8.996, all P<0.01). There was no significant difference in the expression of IL-1β and IL-6 between high dose bLF(7 g/L) and low dose bLF (2 g/L) inter vention groups (IL-1β: q=-0.084, P>0.05; IL-6: q=-1.140, P>0.05). Conclusion:Enteral bLF supplementation can alleviate the damage of intestinal tissue in NEC model of premature SD rats, inhibit the expression of IL-1β and IL-6 inflammatory factors in intestinal tissue, and have a protective effect on intestinal tissue.
5.Autologous ilium graft combination with titanium plate for sternal reconstruction: A case report
Bo YANG ; Bin LI ; Peng JIANG ; Shaobo ZHANG ; Meiyu REN ; Zhipeng SU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(02):329-332
The sternum is the pivotal component of the thoracic cavity. It is connected with the clavicle and ribs on the upper part and both sides respectively, and plays an important role in protecting the stability of the chest wall. Sternal resection usually results in a large segmental chest wall defect that causes the chest wall to float and requires sternal reconstruction. This paper reports a 62 years male patient with thymic squamous cell carcinoma with sternal metastasis, who underwent thymotomy, sternal tumor resection and autologous lilum graft combined with sternal reconstruction by titanium plate after relevant examination was completed and surgical contraindications were eliminated. The patient was followed up for 6 months, the respiratory and motor functions were normal and the thoracic appearance was good.
6.Discovery of a series of dimethoxybenzene FGFR inhibitors with 5pyrrolo2,3-pyrazine scaffold: structure-activity relationship, crystal structural characterization and study.
Peng WEI ; Bo LIU ; Ruifeng WANG ; Yinglei GAO ; Lanlan LI ; Yuchi MA ; Zhiwei QIAN ; Yuelei CHEN ; Maosheng CHENG ; Meiyu GENG ; Jingkang SHEN ; Dongmei ZHAO ; Jing AI ; Bing XIONG
Acta Pharmaceutica Sinica B 2019;9(2):351-368
Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with metabolic stability tests and pharmacokinetic profiling, a representative compound () was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.
7.Novel compound FLZ alleviates rotenone-induced PD mouse model by suppressing TLR4/MyD88/NF-
Zhe ZHAO ; Fangyuan LI ; Jingwen NING ; Ran PENG ; Junmei SHANG ; Hui LIU ; Meiyu SHANG ; Xiu-Qi BAO ; Dan ZHANG
Acta Pharmaceutica Sinica B 2021;11(9):2859-2879
Parkinson's disease (PD) is the second most common neurodegenerative disease, but none of the current treatments for PD can halt the progress of the disease due to the limited understanding of the pathogenesis. In PD development, the communication between the brain and the gastrointestinal system influenced by gut microbiota is known as microbiota-gut-brain axis. However, the explicit mechanisms of microbiota dysbiosis in PD development have not been well elucidated yet. FLZ, a novel squamosamide derivative, has been proved to be effective in many PD models and is undergoing the phase I clinical trial to treat PD in China. Moreover, our previous pharmacokinetic study revealed that gut microbiota could regulate the absorption of FLZ
8.Design, synthesis and biological evaluation of pyrazolo3,4-
Xiaowei WU ; Mengdi DAI ; Rongrong CUI ; Yulan WANG ; Chunpu LI ; Xia PENG ; Jihui ZHAO ; Bao WANG ; Yang DAI ; Dan FENG ; Tianbiao YANG ; Hualiang JIANG ; Meiyu GENG ; Jing AI ; Mingyue ZHENG ; Hong LIU
Acta Pharmaceutica Sinica B 2021;11(3):781-794
Fibroblast growth factor receptors (FGFRs) have emerged as promising targets for anticancer therapy. In this study, we synthesized and evaluated the biological activity of 66 pyrazolo[3,4-
9.Structure-based drug discovery of novel fused-pyrazolone carboxamide derivatives as potent and selective AXL inhibitors.
Feifei FANG ; Yang DAI ; Hao WANG ; Yinchun JI ; Xuewu LIANG ; Xia PENG ; Jiyuan LI ; Yangrong ZHAO ; Chunpu LI ; Danyi WANG ; Yazhou LI ; Dong ZHANG ; Dan ZHANG ; Meiyu GENG ; Hong LIU ; Jing AI ; Yu ZHOU
Acta Pharmaceutica Sinica B 2023;13(12):4918-4933
As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.
10. Impact of hypertensive disorder complicating pregnancy on neonatal mortality and major complications in preterm infants
Meiyu WANG ; Xiangyong KONG ; Zhichun FENG ; Fengdan XU ; Hongyan LYU ; Lihong YANG ; Sujing WU ; Rong JU ; Jin WANG ; Li PENG ; Zhankui LI ; Xiaolin ZHAO ; Shujuan ZENG ; Huixian QIU ; Weixi WEN ; Hui WU ; Ying LI ; Nan LI ; Xuefeng ZHANG ; Wenzheng JIA ; Guo GUO ; Weipeng LIU ; Feng WANG ; Gaimei LI ; Fang LIU ; Wei LI ; Xiao-ying ZHAO ; Hongbin CHENG ; Yunbo XU ; Wenchao CHEN ; Huan YIN ; Yanjie DING ; Xiaoliang WANG ; Ruiyan SHAN ; Ping XU ; Meiying HAN ; Chunyan YANG ; Tieqiang CHEN ; Xiaomei TONG ; Shaojun LIU ; Ziyuan LIU
Chinese Journal of Applied Clinical Pediatrics 2018;33(14):1065-1070
Objective:
To investigate the effect of hypertensive disorder complicating pregnancy (HDCP) on the mortality and early complications of premature infants.
Methods:
The general clinical data of preterm infants with gestational age 24-36+ 6 weeks were collected from the cooperative units in the task group from January 1, 2013 to December 31, 2014.According to the severity of HDCP, the infants were divided into 4 groups: HDCP group, preeclampsia group, eclampsia group and non HDCP group, the mortality and major complications of preterm infants were compared, and the influencing factors were analyzed.
Results:
The mortality rate of preterm in the HDCP group was significantly higher than that of non HDCP group, and there was statistical significance (