1.Chitosan tubular stent combined with muscle flaps for repair of partial defects of the cervical esophagus
Gang CHEN ; Hanyun LIU ; Bin WANG ; Zizheng ZHANG ; Zhiping WANG
Chinese Journal of Tissue Engineering Research 2013;(51):8934-8940
BACKGROUND:Over the years, muscle, skin, skeletal muscle flaps and luminal tissues, such as stomach and intestines, are used as an artificial esophagus to repair esophagus defects, but the results are not good.
OBJECTIVE:To investigate the feasibility of chitosan tube stent combined with muscle flaps to repair partial defects of the cervical esophagus.
METHODS:Thirty white rabbits were used to make animal models of partial cervical esophageal defects, and randomly divided into experimental group (n=20) and control group (n=10). Esophagus defect in rabbits of experimental group was repaired using autologous muscle flap with a chitosan tube stent, and esophagus defect in the control group was repaired only with muscle flap. Gross and histological appearance was observed at weeks 2, 4 and 8 after operation, and barium sulphate X-ray screen was performed at week 10 after operation.
RESULTS AND CONCLUSION:After 2 weeks, muscle tissue structure, cellswel ing, and inflammatory cellinfiltration could be seen in the experiment and control groups, exhibiting an acute inflammatory reaction. After 4 weeks, the experimental group showed clear muscle flaps, reduced inflammatory reaction, and no obvious fibrosis;while in the control group, muscle tissue could be seen at defect site, with growth of fibrous tissue cells and a few of inflammatory cells. After 8 weeks, in the experimental group, squamous metaplasia could be seen on the gross surface of the muscle flaps,esophageal mucosa could be seen, accompanied by chronic inflammatory reaction under the mucosas that had a clear abate than that at 4 weeks after implantation;in the control group, chronic inflammatory reaction could be found, accompanied by clear fibrosis but no squamous metaplasia and mucosal regeneration. Barium sulphate examination found that the esophagus was smooth with a slight motility in the experimental group, but there was a part of stricture in the esophagus without motility. These findings suggest that the chitosan tube stent combined with muscle flaps could better repair partial defects of the cervical esophagus.
2.Migration and invasion abilities of normal fibroblast-like synoviocytes versus fibroblast-like synoviocytes in rheumatoid arthritis
Jun HU ; Zizheng TANG ; Yu ZHANG ; Weigan SHEN ; Guiping LIU ; Wenwen WANG ; Jiahuan LIU
Chinese Journal of Tissue Engineering Research 2017;21(24):3870-3874
BACKGROUND:Fibroblast-like synoviocytes (FLS) in the synovial lining layer are related to the cell proliferation, invasion, migration and apoptosis as well as bone resorption in rheumatoid arthritis. OBJECTIVE:To compare the migration and invasion abilities of FLS (MH7A) in rheumatoid arthritis and normal FLS (HFLS). METHODS:The capacities of cell migration and invasion were evaluated by Transwell cell migration and invasion assays. The primers of the indicated microRNAs were designed and synthesized, and the expression levels of miRNAs were determined by real-time PCR according to the SYBR?PrimeScript?miRNA RT-PCR Kit instruction. RESULTS AND CONCLUSION:MH7A possessed stronger migration and invasion abilities than HFLS. Compared with HFLS, obviously upregulated miR-132, -155, -203, -223 and -124, and significantly downregulated miR-15a, -16, 18a, -19a, -26a and -146a were found in MH7A. These findings suggest that the differentially expressed 11 kinds of rheumatoid arthritis-associated miRNAs participate in the pathogenesis of rheumatoid arthritis probably by enhancing the migration and invasion capacities of MH7A.
3.Primary squamous cell carcinoma of the breast: report of 23 cases
Zizheng WU ; Zhen LIAN ; Jing ZHAO ; Lijuan LI ; Haifei NIU ; Juntian LIU
Chinese Journal of General Surgery 2015;30(9):723-725
Objective To investigate the clinical and pathologic features of squamous cell carcinoma of the breast.Methods The clinical and pathologic data of 23 squamous cell carcinoma of the breast patients admitted between 1984 and 2013 to Tianjin Medical University Cancer Hospital was analyzed retrospectively.Results Primary squamous cell carcinoma of the breast was a very rare tumor accounting for 0.06% of all breast cancers.All of the 23 patients were females aged 28 years to 87 years(median age 49 years).Average tumor size was 4.5 cm.9 patients suffered from lymph node metastasis at admission (39.1%).The positive rates of estrogen receptor (ER),progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) were 13.6% (3/23),4.5% (1/23) and 0 (0/20) respectively.With a follow-up time varying from 5 months to 36 months recurrence or metastasis were found in 8 patients,and another 1 patient was found having distant metastasis at admission.Lung metastasis (7/9) was most common.6 patients died.Conclusions Squamous cell carcinoma of the breast is highly invasive,with low rate of positive receptors and early distant metastasis or recurrence after operation,and poor patients' survival.
4.Clinicopathologic characteristics and prognosis of medullary breast carcinoma
Kun MU ; Zizheng WU ; Haifei NIU ; Nan WU ; Jing ZHAO ; Jun ZHANG ; Juntian LIU
Chinese Journal of General Surgery 2017;32(3):211-214
Objective To investigate the clinicopathologic characteristics and prognosis of medullary breast carcinoma.Methods We conducted a retrospective analysis on clinical and pathologic data of 166 patients with medullary breast cancer.Results All the patients were female with a median age of 52 years old.The proportion of patients with stage Ⅰ,Ⅱ and Ⅲ disease was 16.9%,68.1%,15.0%,respectively.The Luminal,HER-2 overexpressing and triple-negative subtypes constituted 31.3%,8.4%,and 60.3%,respectively.There was significant difference in regional lymph node status of medullary breast cancer patients with different molecular types (x2 =18.248,P =0.003),but not in tumor size,TNM stage,histological grade,and expression of Ki67 (all P > 0.05).Multivariate survival analysis indicated that TNM stage was an independent predictor in the prognosis of medullary breast cancer (HR =5.664,P =0.001).All the patients were followed up from 15 months to 145 months with a median follow-up time of 108 months.The 5-year survival rate was 91.5% and the 10-year survival rate was 87.2%.Conclusions The prognosis of medullary breast cancer is favorable.Personalized treatment according to the TNM stage and histopathologic characteristics achieve a favorable prognosis.
5.Clinico-pathological features and prognosis of 195 patients with invasive micropapillary carcinoma of the breast
Nan WU ; Ying LI ; Zizheng WU ; Jing ZHAO ; Yang ZHAO ; Haifei NIU ; Kun MU ; Juntian LIU
Chinese Journal of General Surgery 2017;32(5):397-401
Objective To explore the clinicopathological characteristics and prognosis of invasive micropapillary carcinoma of the breast (IMPC),and the distinction between IMPC and invasive ductal carcinoma of the breast (IDC).Methods From February 2004 to November 2013,195 IMPC patients and 420 IDC patients were analyzed retrospectively.Results There were significant differences in mammilla invasion,lymph vessel invasion,orange peel sign,soft tissue encroachment,neoadjuvant chemotherapy,radical mastcctomy,lymph node metastasis,clinical stages,tumor size,lymph node staging,estrogen receptor (ER),progestin receptor (PR),human epidermal growth factor receptor 2 (HER2),molecular subtyping,ratio of radiation,ratio of endocrine therapy,disease-free survival (DFS),overall survival (OS)between the two groups,all P <0.05.Patients with IMPC had lower 5-year DFS and OS rates (68.2% and 73.8%,respectively) than IDC patients (85.7% and 88.6%,respectively),all P < 0.05.In IMPC patients with positive ER/PR,HER2-negative,smaller tumor volume,less lymph node metastasis,negative nipple invasion,negative lymphatic vessel tumor thrombus,negative orange peel change had higher 5-year DFS and OS rates than those with negative ER/PR,HER2 overexpression,larger tumor volume,more lymph node metastasis,positive nipple invasion,positive lymphatic vessel tumor thrombus,positive orange peel change,all P < 0.05.Besides,the patients with pathologic stage Ⅰ had higher OS than those with stage Ⅲ (P < 0.05).Cox regression analysis found that orange peel change,lymph vessel invasion and HER2 were the independent risk factors for the survival time of patients with IMPC.Conclusions IMPC patients have lower DFS and OS compared with IDC.
6.MicroRNA-17-92 gene promotes renewal and proliferation of gastric cancer stem cells
Zizheng SONG ; Hua YANG ; Yanhong SHANG ; Bin LIU ; Gang ZHANG ; Hua WANG ; Aimin ZANG
Chinese Journal of Tissue Engineering Research 2015;(50):8077-8083
BACKGROUND:Studies have shown that microRNAs (miRNAs) have moderating effect on the renewal and differentiation of cancer stem cels. However, there is no complete understanding on the effect of microRNA-17-92 gene on gastric cancer stem cel renewal and proliferation.
OBJECTIVE:To explore the effect of miRNA-17-92 in promoting self-renewal and proliferation of gastric cancer stem cels.
METHODS:(1) The gradualy reduced miRNAs during gastric cancer stem cel self-renewal were investigated using miRNA array based on RNAs from differentiated and adherent cels. (2) The miRNA-17-92 was constructed and transfected to gastric cancer stem cels. (3) The effects of miRNA-17-92 on the self-renewal of gastric cancer stem cels were studied by tumor sphere assayin vitro. (4) The effects of miRNA-17-92 on the proliferation of gastric cancer stem cels were investigated by MTT assay and colony formation assay.
RESULTS AND CONCLUSION:(1) miR-19b/20a/92a expression gradualy reduced in the adhesion and differentiation of gastric cancer stem cels. (2) The expression of lentivirus carrying miRNA-17-19 gene in MKN28 cels and CD44-/EpCAM- cels were significantly increased; transient transfection of pre-miR-19b/20a/92a increased the expression of CD44-/EpCAM- and MKN28 miRNA, transient transfection of pre-miR-19b/20a/92a antagonists reduced the expression of SGC7901 and CD44+/EpCAM+ miRNA; overexpression of lenti-miR-19b/20a/92a significantly increased the ability of gastric cels to form tumor spheres; chemotherapy drugs prolonged the survival time of lenti-miR-19b/20a/92a-infected cels; transient transfection of pre-miR-19b/20a/92a significantly increased the number of CD44+/EpCAM+ cels, but transfection of pre-miR-19b/20a/92a antagonist reduced the number of CD44+/EpCAM+ cels. (3) MTT proliferation assay showed that gastric cancer cel proliferation rate in miR-19b/20a/92a stably expressing group was faster than that in the control group. Transient transfection of miR-19b/20a/92a precursor accelerated the growth rate of gastric cancer cels, and transient transfection of its antagonist slowed down the growth rate of gastric cancer cels. Colony formation assay showed that transient transfection of miR-19b/20a/92a precursor significantly increased the colony formation number as compared with the control group; transient transfection of miR-19b/20a/92a antagonist reduced the colony formation as compared with the control group. These findings indicate that miR-19b/20a/92a gene presents with continuous deletion in gastric cancer stem cel differentiation process, and miRNA-17-92 gene can promote the renewal and proliferation of gastric cancer stem cels.
7.Generation of monoclonal antibodies against complexed prostate specific antigen and development of an antibody-based chemiluminescence immune quantifica-tion assay
Luting ZHAN ; Guiping WEN ; Min ZHAO ; Han YI ; Jiangwu LIU ; Xiaoyi GUO ; Haijun LIN ; Liunü HUANG ; Zizheng ZHENG
Chinese Journal of Immunology 2016;32(8):1171-1174,1178
Objective:To construct a chemiluminescense immune quantification assay based one paired mAbs against complexed prostate specific antigen ( c-PSA).Methods:Six week-old female BALB/c mice were immunized with the commercial c-PSA antigen.After serum titer reaching a platform stage ,the spleen was immunized and fused with mouse myeloma cell lines ( Sp2/0 ) .The hybridoma were screened by indirect ELISA ,and eight generated antibodies were paired to obtain a quantitative analysis of the chemical luminescence.Results:7D6 specifically recognized c-PSA,while 1A10 recognized total PSA(t-PSA).And the paired antibody 1A10/7D6 were determined to successfully construct a chemiluminescense immune response quantitative detection method through the detection of c-PSA standard and clinical serum samples .had,positive samples have statistically significant difference ( P<0.000 1 ) with negative samples.And the correlation coefficient R 2 was 0.97 between our c-PSA quantitative results and that of the Siemens c-PSA chemiluminescense immunoassay kit .The detection linear range was 0.1-100 ng/ml,and the sensitivity was 0.005 ng/ml.Conclusion:The paired monoclonal antibodies specifically detecting c-PSA were generated and a c-PSA chemiluminescense immunoassay were developed in this study .The detection capability of our method was comparable with that of the international commercial kit .
8.A Prospective Study in Individual Treatment of Lung Cancer Guided by Molecular Diagnostic Techniques
Gang CHEN ; Xinhui RAO ; Xiaoyang WANG ; Xiao WEN ; Liangming ZENG ; Zizheng ZHANG ; Hanyun LIU
Journal of Shenyang Medical College 2016;18(3):135-137,141
Objective: To investigate the feasibility of molecular diagnostic techniques to guide individualized treatment of lung cancer. Methods:A total of 360 patients with lung cancer confirmed by pathological diagnosis received clinical chemotherapy from Jan 2011 to Dec 2013 were selected as the experimental group who chose chemotherapy drugs for drug?sensitive individualized treat?ment based on molecular diagnostic technology test results. Another 180 patients with lung cancer were selected as the control group who did not carry out individual testing only chose conventional chemotherapy. The efficacy and side effects of drugs were assessed. The progression?free survival and median survival time were followed and recorded, and the survival curve was drawn by the Kaplan?Meier method. Results: There was significant difference in the efficacy between the two groups ( P<0?05) , and there was no signifi?cant difference in side effects of drugs. The progression?free survival time and median survival time were significantly different ( P<0?01) . Conclusions: Molecular diagnostic techniques to guide individual treatment of lung cancer have some clinical significance, it will help to improve the efficacy and worthy of further study.
9.Analysis of Helicobacter pylori infection in patients with oral lichen planus
YAO Xiaowu ; LU Zizheng ; LIU Shaofei
Journal of Prevention and Treatment for Stomatological Diseases 2017;25(11):729-732
Objective :
To explore the correlation between oral mucosal lichen planus and Helicobacter pylori infection by analyzing the infection status of Helicobacter pylori in patients with oral mucosal lichen planus.
Methods:
14C- urea breath test was done in 69 patients with oral lichen planus and 28 patients with chronic inflammation of oral mucosa. Detection of serum anti Helicobacter pylori antibody was done in 32 patients (23 with oral lichen planus and 9 with chronic inflammation of oral mucosa) at the same time.
Results :
The positive rate of 14C-urea breath test was 68.12% in patients with oral lichen planus and 46.43% in chronic inflammation of oral mucosa. There was significant difference between the 2 groups (χ2=3.970, P=0.046). The positive rate of anti Helicobacter pylori antibody was 52.17% in patients with oral lichen planus and 22.22% in chronic inflammation of oral mucosa, and there was no significant difference between the 2 groups (χ2=2.358, P=0.125).
Conclusion
The prevalence of Helicobacter pylori infection in patients with oral lichen planus is higher, and there is a relevance between oral lichen planus and Helicobacter pylori infection.
10.Targeting macrophagic SHP2 for ameliorating osteoarthritis via TLR signaling.
Ziying SUN ; Qianqian LIU ; Zhongyang LV ; Jiawei LI ; Xingquan XU ; Heng SUN ; Maochun WANG ; Kuoyang SUN ; Tianshu SHI ; Zizheng LIU ; Guihua TAN ; Wenqiang YAN ; Rui WU ; Yannick Xiaofan YANG ; Shiro IKEGAWA ; Qing JIANG ; Yang SUN ; Dongquan SHI
Acta Pharmaceutica Sinica B 2022;12(7):3073-3084
Osteoarthritis (OA), in which M1 macrophage polarization in the synovium exacerbates disease progression, is a major cause of cartilage degeneration and functional disabilities. Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported. Here, we report that SHP099, as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2 (SHP2), attenuated osteoarthritis progression by inhibiting M1 macrophage polarization. We demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model mice. Compared to wild-type (WT) mice, myeloid lineage conditional Shp2 knockout (cKO) mice showed decreased M1 macrophage polarization and attenuated severity of synovitis, an elevated expression of cartilage phenotype protein collagen II (COL2), and a decreased expression of cartilage degradation markers collagen X (COL10) and matrix metalloproteinase 3 (MMP3) in OA cartilage. Further mechanistic analysis showed thatSHP099 inhibited lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) signaling mediated by nuclear factor kappa B (NF-κB) and PI3K-AKT signaling. Moreover, intra-articular injection of SHP099 also significantly attenuated OA progression, including joint synovitis and cartilage damage. These results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.