1.Upregulation of miR-489-3p and miR-630 inhibits oxaliplatin uptake in renal cell carcinoma by targeting OCT2.
Lu CHEN ; Le CHEN ; Zhiyuan QIN ; Jinxiu LEI ; Sheng YE ; Kui ZENG ; Hua WANG ; Meidan YING ; Jianqing GAO ; Su ZENG ; Lushan YU
Acta Pharmaceutica Sinica B 2019;9(5):1008-1020
Renal cell carcinoma (RCC) is one of the most common malignant tumors affecting the urogenital system, accounting for 90% of renal malignancies. Traditional chemotherapy options are often the front-line choice of regimen in the treatment of patients with RCC, but responses may be modest or limited due to resistance of the tumor to anticarcinogen. Downregulated expression of organic cation transporter OCT2 is a possible mechanism underlying oxaliplatin resistance in RCC treatment. In this study, we observed that miR-489-3p and miR-630 suppress OCT2 expression by directly binding to the OCT2 3'-UTR. Meanwhile, 786-O-OCT2-miRNAs stable expression cell models, we found that miRNAs could repress the classic substrate 1-methyl-4-phenylpyridinium (MPP), fluorogenic substrate ,-dimethyl-4-(2-pyridin-4-ylethenyl) aniline (ASP), and oxaliplatin uptake by OCT2 both and in xenografts. In 33 clinical samples, miR-489-3p and miR-630 were significantly upregulated in RCC, negatively correlating with the OCT2 expression level compared to that in adjacent normal tissues, using tissue microarray analysis and qPCR validation. The increased binding of c-Myc to the promoter of pri-miR-630, responsible for the upregulation of miR-630 in RCC, was further evidenced by chromatin immunoprecipitation and dual-luciferase reporter assay. Overall, this study indicated that miR-489-3p and miR-630 function as oncotherapy-obstructing microRNAs by directly targeting OCT2 in RCC.
2. Pathologic features on gonadal changes of sexual developmental disorders in children
Peng YI ; Huilin NIU ; Qiu GAO ; Fenghua WANG ; Wei JIA ; Zhengrong CHEN ; Jianqing XIA ; Liping LI ; Yi CAO ; Rongxin ZENG
Chinese Journal of Pathology 2018;47(7):531-535
Objective:
To investigate the pathologic features of gonadal tissues of disorders of sexual development (DSD) in children.
Methods:
Fifty-three cases of gonadal developmental disorders were collected from July 2015 to August 2017 at Guangzhou Women and Children′s Medical Center. Clinical manifestations, karyotypes, sex hormone levels, ultrasound imaging, histology and immunophenotype of gonadal tissues were analyzed.
Results:
The age of patients ranged from 7 months to 17 years with an average of (50.7 ± 47.1) months. Social genders of the patients included 32 males and 21 females. Forty-eight patients had abnormal sex hormone levels. Clinical presentations included: toward female genitalia in 25 cases, male genitalia tendency in 17 cases and ambiguous external genitalia in 11 cases. Hypospadias was seen in 31 cases and short stature was seen in 8 cases. Chromosomal karyotyping of peripheral blood revealed 23 cases of sex chromosome disorders, 22 cases of 46 XY disorders, of which 3 cases were 5α-reductase deficiency and 8 cases of 46 XX disorders. Ultrasound examination showed cryptorchidism in 30 cases, including 16 cases of unilateral, 14 cases of bilateral and 1 case presenting a huge pelvic tumor. A total of 97 gonadal tissues from 53 cases of DSD were examined, including 9 cases of unilateral and 44 cases of bilateral gonads. Microscopically, 55 gonads (56.7%) showed dysplastic testes including 17 unilateral and 19 bilateral gonads. Fourteen were streak gonads (14.4%) including 8 unilateral and 3 bilateral gonadal tissues. Nine streak gonad with epithelial cord-like structures (9.3%) were found, of which 5 were unilateral and 2 were bilateral lesions. Seven gonads were ovotestis (7.2%), unilateral in 5 cases (the other side of the gonads of ovary in 4 cases, 1 case of dysplastic testes) and bilateral in 1 case. Seven gonads showed follicular-rich ovarian tissue (7.2%). One case showed bilateral dysplastic testes with gonadoblastoma and ectopic adrenal cortex. One case of streak gonad showed epithelial cord-like structures and undifferentiated glandular tissue embedded in malignant mixed germ cell tumors (mixed gonadoblastoma, dysgerminoma, mature teratoma and yolk sac tumor). One case had testicular microlithiasis. Uterus and fallopian tube structures were found in 11 cases. Immunohistochemical stains were performed in 15 cases. D2-40, PLAP and CKIT were expressed in germ cells and Calretinin, WT1 and inhibin were positive in Setoli cells. SALL4 and OCT3/4 were positive in 3 cases. Inhibin highlighted interstitial Leydig cells in 2 cases. GPC3 was positive in yolk sac tumor component.
Conclusions
Gonadal dysgenesis presents a broad spectrum of gonadal phenotypes with variable degrees of differentiation. The development of bilateral gonadal tissues has certain variability. Chromosomal karyotypes have no correlation with gonadal phenotypes. Accurate histopathologic diagnosis of gonadal dysgenesis plays an important role in the treatment and prognosis of the patient.
3.Research progress on the animal models and treatment strategies of diabetic foot ulcer.
Siqian GAO ; Yongmei SHEN ; Funeng GENG ; Yanhua LI ; Jianqing GAO ;
Journal of Zhejiang University. Medical sciences 2017;46(1):97-105
The suitable experimental animal model is important in research of pathogenesis and therapeutic strategies of diabetic foot ulcer, and the murine model is the most commonly used one at present. It can be divided into two types: the animal model simulating pathological conditions and the model simulating clinical symptoms. This article reviews the current research progress on the mechanisms of diabetic ulcer pathogenesis, and relevant treatment strategies, including the inhibition of matrix metalloproteinases (MMPs) expression, promotion of angiogenesis and anti-inflammatory therapy.
Animals
;
Anti-Inflammatory Agents
;
therapeutic use
;
Diabetic Foot
;
etiology
;
genetics
;
therapy
;
Disease Models, Animal
;
Humans
;
Matrix Metalloproteinase Inhibitors
;
therapeutic use
;
Matrix Metalloproteinases
;
genetics
;
metabolism
;
Mice
;
Neovascularization, Physiologic
;
physiology
4.Imaging performance of 18F-FDG PET-CT on patients with multiple myeloma
Lin LI ; Chaoming MAO ; Jianming ZHOU ; Jianqing GAO
Practical Oncology Journal 2017;31(3):222-227
Objective The objective of this study was to investigate the imaging findings of 18 F-FDG PET-CT in patients with multiple myeloma(MM).Methods Fifteen patients with multiple myeloma were enrolled in our hospital from January 2014 to October 2016.The clinical data of these patients were retrospectively analyzed to obtain the range of SUVmax values by 18F-FDG PET-CT imaging performance.Results Fifteen MM patients with 18F-FDG PET-CT showed a total number of lesions 202,the number of lesions 176 in PET and the number of lesions 171 in CT.The SUVmax range of 18F-FDG PET-CT imaging in the diagnosis of MM was 1.41 ~ 16.28.Fourteen cases of 15 MM patients were found varying degrees of bone destruction;one case showed a slightly increased bone density and also slightly increased FDG metabolic activity.Bone destruction was more performance for the chisel-like,osteolytic,swelling and flaky bone destruction.The osteogenesis lesions were rare.Conclusion 18F-FDG PET-CT imaging can clearly show the imaging features of MM by combining functional metabolic and anatomical information,and provide more clues for clinical diagnosis,which can improve the diagnostic accuracy of MM.
5.Efficacy of an airway topical anesthesia catheter for topical anesthesia using a spray-as-you-go technique via fiberoptic bronchoscope
Youguang GAO ; Caizhu LIN ; Xianzhong LIN ; Kai ZENG ; Qun LIN ; Jianqing LIN ; Hongda CAI
Chinese Journal of Anesthesiology 2016;36(12):1472-1475
Objective To evaluate the efficacy of an airway topical anesthesia catheter for topical anesthesia using a spray-as-you-go technique via the fiberoptic bronchoscope (FOB).Methods Forty American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients with obstructive sleep apnea syndrome,aged 20-64 yr,with body mass index of 23-35 kg/m2,with no upper respiratory tract infection within 1 week before operation,scheduled for elective uvulopalatopharyngoplasty,were divided into 2 groups (n =20 each) using a random number table:routine control group (group C) and FOB-airway topical anesthesia catheter group (group F).In group C,the pharynx and larynx were sprayed with lidocaine FOB by using a laryngo-tracheal mucosal atomization device,and cricothyroid membrane puncture was performed and then lidocaine was injected.In group F,airway topical anesthesia was performed using a spray-as-you-go technique via the FOB with an airway topical anesthesia catheter spraying lidocaine via the nose.At 5 min after topical anesthesia of the airway,FOB-guided intubation was performed,and dexmedetomidine was intravenously infused at 0.1 μg · kg-1 · min-1 for sedation in both groups.Ramsay sedation scores were assessed after topical anesthesia and before intubation.The scores for the intubating condition and tolerance of tracheal tube were assessed during FOB-guided intubation.Successful intubation and the development of responses to intubation and hypoxemia were recorded.The patients were followed up one day after the end of operation,and parents' satisfaction with the procedure of intubation was recorded.Results Compared with group C,the intubating condition score,tolerance of tracheal tube score,success rate of intubation at first attempt and rate of parents' satisfaction with the procedure of intubation were significantly increased,and the incidence of responses to intubation was decreased (P<0.05),and no significant change was found in Ramsay sedation scores before intubation and incidence of hyoxemia in group F (P>0.05).Conclusion When the FOB is used to guide awake nasotracheal intubation,the airway topical anesthesia catheter provides better efficacy,better intubating conditions,and fewer side effects when applied for topical anesthesia using a spray-as-you-go technique via the FOB,it can be easily accepted by the patients and the efficacy is better that of routine airway topical anesthesia.
6.Research progress on application of carbon nanotubes in bone tissue engineering scaffold.
Mengzhu YAO ; Xiaoxia SHENG ; Jun LIN ; Jianqing GAO
Journal of Zhejiang University. Medical sciences 2016;45(2):161-169
Carbon nanotubes possess excellent mechanical and electrical properties and demonstrate broad application prospects in medical fields. Carbon nanotubes are composed of inorganic materials, natural biodegradable polymer or synthetic biodegradable polymer. The composite bone tissue engineering scaffolds are constructed by particle-hole method, lyophilization, microsphere aggregation method, electrostatic spinning or three-dimensional printing. Composite scaffolds overcome the shortcomings of single material and have good biocompatibility, osteoconduction and osteoinduction. With the study of surface chemistry, toxicology, and biocompatibility, a degradable "human-friendly" carbon nanotubes composite bone tissue scaffold will be available; and under the drive of new fabrication techniques, the clinical application of carbon nanotubes composite bone tissue engineering scaffolds will be better developed.
Biocompatible Materials
;
chemistry
;
Bone Development
;
Humans
;
Microspheres
;
Nanotubes, Carbon
;
chemistry
;
Polymers
;
chemistry
;
Printing, Three-Dimensional
;
Tissue Engineering
;
Tissue Scaffolds
;
chemistry
7.Prognostic significance of MYCN amplification in children neuroblastic tumors.
Huilin NIU ; Tao XU ; Fenghua WANG ; Zhengrong CHEN ; Qiu GAO ; Peng YI ; Jianqing XIA
Chinese Journal of Pathology 2015;44(2):111-117
OBJECTIVETo summarize the clinicopathologic features of neuroblastic tumors (NT), and to explore the prognostic significance of MYCN amplification in NT.
METHODSThe clinicopathologic data of 267 NT were reviewed. MYCN gene amplification was detected by fluorescence in situ hybridization (FISH) in 119 cases and the relationship with pathological characteristics and prognostic significance were analyzed.
RESULTSThe study included 267 cases of children NT from patients aged from 1 day to 13 years (median 27 months). The male to female ratio was 1.43. There were 38 cases (14.2%), 43 cases (16.1%), 71 cases (26.6%), and 115 cases (43.1%) of INSS stages I, II, III and IV respectively.Favorable histology group had 157 cases (59.9%); unfavorable histology group had 110 cases (40.1%).Of the 119 NT cases with MYCN FISH performed, 18 cases (15.1%) showed amplification and the signal ratio of MYCN to CEP2 was 4.08-43.29. One hundred and one cases of non-amplified MYCN included MYCN gain in 79 cases (66.3%) and MYCN negative in 22 cases (18.5%). MYCN expression showed significant difference (P = 0.000) between ages, gender, NT type and MKI, but not INPC and clinical stage (P > 0.05).Of the 18 cases with MYCN amplification, 3 were undifferentiated, and 15 poorly differentiated; 17 had high MKI and one moderate MKI. All 18 cases were in unfavorable histology group; the overall survival rate was 3/18, with an average survival time of (17.9 ± 2.4) months.Of the 101 MYCN non-amplification cases, the overall survival rate was 68.3% (69/101), with an average survival time of (29.8 ± 1.3) months. Survival analysis showed the cases with MYCN amplification had worse prognosis (P < 0.05).
CONCLUSIONSNT were commonly diagnosed in early ages and easily to metastasize. Most of cases with favorable histology. The cases of MYCN amplification showed unfavorable histology, and the majority cases with high MKI; The patients with MYCN gene amplification had poor prognosis.
Adolescent ; Cell Differentiation ; Child ; Child, Preschool ; Female ; Gene Amplification ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Male ; N-Myc Proto-Oncogene Protein ; Neuroblastoma ; genetics ; mortality ; pathology ; Nuclear Proteins ; genetics ; Oncogene Proteins ; genetics ; Prognosis ; Survival Analysis ; Survival Rate
8.Research progress of gene recombinant mesenchymal stem cells as tumor targeting delivery vehicles.
Tianyuan ZHANG ; Yulan HU ; Wenquan LIANG ; Jianqing GAO
Acta Pharmaceutica Sinica 2013;48(8):1209-20
The applications of targeting gene delivery systems in tumor therapy have attracted extensive attention of researchers in recent years, as they can selectively deliver the therapeutic gene to tumor sites, improve the success rate of gene therapy and reduce the side effects. Therefore, design and development of novel gene delivery vehicles have been a hot area of current research. Recent studies have shown that mesenchymal stem cells (MSCs) have the ability to migrate towards and engraft into the tumor sites. Therefore, these properties make them a great hope for efficient targeted-delivery vehicles in cancer gene therapy. In this review, we examine the promising of utilization of MSCs as a targeted-delivery vehicle for cancer gene therapy, and summarize various challenges and concerns regarding this therapy.
9.Molecular mechanisms involved in curcumol induced apoptosis in human gastric carcinoma cell line BGC823
Hong ZHANG ; Lianrong ZHANG ; Haijun JIANG ; Jianguo GAO ; Jianqing DU ; Zhi YANG
Chinese Journal of General Surgery 2013;(6):452-455
Objective To investigate the effect of curcumol on apoptosis of human gastric carcinoma cell line BGC823 and the molecular nechanisms.Methods BGC823 cells were cultured and treated with different curcumol concentration (12.5,25,50 and 100 mg/L) for 24 h and 48 h,and the growth inhibition were tested by thiazolyl blue terazolium bromide (MTF) assay.Flow cytometry (FCM) were used to measure the cell apoptosis rate and cell cycle of BGC823 cells.Caspase-3 activity was assessed by colorimetric assay.Cells treated with 100 mg/L curcunol for 48 h were collected and subjected to RTPCR and Western blot assays for the expression of Caspase-3,Bcl-2,Bax and Survivin.Results There was a time-and dose-dependent inhibition of cell proliferation of BGC823 cells by curcumol.Tbe cells in G0/G1 phase increased,and in S phase decreased on exposure to curcumol for 24 h.FCM analysis also indicated that the apoptosis rate of BGC823 cells increased in dose-dependent manner (P < 0.05).Curcumol increased the activity of Caspase-3 dose-dependently (P < 0.05).RT-PCR and Western blot indicated that curcumol decreased Bcl-2 and Survivin expression as well as increased Caspase-3 and Bax expression (P < 0.05).Conclusions Curcumol inhibits BGC823 cell growth,arresting cells in G0/G1 phase and inducing cell apoptosis.The mechanism may be related with increasing the activity of Caspase-3,down-regulating the expression of Bcl-2 and Survivin,and up-regulating the expression of Caspase-3 and Bax.
10.Efficacy of T-joint endoscopy mask for fiberoptic bronchoscopy-guided awake nasotracheal intubation in patients with cervical spinal cord injury
Youguang GAO ; Caizhu LIN ; Xianzhong LIN ; Kai ZENG ; Qun LIN ; Jianqing LIN ; Hongda CAI
Chinese Journal of Anesthesiology 2012;32(8):970-972
Objective To evaluate the efficacy of T-joint endoscopy mask for fiberoptic bronchoscopy (FOB)-guided awake nasotracheal intubation in patients with cervical spinal cord injury.Methods Forty patients of both sexes aged 21-64 yr with fracture of cervical spine complicated by spinal cord injury scheduled for anterior decompression and interbody fusion under general anesthesia were randomly divided into 2 groups according to the technique for awake nasotracheal intubation (n =20 each):group nasal catheter and group T-joint endoscopy mask.Topical anesthesia of nasal cavity,pharynx,larynx and trachea with 2% lidocaine was conducted and then remifentanil was continuously infused at 0.05-0.15 μg· kg-1 · min-1 in both groups.The incidence of hypoxemia and intubation time were recorded.Arterial blood samples were obtained for determination of PaO2 and PaCO2 before topical anesthesia (baseline),immediately before and 1 min after placement of FOB and immediately after nasotracheal intubation was accomplished.Results The incidence of hypoxemia was significantly lower in group Tjoint endoscopy mask (0) than in group nasal catheter (25%) (P < 0.05).The PaO2 during nasotracheal intubation was significantly higher in group T-joint endoscopy mask than in group nasal catheter (P < 0.05).There was no significant difference in PaCO2 and intubation time between the 2 groups (P > 0.05).Conclusion T-joint endoscopy mask facilitates awake nasotracheal intubation without affecting oxygen inhalation in patients with cervical spinal cord injuries.

Result Analysis
Print
Save
E-mail