1.Clinical significance of MAPT-IT1 in breast cancer and its mechanism of biological effect in vitro
Yang LIU ; Xiangxi DING ; Ziyuan LI
Chinese Journal of Endocrine Surgery 2022;16(2):164-169
Objective:To investigate the clinical significance of MAPT-IT1 in breast cancer and its biological effect in vitro.Methods:The expression of MAPT-IT1 in breast cancer was analyzed by TCGA database. 64 cases of breast cancer and normal adjacent tissues were collected. Human breast cancer MDA-MB-231 and MCF-7 cells were cultured and overexpressed MAPT-IT1 or rescue miR-181a-5p by cell transfection. MDA-MB-231 cells were divided into blank group A, overexpression group A and recovery group A; MCF-7 cells were divided into blank group B, overexpression group B and recovery group B. Real time quantitative PCR (RT-qPCR) was used to detect the expression of MAPT-IT1, miR-181a-5p and MAPT mRNA. Western blot was used to detect the expression of MAPT protein. CCK-8 assay was used to detect cell proliferation, and Transwell invasion assay was used to detect cell invasion.Results:The expression of MAPT-IT1 in normal paracancerous tissues and breast cancer tissues was 0.011±0.002 and 0.028±0.003 respectively. The expressions of MAPT-IT1 in breast cancer tissues were significantly higher than those in adjacent normal tissues, and high expression of MAPT-IT1 was correlated with early tumor progression, ER positive and prolonged prognosis ( P<0.05) . In blank group A, overexpression group A and recovery group A, the expressions of MAPT-IT1 were 1.000±0.078, 8.597±0.320 and 8.540±0.177, miR-181a-5p were 1.000±0.027, 0.263±0.024, 4.433±0.239, MAPT were 1.000±0.071, 3.297±0.243, 0.497±0.029. In blank group B, overexpression group B and recovery group B, the expressions of MAPT-IT1 were 1.000± 0.081, 5.716±0.309, 5.288±0.176, miR-181a-5p were 1.000±0.024, 0.291±0.022, 3.648±0.073, and MAPT were 1.000±0.054, 3.309±0.177, 0.883±0.075. After overexpression of MAPT-IT1, the expression of miR-181a-5p was down-regulated, while the expression of MAPT was significantly increased ( P<0.001) , and the proliferation and invasion ability of MDA-MB-231 and MCF-7 cells were significantly decreased ( P<0.05) . Re-expression of miR-181a-5p down-regulated MAPT and promoted cell proliferation and invasion ( P<0.05) . Conclusion:Overexpression of MAPT-IT1 can significantly down-regulate the expression of miR-181a-5p and enhance MAPT and inhibit the malignant phenotype of breast cancer cells in vitro.
2.Production and purification of solid target PET nuclide 89Zr and its antibody labeling
Feng WANG ; Xiaoyi GUO ; Teli LIU ; Lixin DING ; Lei XIA ; Jin DING ; Xiangxi MENG ; Jinquan JIANG ; Hua ZHU ; Zhi YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2020;40(5):294-297
Objective:To produce the solid target nuclide 89Zr , and prepare the probe 89Zr-desferrioxamine (DFO)-Trastuzumab. Methods:The 89Y(p, n) 89Zr nuclear reaction was used for 89Zr production. 89Y target was irradiated by 20 μA proton in a medical cyclotron ( E=12.5 MeV) for about 1-2 h. 89Zr was purified from hydroxamate resin using 1 mol/L oxalic acid solution. The characteristic peak, radionuclide purity and radiochemical purity of 89Zr were determined by γ-ray spectroscopy. 89Zr-DFO-Trastuzumab probe was synthesized by the reaction of 89Zr-oxalate and DFO-Trastuzumab at room temperature, and the radiochemical purity was measured. Results:89Zr was prepared successfully for 11 times, and the production of 89Zr was 555-1 506 MBq, with production rate of (34.8±5.2) MBq·μA -1·h -1. After the purification (purification rate: 42%-87%), 227.2-991.6 MBq 89Zr was obtained, with the concentration of 1.0×10 6 MBq/L. The γ spectrum showed that the characteristic peak of 89Zr were 511 and 909 keV, and no impurities were found. The radionuclide purity and radiochemical purity were both close to 100%. 89Zr-DFO-Trastuzumab was successfully labeled with radiochemical purity more than 95%, and it was above 90% within 72 h in human serum albumin (HSA) solution. Conclusion:Through the self-designed target assembling, the solid target PET nuclide 89Zr with high quality and labeling are successfully achieved, which provides guarantee for the clinical application of the 89Zr drug.
3.Protective effects of valproic acid on cardiac and cerebral injury in rats subjected to severe scalding combined with seawater immersion injury with delayed fluid replacement
Xiangxi MENG ; Yumo TIAN ; Sen HU ; Lili WANG ; Huiping ZHANG ; Yuxian ZHONG ; Hongwei WANG ; Yu DING
China Pharmacy 2022;33(17):2113-2118
OBJECTIVE To study the protective effects o f valproic acid on cardiac and cerebral injury in rats subjected to severe scalding combined with seawater immersion injury with delayed fluid replacement. METHODS The rats were divided into scalding+delayed fluid replacement group (group S ),scalding+seawater immersion+delayed fluid replacement group (group SS ), scalding+seawater immersion+valproic acid+delayed fluid replacement group (group SSV )according to random number table ,with 60 rats in each group. All groups were subjected to 35%total body surface area third-degree full-thickness scalding with boiled water. Group SS and group SSV were immersed in artificial ;seawater(30 min)immediately after scalding ,and group SSV was subcutaneously injected with valproic acid 300 mg/kg immediately after out of water. Sodium lactate Ringer ’s 0314-2279277。E-mail:125467374@qq.com injection was injected intravenously within 30 minutes according to 1/2 Parkland formula at 2 h after scalding in each group for delayed fluid replacement. The death time of rats was recorded ,and the average survival time and 24 h survival rate of rats in each group were calculat ed. Mean arterial pressure (MAP),heart rate (HR),respiration rate (RR),rectal temperature (RT),arterial blood pH ,arterial partial pressure of oxygen (PaO2),arterial blood partial pressure of carbon dioxide (PaCO2),HCO3-,creatine kinase MB isoenzyme (CK-MB)and neuron specific enolase (NSE)were detected before scalding ,at 0,2,5 h after scalding. The pathological changes of cardiac and cerebral tissue were observed. RESULTS The 24 h survival rate of group SS (55%)was significantly lower than that of group S (90%), while that of group SSV (75%)was increased significantly ,compared with group SS (P<0.05). Compared with group S ,the levels of MAP ,RT,HR,pH,PaO2 and HCO 3- in group SS were significantly lowered ,while the levels of CK-MB and NSE were increased significantly at 0,2,5 h after scalding ;the levels of PaCO 2 were increased significantly at 2,5 h after scalding , while the levels of RR were decreased significantly at 0,2 h after scalding (P<0.05). Compared with group SS ,the levels of MAP,RT,HR,pH,PaO2 and HCO 3- in group SSV were significantly increased ,while the levels of PaCO 2,CK-MB and NSE were decreased significantly at 2,5 h after scalding ;the level of RR was increased significantly at 2 h after scalding (P<0.05). At 2,5 h after scalding ,cardiac and cerebral injury of rats in group SS were aggravated significantly than that in group S ;cardiac and cerebral injury of rats in group SSV were relieved significantly than that in group SS. CONCLUSIONS After severe scalding combined seawater immersion injury ,hypodermic injection of sodium valproate could protect cardiac and cerebral function of rats , improve vital signs and blood gas index ,prolong survival time and improve survival rate in rats.
4.Diagnosis and treatment of multiple myeloma in Hunan Province.
Feiyang LIU ; Qian CHENG ; Kui SONG ; Huan YU ; Junjun LI ; Hui ZHANG ; Guoyu HU ; Ming ZHOU ; Jun WANG ; Zhongqi DING ; Zimian LUO ; Ting PENG ; Liang DING ; Liang ZHAO ; Jing LIU ; Yanjuan HE ; Hongling PENG
Journal of Central South University(Medical Sciences) 2022;47(4):497-504
OBJECTIVES:
There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM.
METHODS:
The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0.
RESULTS:
Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%).
CONCLUSIONS
In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Female
;
Humans
;
Immunologic Factors/therapeutic use*
;
Male
;
Middle Aged
;
Multiple Myeloma/therapy*
;
Neoplasm Staging
;
Pain
;
Prognosis
;
Proteasome Inhibitors/therapeutic use*