1.The mechanism of androgen independent signaling pathway in castration-resistant prostate cancer and the research progress on related drugs
Meng-xia XUE ; Yue GU ; Jian-guo SUN ; Guang-ji WANG ; Ying PENG
Acta Pharmaceutica Sinica 2021;56(1):21-28
Prostate cancer is one of the common malignant tumors of male urogenital system, and the incidence of prostate cancer in China has increased significantly in the past decade. At present, endocrine therapy based on androgen blockade is the main method of clinical treatment except radical surgery and radiotherapy/chemotherapy for prostate cancer. However, the clinical benefit can only be obtained in the early stage of treatment, and nearly 90% of patients will develop to the castration resistance, and among them, nearly 90% of patients will have bone metastasis. The quality of life decreases sharply with the progression of disease for patients. In addition to the androgen signal pathway, studies have shown that many other oncogenic signal pathways have involved in the development of castration resistance, including classic cancer signaling pathways, immune and inflammatory signaling pathways, etc. Understanding the mechanism of androgen independent signal pathway in the formation of castration resistance will help to understand the off-target effect of androgen blocking therapy and introduce new treatment targets or strategies to get rid of the "no drug available" dilemma for clinical treatment of castration resistance.
2.Association of c.553G>T polymorphism in the apolipoprotein A5 gene with coronary heart disease and the levels of serum lipid
Fang QIU ; Kui ZHANG ; Lei LI ; Guang-Yu GU ; Li WANG ; Xun-Yang LUO ; Yong-Quan XIA ; Ping GU ;
Chinese Journal of Laboratory Medicine 2003;0(07):-
T site polymorphism is closely related to CHD and elevated serum triglyceride and total cholesterol.
3.Histiocytic sarcoma of stomach: report of a case.
Ting FENG ; Miao-xia HE ; Wei-yong GU ; Chen-guang BAI ; Da-lie MA ; Jian-ming ZHENG ; Ming-hua ZHU
Chinese Journal of Pathology 2012;41(2):130-131
Aged
;
Antigens, CD
;
metabolism
;
Antigens, Differentiation, Myelomonocytic
;
metabolism
;
Carcinoma, Large Cell
;
metabolism
;
pathology
;
Diagnosis, Differential
;
Histiocytic Sarcoma
;
metabolism
;
pathology
;
surgery
;
Hodgkin Disease
;
metabolism
;
pathology
;
Humans
;
Lymphoma, Large B-Cell, Diffuse
;
metabolism
;
pathology
;
Lymphoma, Large-Cell, Anaplastic
;
metabolism
;
pathology
;
Male
;
Melanoma
;
metabolism
;
pathology
;
Receptors, Cell Surface
;
metabolism
;
Stomach Neoplasms
;
metabolism
;
pathology
;
surgery
4.Application of internal iliac artery embolization and presetting abdominal aorta balloon for complicated pelvic frac-tures
Xiaodong YANG ; Han LIU ; Zongxin ZHOU ; Weiyu HAN ; Guang XIA ; Cheng GU ; Tao LI ; Weiqi HUANG ; Qiguang MAI ; Dadi JIN ; Shicai FAN
Chinese Journal of Orthopaedics 2017;37(1):11-16
Objective To evaluate the clinical outcome of bleeding control by preoperative embolization of internal iliac artery with DSA and intra?operative presetting abdominal aorta balloon, combine with the operation techniques of exposure, reduc?tion and internal fixation of pelvic fracture through lateral?rectus approach. Methods From March 2012 to May 2015, 7 patients with type C3 pelvic fractures admitted to our department from March 2012 to May 2015, treated with preoperative embolization of internal iliac artery under digital subtraction angiography 2 h before surgery and presetting abdominal aorta balloon were retrospec?tively reviewed. There were 3 males and 4 females, with an average age of 34 years (range, 16 to 61 years). According to AO classi?fication, all 7 cases belonged to type C3 (3.2:5 cases;C3.3:2 cases), including 5 cases with limb fracture, 2 cases with craniocere?bral trauma, 4 cases with pulmonary contusion, 2 cases with injury of abdominsal organs. Time from injury to operation was 19 days on average (10 to 33 days). Patients received damage control surgery treatment including bleeding control and temporary ex?ternal fixation, and ipsilateral tractions with heavy weight, intensive care and corrections of general situation before operation. The fracture model was manufactured by 3D printing and fracture reduction was simulated on computer preoperatively. Embolization of internal iliac artery was performed in the side of severe displaced sacroiliac joint with DSA 2 hours preoperatively. Reduction was performed to stabilize anterior-posterior pelvic ring and acetabular fractures via the intraoperative lateral?rectus approach. And 2 cases were performed by temporary balloon occlusion of abdominal aorta (≤60 min) for bleeding control in reduction of in the side of sacroiliac joint fractures. Results All the 7 cases had undergone the operations successfully, and the operating time was from 135-320 min with blood loss from 440-3 350 ml. According to Matta radiological evaluation postoperatively, reduction of pelvic fracture was rated as anatomic in 5 cases, satisfactory in 2, without complications. All 7 cases were complicated with lumbosacral plexus injury or lumbosacral trunk injury at different degrees (M0 2 cases, M1 2 cases, M2 2 cases, M3 1 case). According to the BMRC scoring system, 5 cases had well recovered and the other 2 cases had no improvement after three months (M4 2 cases, M5 3 cases). Conclusion Surgical management of pelvic fracture through preoperative internal iliac artery embolization and intra?oper?ative occlusion of abdominal aorta could effective control bleeding and achieve favorable conditions for reduction. Lateral?rectus approach can provide adequate exposure of the anterior and posterior ring, and this approach could also provide excellent visual control of reduction and fixation.
5.Efficacy evaluation of acupoints massage on asthenopia of video display terminal under different exposure dose.
Yan XU ; Guang-Xia GU ; Xiao-Sheng YANG ; Chun-Ying PAN ; Wen-Li HOU ; Wei ZHAO ; Qin XING
Chinese Acupuncture & Moxibustion 2012;32(4):351-353
OBJECTIVETo observe the efficacy differences of acupoints massage for asthenopia of video display terminal (VDT) under different exposure dose.
METHODSOne hundred and two cases (204 eyes) were divided into a low exposure group and a high exposure group, fifty-one cases in each group. The same intervention of acupoints massage on Cuanzhu (BL 2), Jingming (BL 1), Sizhukong (TE 23), Sibai (ST 2) and Taiyang(EX-HN 5) were given to the two groups, one acupoint for 5 min and once everyday, one month of which made a course. The symptom score, tear film break-up time (BUT) and Schirmer I test(SIT) were observed before and after treatment.
RESULTS(1) The correlation coefficient of cubic curve model of the exposure dose was the biggest with symptom improvement index (P = 0.000), which indicated that the lower VDT exposure index was, the more obvious the symptom improved. The symptom improvement indices of low exposure group and high exposure group, which were (52.31 +/- 16.65)% and (28.93 +/- 13.35)% respectively, were statistical significant difference (P = 0.000). (2) Compared to before treatment, the levels of BUT and SIT in the two groups were both significantly higher (P < 0.05). Compared with the high exposure group, the levels of BUT and SIT in the low exposure group were increased by 0.826 s (P = 0.022) and 1.029 mm (P = 0.033), respectively, after the impact of BUT and SIT was corrected before the research.
CONCLUSIONThe acupoints massage can improve the symptoms and ocular physiology for patients with VDT asthenpia, and it is more effective for the low exposure cases.
Acupuncture Points ; Adult ; Asthenopia ; physiopathology ; therapy ; Computer Terminals ; utilization ; Female ; Humans ; Male ; Massage ; Middle Aged ; Occupational Diseases ; physiopathology ; therapy ; Tears ; secretion ; Treatment Outcome ; Young Adult
6.Effects of triterpenic acid from Prunella vulgaris L. on glycemia and pancreas in rat model of streptozotozin diabetes.
Qiao-xia ZHOU ; Feng LIU ; Jing-shuo ZHANG ; Ji-guang LU ; Zhen-lun GU ; Gui-xiong GU
Chinese Medical Journal 2013;126(9):1647-1653
BACKGROUNDThe effects of triterpenic acid from Prunella vulgaris L. (TAP) on diabetes and its mechanism are uncertain. The aim of this study was to investigate the effects of TAP on antihyperglycemic, antioxidant, and pancreas-protective in streptozotozin (STZ)-diabetic rats.
METHODSThe diabetic model was produced by injection of 60 mg/kg STZ. Blood was drawn from the tail vein of rats after 72 hours. Rats with blood glucose ≥ 16.7 mmol/L were considered diabetic. Diabetic rats were randomly divided into four groups: (1) Diabetes rat (STZ), (2) Diabetic rats treated with 50 mg/kg of triterpenic acid from Prunella vulgaris L (STZ + TAP50), (3) Diabetic rats treated with 100 mg/kg TAP (STZ + TAP100), and (4) Diabetic rats treated with 200 mg/kg TAP (STZ + TAP200). Normal rats (n = 10) acted as the control group (NC). TAP was administered by the intragastric route once each day for six weeks. Body weight and the concentration of blood glucose (BG) were measured after three and six weeks. Fructosamine (FMN), malondialdehyde (MDA), and nitric oxide (NO), and the activities of nitric oxide synthase (NOS) and superoxide dismutase (SOD) in serum were determined after six weeks using commercially available kits following the manufacturer's instructions. Pathologic changes in pancreatic β-cells were also investigated by microscopic examination after hematoxylin-eosin (HE) staining. The level of SOD mRNA in pancreatic β-cells was measured by polymerase chain reaction (PCR).
RESULTSThe levels of BG, FMN, NO, and MDA and the activities of NOS in serum in the four diabetes groups were significantly increased compared with the control group (P < 0.01). The activity of SOD in serum and the body weight was significantly decreased compared with the control group (P < 0.01). After administration of TAP to diabetic rats for six weeks, the body weight and the levels of BG, FMN, MDA, NO and the activity of NOS in serum decreased significantly compared with the STZ group in a dose-dependent manner. The activity of SOD in serum and body weight increased significantly compared with the STZ group in a dose-dependent manner. In addition, diabetic rats showed a significant decrease in SOD mRNA expression in pancreatic β cells. However, these changes were reversed by TAP. Histopathological examination also showed the protective effect of TAP on pancreatic β cells.
CONCLUSIONSTriterpenic acid from Prunella vulgaris L. has an anti-diabetic effect, by controlling blood glucose and antioxidants, and has a protective effect on the pancreas.
Animals ; Blood Glucose ; analysis ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Insulin-Secreting Cells ; drug effects ; pathology ; Male ; Prunella ; chemistry ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Superoxide Dismutase ; genetics ; Triterpenes ; therapeutic use
7.Cartilage repair using induced pluripotent stem cell derived chondrocytes in osteoarthritis
song Zhang WU ; xia Hong ZHU ; qiang Zhi LUO ; min Xiao WU ; yao Guang LIN ; yu Ming ZHANG ; sheng Hong GU ; xia Yan ZHU
Chinese Journal of Tissue Engineering Research 2017;21(33):5339-5347
BACKGROUND: Stem cell-based therapy has been proposed for the treatment of osteoarthritis (OA) and induced pluripotent stem cells (iPSCs) are becoming a promising stem cell source as they have strong proliferation and differentiation potentials and no ethics problem. OBJECTIVE: To explore an effective method of iPSCs differentiating into chondrocytes and to study the therapeutic effect of iPSCs derived chondrocytes on osteoarthritis. METHODS: In this study, three steps were developed to induce human iPSCs to differentiate into chondrocytes which were then transplanted into rat OA models induced by monosodium iodoacetate (MIA). There were four groups in the experiment: control group with normal saline injection, model group with MIA injection, iPSCs group with iPSCs transplantation following MIA injection, and differentiated iPSCs group with transplantation of iPSCs derived chondrocytes following MIA injection. At 15 weeks after transplantation, micro-CT was used and histological analysis of the knee joint was performed. RESULTS AND CONCLUSION: Compared with the iPS group, the expression of chondrocyte specific genes and proteins (Col2A1, GAG and Sox9) were significantly increased in the differentiated iPSCs group after 6 days of embryoid formation and after 2 weeks of cell differentiation. At 15 weeks after cell transplantation, no immune responses were observed, micro-CT showed an improvement in subchondral bone integrity, and histological examinations demonstrated the production of articular cartilage matrix. iPSCs derived chondrocytes showed better effects on articular cartilage repair than the iPSCs. To conclude, iPSCs derived chondrocytes can be effective via transplantation approach for cartilage tissue regeneration in OA rats.
8.The associated study on apolipoprotein A5 gene polymorphisms with carotid artherosclerosis in patients with cerebral infartion.
Kui ZHANG ; Fang QIU ; Lei LI ; Guang-yu GU ; Yue TAO ; Li WANG ; Xun-yang LUO ; Yong-quan XIA
Chinese Journal of Medical Genetics 2008;25(3):284-288
OBJECTIVETo investigate the association of -1131T>C and c.553G>T polymorphisms and their haplotypes in apolipoprotein A5(ApoA5) gene with cereberovascular disease in Chinese.
METHODSUsing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), we analyzed two ApoA5 genetic variants in 272 patients with cerebral infarction (CI) and 316 control individuals respectively. The levels of serum lipid profiles were measured with biochemical methodsìand the other clinical characters were obtained by case file investigation.
RESULTSThe odds ratio (OR) for CI in -1131CC genotype carriers was 2.10 (95%CI 1.01-4.37). The distribution of T-T and T-G haplotypes had obvious differences between CI patients and control individuals. The OR for CI in C-G and T-G haplotype carriers were 1.34 and 0.71(95% CI 1.02-1.76 and 0.55-0.92) respectively, compared with the others. Furthermore, the major haplotypes had significant differences of serum TG(P< 0.05).
CONCLUSIONThe ApoA5 -1131T>C polymorphism may be associated with an increased risk of CI in the Chinese population, but the influence of blood lipids can not be ignored.
Aged ; Apolipoproteins A ; genetics ; Carotid Artery Diseases ; complications ; genetics ; Cerebral Infarction ; complications ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Haplotypes ; genetics ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length
9.Effect of glucocorticoid on dendritic cells in children with chronic immune thrombocytopenia.
Wen-Yong KUANG ; Min-Cui ZHENG ; Guang-Sen ZHANG ; Guo-Cai SONG ; Wan-Li LI ; Hai-Xia YANG ; Xiao-Mei JIANG ; Ben-Shan ZHANG ; Pan WU ; Yan-Yan GU
Chinese Journal of Contemporary Pediatrics 2013;15(2):91-94
OBJECTIVETo investigate the change in dendritic cells (DCs) in children with chronic immune thrombocytopenia (cITP) and the effect of glucocorticoid on DCs in children with cITP.
METHODSFifteen children with cITP and 20 healthy controls were included in the study. Flow cytometry was used to measure the DC subsets count in the 15 children with cITP before and after glucocorticoid treatment as well as the corresponding values in the 20 healthy controls. The DCs derived from peripheral blood monocytes in children with cITP were cultured in vitro and collected, and their immunophenotypes were determined by flow cytometry.
RESULTSBefore glucocorticoid treatment, the children with cITP showed no notable change in the absolute count of myeloid DCs (mDCs) but showed decreased absolute count of plasmacytoid DCs (pDCs) and increased mDC/pDC ratio compared with the healthy controls (P<0.05). After glucocorticoid treatment, the children with cITP demonstrated increased absolute count of pDCs and decreased absolute count of mDCs and mDC/pDC ratio compared with before treatment (P<0.05). Before glucocorticoid treatment, the children with cITP had significantly higher positive rates of HLA-DR, CD80, CD83 and CD86 on peripheral blood DCs than the healthy controls (P<0.01). All the positive rates were significantly decreased after glucocorticoid treatment (P<0.01), so that there was no significant difference from the healthy controls (P>0.05).
CONCLUSIONSDisproportion and functional disturbance of DC subsets is associated with the pathogenesis of cITP in children. Glucocorticoid can strengthen the immunosuppression of DCs in children with cITP, which may contribute to the effectiveness of glucocorticoid as a treatment.
Adolescent ; Child ; Child, Preschool ; Chronic Disease ; Dendritic Cells ; drug effects ; immunology ; Female ; Glucocorticoids ; pharmacology ; Humans ; Immunophenotyping ; Male ; Thrombocytopenia ; drug therapy ; immunology
10.Efficacy comparison between standard and reduced doses of bortezomib combined with adriamycin and dexamethasone in the treatment of patients with multiple myeloma.
Hong-tao GU ; Mi-mi SHU ; Guang-xun GAO ; Bao-xia DONG ; Rong LIANG ; Lan YANG ; Qing-xian BAI ; Tao ZHANG ; Yong-qing ZHANG ; Xie-qun CHEN
Chinese Journal of Hematology 2013;34(7):622-625
OBJECTIVETo compare the efficacy and safety of standard or reduced doses of bortezomib combined with adriamycin and dexamethasone (PAD) in patients with multiple myeloma (MM).
METHODSEighty-two newly diagnosed or refractory/relapsed patients received bortezomib [either 1.2-1.3 mg/m(2) (standard dose) or 1.0-1.1 mg/m(2) (reduced dose) on day 1, 4, 8 and 11], and adriamycin (10 mg/m(2)) plus dexamethasone (40 mg/m(2)) on day 1-4 at 3-week intervals for 1 to 6 courses. The International Myeloma Working Group Criteria were used to evaluate the response. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (Version 3.0).
RESULTSTwo courses of standard dose of PAD resulted in a similar response rate of partial and very good partial complete remissions (PR) compared with reduced dose (80.0% vs 80.8%, P=0.728). Grade III- Ⅳ neutropenia and thrombocytopenia were higher with standard dose than that with reduced doses of PAD (21.1% vs11.1%, P=0.270; 10.5% vs 6.3%, P=0.619, respectively). Grade III-Ⅳ bortezomib-induced peripheral neuropathy, herpes zoster, fatigue or abdominal distention were significantly higher with standard dose than that with reduced dose of PAD (15.8% vs 1.6%, P=0.037; 26.3% vs 6.3%, P=0.028; 36.8% vs 14.3%, P=0.046; 15.8% vs 1.6%, P=0.037, respectively).
CONCLUSIONReduced dose of PAD appears to result in a similar overall response rate, but a better tolerance and safety compared with standard dose.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Boronic Acids ; administration & dosage ; adverse effects ; therapeutic use ; Bortezomib ; Dexamethasone ; administration & dosage ; adverse effects ; Doxorubicin ; administration & dosage ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; adverse effects ; therapeutic use ; Treatment Outcome