BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Abstract; Aim To explore the effect of icariin (ISO) in mice. Methods C57BL/6 mice were ran- (ICA) on myocardial fibrosis induced by isoproterenol domly divided into control group, ISO group, low-dose (15 mg • kg"1), middle-dose (30 mg • kg"1) and high-dose (60 mg • kg"1) of ICA-treated group and Losartan-treated group ( 9 mg • kg"1 ). The control group was subcutaneously injected with normal saline, and the other groups were subcutaneously injected with ISO (5 mg • kg"1, qd) continuously 14 days to established the myocardial fibrosis model. The ICA-treated groups and Losartan-treated group were simultaneously intragastrically administered of ICA or Losartan, respectively. And the other groups received the same a- mount of double distilled water. The left ventricular e- jection fraction (LVEF) and the left ventricular fraction shortening rate ( LVFS) were evaluated by the small animal ultrasound. The heart mass index (HMI) was calculated. The left ventricular collagen deposition was detected by Masson staining. The protein expressions of a-SMA, MMP-2, MMP-9 and TIMP-1 in the left ventricular tissue were detected by Western blot. Results ICA (30, 60 mg • kg"1) and Losartan could inhibit the decreased LVEF and LVFS, the increased HMI and left ventricular collagen deposition, the up- regulated a-SMA and MMP-9 protein expression, the down-regulated MMP-2 and TIMP-1 protein expression in the left ventricular tissues induced by ISO. Conclusions ICA can improve myocardial fibrosis induced by ISO in mice, and the underlying mechanism may be related to the regulation of the protein expression of a- SMA and MMPs/TIMP-1.

Aim To investigate the role of eNOS/PKG- 1 pathway in L-arginine (L-arg) intervention in right ventricular remodeling induced by monocrotaline (MCT) in Sprague Dawley (SD) rats with the aid of the tool medicine L-NAME. Methods Twenty SD rats were randomly divided into control group, MCT group, L-Arg group and L-Arg + L-NAME group. The general condition of rats was observed; the right ventricular pressure of rats was measured by right heart catheterization; the rats and the right ventricle were weighed and the right ventricular mass index was calculated; the morphological changes of the right ventricular were observed by H&E staining; the protein expressions of cTnl, eNOS and PKG-1 were detected by Western blot in the right ventricular. Results Compared with control group, right ventricular max pressure and right ventricular mass index significantly increased ( P < 05) ; the weight of rats in MCT group was significantly reduced ( P < 0. 05); the right ventricular myocytes were hypertrophic, disordered and infiltrated with inflammatory cells; the protein expression of cTnl was obviously up-regulated ( P < 0. 05 ) ; the protein expressions of eNOS and PKG-1 were significantly down- regulated ( P < 0. 05 ) . L-arg could significantly improve the above changes ( P < 0. 05 ). However, the effects of L-arg were inhibited by eNOS inhibitor L- NAME. Conclusions L-arg can improve the right ventricular remodeling in rats induced by MCT, and the mechanism may be related to the up-regulation of the protein levels of eNOS and PKG-1.

Objective To understand the types and distribution of Arboviruses in Hainan province.Methods Blood-sucking insects were collected in Hainan province from 2017 to 2018.After laboratory treatment,BHK-21 cells and C6/36 cells were inoculated with grinding supernatant of all blood-sucking insects to isolate all of involving virus.Arbovirus genes in blood-sucking insects were detected in parallel by RT-PCR method.Results A total of 15 062 mosquitoes were classified into four genera (Culex,Armigeres,Aedes,Anopheles) and 11 360 midges were collected.Culex tritaeniorhynchus was in the majority and accounted for 92.88％ (13 990/15 062) of all the mosquitoes collected.Four strains of virus isolates were notified by tissue culture method.Three strains of viruses belonged to Japanese encephalitis virus (JEV),with the other one as Getah virus (GETV).Five pools of JEV gene amplification were positive,from Culex tritaeniorhynchus.Results from the phylogenetic analysis showed that they belonged to genotype JEV-Ⅰ.The minimum infection rate of JEV was 0.57‰ (8/13 990).A total of 5 pools of Akabane virus (AKV) gene amplification were positive.The minimum infection rate of AKV was 0.44‰ (5/11 360).Based on the S gene and M gene sequences of the virus,data from the phylogenetic analysis showed that the five AKV strains carried by midges in Hainan province were in a separate evolutionary branch and with formed unique geographical distribution.Conclusions JEV and GETV had been isolated again from the mosquito specimens in this survey,since the 1980s.AKV was detected from the midge specimens in Hainan province.These results showed the needs of strengthening the programs on detection and monitor of JEV,GETV and AKV that were related to animal and human diseases in order to reduce the risks of related diseases in this area.

Child ; Child Health ; Child, Preschool ; China ; Diet ; Diet Surveys ; Feeding Behavior ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Rural Population ; statistics & numerical data ; Vulnerable Populations ; statistics & numerical data

Objective To explore the biological functions of E77.43, a gene segment of Microtus fortis, in treating Schistoso-ma japonicum infection. Methods Recombinant retroviral vectors of pRevTRE-E77.43 was constructed, and recombinant retro-viral vectors were transfected into PA317 cells, and the stable cell lines were obtained by hygromycin screening, followed by the packaging, concentration and purification of recombinant retrovirus. The virus was transferred to the mice infected by S. japoni-cum via intravenous or intraperitoneal injection, through which the express of target gene and the treatment function in vivo were observed. Results The experiment showed the recombinant virus injected mice could efficiently express E77.43 on the 7th day after the injection which lasted for forty-five days thereafter. A significant reduction in adult worms (31.0％) and a high reduction (35.0％) in liver eggs were induced by pRevTRE-E77.43, while the reduction in adult worms and that in liver eggs was 1.2％and 0.9％induced by pRevTRE respectively (t=3.524, 9.485, both P<0.01). Conclusion pRevTRE-E77.43 could be used for the treatment of S. japonicum infection, indicating that E77.43 may involve in the natural resistance of M. fortis to S. japonicum infec-tion.

OBJECTIVEThe purpose of this study was to investigate the value of postoperative chemotherapy for locally advanced rectal cancer patients who reached pathological ypT1-4N0 after neo-adjuvant chemoradiotherapy.

METHODSWe performed a retrospective study of 104 patients treated with preoperative chemoradiotherapy followed by radical resection, who achieved pathological ypT1-4N0, between Mar 2003 and Dec 2010. There were 73 patients who received postoperative adjuvant chemotherapy, and the other 31 patients did not. The distribution of final pathologic stages for these patients was ypT1-2N0 in 39 cases and ypT3-4N0 in 65 cases.

RESULTSThe median follow-up was 41 months. The 3-year overall survival rate (OS) and recurrence-free survival rate (RFS) for the whole group (ypT1-4N0) were 93.4% and 85.3%, respectively. The 3-year OS and RFS in the adjuvant chemotherapy group and non-adjuvant chemotherapy group were 95.5%, 88.6% and 88.6%, 77.2%, respectively. There were no significant differences in 3-year RFS (P = 0.108) and OS (P = 0.106) between the two groups. The 3-year local recurrence and distant metastasis rates in the adjuvant chemotherapy group were 4.1% (3/73) and 5.5% (4/73), while for the non-adjuvant chemotherapy group, the 3-year local recurrence rate and distant metastasis rate were 3.2% (1/31) and 16.1% (5/31), respectively. Significant difference was found in distant metastasis rates (P = 0.030) between the two groups, but not in local recurrence rates (P = 0.676).Further subgroup analysis indicated that for the ypT1-2N0 patients, there were no significant differences in 3-year OS (P = 0.296) and RFS (P = 0.939) between the adjuvant and non-adjuvant chemotherapy groups, while negative results displayed in 3-year local recurrence rates (P = 0.676) and distant metastasis rates (P = 0.414). However, for patients with ypT3-4N0, significant differences were showed in both the 3-year OS (P = 0.034) and RFS (P = 0.025), and further analysis revealed that the 3-year distant metastasis rate was significantly higher in the non-adjuvant chemotherapy group than in the adjuvant chemotherapy group (P = 0.010) , but with non-significant difference in the 3-year local recurrence (P = 0.548).

CONCLUSIONSAdjuvant chemotherapy may not improve survival for ypT1-2N0 patients. However, it may be clinically meaningful for ypT3-4N0 patients by decreasing distant metastasis rate. Further randomized controlled clinical trials are needed to confirm our results.

Adenocarcinoma ; drug therapy ; pathology ; radiotherapy ; surgery ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chemoradiotherapy, Adjuvant ; Chemotherapy, Adjuvant ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Female ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Follow-Up Studies ; Humans ; Leucovorin ; therapeutic use ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Organoplatinum Compounds ; therapeutic use ; Postoperative Period ; Radiotherapy, Conformal ; Rectal Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Retrospective Studies ; Survival Rate ; Young Adult

Animals ; Arrestins ; metabolism ; Hypoxia ; metabolism ; Male ; Prefrontal Cortex ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; metabolism ; beta-Arrestin 1 ; beta-Arrestins

High-altitude hypoxia can induce physiological dysfunction and mountain sickness, but the underlying mechanism is not fully understood. Corticotrophin-releasing factor (CRF) and CRF type-i receptors (CRFR1) are members of the CRF family and the essential controllers of the physiological activity of the hypothalamo-pituitary-adrenal (HPA) axis and modulators of endocrine and behavioral activity in response to various stressors. We have previously found that high-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of CRF and CRFR1 in the brain and periphery that include activation of the HPA axis in a time- and dose-dependent manner, impaired or improved learning and memory, and anxiety-like behavioral change. Meanwhile, hypoxia induces dysfunctions of the hypothalamo-pituitary-endocrine and immune systems, including suppression of growth and development, as well as inhibition of reproductive, metabolic and immune functions. In contrast, the small mammals that live on the Qinghai-Tibet Plateau alpine meadow display low responsiveness to extreme high-altitude-hypoxia challenge, suggesting well-acclimatized genes and a physiological strategy that developed during evolution through interactions between the genes and environment. All the findings provide evidence for understanding the neuroendocrine mechanisms of hypoxia-induced physiological dysfunction. This review extends these findings.
Altitude ; Animals ; Brain ; physiopathology ; Corticotropin-Releasing Hormone ; metabolism ; Hypothalamo-Hypophyseal System ; physiopathology ; Hypoxia ; physiopathology ; Pituitary-Adrenal System ; physiopathology ; Receptors, Corticotropin-Releasing Hormone ; metabolism ; Tibet

HIF-1 is composed of HIF-1α and HIF-1β subunits. It promotes target genes transcription under hypoxia and plays essential roles in cell development, physiological adaptations, and pathological processes. In the past 10 years, the research on signaling pathways of HIF-1 in response to cell hypoxia stress, especially on HIF-1α-mediated gene transcription has made great progress.
Animals ; Cell Hypoxia ; physiology ; Humans ; Hypoxia-Inducible Factor 1 ; metabolism ; Signal Transduction