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

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Objective:To analyse the long-term efficacy in childhood T-cell acute lymphoblastic leukemia (T-ALL) cases enrolled in the national protocol of childhood leukemia in China-acute lymphoblastic leukemia (NPCLC-ALL) 2008.Methods:Clinical data of 96 patients diagnosed as T-ALL and treated with NPCLC-ALL2008 protocol between January 2009 and December 2017 in the Department of Hematology-Oncology, the Children′s Hospital, Zhejiang University School of Medicine were analyzed retrospectively. Predictive value of minimal residual disease (MRD) monitored by flow cytometry was analyzed. Kaplan-Meier method was used for long-term survival analysis.Results:A total of 96 evaluable patients with newly diagnosed T-ALL were analysed, including 72 males and 24 females. The age was 9.5 (ranged from 1.0 to 16.0) years. The follow-up time was 5.7 (ranged from 1.0 to 9.7) years. Among 96 patients, 92 (96%) achieved complete remission. The 5-year event free survival (EFS) and overall survival (OS) rates were (61±6) % and (70±5) %, respectively. Relapse occurred in 18 cases and the 5-year cumulative incidence of relapse was (27±6) %. Twenty-four patients died. The 5-year OS rates of patients with MRD>5% on day 15 of induction therapy was significantly worse than those with MRD≤5% ((60±12) % vs. (72±6) %, χ 2=3.904, P=0.048) . The 5-year EFS and OS rates were obviously lower in patients with MRD>10% before the consolidation therapy ((50±35) %). The 5-year OS rates of patients with relapsed disease was significantly worse than those without ((26±13) % vs. (81±5) %, χ 2=18.411, P<0.01). The earlier the relapse, the worse the prognosis. The 5-year OS rates for patients relapsed within 6 months, within 3 years and more than 3 years, were (25±22) %, (30±14) % and (50±35) % respectively (χ 2=13.207, P<0.01). Conclusions:NPCLC-ALL2008 protocol is effective for childhood T-ALL. The MRD guided accurate risk stratification and individualized treatment can reduce the relapse and improve the survival rate of pediatric T-ALL.

Objective To evaluate the role of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)or Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT-3)signaling pathways in reduction of myocardial ischemia-reperfusion(I/R)injury by combination of limb ischemic and morphine postconditioning in rats.Methods Eighty SPF healthy male Sprague-Dawley rats,aged 8 weeks,weighing 280-320 g,were used in the study.Myocardial I/R was induced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion.The rats were divided into 8 groups(n=10 each)using a random number table:I/R group,limb ischemic postconditioning group(LIP group),morphine postconditioning group(group MP),combination of limb ischemic and morphine postconditioning group(LIP+MP group)and signaling pathway blocker groups(I/Rb group,LIPb group,MPb group,LIP+MPb group).In I/R,LIP,MP and LIP+MP groups,the animals were sacrificed at the end of reperfusion,and myocardial specimens in ischemic and non-ischemic regions were obtained for determination of phosphorylated STAT-3(p-STAT-3),STAT-3,phosphorylated Akt(p-Akt)and Akt expression(by Western blot)and STAT-3 and Akt mRNA expression(by polymerase chain reaction).In I/Rb,LIPb,MPb and LIP+MPb groups,PI3K/Akt signaling pathway blocker LY294002 0.3 mg/kg was intravenously injected in 5 rats of each group,and JAK/STAT-3 signaling pathway blocker AG490 5 mg/kg was intravenously injected in the other 5 rats of each group.The animals were sacrificed at the end of reperfusion,and myocardial specimens in the ischemic region were obtained for determination of myocardial infarct size.Results Compared with I/R group,the p-STAT-3/STAT-3 ratio in LIP,MP and LIP+MP groups and p-Akt/Akt ratio in LIP+MP group were significantly increased,and the expression of STAT-3 and Akt mRNA was up-regulated in LIP+MP group(P<0.05).Compared with LIP and MP groups,the p-STAT-3/STAT-3 and p-Akt/Akt ratios were significantly increased,and the expression of STAT-3 and Akt mRNA was up-regulated in LIP+MP group(P<0.05).There was no significant difference in myocardial infarct size between the four groups when PI3K inhibitor LY294002 was applied(P>0.05).When JAK2 inhibitor AG490 was applied,the myocardial infarct size was significantly smaller in LIP+MPb group than in I/Rb,LIPb and MPb groups(P<0.05),and there was no significant difference in myocardial infarct size between I/Rb,LIPb and MPb groups(P>0.05).Conclusion Combination of limb ischemic and morphine postconditioning can enhance the activation of PI3K/Akt or JAK/STAT-3 signaling pathways,and the cardioprotection is dependent on the integrity of the PI3K/Akt signaling pathway and partially dependent on the integrity of the JAK/STAT-3 signaling pathway when applied in combination in rats.

Microthrombosis may be involved in the pathogenesis of cardiac microangiopathy due to diabetes. Recent studies have shown that fibrinogen-like protein 2 (fgl2) plays a pivotal role in microthrombosis in viral hepatitis, acute vascular xenograft rejection and cytokine-induced fetal loss syndrome. The current study was designed to examine the expression of fgl2 in microvascular endothelial cells and investigate the effects of microthrombi due to fgl2 on cardiac function and structure in rats with type 2 diabetes. Following induction of type 2 diabetes, 24 rats were observed dynamically. Fgl2 expression and related cardiac microthrombosis were examined. Local or circulating TNF-α was measured. Coronary flow (CF) per min was calculated as an index of cardiac microcirculation. Cardiac function and morphology were evaluated. It was found that Fgl2 was highly expressed in cardiac microvascular endothelial cells of rats with type 2 diabetes, which was promoted by local or circulating TNF-α. The Fgl2 expression was associated with cardiac hyaline microthrombosis. In parallel with the fgl2 expression, CF per min, cardiac diastolic or systolic function and cardiac morphology were aggravated to some extent. It was concluded that in rats with type 2 diabetes, microthrombosis due to fgl2 contributes to the impairment of cardiac diastolic or systolic function and morphological changes.

Microthrombosis may be involved in the pathogenesis of cardiac microangiopathy due to diabetes. Recent studies have shown that fibrinogen-like protein 2 (fgl2) plays a pivotal role in microthrombosis in viral hepatitis, acute vascular xenograft rejection and cytokine-induced fetal loss syndrome. The current study was designed to examine the expression of fgl2 in microvascular endothelial cells and investigate the effects of microthrombi due to fgl2 on cardiac function and structure in rats with type 2 diabetes. Following induction of type 2 diabetes, 24 rats were observed dynamically. Fgl2 expression and related cardiac microthrombosis were examined. Local or circulating TNF-a was measured. Coronary flow (CF) per min was calculated as an index of cardiac microcirculation. Cardiac function and morphology were evaluated. It was found that Fgl2 was highly expressed in cardiac microvascular endothelial cells of rats with type 2 diabetes, which was promoted by local or circulating TNF-α. The Fgl2 expression was associated with cardiac hyaline microthrombosis. In parallel with the fgl2 expression, CF per min, cardiac diastolic or systolic function and cardiac morphology were aggravated to some extent. It was concluded that in rats with type 2 diabetes, microthrombosis due to fgl2 contributes to the impairment of cardiac diastolic or systolic function and morphological changes.

OBJECTIVETo identify the small supernumerary marker chromosomes (sSMC) and guide the genetic counseling and medical treatment in two patients with Turner syndrome.

METHODSHigh resolution GTG and C banding, SRY amplification by PCR and fluorescence in situ hybridization (FISH) on metaphase chromosomes were performed to the two patients.

RESULTSThe karyotypes of the two patients were 45, X [29]/46,X, +mar[31] and 45,X[71]/46,X, +mar[29] respectively. SRY test indicated SRY-positive for patient 1, whose sSMC was originated from chromosome Y. The karyotype was confirmed as 45,X[29]/46,X,idic(Y)(q10)[31]. ish idic(Y)(q10)(RP11-115H13x2) (SRY+) by FISH. While in patient 2, the sSMC was originated from chromosome X, whose karyotype was determined as 45, X[71]/46,X, r(X)(p11.23q21)[29]. ish r(X) (p11.23q21)(AL591394.11xAC092268.3).

CONCLUSIONUsing cytogenetic and molecular cytogenetic analyses, we have identified the sSMCs in two patients with Turner syndrome, which was helpful to the clinical diagnosis and treatment.

Adolescent ; Child ; Chromosomes, Human, X ; genetics ; Chromosomes, Human, Y ; genetics ; Female ; Genetic Markers ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Turner Syndrome ; genetics

0.05). CONCLUSIONS Proper use of disinfectants based on routine cleaning can achieve good results in the nosocomial infection control of the NICU.

To observe the dynamic changes of the TGF-beta1 expressed in the infarct and non-infarcted region of rat heart during the ventricular remodeling (day 3, 7, 28, 180), myocardial infarction rat model was made and relationship between the cytokine and indicator of myocardial remodeling was analyzed. After the detection of hemodynamic parameter was performed by the Powerlab devices, the size of myocardial infarction and the morphology change was detected by TTC and HE, respectively. The relative levels of mRNA of TGF- beta1, collagen type I, III, and fetal gene beta-MHC were detected by RT-PCR. The distribution of TGF- beta1 protein in the myocardium was detected by immunohistochemistry. The results showed that the size of infarction was higher than that of the sham operated groups in the infarcted group (44.5 +/- 0.5 vs 0). The difference in hemodynamic parameters between the infarcted group and sham operated group was significant (P < 0.01). HE staining showed that inflammatory cells were accumulated in the infarcted region at the beginning of the 3rd day, which lasted 4 weeks. Then, it decreased gradually. beta-MHC in the non-infarcted region rose from the 3rd day, reaching its peak at the 4th week, and it decreased gradually. The ratio of the collagen type I/III showed similar changes as compared with the sham operated groups (P < 0.01). And the relative mRNA levels in the non-infarcted group were significantly higher than that in the infarcted and sham operated group (P < 0.01) at day 180. Linear regression analysis indicated that the TGF-beta1 was positively correlated with the ventricular remodeling. It was concluded that the cytokine TGF-beta1 participates in the process of the myocardial remodeling, which could be a strategy in the interference of myocardial remodeling.

To observe the dynamic changes of the TGF-β1 expressed in the infarct and non-infarcted region of rat heart during the ventricular remodeling (day 3, 7, 28, 180), myocardial infarction rat model was made and relationship between the cytokine and indicator of myocardial remodeling was analyzed. After the detection of hemodynamic parameter was performed by the Powerlab devices, the size of myocardial infarction and the morphology change was detected by TTC and HE, respectively.The relative levels of mRNA of TGF- β 1, collagen type Ⅰ, Ⅲ, and fetal gene beta-MHC were detected by RT-PCR. The distribution of TGF- β1 protein in the myocardium was detected by immunohistochemistry. The results showed that the size of infarction was higher than that of the sham operated groups in the infarcted group (44.5±0.5 vs 0). The difference in hemodynamic parameters between the infarcted group and sham operated group was significant (P＜0.01). HE staining showed that inflammatory cells were accumulated in the infarcted region at the beginning of the 3rd day,which lasted 4 weeks. Then, it decreased gradually. β-MHC in the non-infarcted region rose from the 3rd day, reaching its peak at the 4th week, and it decreased gradually. The ratio of the collagen type Ⅰ/Ⅲ showed similar changes as compared with the sham operated groups (P＜0.01). And the relative mRNA levels in the non-infarcted group were significantly higher than that in the infarcted and sham operated group (P＜0.01) at day 180. Linear regression analysis indicated that the TGF-β1 was positively correlated with the ventricular remodeling. It was concluded that the cytokine TGF- β1 participates in the process of the myocardial remodeling, which could be a strategy in the interference of myocardial remodeling.