Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To observe the effect of Shenghui Granule on EC and CA1 regions of scopolamine-induced dementia rats and explore its mechanism based on p38 MAPK signal pathway.Methods 40 SD rats were randomly divided into four groups(blank group,model group,Shenghui granule group,donepezil group),and were treated with scopolamine.Morris water maze and open field test were used to evaluate the cognition and anxiety behavior of rats.The nerve injury of EC and CA1 was observed by HE staining.The activity of neurons in EC and CA1 regions was observed by c-Fos immunofluorescence staining.Western blot was used to detect p38 MAPK pathway related proteins.Results The behavioral experiment found that Shenghui Granule could improve the cognitive impairment and anxiety-like behavior of AD model rats.The results of HE staining showed that Shenghui granules had protective effects on EC and CA1 regions.The results of c-Fos immunofluorescence staining showed that Shenghui granules could increase the activity of neurons in EC and CA1 regions.Western blot results showed that Shenghui Granule could down-regulate the expression of Bax,reduce the levels of phosphorylated p38 and Tau,and increase the expression of Bcl-2.Conclusion Shenghui granule has protective effect on EC and CA1 regions of AD model rats,and may play a therapeutic role through p38 MAPK signal pathway.

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with al-terations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,trans-mission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assess-ment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

Objective To evaluate the variables which can be used as prognostic factors in predicting the outcome of Graves disease(GD)after treatment with antithyroid drugs.Methods We performed a retrospective audit of 204 patients with newly diagnosed Graves disease consecutively at the Ruijin Hospital.Results Overall,110 patients(53.9%)were considered to be treatment failures.Age at the time of diagnosis was(31.0±12.2)years in the successful group and(36.3±14.0)years in the failure group.Free T3(FT3)was(25.60±9.52)pmol/L and(19.16±6.38)pmol/L in the failure and the successful group(P=0.001).FT3 to FT4 ratio and thyrotrophin recptor antibody(TRAb)levels were higher in the failure group(P=0.001).Logistic regression analysis showed that thyroid size,FT3 to FT4 ratio and TRAb at the time of diagnosis were associated with failure outcome.The patients reached euthyroid state at 3,6,9 and 12 months respectively and in the failure group the patients with continued thyrotropin suppression were more than those in the successful group(P=0.001).Conclusions Graves disease patients with large thyroid size,high levels of TRAb and FT3 to FT4 ratio before drug treatment are more likely to fail to respond to antithyroid drug treatment.We also found that patients with continuing thyrotropin suppression and attainmen of euthyroid state in the course of treatment had low remission rate and prolonged therapy.

A total of 115 patients with Hoshimoto thyroiditis were classified under 2 groups: one group being treated with selenium and L-throxine (L-T4) and other group with L-T4 alone.All patients were followed up for 3 months.In the selenium treated group thyroid peroxidase antibody level was decreased in 33 patients (56%) and thyroglobulin antibody level was decreased in cases.

Objective To explore the mechanism of persistent thyrotropin suppression in euthyroid patients with Graves′ disease after antithyroid drugs (ATD) treatment. Methods A prospective clinical study was performed in 122 patients with newly diagnosed Graves′ disease. All the patients were treated with 30 mg methimazole or 300 mg propylthiouracil daily, to whom L-T4was added, aiming at normalizing FT3 and FT4 but avoiding elevated TSH level. When the patients were clinically and biochemically euthyroid for at least 3 months, their blood levels of thyroid hormones, TSH, TSH receptor antibody(TRAb) and thyroid peroxidase antibody(TPOAb) were detected again and the cases were divided into two groups according to negative or positive TRAb. Results After treatment as long as (7.1±1.1) months, stable euthyroid status was restored for 3 months. When the patients reached the euthyroid state, 64 of them still had detectable TRAb levels, and 58 became negative TRAb. The two groups had similar levels of FT3 and FT4, but patients with positive TRAb had lower TSH level than patients with negative TRAb[0.044 mIU/L(0.001-4.163 mIU/L) vs 1.749 mIU/L(0.079-4.646 mIU/L),P＜0.01]. In addition, the TSH level was negatively correlated with TRAb level (r=-0.539, P＜0.01), and not with FT3, FT4 levels or other factors. Conclusion The present study showed that elevated TRAb level is associated with persistent suppression of TSH in patients with Graves′ disease after being rendered euthyroid. This finding may be due to the binding of TRAb to pituitary TSH receptor.