OBJECTIVE:Most of the existing studies are based on traditional Meta-analysis to study the efficacy of single stimulation protocols such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor dysfunction in stroke patients,and it is not possible to clarify which stimulation protocol is the optimal choice.This study used network meta-analysis to systematically evaluate the clinical efficacy of different regimens of non-invasive brain stimulation in the treatment of lower limb motor dysfunction after stroke.METHODS:CNKI,WanFang,VIP,CBM,PubMed,Medline and Web of Science databases were searched to collect randomized controlled trials on different regimens of non-invasive brain stimulation for lower limb motor dysfunction after stroke from inception to October 1,2024.Data extraction was performed on the included studies.RevMan 5.4.1 software was used for traditional meta-analysis and the quality of the included studies was evaluated.Stata 17.0 software was used for network meta-analysis.RESULTS:(1)A total of 39 studies involving 2 920 patients were included,involving 6 treatment methods:conventional rehabilitation training,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,continuous theta burst stimulation,and transcranial direct current stimulation.(2)The results of network meta-analysis showed that high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training in the Fugl-Meyer assessment for lower extremity motor function.(3)In terms of improving Berg balance scale score,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,and intermittent theta burst stimulation were significantly different from conventional rehabilitation training(P＜0.05),and there was a significant difference between high-frequency repetitive transcranial magnetic stimulation and intermittent theta burst stimulation(P＜0.05).(4)In improving modified Barthel index and Barthel index,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training.(5)Under the cumulative ranking chart,high-frequency repetitive transcranial magnetic stimulation showed the best efficacy in Fugl-Meyer assessment for lower extremity motor function,Berg balance scale score,modified Barthel index and Barthel index,followed by low-frequency repetitive transcranial magnetic stimulation.CONCLUSION:Both high-and low-frequency repetitive transcranial magnetic stimulation can improve the lower limb motor function and balance function of patients with stroke,and can improve the activities of daily living of patients to varying degrees.Moreover,the effect of high-frequency repetitive transcranial magnetic stimulation is better than that of low-frequency repetitive transcranial magnetic stimulation.

OBJECTIVE:Most of the existing studies are based on traditional Meta-analysis to study the efficacy of single stimulation protocols such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor dysfunction in stroke patients,and it is not possible to clarify which stimulation protocol is the optimal choice.This study used network meta-analysis to systematically evaluate the clinical efficacy of different regimens of non-invasive brain stimulation in the treatment of lower limb motor dysfunction after stroke.METHODS:CNKI,WanFang,VIP,CBM,PubMed,Medline and Web of Science databases were searched to collect randomized controlled trials on different regimens of non-invasive brain stimulation for lower limb motor dysfunction after stroke from inception to October 1,2024.Data extraction was performed on the included studies.RevMan 5.4.1 software was used for traditional meta-analysis and the quality of the included studies was evaluated.Stata 17.0 software was used for network meta-analysis.RESULTS:(1)A total of 39 studies involving 2 920 patients were included,involving 6 treatment methods:conventional rehabilitation training,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,continuous theta burst stimulation,and transcranial direct current stimulation.(2)The results of network meta-analysis showed that high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training in the Fugl-Meyer assessment for lower extremity motor function.(3)In terms of improving Berg balance scale score,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,and intermittent theta burst stimulation were significantly different from conventional rehabilitation training(P＜0.05),and there was a significant difference between high-frequency repetitive transcranial magnetic stimulation and intermittent theta burst stimulation(P＜0.05).(4)In improving modified Barthel index and Barthel index,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training.(5)Under the cumulative ranking chart,high-frequency repetitive transcranial magnetic stimulation showed the best efficacy in Fugl-Meyer assessment for lower extremity motor function,Berg balance scale score,modified Barthel index and Barthel index,followed by low-frequency repetitive transcranial magnetic stimulation.CONCLUSION:Both high-and low-frequency repetitive transcranial magnetic stimulation can improve the lower limb motor function and balance function of patients with stroke,and can improve the activities of daily living of patients to varying degrees.Moreover,the effect of high-frequency repetitive transcranial magnetic stimulation is better than that of low-frequency repetitive transcranial magnetic stimulation.

OBJECTIVE To establish a determination method for the related substances of LPM3480392, a novel Gi protein-biased opioid receptor(MOR) agonist. METHODS The separation was carried out with Waters Symmetry Shield RP18 (150 mm×4.6 mm, 3.5 μm) by gradient elution method, using a mixture of 0.002 5 mol·L–1 sodium 1-octanesulfonate monohydrate in 0.01 mol·L–1 potassium dihydrogen phosphate-water solution(containing 0.1% triethylamine, adjusted pH to 2.50 with phosphate acid) and acetonitrile as the mobile phase at a flow rate of 1.0 mL·min–1 and the UV detection wavelength was set at 210 nm. RESULTS The chromatographic peaks of LPM3480392 and impurity A, impurity B, impurity C, impurity E and impurity F could be completely separated, the linear relationship of LPM3480392 was good in 0.064 9−5.191 2 μg·mL–1, while impurity A, impurity B, impurity C, impurity E and impurity F showed good linear relationship within 0.066 6−7.610 4 μg·mL–1, 0.166 0−3.794 0 μg·mL–1, 0.209 2−4.463 2 μg·mL–1, 0.167 9−7.672 6 μg·mL–1 and 0.016 4−7.505 7 μg·mL–1, respectively. The recovery rate was within 93.0%−103.2%. CONCLUSION The method is suitable for the determination of related substances in LPM3480392, and can provide valuable reference for the follow-up research and development of LPM3480392.

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