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Background: There are currently limited systemic treatment options for patients with advanced neuroendocrine tumours (NETS) and the efficacy of existing treatments is sub-optimal. We evaluated the efficacy and safety of Tegafur/gimeracil/oteracil/potassium capsules (S-1)/Temozolomide with or without thalidomide for the treatment of NETS (STEM trial). Methods: A randomised, controlled, open-label, phase 2 trial conducted at eight hospitals in China. Adults (≥18 years) with unresectable/metastatic, pancreatic or non-pancreatic NETS, with an Eastern Cooperative Oncology Group (ECOG) PS of 0-1, and progression on ≤2 previous therapies were randomised (1:1, using hierarchical block randomization with block length 4, stratified by pancreatic/non-pancreatic disease to receive S-1 40-60 mg orally twice daily on days 1-14 plus temozolomide 200 mg orally daily on days 10-14 in a 21-day cycle OR S-1 and temozolomide plus thalidomide orally nightly (100 mg on days 1-7, 200 mg on days 8-14, and 300 mg from day 15), until disease progression, death, intolerable toxicity, withdrawal of informed consent or at the investigator's discretion. The primary endpoint was objective response rate (ORR) by RECIST 1.1 in an intention-to-treat population. Safety was assessed in all patients who received treatment. The study was registered at ClinicalTrials.gov: NCT03204019 (pancreatic group) and NCT03204032 (non-pancreatic group). Findings: Between March 23, 2017 and November 16, 2020, 187 patients were screened and 140 were randomly assigned to S-1/temozolomide plus thalidomide (n = 69) or S-1/temozolomide (n =71). After a median follow-up of 12·1 months (IQR: 8·4-16·6), the ORR was comparable in the S-1/temozolomide plus thalidomide and S-1/temozolomide groups 26·1% [95% CI 17·2-37·5] versus 25·4% [95% CI 16·7-36·6]; odds ratio: 1·03 [95% CI 0·48-2·22]; P = 0·9381). In the S-1/temozolomide plus thalidomide group, the most common grade 3-4 treatment-related adverse event was fatigue (2/68, 3%), and in the control group were thrombocytopenia and diarrhea (both 1/71, 2%). There were no treatment-related deaths in either group. Interpretation: S-1/temozolomide with or without thalidomide leads to a comparable treatment response in patients with advanced/metastatic NETS. Funding: This work was supported by CAMS Innovation Fund for Medical Sciences (CIFMS,2021-I2M-1-066, 2017-I2M-4-002, 2021-I2M-1-019, 2017-I2M-1-001), the National Natural Science Foundation of China (81972311, 82141127, 31970794,), the State Key Project on Infection Diseases of China (2017ZX10201021-007-003), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019PT310026), Sanming Project of Medicine in Shenzhen (SZSM202011010), and the State Key Laboratory Special fund from the Ministry of Science (2060204).
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Mode coupling characteristics in metal-coated microsphere are comprehensively studied by analytical method with Mie theory. The dispersion relation, field distribution and Q factor of the eigenmodes are calculated according to the modal eigenequation. In metal-coated microcavity, symmetric SPP mode can couple with asymmetric SPP mode and TM eigenmodes strongly at the different characteristic radius of microsphere. In the coupling range, the generated supermode possesses both high Q factor and high surface enhancement factor, which is expected to have many interesting potential applications. Furthermore, the sensitivity and figure of merit of supermode in biochemical sensing applications has been studied. The results show that both high sensitivity and large figure of merit can be achieved simultaneously.
RESUMEN
OBJECTIVE: To study the conditions and parameters of purifying 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glycoside from Polygonum multiflori. METHOD: Absorption capacity of four resins for 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glycoside was compared. With the adsorption ability as indexes, the process of absorbing and purifying 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glycoside from P. multiflori with S-8 macroporous resin absorbent was selected by orthogonal design. RESULT: The S-8 resin was the best of the four resins. The optimum process condition was 50% ethanol as eluting solvent, the flow rate at 1.5 mL x min(-1), pH at 7-8, and the solution concentration at 0.2 g x mL(-1). The absorption capacity by this process was 36.89 mg x g(-1). CONCLUSION: The process is simple and convenient and the regeneration of resin is easy, so this method of purification is advisable.
