[Efficacy analysis of a novel dose-adjusting regimen for prolonged delayed injection allergen- specific immunotherapy for allergic rhinitis].

Objective: To investigate the efficacy and safety of a novel dose adjustment schedule based on subcutaneous immunotherapy (SCIT) after a 16 weeks delayed injection during the maintenance period. Methods: Sixty-eight patients with allergic rhinitis (AR) who received dust mite cluster SCIT and had interrupted treatment for more than 16 weeks during the maintenance period were recruited at Beijing TongRen Hospital, from July to September 2020. They were randomly divided into the novel schedule group (n=34) and the guideline recommended schedule group (n=34). In addition, 34 patients who received dust mite SCIT at the same period were selected as the continuous treatment group (n=34). When receiving treatment again after delayed injection, the novel schedule group was injected directly with the initial dose of maintenance period (10 000 SQ), and the guideline recommended schedule group started the dosage accumulation again from the lowest dose (10 SQ), while the continuous treatment group was injected according to the original schedule. Changes in the combined symptom and medication score (CSMS) from baseline after 3 years of SCIT were used as the primary efficacy evaluation index. Local and systemic adverse events were recorded to evaluate safety. SPSS 23.0 was used for statistical analysis. Results: At the end of 3 years, CSMS in all three groups decreased significantly from baseline, and there was no significant difference in the 3-year change value of CSMS from baseline between the novel schedule group and the guideline recommended schedule group (-1.0±0.3 vs -1.3±0.4, P=0.655). There was also no significant difference in the change of CSMS between the two dose-adjusted groups and the continuous treatment groups (-0.8±0.3 vs -1.3±0.3, P=0.156). No systemic adverse events occurred between the novel schedule group and the guideline recommended schedule group after restarting treatment, and there was no significant difference in frequency of adverse events (0.5% vs 0.5%, P=0.698). Conclusion: There is no significant difference in efficacy and safety between the novel dose adjustment schedule and the recommended dose adjustment schedule when SCIT interrupted injection for more than 16 weeks. Furthermore, SCIT discontinuation of injection for more than 16 weeks doesn't significantly impact on 3-year efficacy.

Serum 25-hydroxyvitamin D levels and peripheral neuropathy in patients with type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: Vitamin D is a multifunctional pro-hormone and has widespread actions in human body. Several studies showed a possible association between vitamin D deficiency and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes, but no definite conclusion was available. METHODS: A systematic review and meta-analysis was performed to comprehensively assess the association between serum 25-hydroxyvitamin D [25(OH)D] levels and DPN in patients with type 2 diabetes. Data from eligible studies were pooled using meta-analysis. RESULTS: Six studies that involved a total of 1,484 type 2 diabetic patients were finally included into the meta-analysis. Meta-analysis showed that there were obviously decreased serum 25(OH)D levels in DPN patients [weighted mean difference (WMD) = -6.36 ng/ml, 95 % confidence interval (95 % CI) -8.57 to -4.14, P < 0.00001]. Vitamin D deficiency was also significantly associated with increased risk of DPN in patients with type 2 diabetes [odds ratio (OR) 2.88, 95 % CI 1.84-4.50, P < 0.00001]. Meta-analysis of three studies with adjusted estimates showed that vitamin D deficiency was independently associated with increased risk of DPN in patients with type 2 diabetes (OR 2.68, 95 % CI 1.67-4.30, P < 0.0001). Sensitivity analysis showed that there was no obvious change in the pooled estimates. CONCLUSION: Vitamin D is involved in the development of DPN in type 2 diabetic patients, and vitamin D deficiency is very likely to be associated with DPN in type 2 diabetic patients. Further studies are needed to validate the association between vitamin D deficiency and DPN.

Expansion of CD133(+) colon cancer cultures retaining stem cell properties to enable cancer stem cell target discovery.

BACKGROUND: Despite earlier studies demonstrating in vitro propagation of solid tumour cancer stem cells (CSCs) as non-adherent tumour spheres, it remains controversial as to whether CSCs can be maintained in vitro. Additional validation of the CSC properties of tumour spheres would support their use as CSC models and provide an opportunity to discover additional CSC cell surface markers to aid in CSC detection and potential elimination. METHODS: Primary tumour cells isolated from 13 surgically resected colon tumour specimens were propagated using serum-free CSC-selective conditions. The CSC properties of long-term cultured tumour spheres were established and mass spectrometry-based proteomics performed. RESULTS: Freshly isolated CD133(+) colorectal cancer cells gave rise to long-term tumour sphere (or spheroids) cultures maintaining CD133 expression. These spheroid cells were able to self-renew and differentiate into adherent epithelial lineages and recapitulate the phenotype of the original tumour. Relative to their differentiated progeny, tumour spheroid cells were more resistant to the chemotherapeutic irinotecan. Finally, CD44, CD166, CD29, CEACAM5, cadherin 17, and biglycan were identified by mass spectrometry to be enriched in CD133(+) tumour spheroid cells. CONCLUSION: Our data suggest that ex vivo-expanded colon CSCs isolated from clinical specimens can be maintained in culture enabling the identification of CSC cell surface-associated proteins.