Alterations in immune cell heterogeneities in the brain of aged zebrafish using single-cell resolution.

Immunocytes, including the microglia, are crucial in the neurodegenerative process in old people. However, the understanding of regarding microglia heterogeneity and other involved immunocytes remains elusive. We analyzed 26,456 immunocytes from 12-and 26-month-old zebrafish brains at single-cell resolution. Microglia and T lymphocytes were detected in the brain at both time points. Two types of microglia were annotated, namely, ac+ microglia and xr+ microglia, which were clustered into subsets 1, 2, 3, 4, 5, and subsets 6, 7, 8, 9, respectively. Diversified microglia predominated the adult brains and cooperated with T cells to perform the functions of immune response and neuronal nutrition. We validated the specific microglia markers. The novel transgenic lines, Tg(lgals3bpb:eGFP) and Tg(apoc1:eGFP), were created, which faithfully labeled ac+ microglia and served as valuable labeling tools. However, the microglia population reduced while T cells of six subtypes intriguingly increased to serve as the primary immune cells in aged brains. Unlike in 12-month-old brains, T cells, together with microglia, exhibited a coordinated signature of inflammation in the 26-month-old brains. Our findings revealed the immunocytes atlas in aged zebrafish brains. It implied the involvement of microglia and T cells in the progression of neurodegeneration in aging.

A multi-center, randomized, single-blind, controlled clinical study on the efficacy of composite sophora colon-soluble capsules in treating ulcerative colitis.

OBJECTIVE: To evaluate the safety and efficacy of composite sophora colon-soluble capsule (CSCC) in treating ulcerative colitis (UC) of the damp-heat accumulation syndrome pattern (DHAS) and to prepare a basis for a phase III clinical trial. METHODS: A multi-center, randomized, single-blind, and positive drug parallel-controlled design was adopted. There were 126 patients of UC-DHAS stratified and assigned equally to three groups. Patients in two CSCC treated groups, Groups T1 and T2, were treated orally with high (six capsules, thrice a day) and low (four capsules, thrice a day) doses CSCC, and patients in the control group were treated orally with Mesalazine Enteric-coated Tablets (four tablets, thrice a day), respectively, all for eight weeks. The clinical efficacy and safety of treatments were evaluated through clinical symptom observations and colonoscopic examinations. RESULTS: (1) Full analysis set (FAS) and per-protocol set (PPS) analyses showed the comprehensive curative effect in Groups T1, T2, and the control group, obtaining the values of 85.7%, 92.9%, and 71.4% (P=0.330), and 89.5%, 92.7%, and 73.2% (P=0.552), respectively, demonstrating no statistical significance among the three groups. (2) FAS and PPS analysis showed the efficacy on membranous lesions in Groups T1, T2, and the control group, obtaining the values of 83.3%, 92.9%, and 73.8% (P=0.063), and 86.8%, 92.7%, and 75.6% (P=0.070), respectively, showing statistical insignificance among the three groups. (3) FAS analysis showed an efficacy tendency on improving tenesmus (P=0.056). No changes were found in improving the other symptoms, and statistical significance was not shown among the three groups (P>0.05). PPS analysis showed the efficacy on single item symptom in Groups T1, T2, and the control group was not statistically significant among the three groups (P=0.082). CONCLUSIONS: The comprehensive effect of CSCC in treating UC is basically equivalent to that of Mesalazine enteric-coated tablet; however, the tendency was shown to improve symptoms. Its efficacy could not be raised by increasing the dosage used. Therefore, the recommended dosage of CSCC is four capsules, three times a day.