Bushen Formula promotes the decrease of HBsAg levels in patients with CHB by regulating Tfh cells and B-cell subsets.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Formula (BSF) is the effective traditional Chinese medicine (TCM) for chronic hepatitis B (CHB) according to our previous researches. However, the special effectiveness of BSF treating CHB patients in different stages and the immunoregulatory mechanisms remain to be explored. AIM OF THE STUDY: To compare the therapeutic effects of BSF in both treatment-naive patients and Peg-IFN-α-treated patients, and explore the potential mechanism of immunomodulation. MATERIALS AND METHODS: Ultra-high performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry and the TCMSP database were used to determine the main components of BSF. Two hundred and sixty-six patients were enrolled in the retrospective study, and they were divided into the treatment group (T-Group, BSF plus Peg-IFN-α) and the control group (C-Group, Peg-IFN-α monotherapy). Within each group, patients were further grouped into subgroups, namely T1/C1 groups (treatment-naive patients, T1 = 34, C1 = 94) and T2/C2 groups (Peg-IFN-α-treated patients, T2 = 56, C2 = 82). Serum HBV markers, serum HBV DNA levels, serum ALT/AST and TCM symptoms were obtained from the record. Bioinformatics analysis was employed to obtain the potential immunoregulatory mechanisms of BSF treating CHB patients. Among patients in T2 and C2 group, peripheral mononuclear cells from 36 patients were used to analyze the characteristics of peripheral follicular helper T (Tfh) cells and B-cell subtypes by flow cytometry. Preparation of BSF-containing serum in rats. In vitro, the co-culture system of CXCR5+ cells and HepG2.2.15 cells was built to investigate the immunoregulatory effects of BSF. RESULTS: A total of 14 main active compounds were detected in BSF, which were deemed critical for the treatment of CHB. Our findings indicated that the T2-Group exhibited the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the C2-Group (35.7% vs. 15.9%, P = 0.033; 33.9% vs. 11.0%, P = 0.002). Additionally, the T2-Group demonstrated the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the T1-Group (35.7% vs. 14.7%, P = 0.031; 33.9% vs. 2.9%, P = 0.000). The total effective rate based on TCM clinical syndrome in T1-Group and T2-Group were significantly greater than those in C1-Group and C2-Group (85.3% vs. 61.7%, P = 0.012; 89.1% vs. 63.4%, P = 0.000). Bioinformatics analysis indicated that the immunoregulatory mechanisms of BSF treating CHB patients were mainly linked to the growth and stimulation of B-cell, T-cell differentiation, and the signaling pathway of the B-cell receptor. Furthermore, the frequencies of Tfh cells and its IL-21 level, and the IL-21R expressed by B-cell were all increased after BSF treatment. Additionally, in the co-culture system of CXCR5+ cells and HepG2.2.15 cells, HBsAg and HBeAg levels were decreased after BSF-containing serum treatment，as well as the up-regulating of Tfh cell frequencies and down-regulating of B-cell frequencies. CONCLUSIONS: BSF have the higher percentage of HBsAg decline and HBeAg seroclearance in Peg-IFN-α-treated patients compared with treatment-naive patients. The potential immunoregulatory mechanism may correlate with promoting the interaction between Tfh cells and B-cell through IL-21/IL-21R signaling pathway.

Pitch and loudness information encoded in auditory imagery as revealed by event-related potentials.

Two experiments using the ERP method and a task that involved comparing an imagined-S1 (the first stimulus) with a perceived-S2 (the second stimulus) were conducted to investigate whether imagined auditory representations encode pitch and loudness information. It was found that the amplitude of the imagery-related late positive complex (LPC) decreased with pitch but increased with loudness of the imagined sound, which was consistent with amplitude modulations of the auditory perception-related N1 component, thereby providing the first neural evidence that auditory imagery encodes perceptual attributes of auditory experiences.

A pilot study of functional magnetic resonance imaging of the brain during manual and electroacupuncture stimulation of acupuncture point (LI-4 Hegu) in normal subjects reveals differential brain activation between methods.

OBJECTIVES: To characterize the brain activation patterns evoked by manual and electroacupuncture on normal human subjects. DESIGN: We used functional magnetic resonance imaging (fMRI) to investigate the brain regions involved in electroacupuncture and manual acupuncture needle stimulation. A block design was adopted for the study. Each functional run consists of 5 minutes, starting with 1-minute baseline and two 1-minute stimulation, the interval between the two stimuli was 1 minute. Four functional runs were performed on each subject, two runs for electroacupuncture and two runs for manual acupuncture. The order of the two modalities was randomized among subjects. During the experiment, acupuncture needle manipulation was performed at Large Intestine 4 (LI4, Hegu) on the left hand. For each subject, before scanning started, the needle was inserted perpendicular to the skin surface to a depth of approximately 1.0 cm. Electroacupuncture stimulation was delivered using a continuous rectangular wave form (pulse width 30 ms) at a frequency of 3 Hz. For manual acupuncture, the needle was rotated manually clockwise and counterclockwise at a rate of about 180 times per minute (3 Hz). SUBJECTS: Eleven right-handed, normal, healthy volunteer adults, 6 male and 5 female, ages 21-64 participated in the experiment. RESULTS: Results showed that electroacupuncture mainly produced fMRI signal increases in precentral gyrus, postcentral gyrus/inferior parietal lobule, and putamen/insula; in contrast, manual needle manipulation produced prominent decreases of fMRI signals in posterior cingulate, superior temporal gyrus, putamen/insula. CONCLUSION: These results indicate that different brain networks are involved during manual and electroacupuncture stimulation. It suggests that different brain mechanisms may be recruited during manual and electroacupuncture.