ABSTRACT
Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.
Subject(s)
Humans , Fecal Microbiota Transplantation/methods , Treatment Outcome , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , SteroidsABSTRACT
Objective: To investigate the dynamic regulation of self-assembled aggregations (SAA) in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying. Methods: The effects of SAA on berberine (Ber) absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer's patches (PPs). The expression levels of ZO-1, Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction (TJ) between intestinal epithelium cells. The expression levels of T-box-containing protein expressed in T cells, signal transducers and activators of tranion-6, retinoic acid receptor-related orphan receptor γt and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) in PPs were evaluated by immunohistochemistry, to reflect the differentiation of T lymphocyte in PPs to helper T (Th) cell 1, Th2, Th17 and regulatory T (Treg) cell. To confirm the correlation between SAA in Coptidis Rhizoma decoction, PPs-associated immunity and intestinal epithelium permeability, SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression. Results: SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment, with the participation of PPs. The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs. The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation, inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression. Conclusion: SAA can improve the Ber absorption in small intestine, through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression. These findings might enlighten the research of traditional Chinese medicine decoction.
ABSTRACT
<p><b>OBJECTIVE</b>To analyze the prevalence and risk factors of multiple musculoskeletal disorders (MSDs) in auto workers and the associations between MSDs at different sites.</p><p><b>METHODS</b>A cross-sectional survey was conducted in 3998 workers, who were selected from a Chinese auto corporation by cluster random sampling, using the revised Nordic MSDs standard questionnaire; 3800 completed questionnaires were returned. Multinomial logistic regression analysis was performed to assess the risk factors for multiple MSDs. The logbinomial model was used to calculate the prevalence ratios (PRs) of MSDs at different sites and evaluate the associations between MSDs at different sites.</p><p><b>RESULTS</b>Of the 3800 subjects, 2452 (64.5%) had MSDs at two or more sites, and 469 (12.3%) had MSDs at one site. The PRs varied from 1.5 to 6.7, with significant differences among different sites (P < 0.01). Relatively close associations were found between the MSDs at neck and shoulders, back and shoulders/waist, elbows and wrists/hands, waist and neck, wrists/hands and waist, hip and waist, knees and waist, and ankles/feet and elbows. The multinomial logistic regression analysis indicated that the highest risk factor for MSDs was poor posture, including often working in an uncomfortable posture, neck bending forward, and neck twisting (ORs = 3.39, 1.93, and 1.38), followed by labor organization, in which break between tasks could decrease the risk of MSDs at three or more sites to 31%, staff shortage, which could increase the risk of MSDs by 75%, and pushing and pulling heavy objects (> 20 kg) (OR = 1.76).</p><p><b>CONCLUSION</b>Most auto workers with MSDs have multiple sites affected, and there are high associations between the MSDs at different sites. The major risk factors for multiple MSDs in auto workers include poor posture, labor organization, and heavy physical labor.</p>