Objective. To investigate the Th17/Treg immune balance in the ulcerative colitis (UC) patients in a Chinese Han population. Methods. Ninety UC patients and 30 healthy subjects were enrolled. The serum IL-17 and TGF-β1 levels of these participants were measured with ELISA; the percentage of Th17 and Treg cells in peripheral blood was determined with flow cytometry. Results. In UC patients, the levels of IL-17 and Th17 were significantly higher compared with healthy subjects; the percentage of Th17 and IL-17 level in moderate and severe subgroup was significantly higher than in mild subgroup; a positive correlation existed between these two indexes and clinical activity index and endoscopic evaluation. TGF-β1 level and Treg cells in UC patients were lower than healthy subjects. TGF-β1 level in moderate and severe subgroup was lower than in mild subgroup. There was a negative linear correlation between Treg cells and clinical activity index, endoscopic evaluation. A positive correlation was detected between Treg cells and TGF-β1 level. Conclusions. Th17/Treg immune imbalance might play a crucial role in the development of UC. To induce the production of Treg cells and TGF-β1, inhibit the level of Th17 and IL-17, and thus recover the Th17/Treg immune balance might imply new therapeutic targets in UC management.

Guizhi-Shaoyao-Zhimu decoction (GSZ), a traditional Chinese medicine (TCM) herbal formula, has been shown effective in the treatment of diabetic peripheral neuropathy (DPN). In this study, network analysis was performed to decipher the molecular mechanisms of GSZ in the treatment of DPN. The chemical components of the 3 herbs forming GSZ, ie, Ramulus Cinnamomi (Guizhi), Paeonia lactiflora (Shaoyao) and Rhizoma Anemarrhenae (Zhimu), were searched in Chinese medicine dictionaries, and their target proteins were identified in PubChem. DPN genes were searched in PubMed gene databases. Ingenuity Pathway Analysis (IPA) was used to build the GSZ pharmacological network and DPN molecular network. The canonical pathways between the two networks were compared to decipher the molecular mechanisms of GSZ in the treatment of DPN. Sixty-one protein targets for Guizhi, 31 targets for Shaoyao, 47 targets for Zhimu, as well as 23 genes related to DPN were identified and uploaded to IPA. The primary functions of the DPN molecular network were inflammatory response, metabolic disease, cellular assembly and organization. As far as the pharmacological network functions were concerned, Guizhi target proteins were involved in neurological disease, inflammatory disease, cellular growth and proliferation, cell signaling, molecular transport, and nucleic acid metabolism, Shaoyao target proteins were related to neurological disease, inflammatory disease, and Zhimu target proteins focused on cell death and survival, cellular movement, immune cell trafficking, DNA replication, recombination and repair, and cell cycle. In the three-herb combination GSZ, several new network functions were revealed, including the inflammatory response, gene expression, connective tissue development and function, endocrine system disorders, and metabolic disease. The canonical pathway comparison showed that Shaoyao focused on IL-12 signaling and production in macrophages, and Zhimu focused on TNFR2 signaling, death receptor signaling, ILK signaling, IL-17A in gastric cells, IL-6 signaling, IL-8 signaling, the role of JAK1, JAK2, and TYK2 in interferon signaling, IL-9 signaling, HMGB1 signaling, NO production and ROS production in macrophages, whereas GSZ focused aryl hydrocarbon receptor signaling and apoptosis signaling in addition to those pathways induced by Guizhi, Shaoyao and Zhimu. Although each single herb can affect some DPN-related functions and pathways, GSZ exerts more effects on DPN-related functions and pathways. The effects of GSZ on aryl hydrocarbon receptor signaling and apoptosis signaling pathways may be the key components of its total molecular mechanisms.

(1) Many studies have attempted to utilize metabolomic approaches to explore potential biomarkers for the early detection of osteoarthritis (OA), but consistent and high-level evidence is still lacking. In this study, we performed a systematic review and meta-analysis of differential small molecule metabolites between OA patients and healthy individuals to screen promising candidates from a large number of samples with the aim of informing future prospective studies. (2) Methods: We searched the EMBASE, the Cochrane Library, PubMed, Web of Science, Wan Fang Data, VIP Date, and CNKI up to 11 August 2022, and selected relevant records based on inclusion criteria. The risk of bias was assessed using the Newcastle–Ottawa quality assessment scale. We performed qualitative synthesis by counting the frequencies of changing directions and conducted meta-analyses using the random effects model and the fixed-effects model to calculate the mean difference and 95% confidence interval. (3) Results: A total of 3798 records were identified and 13 studies with 495 participants were included. In the 13 studies, 132 kinds of small molecule differential metabolites were extracted, 58 increased, 57 decreased and 17 had direction conflicts. Among them, 37 metabolites appeared more than twice. The results of meta-analyses among four studies showed that three metabolites increased, and eight metabolites decreased compared to healthy controls (HC). (4) Conclusions: The main differential metabolites between OA and healthy subjects were amino acids (AAs) and their derivatives, including tryptophan, lysine, leucine, proline, phenylalanine, glutamine, dimethylglycine, citrulline, asparagine, acetylcarnitine and creatinine (muscle metabolic products), which could be potential biomarkers for predicting OA.

Distal arthrogryposes (DAs) are a group of disorders that mainly involve the distal parts of the limbs and at least ten different DAs have been described to date. DAs are mostly described as autosomal dominant disorders with variable expressivity and incomplete penetrance, but recently autosomal recessive pattern was reported in distal arthrogryposis type 5D. Mutations in the contractile genes are found in about 50% of all DA patients. Of these genes, mutations in the gene encoding myosin binding protein C slow MYBPC1 were recently identified in two families with distal arthrogryposis type 1B. Here, we described two large Chinese families with autosomal dominant distal arthrogryposis type 2(DA2) with incomplete penetrance and variable expressivity. Some unique overextension contractures of the lower limbs and some distinctive facial features were present in our DA2 pedigrees. We performed follow-up DNA sequencing after linkage mapping and first identified two novel MYBPC1 mutations (c.1075G>A [p.E359K] and c.956C>T [p.P319L]) responsible for these Chinese DA2 families of which one introduced by germline mosacism. Each mutation was found to cosegregate with the DA2 phenotype in each family but not in population controls. Both substitutions occur within C2 immunoglobulin domain, which together with C1 and the M motif constitute the binding site for the S2 subfragment of myosin. Our results expand the phenotypic spectrum of MYBPC1-related arthrogryposis multiplex congenita (AMC). We also proposed the possible molecular mechanisms that may underlie the pathogenesis of DA2 myopathy associated with these two substitutions in MYBPC1.

Objective. To investigate the Th17/Treg immune balance in the ulcerative colitis (UC) patients with two Chinese syndrome: dampness-heat in large intestine (DHLI) and spleen and kidney Yang deficiency (SKYD).Methods. Ninety UC patients (45 were diagnosed with DHLI and 45 with SKYD syndrome) and 23 healthy people were recruited. The serumIL-17 and TGF-β1 levels of these participants were measured with ELISA; the expression of IL-17 and TGF-β1 in colonic mucosa tissue was determined with immunohistochemistry and the percentage of Th17 and Treg in peripheral blood with flow cytometry.Results. The levels of IL-17 and Th17 were significantly higher in both DHLI and SKYD groups than in healthy control group and higher in DHLI than in SKYD group (P<0.05). The levels of TGF-β1 and Treg were significantly lower in the two UC patients groups than in healthy control group; and lower in SKYD group than in DHLI group (P<0.05).Conclusions. UC with DHLI syndrome could be characterized by the elevation of Th17 and IL-17 levels, which indicated an accentuation of inflammatory reaction; UC with SKYD syndrome could be characterized by the reduction of serum Treg and TGF-β1 levels, which represented a depression of immune tolerance.