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Tendon injury is a common disorder of the musculoskeletal system, with a higher possibility of occurrence in elderly individuals and athletes. After a tendon injury, the tendon suffers from inadequate and slow healing, resulting in the formation of fibrotic scar tissue, ending up with inferior functional properties. Therapeutic strategies involving the application of growth factors have been advocated to promote tendon healing. Growth and differentiation-5 (GDF-5) represents one such factor that has shown promising effect on tendon healing in animal models and in vitro cultures. Although promising, these studies are limited as the molecular mechanisms by which GDF-5 exerts its effect remain incompletely understood. Starting from broadly introducing essential elements of current understanding about GDF-5, the present review aims to define the effect of GDF-5 and its possible mechanisms of action in tendon healing. Nevertheless, we still need more in vivo studies to explore dosage, application time and delivery strategy of GDF-5, so as to pave the way for future clinical translation.

Objective: This study aimed to explore the structural and functional characteristics of the fecal-associated microbiome (FAM) between the phlegm-dampness constitution (PDC) and balanced constitution (BC), and to screen the related specific operational taxonomic unit (OTU) biomarkers. Methods: This was a cross-sectional study. After strictly identifying the constitution of subjects, their clinical index was recorded and counted. Fecal samples were collected for 16S rDNA sequencing. Alpha diversity, beta diversity, and the relative abundance of dominant bacterial taxa were used to describe the FAM structure, and the Wilcoxon rank-sum test, MetagenomeSeq, and linear discriminant analysis effect size (LEfSe) were used to screen specific bacterial taxa. Specific OTUs were screened to construct receiver operating characteristic (ROC) curves. Results: Thirty-two subjects were enrolled, including 22 subjects with BC and 10 subjects with PDC. There were significant differences in cold preference, levels of aspartate transaminase, β2-microglobulin, and creatine kinase MB, and alpha diversity indices (Shannon and Shannoneven) between the two groups. In principal coordinate analysis by abund-jaccard distance measure and partial least squares discriminant analysis, bacterial communities clustered separately between the two groups. Furthermore, based on MetagenomeSeq, LEfSe, and the Wilcoxon rank-sum test, a total of 43, 18, and 130 OTUs were differentially distributed between BC group and PDC group, respectively, and OTU200, OTU133, and OTU353 were screened when P≤ .01. The area under the ROC curve constructed from the 3 selected OTUs was 0.93. Conclusion: The FAM structure and related functional characteristics of the PDC group differed from those of the BC group. In particular, OTU200, OTU133, and OTU353 can be used as unique markers of PDC to assist clinical diagnosis.

Objective: To clarify the structural and functional characteristics of the gut microbiota in individuals with qi stagnation constitution (QSC) and identify the potential biomarkers related to QSC. Methods: This cross-sectional study involved individuals with QSC and balanced constitution (BC) confirmed by TCM clinicians. The clinical features were recorded, and fecal samples were collected for 16S rDNA sequencing. The structure of the fecal-associated microbiome (FAM) was described by the alpha-diversity indexes, beta-distances, and relative abundances of dominant taxa. The differences in FAM distribution were analyzed by the Wilcoxon rank-sum test, MetagenomeSeq, and LEfSe analysis. The 16S rDNA gene sequences were assigned to the KEGG dataset to predict the functional information of bacterial metabolic pathways by using PICRUSt. Differences in functional pathways between groups were assessed with the Wilcoxon rank-sum test. The ROC curve based on specific operational taxonomic units (OTUs) was constructed, and the AUC was calculated. Results: Twenty-two individuals with BC and 8 with QSC were recruited. Significant differences between the two groups were found in body mass index, health status, and low-density lipoprotein, etc. There was no significant difference in the alpha-diversity index. PCoA showed no evident clustering of bacterial communities according to constitutions. Bacteroidaceae, Lachnospiraceae, Ruminococcaceae, and Prevotellaceae were the four common bacteria with high abundances. Notably, MetagenomeSeq, LEfSe analysis, and the Wilcoxon rank-sum test identified significantly different distributions of 66, 42, and 36 OTUs, respectively. Predictive function analysis showed that 13 metabolic pathways were significantly differentially distributed, including those related to fatty acid synthesis. Five specific OTUs were selected as potential biomarkers of a QSC, and the AUC was 0.94. Conclusion: Individuals with QSC have unique FAM structure and related functional characteristics. Five specific OTUs were identified to serve as potentially effective biomarkers related to QSC.

Objective: To explore the structural and functional characteristics of the fecal-associated microbiome (FAM) in a traditional Chinese medicine (TCM) qi-deficiency constitution (QDC) by comparing with balanced constitution (BC) and screen the related biomarkers. Methods: In this cross-sectional study, the TCM constitutions of subjects were determined based on published the Classification and Determination of constitution in TCM and further confirmed by a TCM clinician. Clinical characteristics were recorded, and fecal samples were collected for 16S rDNA sequencing using the Illumina Miseq platform. The FAM structure was described using alpha-diversity indexes, beta-diversity indexes, and the relative abundances of the dominant taxa. Differences in the FAM distribution and function were analyzed with a Wilcoxon rank-sum test, MetagenomeSeq, and LEfSe analysis, after which a receiver operating characteristic curve based on the specific operational taxonomic units (OTUs) was constructed to calculate the area under the curve. Results: Our study population was composed of 22 BCs and 9 QDCs. There were no significant differences between the two groups in the distribution of clinical characteristics or alpha-diversity indexes, except for the sweets preference and blood glucose level. In principal coordinate analysis and partial least squares discriminant analysis, the bacterial communities in the BC group samples and QDC group samples clustered separately. Notably, there were 214 OTUs significantly distributed between groups in the MetagenomeSeq analysis, 200 OTUs identified by the Wilcoxon rank-sum test, and 6 OTUs found by the LEfSe analysis. Predicted function analysis revealed that six metabolic pathways were distinctly distributed between the two groups. The area under the curve for the receiver operating characteristic curve based on the four specific OTUs was 0.88. Conclusion: Unique FAM structural and related functional characteristics are displayed in individuals with a QDC, and four specific OTUs could be used as QDC biomarkers to assist in clinical diagnosis.