This study aimed to evaluate and compare the effects of extracorporeal shock wave therapy (ESWT) and conventional wound therapy (CWT) for acute and chronic soft tissue wounds. All English‐language articles on ESWT for acute and chronic soft tissue wounds indexed in PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, Physiotherapy Evidence Database, and HealthSTAR published prior to June 2017 were included, as well as corresponding articles cited in reference lists of related review articles. The methodological quality of the selected studies was assessed with the Cochrane Collaboration's “risk of bias” tool. Study design, subject demographics, wound aetiology, treatment protocols, assessment indexes, and follow‐up duration were extracted. The fixed or random‐effects model was used to calculate the pooled effect sizes according to studies’ heterogeneity. Ten randomised controlled trials (RCTs) involving 473 patients were included in this systematic review and meta‐analysis. The meta‐analysis showed that ESWT statistically significantly increased the healing rate of acute and chronic soft tissue wounds 2.73‐fold (odds ratio, OR = 3.73, 95% confidence interval, CI: 2.30‐6.04, P < .001) and improved wound‐healing area percentage by 30.45% (Standardized Mean Difference (SMD) = 30.45; 95% CI: 23.79‐37.12; P < .001). ESWT reduced wound‐healing time by 3 days (SMD = −2.86, 95% CI:‐3.78 to −1.95, P < .001) for acute soft tissue wounds and 19 days (SMD = −19.11, 95% CI: −23.74 to −14.47, P < .001) for chronic soft tissue wounds and the risk of wound infection by 53% (OR = 0.47, 95% CI: 0.24‐0.92, P = .03) when compared with CWT alone. Serious adverse effects were not reported. ESWT showed better therapeutic effects on acute and chronic soft tissue wounds compared with CWT alone. However, higher‐quality and well‐controlled RCTs are needed to further assess the role of ESWT for acute and chronic soft tissue wounds.

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a serious debilitating disease caused by anti-resorption and anti-angiogenesis drugs, significantly affecting patients' quality of life. Recent studies suggested that primary gingival wound healing may effectively prevent the development of MRONJ. This study aimed to evaluate the effects of low-level light therapy (LLLT) on promoting gingival wound healing in extraction sockets of MRONJ-like mice and preventing the occurrence of MRONJ. Furthermore, we explored underlying mechanisms. Methods: Mice were randomly divided into the Ctrl, Zol, and Zol + LLLT groups. Administration of zoledronate and tooth extraction of bilateral maxillary second molars were used to build the MRONJ model, and LLLT was locally administered into the tooth sockets to examine the effect of LLLT. Next, to explore the function of IL-1RA, we performed LLLT with interleukin-1 receptor antagonist (IL-1RA) neutralizing antibody (named Zol + LLLT + IL-1RA NAb group) or negative control antibodies for tooth extraction in subsequent rescue animal experiments. Stereoscope observations, micro-computed tomography, and histological examination were conducted to evaluate gingival wound healing and bone regeneration in tooth sockets. The effects of LLLT on the migration capacities of zoledronate-treated epithelial cells were assessed in vitro. Results: LLLT promoted primary gingival wound healing without exposed necrotic bone. Micro-computed tomography results showed higher bone volume and mineral density of the tooth sockets after LLLT. Histology analysis showed complete gingival coverage, obvious bone regeneration, and reduced soft tissue inflammation, with down-regulated pro-inflammation cytokines, like interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α), and up-regulated IL-1RA expression in the gingival tissue in the LLLT group. The rescue assay further showed that the effects of LLLT promoting gingival wound healing and preventing MRONJ might be partially abolished by IL-1RA neutralizing antibodies. In vitro studies demonstrated that LLLT accelerated zoledronate-treated epithelial cell migration. Conclusions: LLLT might promote primary gingival wound healing and contribute to subsequent bone regeneration of the tooth extractions in MRONJ-like lesions via IL-1RA-mediated pro-inflammation signaling suppression.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe disease with unclear pathogenesis. Adipose tissue-derived mesenchymal stromal cells (MSC(AT)s) serve as a special source for cell therapy. Herein, we explored whether exosomes (Exo) derived from MSC(AT)s promote primary gingival wound healing and prevent MRONJ. An MRONJ mice model was constructed using zoledronate (Zol) administration and tooth extraction. Exosomes were collected from the conditioned medium (CM) of MSC(AT)s (MSC(AT)s-Exo) and locally administered into the tooth sockets. Interleukin-1 receptor antagonist (IL-1RA)-siRNA was used to knock down the expression of IL-1RA in MSC(AT)s-Exo. Clinical observations, micro-computed tomography (microCT), and histological analysis were used to evaluate the therapeutic effects in vivo. In addition, the effect of exosomes on the biological behavior of human gingival fibroblasts (HGFs) was evaluated in vitro. MSC(AT)s-Exo accelerated primary gingival wound healing and bone regeneration in tooth sockets and prevented MRONJ. Moreover, MSC(AT)s-Exo increased IL-1RA expression and decreased interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α) expression in the gingival tissue. The sequent rescue assay showed that the effects of preventing MRONJ in vivo and improving the migration and collagen synthesis abilities of zoledronate-affected HGFs in vitro were partially impaired in the IL-1RA-deficient exosome group. Our results indicated that MSC(AT)s-Exo might prevent the onset of MRONJ via an IL-1RA-mediated anti-inflammatory effect in the gingiva wound and improve the migration and collagen synthesis abilities of HGFs.

Background: Colorectal cancer (CRC) is a common human malignancy worldwide. The prognosis of patients is largely frustrated by delayed diagnosis or misdiagnosis. DNA methylation alterations have been previously proved to be involved in CRC carcinogenesis.Methods: In this study, we proposed to identify CRC-related diagnostic biomarkers by analyzing DNA methylation and gene expression profiles. TCGA-COAD datasets downloaded from the Cancer Genome Atlas (TCGA) were used as the training set to screen differential expression genes (DEGs) and methylation CpG sites (dmCpGs) in CRC samples. A logistic regression model was constructed based on hyper-methylated CpG sites which were located in downregulated genes for CRC diagnosis. Another two independent datasets from the Gene Expression Omnibus (GEO) were used as a testing set to evaluate the performance of the model in CRC diagnosis.Results: We found that CpG island methylator phenotype (CIMP) was a potential signature of poor prognosis by dividing CRC samples into CIMP and noCIMP groups based on a set of CpG sites with methylation standard deviation (sd) > 0.2 among CRC samples and low methylation levels (mean β < 0.05) in adjacent samples. Hyper-methylated CpGs tended to be more closed to CpG island (CGI) and transcription start site (TSS) relative to hypo-methylated CpGs (p-value < 0.05, Fisher exact test). A logistic regression model was finally constructed based on two hyper-methylated CpGs, which had an area under receiver operating characteristic curve of 0.98 in the training set, and 0.85 and 0.95 in the two independent testing sets.Conclusions: In conclusion, our study identified promising DNA methylation biomarkers for CRC diagnosis.