Local Management for Diabetic Foot Ulcers: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This study evaluated the efficacy of various local management strategies for diabetic foot ulcers (DFUs). BACKGROUND: Several surgical and non-surgical local interventional approaches are available for the treatment of DFUs. The comparative effectiveness of different treatments is unknown, and it remains unclear which approach is the optimal choice for DFUs treatment due to limited direct comparisons. METHODS: We did a systematic review and meta-analysis to select the optimal approach to DFUs local management. We searched Medline, Embase, Web of Science, and ClinicalTrials.gov from inception to September 1, 2023, to identify relevant randomized controlled trials (RCTs). We analysed data by pairwise meta-analyses with a random-effects model. A network meta-analysis using the surface under the cumulative ranking curve (SUCRA) was performed to evaluate the comparative efficacy of different interventional approaches in the early (within 12 wk) and late stages (over 12 wk). RESULTS: 141 RCTs involving 14076 patients and exploring 14 interventional strategies were eligible for inclusion. Most studies (102/141) had at least one risk-of-bias dimension. Good consistency was observed during the analysis. Local pairwise comparisons demonstrated obvious differences in the early-stage healing rate and early- and late-stage healing times, while no significant difference in the late-stage healing rate or adverse events were noted. SUCRAs identified the standard of care (SOC) + decellularized dressing (DD), off-loading (OL), and autogenous graft (AG) as the three most effective interventions within 12 weeks for both healing rate (97%, mean rank: 1.4; 90%, mean rank: 2.3; 80.8%, mean rank: 3.5, respectively) and healing time (96.7%, mean rank: 1.4; 83.0%, mean rank: 3.0; 76.8%, mean rank: 3.8, respectively). After 12 weeks, local drug therapy (LDT) (89.5%, mean rank: 2.4) and OL (82.4%, mean rank: 3.3) ranked the highest for healing rate, and OL (100.0%, mean rank: 1.0) for healing time. With respect to adverse events, moderate and high risks were detected in the SOC + DD (53.7%, mean rank: 7.0) and OL (24.4%, mean rank: 10.8) groups, respectively. CONCLUSION: The findings suggest that OL provided considerable benefits for DFU healing in both the early and late stages, but the high risk of adverse events warrants caution. SOC+DD may be the preferred option in the early stages, with an acceptable risk of adverse events.

TBAI-Mediated Cyclization and Methylsulfonylation of Propargylic Amides with Dimethyl Sulfite.

A tetramethylammonium iodide (TBAI)-mediated cyclization and methylsulfonylation of propargylic amides enabled by dimethyl sulfite as a SO2 surrogate and methyl source have been developed. The transition metal-free and oxidant-free reaction provides a practical and efficient approach for the selective synthesis of methylsulfonyl oxazoles in moderate to excellent yields with good functional group compatibility.

Big data-driven intelligent governance of college students' physical health: System and strategy.

With the development of information technology, the application of a new generation of information technologies, such as big data, Internet Plus, and artificial intelligence, in the sports field is an emerging, novel trend. This paper examined the relevant research results and literature on physical education, computer science, pedagogy, management, and other disciplines, then used a self-made questionnaire to investigate the physical health status of Chinese college students. The big data were subsequently analyzed, which provided a scientific basis for the construction of an intelligent governance system for college students' physical health. Intelligent devices may be used to obtain big data resources, master the physical sports development and psychological status of college students, and push personalized sports prescriptions to solve the problems existing in college students' physical health. Research shows that there are four reasons for the continuous decline in Chinese college students' physical health levels. These are students' lack of positive exercise consciousness and healthy sports values (85.43%), a weak family sports concept and lack of physical exercise habits (62.76%), poor implementation of school sports policies (55.35%), and people's distorted sports value orientation (42.27%). Through the connecting effect of data, we can bring together the positive role of the government, school, society, family, and students so as to create an interlinked impact to promote students' physical health. The problems of insufficient platform utilization, lack of teaching resources, lagging research, and insufficient combination with big data in the intelligent governance of physical health of Chinese college students can be solved by building an intelligent governance system of physical health. Such a system would be composed of school infrastructure, data resources and technology processing, and intelligent service applications. Among these, school infrastructure refers to the material foundation and technical support. The material foundation includes perceptions, storage, computing, networks, and other equipment, and the technical support includes cloud computing, mobile Internet, the Internet of Things, artificial intelligence, and deep learning. Data resources refer to smart data, such as stadium data, physical health management data, and students' sports behavior data, which are mined from data resources such as students' physical development, physical health, and sports through big data technology and intelligent wearable devices. Intelligent managers provide efficient, intelligent, accurate, and personalized intelligent sports services for college students through data resource value mining, venue space-time optimization, health knowledge discovery, sports prescription pushes, etc. Finally, we put forward the development strategy for further deepening and improving the big data-driven intelligent governance system for college students' physical health. The intelligent governance system of physical health driven by big data and its development strategy can not only accurately guide and improve the physical health level of college students but also realize integrated teaching inside and outside physical education classes.

Effects of 16 Weeks of Cheerleading on Physical Self-Esteem and Mental Health of Female College Students.

Objective: This study aimed to analyze the influence of cheerleading on female college students' physical self-esteem and mental health. Materials and Methods: In total, 63 female college students from the University of Electronic Science and Technology of China were trained in cheerleading for 16 weeks. The scores of each sub-field of physical self-esteem and psychological symptoms were analyzed by using Physical Self-Perception Profile (PSPP) and Symptom Checklist 90 (SCL-90), respectively, at 0 and 16 weeks of the experiment. Results: After 16 weeks of cheerleading exercise, female college students had significant differences in physical attractiveness (T = 4.18), physical quality (T = 4.39), and physical self-worth (T = 3.35) before and after the experiment (P < 0.01). There were significant differences in physical condition (T = 3.87) and athletic ability (T = 2.88) before and after the experiment (P < 0.05). Somatization (T = 6.485), obsessive-compulsive symptoms (T = 11.716), interpersonal sensitivity (T = 10.077), depression (T = 8.403), anxiety (T = 10.767), hostility (T = 10.866), terror (T = 9.260), paranoia (T = 10.414), psychosis (T = 9.610), sleep and eating disorders (T = 9.323), total symptom index (T = 13.245), and mean score of positive symptoms (T = 12.237) were significantly different (P < 0.01). Conclusion: Cheerleading can significantly improve the level of female college students' physical self-esteem, especially the self-esteem level of physical attractiveness, physical quality, and physical self-worth. They also experienced significant improvement in their psychological disorders, especially somatization, depression, and sleep and eating disorders, which effectively improved their overall mental health.

Palladium-Catalyzed Methylsulfonylation of Alkyl Halides Using Dimethyl Sulfite as SO2 Surrogate and Methyl Source.

A novel and efficient method for the synthesis of methyl sulfone derivatives via palladium-catalyzed methylsulfonylation of alkyl halides with dimethyl sulfite has been described. A variety of aryl and alkyl iodides underwent the sulfonylation smoothly to furnish methyl sulfites in moderate to excellent yields.

Emodin alleviates hypertrophic scar formation by suppressing macrophage polarization and inhibiting the Notch and TGF-ß pathways in macrophages.

Hypertrophic scar (HS) formation is a common complication that develops after skin injury; however, there are few effective and specific therapeutic approaches for HS. Emodin has previously been reported to inhibit mechanical stress-induced HS inflammation. Here, we investigated the molecular mechanisms underlying the inhibitory effects of emodin on HS formation. First, we conducted in vitro assays that revealed that emodin inhibited M1 and M2 polarization in rat macrophages. We subsequently established a combined rat model of tail HS and dorsal subcutaneous polyvinyl alcohol (PVA) sponge-induced wounds. Rats were treated with emodin or vehicle (DMEM). Tail scar specimens were harvested at 14, 28, and 42 days post-incision and subjected to H&E staining and Masson's trichrome staining. Histopathological analyses confirmed that emodin attenuated HS formation and fibrosis. Macrophages were separated from wound cells collected from the PVA sponge at 3 and 7 days after implantation. Flow cytometry analysis demonstrated that emodin suppressed in vivo macrophage recruitment and polarization at the wound site. Finally, we explored the molecular mechanisms of emodin in modulating macrophage polarization by evaluating the expression levels of selected effectors of the Notch and TGF-ß pathways in macrophages isolated from PVA sponges. Western blot and qPCR assays showed that Notch1, Notch4, Hes1, TGF-ß, and Smad3 were downregulated in response to emodin treatment. Taken together, our findings suggested that emodin attenuated HS formation and fibrosis by suppressing macrophage polarization, which is associated with the inhibition of the Notch and TGF-ß pathways in macrophages.

Iodine-promoted ring-opening methylation of benzothiazoles with dimethyl sulfite.

A halogen-bond promoted ring-opening methylation of benzothiazoles has been developed using dimethyl sulphite as a methylating reagent in the presence of a base. This approach represents a simple and efficient synthesis of N-methyl-N-(o-methylthio)phenyl amides, and features direct construction of both N-Me and S-Me bonds in a one-pot reaction through the decomposition of easily prepared benzothiazoles.

An Application of a Negative-Pressure Wound Dressing for Partial- or Full-Thickness Burn Wounds.

Negative-pressure wound therapy is widely used in burn populations. Traditionally, negative-pressure devices use persistent vacuum suction, requiring a longer hospital stay. In this study, we applied a novel negative-pressure wound dressing for burn wounds, which eliminates the hospital stay. The medical records of 39 patients with partial-/full-thickness burns treated by negative-pressure wound dressing were retrospectively analyzed. The average burn area, burn degree, healing duration, cost, and incidents during treatment were determined and compared with previous data for conventional therapies. In conclusion, for patients diagnosed with partial-thickness or full-thickness burns and a burn area <34.6 ± 2.21 cm2, the negative-pressure wound dressing is a reliable option, especially for burnt children. Moreover, the negative-pressure wound dressing treatment was not only much cheaper than conventional therapies, but also eliminated hospital stay in patients with small-area deep burn wounds.

Emodin alleviates hypertrophic scar formation by suppressing macrophage polarization and inhibiting the Notch and TGF-β pathways in macrophages

Hypertrophic scar (HS) formation is a common complication that develops after skin injury; however, there are few effective and specific therapeutic approaches for HS. Emodin has previously been reported to inhibit mechanical stress-induced HS inflammation. Here, we investigated the molecular mechanisms underlying the inhibitory effects of emodin on HS formation. First, we conducted in vitro assays that revealed that emodin inhibited M1 and M2 polarization in rat macrophages. We subsequently established a combined rat model of tail HS and dorsal subcutaneous polyvinyl alcohol (PVA) sponge-induced wounds. Rats were treated with emodin or vehicle (DMEM). Tail scar specimens were harvested at 14, 28, and 42 days post-incision and subjected to H&E staining and Masson's trichrome staining. Histopathological analyses confirmed that emodin attenuated HS formation and fibrosis. Macrophages were separated from wound cells collected from the PVA sponge at 3 and 7 days after implantation. Flow cytometry analysis demonstrated that emodin suppressed in vivo macrophage recruitment and polarization at the wound site. Finally, we explored the molecular mechanisms of emodin in modulating macrophage polarization by evaluating the expression levels of selected effectors of the Notch and TGF-β pathways in macrophages isolated from PVA sponges. Western blot and qPCR assays showed that Notch1, Notch4, Hes1, TGF-β, and Smad3 were downregulated in response to emodin treatment. Taken together, our findings suggested that emodin attenuated HS formation and fibrosis by suppressing macrophage polarization, which is associated with the inhibition of the Notch and TGF-β pathways in macrophages.

Human-specific gene CHRFAM7A mediates M2 macrophage polarization via the Notch pathway to ameliorate hypertrophic scar formation.

Hypertrophic scars often cause great pain to patients. It is generally believed that anti-inflammatory scar therapies are the best strategies for treatment because excessive inflammation is observed in hypertrophic scar tissue. However, the results of such treatment are unsatisfactory. In recent studies, immune stimulatory therapies have been suggested to be a preferable method for ameliorating hypertrophic scars. In this study, the expression of the human-specific gene CHRFAM7A, which has been reported to be a promoter of inflammation, was found to be lower in human hypertrophic scars than in normotrophic scars. The CHRFAM7A gene was overexpressed in a hypertrophic scar mouse model using a lentivirus system. Scar fibrosis decreased in the CHRFAM7A transfection group compared to the control group, and the proportion of M2 macrophages decreased at 4 and 8 weeks after establishing the model. We also found that CHRFAM7A increased the activation of the Notch pathway, which eventually attenuated M2 polarization. In the CHRFAM7A-transfected hypertrophic scar mouse group, the number of M1 macrophages increased dramatically in the initial period. Moreover, the expression of the inflammatory gene TNFα was also increased in transfected mice. Our results demonstrate that CHRFAM7A can effectively ameliorate hypertrophic scar formation via regulation of macrophage phenotypic transition. CHRFAM7A might be a therapeutic target for hypertrophic scars.

miR-499 released during myocardial infarction causes endothelial injury by targeting α7-nAchR.

The surged systemic vascular inflammation after acute myocardial infarction (AMI) aggravates the atherosclerotic endothelial injury. To explore roles of miR-499 released from cardiomyocytes during AMI in endothelial injury. Using qPCR and ELISA, we discovered that patients with AMI had significantly increased plasma miR-499, which was directly correlated with serum thrombomodulin, a marker for endothelial injury. Plasma of AMI patients, when incubated with human umbilical vein endothelial cells (HUVECs), significantly increased the expression of endothelial injury markers, which could be abrogated by antagomiR-499. In vitro, neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation (HX/R) released miR-499 that could be internalized into rat pulmonary microvascular endothelial cells (RPMECs), worsening the high glucose-induced injury. In silico analysis demonstrated that CHRNA7 encoding α7-nAchR is a target of miR-499, which was validated in cell lines expressing endogenous α7-nAchR. In high glucose-induced RPMECs injury model, miR-499 aggravated, whereas forced CHRNA7 expression ameliorated the injury. Moreover, the perfusate from Langendorff perfused rat heart subjected to HX/R contained higher level of miR-499 that significantly impaired the Bradykinin-mediated endothelium-dependent relaxation in both conduit and resistance arteries, which could be partially abrogated by antagomiR-499. Finally, the correlation between plasma miR-499 and endothelial injury was further confirmed in another cohort of AMI patients. We conclude that miR-499 released from injured cardiomyocytes contributes to the endothelial injury by targeting α7-nAchR. This study implies that miR-499 may serve as a potential target for the treatment of the surged vascular inflammation post-AMI.

Esophageal cancer related gene-4 inhibits the migration and proliferation of oral squamous cell carcinoma through BC200 lncRNA/MMP-9 and -13 signaling pathway.

Esophageal cancer related gene-4 (ECRG4) inhibits the malignant phenotype of oral squamous cell carcinoma. However, the molecular mechanisms remain to be explored. Using the tongue carcinoma cell line, TCA8113 as a cell model, we showed that forced expression of ECRG4 down-regulated the expression of the BC200 long non-coding RNA (lncRNA) and matrix metalloproteinases (MMP-9 and MMP-13). Restoration of BC200 lncRNA rescued ECRG4-mediated down-regulation of MMP-9 and -13. Furthermore, over-expression of Ecrg4 inhibited cell proliferation and migration, which was abolished by forced expression of BC200 lncRNA in TCA8113 cells. Our results indicate that ECRG4 inhibits the malignant phenotype of TCA8113 cells most likely through suppression of BC200 lncRNA/MMPs signaling pathway, rationalizing that BC200 lncRNA may be a potential target for oral squamous cell carcinoma (OSCC) therapy.

CTHRC1 promotes wound repair by increasing M2 macrophages via regulating the TGF-ß and notch pathways.

The healing of acute wounds is vital to humans and is a well-orchestrated process that involves systemic and local factors. However, there is a lack of effective and safe clinical therapies. The collagen triple helix repeat containing 1 (CTHRC1) protein is a type of exocrine protein that has been recently reported to contribute to tissue repair. Our aim is to validate the promoting effects of CTHRC1 on the healing of acute wounds and to elucidate the underlying molecular mechanism. Therefore, we first established acute wound healing mouse models and confirmed that CTHRC1 accelerates the healing process of acute wounds. Then, we characterized wound macrophages using a polyvinylalcohol (PVA) sponge model and used Western blotting to investigate the molecular mechanism. We found that CTHRC1 increased the M2 macrophage population and the TGF-ß expression level as a result of the activation of the TGF-ß and Notch pathways, which eventually contributed to the promotion of wound healing. Inhibition of the Notch pathway showed attenuated M2 macrophage recruitment, and it decreased the TGF-ß expression level. These results substantiate our hypothesis that CTHRC1 promotes wound healing by recruiting M2 macrophages and regulating the TGF-ß and Notch pathways.

Mice engrafted with human hematopoietic stem cells support a human myeloid cell inflammatory response in vivo.

Mice engrafted with human CD34+ hematopoietic stem and progenitor cells (CD34+ -HSPCs) have been used to study human infection, diabetes, sepsis, and burn, suggesting that they could be highly amenable to characterizing the human inflammatory response to injury. To this end, human leukocytes infiltrating subcutaneous implants of polyvinyl alcohol (PVA) sponges were analyzed in immunodeficient NSG mice reconstituted with CD34+ -HSPCs. It was reported that human CD45+ (hCD45+ ) leukocytes were present in PVA sponges 3 and 7 days postimplantation and could be localized within the sponges by immunohistochemistry. The different CD45+ subtypes were characterized by flow cytometry and the profile of human cytokines they secreted into PVA wound fluid was assessed using a human-specific multiplex bead analyses of human IL-12p70, TNFα, IL-10, IL-6, IL1ß, and IL-8. This enabled tracking the functional contributions of HLA-DR+ , CD33+ , CD19+ , CD62L+ , CD11b+ , or CX3CR1+ hCD45+ infiltrating inflammatory leukocytes. PCR of cDNA prepared from these cells enabled the assessment and differentiation of human, mouse, and uniquely human genes. These findings support the hypothesis that mice engrafted with CD34+ -HSPCs can be deployed as precision avatars to study the human inflammatory response to injury.

Copper-mediated stereospecific C-H oxidative sulfenylation of terminal alkenes with disulfides.

A copper and iodine-mediated C-H oxidative sulfenylation of olefins with diaryl disulfides has been developed for the stereospecific synthesis of vinyl thioether. With the combination of Cu(OTf)2 and I2, a variety of terminal alkenes underwent oxidative coupling reaction with various diaryl disulfides successfully to afford the corresponding E-vinyl sulfides in moderate to good yields.

Palladium-catalyzed oxidative carbamoylation of isoquinoline N-oxides with formylamides by means of dual C-H oxidative coupling.

A new palladium-catalyzed oxidative carbamoylation reaction of isoquinoline N-oxides with formylamides for the synthesis of isoquinoline-1-carboxamides is established. The method represents the first example of the carbamoylation of isoquinoline N-oxides with formylamides to furnish arylamides using the dual C-H oxidation strategy.

Suppressive effects of induced pluripotent stem cell-conditioned medium on in vitro hypertrophic scarring fibroblast activation.

Hypertrophic scarring (HS) is a type of fibrosis that occurs in the skin, and is characterized by fibroblast activation and excessive collagen production. However, at present, therapeutic strategies for this condition are ineffective. Previous studies have identified that the mutual regulation of chronic inflammation, mechanical force and fibroblast activation leads to the formation of HS. Induced pluripotent stem cells (iPSCs) are novel bioengineered embryonic­like stem cells, initially created from mouse adult fibroblasts. The current study demonstrated that iPSC­conditioned medium (iPSC­CM) may significantly suppress hypertrophic scar fibroblast activation. It was observed that in the presence of iPSC­CM, the level of collagen I was markedly reduced and α­smooth muscle actin, a marker for myofibroblasts (activated fibroblasts that mediate mechanical force­induced HS formation), exhibited a significantly lower level of expression in human dermal fibroblasts (HDFs) activated with transforming growth factor­ß1. Additionally, iPSC­CM attenuated the local inflammatory cell response by blocking the adhesion of human acute monocytic leukemia cell monocytes and fibroblasts in vitro. In addition, the contractile ability of HDFs may be reduced by iPSC­CM. These observations suggest that iPSC­CM may protect against processes leading to hypertrophic scarring by attenuating fibroblast activation, blocking inflammatory cell recruitment and adhesion and reducing the contractile ability of fibroblasts.

Reprogramming human adipose tissue stem cells using epidermal keratinocyte extracts.

Human adipose tissue stem cells (ATSCs) can differentiate into various types of cell in response to lineage-specific induction factors. Reprogramming cells using nuclear and cytoplasmic extracts derived from another type of somatic cell is an effective method of producing specific types of differentiated cell. In the present study, the ability of reprogrammed ATSCs to acquire epidermal keratinocyte properties following transient exposure to epidermal keratinocyte extracts was demonstrated. Reversibly permeabilized ATSCs were incubated for 1 h in nuclear and cytoplasmic extracts from epidermal keratinocytes, resealed with CaCl2 and cultured. ATSC reprogramming is demonstrated by nuclear uptake of epidermal keratinocyte extracts. After one week of exposure to extracts, ATSCs underwent changes in cell morphology, cell-specific genes were activated, and epidermal keratinocyte markers including K19 and K1/K10 (markers of stem cells and terminally differentiated keratinocytes, respectively) were expressed. This study indicates that the reprogramming of ATSCs using nuclear and cytoplasmic extracts from epidermal keratinocytes is a viable option for the production of specific types of cell.

A novel Pd-catalyzed N-dealkylative carbonylation of tertiary amines for the preparation of amides.

A novel and convenient protocol for the formation of amides via palladium-catalyzed N-dealkylative carbonylation of alkyl tertiary amines has been developed. In the presence of PdCl2(PhCN)2, CuO, PhCN and CO, a range of substituents on both aryl iodides and alkyl tertiary amines were compatible with the reaction to afford a series of N,N-disubstituted amides in moderate to excellent yields.

Oxidative tandem nitrosation/cyclization of N-aryl enamines with nitromethane toward 3-(trifluoromethyl)quinoxalines.

A novel one-pot strategy for the synthesis of 3-trifluoromethylquinoxalines from N-aryl enamines and nitromethane was developed. The tandem reaction is achieved through nitrosation of alkenes, tautomerization and cyclization, which can be applicable to a wide range of enamines with excellent functional group tolerance and afford quinoxalines in moderate to good yields.