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The present study was designed to fabricate a new chitosan-collagen sponge (CCS) for potential wound dressing applications. CCS was fabricated by a 3.0% chitosan mixture with a 1.0% type I collagen (7:3(w/w)) through freeze-drying. Then the dressing was prepared to evaluate its properties through a series of tests. The new-made dressing demonstrated its safety toward NIH3T3 cells. Furthermore, the CCS showed the significant surround inhibition zone than empty controls inoculated by E. coli and S. aureus. Moreover, the moisture rates of CCS were increased more rapidly than the collagen and blank sponge groups. The results revealed that the CCS had the characteristics of nontoxicity, biocompatibility, good antibacterial activity, and water retention. We used a full-thickness excisional wound healing model to evaluate the in vivo efficacy of the new dressing. The results showed remarkable healing at 14th day post-operation compared with injuries treated with collagen only as a negative control in addition to chitosan only. Our results suggest that the chitosan-collagen wound dressing were identified as a new promising candidate for further wound application.

Wound dressings are always needed after skin injury; however, most of the dressings still leave room for improvement. Here, we would like to develop an effective dressing with the ability to improve wound healing. A chitosan-Vaseline gauze (CVG) dressing was developed by coating the chitosan mixture and Vaseline on sterile gauze with subsequent drying. Infrared spectroscopy and electron microscopy were used to investigate the miscibility and structure of the dressing. The cytotoxicity and antibacterial nature were evaluated in vitro. The studies of water retention rate, wound healing, and tissue compatibility were carried out over a period of 14 days on full-thickness skin wounds of male Sprague-Dawley rats. It was observed that the CVG dressing demonstrated functional structure by miscibility, non-cytotoxicity, and good antibacterial effects against both Gram-positive and Gram-negative bacteria. The water retention rate incresased up to 25% after applying CVG for 3 hours. Besides, CVG treatment increased angiogenesis and improved microvascular density in wounds. The wounds treated with CVG showed size deduction with new collagen aggregations similar to those in the normal dermis. All the aforementioned results suggest that CVG dressing could be a promising candidate for wound treatment.

The renin-angiotensin system (RAS) plays an important role in scar formation. We have previously shown that oral administration of ramipril and losartan could inhibit scarring. For easier application, here we developed a series of topical ramipril and losartan creams in different concentrations and formulations to explore the effect on scar formation in a C57BL/6 mouse scar model. The harvested scar tissues were analyzed with H&E staining, Masson staining and immunohistochemical staining. We found the group treated with 0.2% losartan urea cream (Prep. 1) or 0.1% ramipril cream (Prep. 2) had significantly smaller scars compared to the negative control, while the proliferation of fibroblasts was less active and the collagen fibers were more regular; both groups showed similar efficacy with the positive control (triamcinolone acetonide urea). We also found that drug transdermalness couldn’t directly determine the efficacy. Our findings indicate that local application of angiotensin converting enzyme inhibitor drugs (ACEIs) and angiotensin receptor blocker drugs (ARBs) can reduce scarring by reducing the expression of collagen I, collagen III, phosphorylated small mothers against decapentaplegic 3 (p-Smad3) and transforming growth factor-β 1 (TGF-β1). This may provide new insight on scar treatment in clinic.

Background AlloDerm-RTU is a new member of human acellular dermal matrix (HADM) which was launched in 2012. The present meta-analysis aimed to investigate whether AlloDerm-RTU was superior compared with previous HADMs. Methods All available databases were searched for retrospective or prospective studies regarding breast reconstruction with AlloDerm-RTU compared with other HADMs. The primary outcome was the incidence of complications among different HADMs. Results Two prospective and seven retrospective studies with a total of 1406 patients were enrolled. There was no significant difference in any of the complications, including the incidence of hematoma (RR 0.78, 95%CI 0.19 to 3.19; P = 0.73), seroma (RR 0.98, 95%CI 0.43 to 2.26; P = 0.97), cellulitis (RR 0.82, 95%CI 0.32 to 2.11; P = 0.68), necrosis (RR 0.69, 95%CI 0.44 to 1.10; P = 0.12), infection (RR 0.68, 95%CI 0.37 to 1.25; P = 0.22), explantation (RR 0.61, 95%CI 0.35 to 1.06; P = 0.08), and total complications (RR 0.91, 95%CI 0.55 to 1.52; P = 0.73). Subgroup analysis showed that AlloDerm-RTU demonstrated no superiority compared with FD AlloDerm, AlloMax, or DermACELL. Sensitivity analysis indicated that the outcomes were stabilized. No publication bias existed in the present meta-analysis. Conclusion Four HADM products, AlloDerm-RTU, FD AlloDerm, AlloMax, and DermACELL, showed similar risks of complications. However since most of the included studies had a low level of evidence, further random trials with large numbers of patients are needed.

Objectives: To evaluate the feasibility, effectiveness, and safety of computed tomography–assisted auricular cartilage grafting for treating alar base depression secondary to unilateral cleft lip. Design and Setting: For patients with obvious depression of the alar base, the difference in heights of the alar base and the piriform margin between the cleft side and the noncleft side were measured with computed tomography. If both were >3.0 mm, the cartilage was harvested postauricularly and subdivided into 2 to 4 pieces. A multiple layer graft was inserted under the depressed alar base. The procedure was performed from 2006 to 2013, and the follow-up period was 3 to 15 months. Participants: Chinese patients with alar base depression secondary to unilateral cleft lip were selected. Intervention: Suture and cartilage graft techniques. Main Outcomes Measures: Differences in bilateral alar base heights and piriform apertures. Results: There was no wound dehiscence, exposure of bone, or donor site morbidity. The difference in heights in the bilateral alar bases and piriform apertures decreased. There were no obvious scars in any of the cases. Conclusions: This technique has several advantages including ease of operation, minimal trauma, satisfactory outcomes, and useful references for operation provided by computed tomography. It is a superior alternative for reconstruction of secondary alar depression.

Background: The aim of this systematic review was to evaluate the available evidence from randomized controlled trials (RCTs) of auricular acupressure (AA) therapy for preventing constipation in leukemia patients undergoing chemotherapy. Methods: We searched 5 English databases and 4 Chinese databases, from their inception until August 2017. Quantitative syntheses of RCTs were conducted using RevMan 5.3 software. Study selection, data extraction, and validation were performed independently by 2 reviewers. Cochrane criteria for risk-of-bias were used to assess the methodological quality of the trials. Results: Five RCTs met the inclusion criteria, and most were of low methodological quality. All RCTs compared AA + routine care with routine care alone. Our analysis found that complementary effects of AA can improve the scores of the Bristol Stool Form (BSF), the Constipation Assessment Scale (CAS), and the Patient Assessment of Constipation-Quality of Life (PAC-QOL). However, the same positive results were not found in terms of the Fatigue Severity Scale (FSS), the EuroQoL 5-domain (EQ-5D), and the Hospital Anxiety Depression Scale (HADS). Conclusions: Overall, as a potential safety therapy, AA may be recommended in addition to routine care including use of laxatives to prevent constipation in leukemia patients undergoing chemotherapy. In the future, more rigorous RCTs must be conducted to overcome the limitations of our existing data and to confirm the effect and safety of AA for managing constipation in leukemia patients undergoing chemotherapy.

Targeting LDHA represents a promising strategy for the development of new anti-cancer agents. We report herein the identification of a potent compound as a direct LDHA inhibitor. The in vitro enzymatic assay revealed that the VS-2 had good inhibitory potency (IC50=0.25μM) to LDHA. Cytotoxic assay suggested that the VS-2 could inhibit MCF-7 cancer cell growth, with the IC50 value low to 1.54μM. The seahorse XF24 experiment validated that the VS-2 served as a modulator to reprogram MCF-7 cancer cell metabolism from glycolysis to mitochondrial respiration.

Background Although there are numerous skin closure methods, there is no special method for suturing triangular skin wounds. The authors have summarized and modified their experience with a 3-dimensional (3D) continuous suturing technique for triangular wounds. Methods From December 2015 to September 2017, the 3D continuous suturing technique for triangular wounds has been used in 32 cleft lip repairs (48 surgical triangular incisions) and 11 cases of facial trauma (15 traumatic triangular wounds). The patients, 3 months to 39 years of age, had triangular flaps designed for esthetic purposes or triangular defects secondary to accidents. To evaluate the effectiveness of this technique, the mean follow-up was 7 months (range, 1-15 months). Results The 3D continuous suturing technique for triangular wounds can shorten the suturing time, decrease the number of thread knots, and shorten the time of surgery. All patients healed well and the stitches were removed 7 days postoperatively. The wound on both sides of the triangle was well arranged, with a good appearance and no scar hyperplasia. Conclusions Our experience showed that the 3D continuous suturing technique for triangular wounds is a time-saving and convenient method and can make the wounds closed tighter, more stable, and reliable. The technique can be applied to any type of triangular wounds or incisions and is not limited to the clinical scenarios described in this article.

Angiotensin-converting enzyme (ACE) has been found in the pathogenesis of various fibrosis diseases, and ACE inhibitor (ACEI) may affect wound healing and cutaneous fibrosis. However, there is no scientific evidence as to where the ACE is produced during scar formation. Whether it is from the cutaneous tissue or the bone marrow, or both remains unknown. In this study, we investigated the source of ACE using bone marrow transplantation in genetically modified mice, analyzed the inflammatory milieu and some growth factors in the middle of the wound healing period (4 d after the wound was induced). After having deleted the ACE from bone marrow or skin tissue, the wound/scar width in the low-ACE groups were narrower than those in wild-type (WT) controls. Loosely arranged collagen deposition and reduced vessel density were also detected in ACE-deficient mice. Lower ACE levels during scar formation were also accompanied by lower levels of TGF-β1. In the middle of the wound healing period, ACE levels affected the inflammatory cells significantly. In the mice with a deficiency in ACE, the expression of TGF-β1 and TNF-α decreased, but not that of IL-4. Our findings indicate that both bone marrow and skin tissue release ACE during scar formation. Deleting either of them can affect the inflammatory cells and growth factors and reduce the expression of TGF-β1, resulting in a decreased level of scarring.-Fang, Q.-Q., Wang, X.-F., Zhao, W.-Y., Chen, C.-Y., Zhang, M.-X., Shi, B.-H., Zhang, L.-Y., Tan, W.-Q. The source of ACE during scar formation is from both bone marrow and skin tissue.

Background.Madelung’s disease is a rare lipid metabolic disorder characterized by diffuse, uncapsulated lipomas in the neck, shoulder, and other areas. It mainly affects middle-aged men and is related to alcohol abuse, and the cause is not clear. Surgical treatments include lipectomy and liposuction.Methods.This systematic review analyzed the treatment of Madelung’s disease described in 52 articles including complete patient details, published between 2000 and 2015, and retrieved from the Web of Science, PubMed, Medline, and Embase.Results.Lipectomy was performed in most cases and achieved more complete removal and better control of iatrogenic lesions of nearby structures than liposuction. Liposuction achieved good cosmetic results and is simpler and less invasive than lipectomy, but clinical experience is limited.Conclusions.Both lipectomy and liposuction have advantages and drawbacks. Surgeons should base the choice of optimal treatment on patient characteristics. Novel surgical techniques and etiologically targeted treatments hold promise as future therapies.

Background. Skin grafts and pedicled flaps are the traditional methods of reconstructing injuries; both have some disadvantages. Here, we introduce a new clinical application of split-thickness skin with pedicle for repairing finger wounds. Methods. We present the new method of split-thickness skin with pedicle used on 12 patients (18 fingers) between 2012 and 2016. The graft was sketched on the abdomen at random according to the shape of the wounds on a skin area of 1.0 × 1.0 cm–8.0 × 1.5 cm. The pedicle was divided at 7–22 days. Results. During the follow-up time of 13–20 months, there were no reported cases of skin necrosis; 17 fingers obtained primary healing except 1, which required a dressing change. Conclusion. The split-thickness skin with pedicle proved to be valuable in the treatment of finger wounds and has the advantages of both pedicled flaps and free skin grafting.

Soluble dietary fiber (DF) reduces the risk of developing diabetes and may have therapeutic effects in patients with type 2 diabetes mellitus (DM2). The present study aimed to investigate the effect of soluble DF on metabolic control in patients with DM2. A total of 117 patients with DM2 between the ages of 40 and 70 were assessed. Patients were randomly assigned to one of two groups, and administered extra soluble DF (10 or 20 g/day), or to a control group (0 g/day) for one month. Blood glucose, serum insulin and connecting peptide (C-peptide) levels, and the insulin resistance index, as determined using the homeostatic model assessment method, were measured during fasting and up to 2-h postprandially prior to and following one month of treatment. Other measurements included serum levels of glycated albumin (GA), blood lipid profiles, and an analysis of the blood pressure, body weight and waist/hip ratio of all patients. Following intervention, the levels of 2-h blood glucose, fasting insulin and lipoprotein(a), and the insulin resistance index, were significantly improved in all groups. Furthermore, the fasting blood glucose, 2-h insulin, fasting C-peptide, 2-h C-peptide, GA and triglyceride (TG) levels were significantly improved in the soluble DF groups. The 20 g/day soluble DF group exhibited significantly improved fasting blood glucose and low-density lipoprotein levels, as well as a significantly improved insulin resistance index. In addition, 10 and 20 g/day soluble DF significantly improved the waist and hip circumferences and levels of TGs and apolipoprotein A. The results of the present study suggested that increased and regular consumption of soluble DF led to significant improvements in blood glucose levels, insulin resistance and metabolic profiles, without improving the secretory function of the islets of Langerhans, over a short-term intervention period in patients with DM2.

Cutaneous scars (particularly hypertrophic and keloid scars), not only can cause adverse cosmetic problems, but also can be associated with emotional distress such as anxiety and depression. Comparing with other surgical treatments, patients who do not opt for or cannot opt for invasion therapies are more eligible for using the topical anti-scarring agents. In this mini-review, we have researched for and collected the data between October 2005 and October 2015, in PubMed and Web of Science, and identified those agents including silicone-based products, imiquimod, corticosteroids, 5-fluorouracil, bleomycin, mitomycin, and plant extracts such as onion extract, asiaticoside, aloe vera, vitamin E, and so on. Besides, we have listed these popular products in commercial market with their useful information. We have also described the combined process according to our clinical experience. However, to establish the more effective treatment among different types of topical agents or their combined process, large, well-designed head-to-head comparisons between individual and combined preparations in relevant patient populations are urgently needed.

Background Reduction mammoplasty (RM) is a proven method of treating macromastia, but the risk factors for postoperative complications have not been clearly identified. Through this meta-analysis, the authors aimed to identify the risk factors of RM complications. Methods An extensive search of the literature describing complications after RM was performed using the PubMed Central, Embase, and Cochrane databases. The following risk factors were extracted: age, body mass index (BMI), tissue resection weight per breast (TRW), smoking and radiation therapy. Odds ratios (OR) were pooled with 95% confidence intervals (CI) to evaluate the relationship between these risk factors and complications after RM. Results A total of 16 unique studies including 10 593 patients were included in the final analysis. It showed that there was a significant difference in complications in BMI ≥30 kg/m2 (OR 0.73; 95% CI: 0.61-0.89, p = 0.001) and smoking (OR 1.56; 95% CI: 0.98-2.49, p = 0.06). Infection in those with BMI ≥30 kg/m2 showed a significant difference (OR 0.68; 95% CI: 0.52-0.89, p = 0.004), as well as wound dehiscence in smokers (OR 2.73; 95% CI: 1.60-4.67, p = 0.0002) and infection in irradiated breasts (OR 20.38; 95% CI: 3.42-121.35, p = 0.0009). However, there was no significant difference in age ≥50 years (OR 0.96; 95% CI: 0.71-1.29, p = 0.78), combined TRW ≥1000 g (OR 1.04; 95% CI: 0.43-2.50, p = 0.93). Conclusions BMI ≥30 kg/m2 and smoking increase the risk of complications. Persons who are obese or irradiated are more likely to develop infections, and smokers experienced a higher incidence of wound dehiscence than did nonsmokers. However, patients aged ≥50 years and TRW ≥1000 g are not associated with complications from RM.

Increased intracellular reactive oxygen species (ROS) is crucial for vascular endothelial dysfunction, a key step in the initiating of atherosclerosis (AS). The antioxidant activity of flavonoids has been suggested to contribute to AS prevention. However, The association of the structure characteristics to antioxidant capacities in relation to the inhibitory effects on endothelial dysfunction has not been well established. In this study, four subclasses of flavonoids with similar structures, including two anthocyanins (delphinidin and cyanidin), two flavonols (myricetin and quercetin), two flavones (luteolin and apigenin) and two isoflavones (genistein and daidzein) were examined for their inhibitory effects on intracellular ROS-mediated signaling pathway in the human umbilical vein endothelial cell EA.hy926. Cells were pretreated with different flavonoids for 2 h and then exposed to oxLDL of 100 μg/ml for another 24 h. It was found that treatment with different flavonoids alone had no notable effects on cell viability. However, the oxLDL-induced decrease of cell viability, generation of O2·− and ROS, p38MAPK activation, NF-κB nuclear translocation, NF-κB-modulated transcriptional activity as well as the mRNA expression of genes including ICAM-1, VCAM-1, E-selectin, MMP-1, MMP-2 and MMP-9 were notably inhibited by the pretreatment of different flavonoids through blunting ROS-triggered signaling pathway, in spite of apparent differences. And the number of hydroxyl groups in total, 3′,4′-ortho-dihydroxyl in B-ring and 3-hydroxyl group in C-ring of flavonoids were important structure characteristics for the inhibitory effects. Thus, anthocyanins and flavonols such as delphinidin and myricetin exert higher ROS scavenging activities and more significant endothelium-protective effects compared to the other compounds. Our results provide evidence for AS prevention and a basis for designing the potent anti-atherosclerotic agents.

Vascular endothelial dysfunction induced by oxidative stress has been demonstrated to be the initiation step of atherosclerosis (AS), and flavonoids may play an important role in AS prevention and therapy. Twenty-three flavonoids categorized into flavones, flavonols, isoflavones, and flavanones, all with 4-oxo-pyronenucleus, were examined for what structural characteristics are required for the inhibitory effects on endothelial dysfunction induced by oxidized low-density lipoprotein (oxLDL). Human vascular endothelial cells EA.hy926 were pretreated with different 4-oxo-flavonoids for 2 hs, and then exposed to oxLDL for another 24 hs. Cell viability and the level of malondialdehyde (MDA), nitric oxide (NO) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured, respectively. Then, correlation analysis and paired comparison were used to analyze the structure-activity relationships. Significant correlations were observed between the number of -OH moieties in total or in B-ring and the inhibitory effectson endothelial dysfunction. Furthermore, 3',4'-ortho-dihydroxyl on B-ring, 3-hydroxyl on C-ring and 2,3-double bondwere correlated closely to the inhibitory effects of flavonolson cell viability decrease and lipid peroxidation. 5,7-meta-dihydroxyl group on A-ring was crucial for the anti-inflammatory effects of flavones and isoflavones in endothelial cells. Moreover, the substituted position of B-ring on C3 rather than C2 was important for NO release. Additionally, hydroxylation at C6 position significantly attenuated the inhibitory effects of 4-oxo-flavonoids on endothelial dysfunction. Our findings indicated that the effective agents in inhibiting endothelial dysfunction include myricetin, quercetin, luteolin, apigenin, genistein and daidzein. Our work might provide some evidence for AS prevention and a strategy for the design of novel AS preventive agents.

Monocyte adhesion to the vascular endothelium and their subsequent trans-endothelial migration are pivotal early events in atherogenesis. In this study, the effect of delphinidin, belonging to the group of anthocyanin, on adhesion of monocytes to endothelial cells induced by ox-LDL was investigated. The results showed that the pre-treatment with delphinidin (50, 100, or 200 μM) dose-dependently decreased the ox-LDL-induced up-regulation of the expression of ICAM-1 and P-selectin, and the enhanced adhesion and transmigration of monocytes. To determine the role of ROS/p38MAPK/NF-κB pathway, intracellular ROS level, p38MAPK protein expression, NF-κB transcription activity and protein expression, IκB-α degradation, NADPH oxidase subunit (Nox2 and p22phox) protein, and mRNA expression were measured. The results showed that delphinidin attenuated ox-LDL-induced generation of ROS, p38MAPK protein expression, NF-κB transcription activity and protein expression, IκB-α degradation, NADPH oxidase subunit (Nox2 and p22phox) protein and mRNA expression in endothelial cells in a dose-dependent manner. These results suggest that delphinidin attenuates ox-LDL induced expression of adhesion molecules (P-selectin and ICAM-1) and the adhesion of monocytes to endothelial cells by inhibiting ROS/p38MAPK/NF-κB pathway. These findings provide a basis for the design of potent antiatherosclerotic agents that will have therapeutic potential in the prevention of AS.

Anthocyanins may play an important role in atherosclerosis prevention. However, the structure–function relationships are not well understood. The objective of this study was to compare the inhibitory effect of 21 anthocyanins against oxidized low-density lipoprotein-induced endothelial injury to understand the relationship between anthocyanin chemical structure and the endothelial protective properties, measured as cell viability, MDA production and NO release. Additionally, the intracellular anti-radical activity of the selected anthocyanins was investigated to identify the correlation with endothelial protection. Our results provide evidence that the number of –OH in total or in B-ring, 3′,4′-ortho-dihydroxyl and 3-hydroxyl are the main structural requirements of anthocyanins in suppressing oxidative stress-induced endothelial injury and such inhibitory effect was significantly correlated with the intracellular radical scavenging activity.

Moderate consumption of natural dietary polyphenolic compounds can reduce the risk of cardiovascular diseases. Here we investigated the protective effects of delphinidin against oxidized low-density lipoprotein (oxLDL)-induced damage in human umbilical vein endothelial cells (HUVECs). The MTT assay showed that 2 h pre-incubation with delphinidin markedly restored the oxLDL-induced viability loss in HUVECs in a concentration-dependent manner. This effect was accompanied by a significant decrease in intracellular reactive oxygen species. Moreover, delphinidin imposed preventive effects on suppressing the production of lipid peroxidation, restoring the activities of endogenous antioxidants, and increasing the level of nitric oxide. Pre-incubation of delphinidin with HUVECs led to the reduction of apoptosis. Finally, delphinidin can efficiently prevent the down-regulation of Bcl-2 protein and up-regulation of Bax protein. Together, our findings suggest that delphinidin can effectively protect HUVECs against oxidative stress induced by oxLDL, which may be important for preventing both plaque development and stability in atherosclerosis.

Delphinidin-3-glucoside (Dp) is a member of a family of bioactive compounds known as anthocyanins that occur naturally in pigmented plants and are known to ameliorate oxidative stress. Previous studies have showed that Dp decreased oxidative stress in vascular endothelial cells, however, the underlying mechanisms remain largely unknown. In the present study, we showed that pretreatment with Dp significantly suppressed oxidized low-density lipoprotein (oxLDL)-induced cell proliferation inhibition and apoptosis in primary human umbilical vein endothelial cells (HUVECs). Also, Dp pretreatment attenuated oxLDL-induced mitochondrial dysfunction via decreased reactive oxygen species (ROS) and superoxide anion generation, thereby repressing mitochondrial membrane potential and closing mitochondrial permeability transition pore. Furthermore, in vitro and in vivo data showed that Dp was transported into endothelial cells in a temperature, concentration, and time-dependent manner via the sodium-dependent glucose transporter (SGLT1). Suppression of SGLT1 by its substrate glucose, its inhibitor phlorizin or SGLT1 siRNA blocked Dp transportation. Repression of SGLT1 significantly inhibited Dp function of ameliorating mitochondrial dysfunction induced by pro-apoptotic factors (Apoptosis-inducing factor, Cytochrome c, Caspase-3 and Bax/Bcl-2 ratio). Taken together, our data indicate that Dp protects VECs via the SGLT1-ROS-mitochodria pathway. This new insight may help to elucidate the molecular mechanisms underlying the vascular protection afforded by Dp, and anthocyanins in general, in the context of prevention of endothelial dysfunction and atherosclerosis.