Publications by authors named "Wei-Qiang Tan"

57 Publications

Photochemical Reactivity of Humic Substances in an Aquatic System Revealed by Excitation-Emission Matrix Fluorescence.

Front Chem 2021 28;9:679286. Epub 2021 May 28.

School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao, China.

The photochemical reactivity of humic substances plays a critical role in the global carbon cycle, and influences the toxicity, mobility, and bioavailability of contaminants by altering their molecular structure and the mineralization of organic carbon to CO. Here, we examined the simulated irradiation process of Chinese standard fulvic acid (FA) and humic acid (HA) by using excitation-emission matrix fluorescence combined with fluorescence regional integration (FRI), parallel factor (PARAFAC) analysis, and kinetic models. Humic-like and fulvic-like materials were the main materials (constituting more than 90%) of both FA and HA, according to the FRI analysis. Four components were identified by the PARAFAC analysis: fulvic-like components composed of both carboxylic-like and phenolic-like chromophores (C1), terrestrial humic-like components primarily composed of carboxylic-like chromophores (C2), microbial humic-like overwhelming composed of phenolic-like fluorophores (C3), and protein-like components (C4). After irradiation for 72 h, the maximum fluorescence intensity ( ) of C1 and C2 of FA was reduced to 36.01-58.34%, while the of C3 of both FA and HA also decreased to 0-9.63%. By contrast, for HA, the of its C1 and C2 increased to 236.18-294.77% when irradiated for 72 h due to greater aromaticity and photorefractive tendencies. The first-order kinetic model ( = 0.908-0.990) fitted better than zero-order kinetic model ( = 0-0.754) for the C1, C2, and C3, of both FA and HA, during their photochemical reactivity. The photodegradation rate constant ( ) of C1 had values (0.105 for FA; 0.154 for HA) that surpassed those of C2 (0.059 for FA, 0.079 for HA) and C3 (0.079 for both FA and HA) based on the first-order kinetic model. The half-life times of C1, C2, and C3 ranged from 6.61-11.77 h to 4.50-8.81 h for FA and HA, respectively. Combining an excitation-emission matrix with FRI and PARAFAC analyses is a powerful approach for elucidating changes to humic substances during their irradiation, which is helpful for predicting the environmental toxicity of contaminants in natural ecosystems.
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http://dx.doi.org/10.3389/fchem.2021.679286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193985PMC
May 2021

A 3-DNA methylation signature as a novel prognostic biomarker in patients with sarcoma by bioinformatics analysis.

Medicine (Baltimore) 2021 May;100(20):e26040

Department of Nephrology, Huzhou Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Huzhou, Zhejiang, China.

Background: Tumor-specific DNA methylation can potentially be a useful indicator in cancer diagnostics and monitoring. Sarcomas comprise a heterogeneous group of mesenchymal neoplasms which cause life-threatening tumors occurring throughout the body. Therefore, potential molecular detection and prognostic evaluation is very important for early diagnosis and treatment.

Methods: We performed a retrospective study analyzing DNA methylation of 261 patients with sarcoma from The Cancer Genome Atlas (TCGA) database. Cox regression analyses were conducted to identify a signature associated with the overall survival (OS) of patients with sarcoma, which was validated in a validation dataset.

Results: Three DNA methylation signatures were identified to be significantly associated with OS. Kaplan-Meier analysis showed that the 3-DNA methylation signature could significantly distinguish the high- and low-risk patients in both training (first two-thirds) and validation datasets (remaining one-third). Receiver operating characteristic (ROC) analysis confirmed that the 3-DNA methylation signature exhibited high sensitivity and specificity in predicting OS of patients. Also, the Kaplan-Meier analysis and the area under curve (AUC) values indicated that the 3-DNA methylation signature was independent of clinical characteristics, including age at diagnosis, sex, anatomic location, tumor residual classification, and histological subtypes.

Conclusions: The current study showed that the 3-DNA methylation model could efficiently function as a novel and independent prognostic biomarker and therapeutic target for patients with sarcoma.
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http://dx.doi.org/10.1097/MD.0000000000026040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137010PMC
May 2021

Co-transfection with and via chitosan nanoparticles potentiates osteogenesis in human adipose-derived stromal cells .

J Int Med Res 2021 Mar;49(3):300060521997679

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.

Objective: To investigate if co-transfection of human bone morphogenetic protein 2 (BMP-2, ) and human fibroblast growth factor 2 (FGF2, ) via chitosan nanoparticles promotes osteogenesis in human adipose tissue-derived stem cells (ADSCs) .

Materials And Methods: Recombinant and/or expression vectors were constructed and packaged into chitosan nanoparticles. The chitosan nanoparticles were characterized by atomic force microscopy. Gene and protein expression levels of BMP-2 and FGF2 in ADSCs were evaluated by real-time polymerase chain reaction (PCR), western blot, and enzyme-linked immunosorbent assay. Osteocalcin (OCN) and bone sialoprotein (BSP) gene expression were also evaluated by real-time PCR to assess osteogenesis.

Results: The prepared chitosan nanoparticles were spherical with a relatively homogenous size distribution. The and vectors were successfully transfected into ADSCs. BMP-2 and FGF2 mRNA and protein levels were significantly up-regulated in the co-transfection group compared with the control group. OCN and BSP mRNA levels were also significantly increased in the co-transfection group compared with cells transfected with or alone, suggesting that co-transfection significantly enhanced osteogenesis.

Conclusions: Co-transfection of human ADSCs with via chitosan nanoparticles efficiently promotes the osteogenic properties of ADSCs .
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http://dx.doi.org/10.1177/0300060521997679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166400PMC
March 2021

Effects of chitosan-collagen dressing on wound healing in vitro and in vivo assays.

J Appl Biomater Funct Mater 2021 Jan-Dec;19:2280800021989698

Department of Plastic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang Province, P.R. China.

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 and . 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.
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http://dx.doi.org/10.1177/2280800021989698DOI Listing
February 2021

The Roles of Inflammation in Keloid and Hypertrophic Scars.

Front Immunol 2020 4;11:603187. Epub 2020 Dec 4.

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

The underlying mechanisms of wound healing are complex but inflammation is one of the determining factors. Besides its traditional role in combating against infection upon injury, the characteristics and magnitude of inflammation have dramatic impacts on the pathogenesis of scar. Keloids and hypertrophic scars are pathological scars that result from aberrant wound healing. They are characterized by continuous local inflammation and excessive collagen deposition. In this review, we aim at discussing how dysregulated inflammation contributes to the pathogenesis of scar formation. Immune cells, soluble inflammatory mediators, and the related intracellular signal transduction pathways are our three subtopics encompassing the events occurring in inflammation associated with scar formation. In the end, we enumerate the current and potential medicines and therapeutics for suppressing inflammation and limiting progression to scar. Understanding the initiation, progression, and resolution of inflammation will provide insights into the mechanisms of scar formation and is useful for developing effective treatments.
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http://dx.doi.org/10.3389/fimmu.2020.603187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746641PMC
June 2021

Refined tumescent liposuction-curettage with pruning in small incisions for treatment of axillary bromhidrosis.

Dermatol Ther 2021 01 11;34(1):e14690. Epub 2021 Jan 11.

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang Province, Hangzhou, China.

Axillary bromhidrosis is a widespread social problem in our society. Various modalities have been developed for the destruction or removal of the apocrine sweat glands to eliminate underarm odor. However, conventional surgical treatments often result in a high complication rate and frequent recurrence. In this study, we aimed to evaluate the effect of refined tumescent liposuction-curettage with pruning in small incisions as treatment for axillary bromhidrosis. Between July 2013 and April 2019, 110 patients (75 women and 35 men) with axillary bromhidrosis underwent refined tumescent liposuction-curettage with pruning. The results of eliminating underarm odor were evaluated by both the patients and doctors and rated as very satisfied (excellent), satisfied (good), slightly satisfied (fair), and not satisfied (poor). Postoperative complications, such as dehiscence, infection, wound contracture, cyst, subcutaneous hydrops, hematoma, or seroma, were also evaluated. Preoperative and postoperative histological examinations of axillary tissues were performed in two patients. In the subjective evaluation of 110 patients, 33 (30.0%) were very satisfied with the results, 70 (63.6%) were satisfied, and seven (6.4%) were slightly satisfied. The objective evaluation showed that 43 (39.1%) patients graded the results as excellent, whereas others graded the results as good. No serious complications occurred, except three patients with slight local subcutaneous hydrops and hematoma. Histologic examinations showed that the apocrine glands were significantly decreased or destroyed after the surgery. Refined tumescent liposuction-curettage with pruning in small incisions is an effective method for the treatment of axillary bromhidrosis.
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http://dx.doi.org/10.1111/dth.14690DOI Listing
January 2021

A Novel Signature of 23 Immunity-Related Gene Pairs Is Prognostic of Cutaneous Melanoma.

Front Immunol 2020 19;11:576914. Epub 2020 Oct 19.

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

In this study, we aimed to identify an immune-related signature for predicting prognosis in cutaneous melanoma (CM). Sample data from The Cancer Genome Atlas (TCGA; n = 460) were used to develop a prognostic signature with 23 immune-related gene pairs (23 IRGPs) for CM. Patients were divided into high- and low-risk groups using the TCGA and validation datasets GSE65904 (n = 214), GSE59455 (n = 141), and GSE22153 (n = 79). The ability of the 23-IRGP signature to predict CM was precise, with the stratified high-risk groups showing a poor prognosis, and it had a significant predictive power when used for immune microenvironment and biological analyses. We subsequently established a novel promising prognostic model in CM to determine the association between the immune microenvironment and CM patient results. This approach may be used to discover signatures in other diseases while avoiding the technical biases associated with other platforms.
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http://dx.doi.org/10.3389/fimmu.2020.576914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604355PMC
June 2021

The efficacy of fractional CO laser in acne scar treatment: A meta-analysis.

Dermatol Ther 2021 01 23;34(1):e14539. Epub 2020 Nov 23.

Department of Plastic Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Zhejiang, China.

Fractional CO laser is a good option for treating acne scars. However, the clinical efficacy of this treatment modality requires further evidence. To perform a meta-analysis to assess clinical improvements in acne scars with fractional CO laser and non-CO laser therapies. Databases (PubMed, Embase, Cochrane Library) were searched using the search strategy to identify eligible studies. All statistical analyses were performed using the Review Manager 5.0, and a meta-analysis was conducted to assess the effects of fractional CO laser used as a treatment for acne scars. Eight studies were included for further analysis. There was no significant difference between fractional CO laser and non-CO laser therapies in terms of clinical improvement, observer assessment (P = .19), patient assessment (P = .91), and incidence of post-inflammatory hyperpigmentation (P = .69). The subgroup analyses showed that the duration of follow-up had little effect on the evaluation of treatment effect. The efficacy of fractional CO laser therapy in acne scars appeared to be equal to that of non-CO laser therapies. More well designed randomized controlled trials and more credible and standard evaluation criteria are needed, and the efficiency of combination therapy requires further analysis.
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http://dx.doi.org/10.1111/dth.14539DOI Listing
January 2021

Flexible electrical stimulation device with Chitosan-Vaseline® dressing accelerates wound healing in diabetes.

Bioact Mater 2021 Jan 19;6(1):230-243. Epub 2020 Aug 19.

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, PR China.

The healing process of diabetic wounds is typically disordered and prolonged and requires both angiogenesis and epithelialization. Disruptions of the endogenous electric fields (EFs) may lead to disordered cell migration. Electrical stimulation (ES) that mimics endogenous EFs is a promising method in treating diabetic wounds; however, a microenvironment that facilitates cell migration and a convenient means that can be used to apply ES are also required. Chitosan-Vaseline® gauze (CVG) has been identified to facilitate wound healing; it also promotes moisture retention and immune regulation and has antibacterial activity. For this study, we created a wound dressing using CVG together with a flexible ES device and further evaluated its potential as a treatment for diabetic wounds. We found that high voltage monophasic pulsed current (HVMPC) promoted healing of diabetic wounds . In studies carried out , we found that HVMPC promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs) by activating PI3K/Akt and ERK1/2 signaling. Overall, we determined that the flexible ES-chitosan dressing may promoted healing of diabetic wounds by accelerating angiogenesis, enhancing epithelialization, and inhibiting scar formation. These findings provide support for the ongoing development of this multidisciplinary product for the care and treatment of diabetic wounds.
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http://dx.doi.org/10.1016/j.bioactmat.2020.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451868PMC
January 2021

p53 isoform Δ113p53 promotes zebrafish heart regeneration by maintaining redox homeostasis.

Cell Death Dis 2020 07 23;11(7):568. Epub 2020 Jul 23.

MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University, 310058, Hangzhou, China.

Neonatal mice and adult zebrafish can fully regenerate their hearts through proliferation of pre-existing cardiomyocytes. Previous studies have revealed that p53 signalling is activated during cardiac regeneration in neonatal mice and that hydrogen peroxide (HO) generated near the wound site acts as a novel signal to promote zebrafish heart regeneration. We recently demonstrated that the expression of the p53 isoform Δ133p53 is highly induced upon stimulation by low-level reactive oxygen species (ROS) and that Δ133p53 coordinates with full-length p53 to promote cell survival by enhancing the expression of antioxidant genes. However, the function of p53 signalling in heart regeneration remains uncharacterised. Here, we found that the expression of Δ113p53 is activated in cardiomyocytes at the resection site in the zebrafish heart in a full-length p53- and ROS signalling-dependent manner. Cell lineage tracing showed that Δ113p53-positive cardiomyocytes undergo cell proliferation and contribute to myocardial regeneration. More importantly, heart regeneration is impaired in Δ113p53 mutant zebrafish. Depletion of Δ113p53 significantly decreases the proliferation frequency of cardiomyocytes but has little effect on the activation of gata4-positive cells, their migration to the edge of the wound site, or apoptotic activity. Live imaging of intact hearts showed that induction of HO at the resection site is significantly higher in Δ113p53 mutants than in wild-type zebrafish, which may be the result of reduced induction of antioxidant genes in Δ113p53 mutants. Our findings demonstrate that induction of Δ113p53 in cardiomyocytes at the resection site functions to promote heart regeneration by increasing the expression of antioxidant genes to maintain redox homeostasis.
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http://dx.doi.org/10.1038/s41419-020-02781-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378207PMC
July 2020

Angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker: Potential agents to reduce post-surgical scar formation in humans.

Basic Clin Pharmacol Toxicol 2020 Dec 19;127(6):488-494. Epub 2020 Jul 19.

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Studies on the effectiveness and mechanisms of reducing scar formation by interfering with the renin-angiotensin-aldosterone-system (RAAS) have been demonstrated in animals, but not in humans due to the lack of clinical support. Our aim was to investigate whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor blocker (ARB) could inhibit scar formation in humans. Thus, an observational and hypothesis-generating study using a designed questionnaire was carried out. A total of 347 patients with postoperative scars secondary to thyroid tumours were enrolled. They were divided into four groups: ACEI group, ARB group, other antihypertensive drugs control group and blank control group according to the administration of antihypertensive drugs. The width of scar was measured, and the Scar Cosmesis Assessment and Rating (SCAR) Scale was filled out. Results showed that patients of ACEI group (mean scar width 1.60 mm) and ARB group (mean scar width 1.57 mm) formed smaller scars than those of other antihypertensive drugs control group (mean scar width 2.09 mm) and blank control group (mean scar width 2.0 mm). Oral administration of ACEI and ARB may be associated with better post-surgical scar formation in humans. These two kinds of antihypertensive drugs may be active components of anti-scar medicine.
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http://dx.doi.org/10.1111/bcpt.13458DOI Listing
December 2020

Current potential therapeutic strategies targeting the TGF-β/Smad signaling pathway to attenuate keloid and hypertrophic scar formation.

Biomed Pharmacother 2020 Sep 12;129:110287. Epub 2020 Jun 12.

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, PR China. Electronic address:

Aberrant scar formation, which includes keloid and hypertrophic scars, is associated with a pathological disorganized wound healing process with chronic inflammation. The TGF-β/Smad signaling pathway is the most canonical pathway through which the formation of collagen in the fibroblasts and myofibroblasts is regulated. Sustained activation of the TGF-β/Smad signaling pathway results in the long-term overactivation of fibroblasts and myofibroblasts, which is necessary for the excessive collagen formation in aberrant scars. There are two categories of therapeutic strategies that aim to target the TGF-β/Smad signaling pathway in fibroblasts and myofibroblasts to interfere with their cellular functions and reduce cell proliferation. The first therapeutic strategy includes medications, and the second strategy is composed of genetic and cellular therapeutics. Therefore, the focus of this review is to critically evaluate these two main therapeutic strategies that target the TGF-β/Smad pathway to attenuate abnormal skin scar formation.
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http://dx.doi.org/10.1016/j.biopha.2020.110287DOI Listing
September 2020

Flexible liposomal gel dual-loaded with all-trans retinoic acid and betamethasone for enhanced therapeutic efficiency of psoriasis.

J Nanobiotechnology 2020 May 24;18(1):80. Epub 2020 May 24.

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease without effective treatment. The utilization of all trans-retinoic acid (TRA) and betamethasone (BT) for the treatment of psoriasis is still facing difficulties, due to their relatively poor stability, limited skin permeation, and systemic side effects. Flexible liposomes are excellent in deeper skin permeation and reducing the side effects of drugs, which is promising for effective treatment of skin disorders. This work aimed to establish dual-loaded flexible liposomal gel for enhanced therapeutic efficiency of psoriasis based on TRA and BT.

Results: Flexible liposomes co-loaded with TRA and BT were successfully prepared in our study. The characterization examination revealed that flexible liposomes featured nano-sized particles (around 70 nm), high drug encapsulation efficiency (> 98%) and sustained drug release behaviors. Flexible liposomes remarkably increased the drug skin permeation and retention as compared with free drugs. Results on HaCaT cells suggested that flexible liposomes were nontoxic, and its cellular uptake has a time-dependent manner. In vivo studies suggested the topical application of TRA and BT dual-loaded liposomal gel had the best ability to reduce the thickness of epidermal and the level of cytokines (TNF-α and IL-6), largely alleviating the symptoms of psoriasis.

Conclusions: Flexible liposomal gel dual-loaded with TRA and BT exerted a synergistic effect, which is a promising topical therapeutic for the treatment of psoriasis.
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http://dx.doi.org/10.1186/s12951-020-00635-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245867PMC
May 2020

Gene-activated dermal equivalents to accelerate healing of diabetic chronic wounds by regulating inflammation and promoting angiogenesis.

Bioact Mater 2020 Sep 8;5(3):667-679. Epub 2020 May 8.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, PR China.

Diabetic chronic wound, characterized by prolonged inflammation and impaired angiogenesis, has become one of the most serious challenges in clinic and pose a significant healthcare burden worldwide. Although a great variety of wound dressings have been developed, few of encouraged achievements were obtained so far. In this study, the gene-activated strategy was applied to enhance sustained expression of vascular endothelial growth factor (VEGF) and achieve better healing outcomes by regulating inflammation and promoting angiogenesis. The gene-activated bilayer dermal equivalents (Ga-BDEs), which has good biocompatibility, were fabricated by loading the nano-sized complexes of Lipofectamine 2000/plasmid DNA-encoding VEGF into a collagen-chitosan scaffold/silicone membrane bilayer dermal equivalent. The DNA complexes were released in a sustained manner and showed the effective transfection capacities to up-regulate the expression of VEGF in vitro. To overcome cutaneous contraction of rodents and mimic the wound healing mechanisms of the human, a reformative rat model of full-thickness diabetic chronic wound was adopted. Under the treatment of Ga-BDEs, speeding wound healing was observed, which is accompanied by the accelerated infiltration and phenotype shift of macrophages and enhanced angiogenesis in early and late healing phases, respectively. These proved that Ga-BDEs possess the functions of immunomodulation and pro-angiogenesis simultaneously. Subsequently, the better regeneration outcomes, including deposition of oriented collagen and fast reepithelialization, were achieved. All these results indicated that, being different from traditional pro-angiogenic concept, the up-regulated expression of VEGF by Ga-BDEs in a sustained manner shows versatile potentials for promoting the healing of diabetic chronic wounds.
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http://dx.doi.org/10.1016/j.bioactmat.2020.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217806PMC
September 2020

Flexible wound healing system for pro-regeneration, temperature monitoring and infection early warning.

Biosens Bioelectron 2020 Aug 6;162:112275. Epub 2020 May 6.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, PR China. Electronic address:

To break the "Black-Box" status of the wound healing process under traditional dressing, which cannot achieve satisfactory repair outcome of skin wounds, a wound healing system with the abilities of pro-regeneration and real-time monitoring of wound status has become a considerable necessity. Here, by integrating the emerging bioelectronics and software, we created a flexible wound healing system. The hardware system was designed as Band-Aid shaped with a double-layer structure; the upper is the flexible temperature-sensing layer comprising the temperature sensor STH21, power manager circuit and data processing circuit, and the lower is a collagen-chitosan dermal equivalent for skin regeneration. A customized software application (app) installed on a smartphone to receive data from the sensing layer by BLE4.0 can display and analyze real-time wound temperature. Our system had high monitoring sensitivity and stability, good stretchability, excellent reliability and biocompatibility. It was applied to a pig skin wound model to reveal temperature fluctuation during the entire wound regeneration process. As a credible reference and foundation for further early warning of an adverse event, three main phases of temperature fluctuation were found: the rising phase (below 39 °C), plateau phase (39-39.5 °C), and falling phase (below 39 °C), which were accompanied by significant wound biological events, including inflammatory cell infiltration, angiogenesis and wound healing. Furthermore, verified by wound infection models of different healing phases and wound Gram's staining, early warning ahead of serious infection was realized with the use of a customized app's alarm.
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http://dx.doi.org/10.1016/j.bios.2020.112275DOI Listing
August 2020

Long Noncoding RNA LUADT1 Is Upregulated in Melanoma and May Sponge miR-28-5p to Upregulate RAP1B.

Cancer Biother Radiopharm 2020 May 19;35(4):307-312. Epub 2020 Mar 19.

Department of Hand Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, P.R. China.

Long noncoding RNA (lncRNA) LUADT1 is a known oncogenic lncRNA in lung cancer. This study aimed to explore the roles of LUADT1 in melanoma. Sixty pairs of melanoma and nontumor tissues were obtained from 60 melanoma patients (37 men and 23 women, 38-68 years, 52.1 ± 4.9 years) at the First Affiliated Hospital of Zhejiang University School of Medicine. Gene expression was analyzed by quantitative polymerase chain reaction and western blot. Cell transfections were performed to analyze gene expression. We found that LUADT1 was upregulated in melanoma and high levels of LUADT1 predicted poor survival. RNA interaction prediction showed that LUADT1 can form base pairing with miR-28-5p. In melanoma cells, LUADT1 overexpression mediated the upregulated Ras-related protein Rap-1b (RAP1B). Cell proliferation assay showed that LUADT1 and RAP1B overexpression mediated the increased proliferation rate of melanoma cells. In addition, miR-28-5p overexpression played opposite roles attenuating the effects of LUADT1 overexpression on both RAP1B expression and cancer cell proliferation. LUADT1 in melanoma and may sponge miR-28-5p to upregulate RAP1B, thereby promoting cancer cell proliferation.
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http://dx.doi.org/10.1089/cbr.2019.3149DOI Listing
May 2020

Potential effect of non-thermal plasma for the inhibition of scar formation: a preliminary report.

Sci Rep 2020 01 23;10(1):1064. Epub 2020 Jan 23.

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, P.R. China.

Non-thermal plasma (NTP) is a promising biomedical tool for application to wound healing. However, there is limited scientific evidence that confirms its efficacy to inhibit scar formation. This study aims to investigate the role of non-thermal plasma in scar formation. Two full-thickness dorsal cutaneous wounds of rats were treated with either a non-thermal helium plasma jet or helium. It was determined that the non-thermal plasma jet accelerated the wound healing process from 5 days after surgery (day 5: 41.27% ± 2.351 vs 54.7% ± 5.314, p < 0.05; day 7: 56.05% ± 1.881 vs 75.28% ± 3.914, p < 0.01; day 14: 89.85% ± 2.991 vs 98.07% ± 0.839, p < 0.05). The width of the scars for the NTP group was narrower than those of control group (4.607 ± 0.416 mm vs 3.260 ± 0.333 mm, p < 0.05). In addition, a lower level of TGF-β1, p-Smad2 and p-Smad3 were detected in the NTP treated wounds (p < 0.05, p < 0.01 and p < 0.01). As expected, α-SMA was also significantly decreased in the NTP treatment group (p < 0.01). Moreover, the expression of type I collagen and the proportion of type I to III collagen were lower in the NTP group (p < 0.05). The results of the study suggest that NTP may play a potential role in scar formation by inhibiting the TGF β1 signal pathway and reducing the levels of α-SMA and type I collagen, and may have clinical utility in the future.
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http://dx.doi.org/10.1038/s41598-020-57703-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978306PMC
January 2020

CO Laser Punch-Assisted Minimally Invasive Surgery for Sebaceous Cysts.

Lasers Surg Med 2020 10 13;52(8):743-746. Epub 2020 Jan 13.

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, P.R. China.

Background And Objectives: Traditional surgical excision for a sebaceous cyst can completely eradicate the cyst, but the surgical processes are relatively complicated and may cause obvious scarring. Some patients are reluctant to choose this method because of the inconvenient procedures and the risk of conspicuous scarring, especially in esthetically important areas. We present a simple treatment method to prevent formation of a conspicuous scar.

Study Design/materials And Methods: First, the cyst wall was pre-separated from the surrounding tissues by injecting a large volume of anesthetic around the cyst. Then, the cyst contents were removed through a small hole created by using a CO laser on the skin surface, which adhered closely to the cyst. Finally, the cyst wall was removed using a hemostat that clamps it at the base. Between August 2017 and July 2019, 32 patients with 33 sebaceous cysts (12 infected and 21 uninfected) were treated by this method to remove the cyst contents and cyst wall. Mean operative time, complications, and patient satisfaction were evaluated.

Results: All patients were satisfied with the good esthetic outcome and the simplicity of the surgical procedure. Only two of the 33 cysts (6.0%) recurred 2 and 3 months postoperatively, including 0 of 21 uninfected cysts (0.0%) and 2 of 12 infected cysts (16.7%). No complications were found during the follow-up period. The mean operation time was 13 ± 2.1 minutes.

Conclusions: CO laser punch-assisted surgery was associated with minimal scarring and high patient satisfaction. With acceptable recurrence rates, it is a convenient, effective and minimally-invasive treatment option for sebaceous cysts. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/lsm.23216DOI Listing
October 2020

Co-transfection of hepatocyte growth factor and truncated TGF-β type II receptor inhibit scar formation.

Braz J Med Biol Res 2020 13;53(1):e9144. Epub 2020 Jan 13.

Department of Hand Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Wound scarring remains a major challenge for plastic surgeons. Transforming growth factor (TGF)-β plays a key role in the process of scar formation. Previous studies have demonstrated that truncated TGF-β type II receptor (t-TGF-βRII) is unable to continue signal transduction but is still capable of binding to TGF-β, thereby blocking the TGF-β signaling pathway. Hepatocyte growth factor (HGF) is a multifunctional growth factor that promotes tissue regeneration and wound healing. Theoretically, the combination of HGF and t-TGF-βRII would be expected to exert a synergistic effect on promoting wound healing and reducing collagen formation. In the present study, lentivirus-mediated transfection of the two genes (t-TGF-βRII/HGF) into fibroblasts in vitro and in a rat model in vivo was used. The results demonstrated that the expression of t-TGF-βRII and HGF in NIH-3T3 cells was successfully induced. The expression of both molecules significantly reduced collagen I and III expression, and also inhibited fibroblast proliferation. Furthermore, histological examination and scar quantification revealed less scarring in the experimental wound in a rat model. Moreover, on macroscopic inspection, the experimental wound exhibited less visible scarring compared with the control. Therefore, the present study demonstrated that the combination gene therapy of t-TGF-βRII and HGF promoted wound healing, with less scarring and more epithelial tissue formation, not only by suppressing the overgrowth of collagen due to its antifibrotic effect, but also by promoting tissue regeneration.
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http://dx.doi.org/10.1590/1414-431X20199144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6967399PMC
February 2020

An automatic beam alignment system based on relative reference points for Thomson scattering diagnosis system.

Rev Sci Instrum 2019 Dec;90(12):126102

Department of Engineering and Applied Physics, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.

An automatic beam alignment system based on relative reference points is developed for the Thomson scattering system on Keda Torus eXperiment. Two critical apertures around the vacuum vessel are designed to shield stray light, and a probe beam is required to go through the centers of these two apertures, which are the reference points for alignment. Since these two apertures are coated with light absorbing materials, three fibers with glowing tips are employed to indicate the centers of two apertures. CMOS cameras are used to monitor beam deviations. The misalignment correction is achieved by driving piezomotor mirror mounts via a program developed with LabVIEW, which includes the image acquisition and processing module and the deviation correction module. As a result, this system can correct beam misalignment in less than 20 s and suppress the long-term drift of laser pointing in ±10 μrad. Also, this system has the capability to correct up to about 2.3 mm of camera shift with our experiment condition.
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http://dx.doi.org/10.1063/1.5123301DOI Listing
December 2019

Chitosan-calcium alginate dressing promotes wound healing: A preliminary study.

Wound Repair Regen 2020 05 23;28(3):326-337. Epub 2019 Dec 23.

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang Province, Hangzhou, China.

Dressings are necessary during the process of wound healing. Since the early 1980s, several types of wound dressings have been produced, but they cannot always take into account some effects include antibacterial effect, wound healing promotion, and other properties. In this study, we would like to develop an effective dressing with the above properties, especially accelerating wound healing effect. A chitosan-calcium alginate dressing (CCAD) was developed by coating mixture of chitosan with high-low molecular weight on calcium alginate dressing (CAD). We investigated the structural characteristics of CCAD with Fourier-transform infrared spectroscopy (FTIR) and electron microscopy. The cytotoxicity and antibacterial property were evaluated in vitro using CCK-8 and inhibition zone method. Moisture retention was tested on the skin of Sprague-Dawley (SD) rats, and wound healing studies were performed on a full-thickness skin wound model in SD rats. CCAD showed good moisturizing and antibacterial properties with no cytotoxicity. CCAD could inhibit inflammation by decreasing IL-6, and it could also promote angiogenesis by increasing VEGF, resulting in better wound healing than CAD. CCAD is a better choice in wound care due to its antibacterial property, biocompatibility, moisture retention, healing promotion, and non-cytotoxicity characteristics.
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http://dx.doi.org/10.1111/wrr.12789DOI Listing
May 2020

p53 Protects Cells from Death at the Heatstroke Threshold Temperature.

Cell Rep 2019 Dec;29(11):3693-3707.e5

MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

When the core body temperature is higher than 40°C, life is threatened due to heatstroke. Tumor repressor p53 is required for heat-induced apoptosis at hyperthermia conditions (>41°C). However, its role in sub-heatstroke conditions (≤40°C) remains unclear. Here, we reveal that both zebrafish and human p53 promote survival at 40°C, the heatstroke threshold temperature, by preventing a hyperreactive heat shock response (HSR). At 40°C, both Hsf1 and Hsp90 are activated. Hsf1 upregulates the expression of Hsc70 to trigger Hsc70-mediated protein degradation, whereas Hsp90 stabilizes p53 to repress the expression of Hsf1 and Hsc70, which prevents excessive HSR to maintain cell homeostasis. Under hyperthermia conditions, ATM is activated to phosphorylate p53 at S37, which increases BAX expression to induce apoptosis. Furthermore, growth of p53-deficient tumor xenografts, but not that of their p53 counterparts, was inhibited by 40°C treatment. Our findings may provide a strategy for individualized therapy for p53-deficient cancers.
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http://dx.doi.org/10.1016/j.celrep.2019.11.032DOI Listing
December 2019

Development of a Chitosan-Vaseline Gauze Dressing with Wound-Healing Properties in Murine Models.

Am J Trop Med Hyg 2020 02;102(2):468-475

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China.

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.
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http://dx.doi.org/10.4269/ajtmh.19-0387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008328PMC
February 2020

The effect of topical ramipril and losartan cream in inhibiting scar formation.

Biomed Pharmacother 2019 Oct 31;118:109394. Epub 2019 Aug 31.

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, PR China; Department of Plastic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang Province, PR China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.biopha.2019.109394DOI Listing
October 2019

Arterial thoracic outlet syndrome caused by cervical ribs-an unusual case report.

Medicine (Baltimore) 2019 Mar;98(11):e14778

Department of Hand Surgery, The First Affiliated Hospital.

Rationale: Cervical ribs are rare conditions, occurring in 0.05% to 3.0% of the population. This manuscript reports a case of arterial thoracic outlet syndrome (ATOS) associated with this congenital anomaly.

Patient Concerns: We report a 32-year-old female worker presenting pain in her left upper-extremity for 7 months. Her left hand became paler and cold when the temperature decreased, and the symptoms could not be eased through rest, physiotherapy and drugs medication.

Diagnoses: Compression of left subclavian artery with axillary and brachial arteries thrombosis was confirmed by duplex ultrasound and computed tomography angiography. ATOS caused by cervical ribs was confirmed by medical history, physical examination, and imaging.

Interventions: The patients underwent acute thrombolysis and balloon angioplasty.

Outcomes: Symptoms of pain and weakness disappeared after surgery. The patient had not experienced any apparent symptom recurrence at 1-year follow-up.

Lessons: Successful treatment of ATOS depends upon urgent assessment, accurate identification of causative factors and compression site and early diagnosis before the event of arterial thrombosis. The surgery combined with anticoagulation treatment can improve the treatment outcome of ATOS.
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http://dx.doi.org/10.1097/MD.0000000000014778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426594PMC
March 2019

Tranexamic Acid for Adults with Melasma: A Systematic Review and Meta-Analysis.

Biomed Res Int 2018 6;2018:1683414. Epub 2018 Nov 6.

Department of Plastic Surgery, Zhejiang Hospital, Hangzhou 310013, China.

Objective: Melasma is a highly prevalent, chronic, and pigmentary disorder. This systematic review aims to evaluate the efficacy and safety of tranexamic acid (TA) for the treatment of adults with melasma.

Methods: We independently searched 3 databases from beginning to 26 April, 2018. The study included 21 eligible trials. Two writers extracted data at the same time independently. Study outcomes were calculated by standardized mean differences (SMD) with 95% confidence intervals (CIs). All statistical analyses were performed using Review Manager Version 5.3 and STATA Version 15.1.

Results: The combined results showed that the use of TA was associated with reduced Melasma Area and Severity Index (MASI) and Melanin Index (MI). No significant difference in Erythema Index (EI) was observed with TA treatment. Side effects were minor, with a few cases reporting mild gastrointestinal reaction, oligomenorrhoea, hypopigmentation, urticarial rash, and skin irritation xerosis.

Conclusion: The meta-analysis suggested that TA treatment appeared to be a promising therapeutic approach for melasma.
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http://dx.doi.org/10.1155/2018/1683414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247725PMC
March 2019

Angiotensin-converting enzyme inhibitor works as a scar formation inhibitor by down-regulating Smad and TGF-β-activated kinase 1 (TAK1) pathways in mice.

Br J Pharmacol 2018 11 8;175(22):4239-4252. Epub 2018 Oct 8.

Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

Background And Purpose: Angiotensin-converting enzyme (ACE), an important part of the renin-angiotensin system, is implicated in stimulating the fibrotic processes in the heart, lung, liver and kidney, while an ACE inhibitor (ACEI) promotes physiological tissue repair in these organs. The mechanism is closely related to TGF-β1 pathways. However, the reported effects of applying ACEIs during scar formation are unclear. Hence, we explored the anti-fibrotic effects of an ACEI and the molecular mechanisms involved in a mouse scar model.

Experimental Approach: After a full-thickness skin wound operation, ACE wild-type mice were randomly assigned to receive either ramipril, losartan or hydralazine p.o. ACE knockout (KO) mice and negative control mice only received vehicle (water). Wound/scar widths during wound healing and histological examinations were recorded at the final day. The ability of ACEI to reduce fibrosis via TGF-β1 signalling was evaluated in vitro and in vivo.

Key Results: ACE KO mice and mice that received ramipril showed narrower wound/scar width, reduced fibroblast proliferation, decreased collagen and TGF-β1 expression. ACEI attenuated the phosphorylation of small mothers against decapentaplegic (Smad2/3) and TGF-β-activated kinase 1 (TAK1) both in vitro and in vivo. The expression of ACE-related peptides varied in murine models with different drug treatments.

Conclusions And Implications: ACEI showed anti-fibrotic properties in scar formation by mediating downstream peptides to suppress TGF-β1/Smad and TGF-β1/TAK1 pathways. These findings suggest that dual inhibition of Smad and TAK1 signalling by ACEI is a useful strategy for the development of new anti-fibrotic agents.
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http://dx.doi.org/10.1111/bph.14489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193878PMC
November 2018

Clinical Application of Split-Thickness Skin with Pedicle for Finger Wounds.

Biomed Res Int 2018 27;2018:9470198. Epub 2018 Jun 27.

Department of Plastic Surgery, Hangzhou Plastic Surgery Hospital, Hangzhou, Zhejiang Province, China.

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.
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http://dx.doi.org/10.1155/2018/9470198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040272PMC
January 2019

Clinical Application of 3-Dimensional Continuous Suturing Technique for Triangular Wounds.

Ann Plast Surg 2018 09;81(3):316-321

Department of Plastic Surgery, Hangzhou Plastic Surgery Hospital, Hangzhou, Zhejiang Province, PR China.

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.
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http://dx.doi.org/10.1097/SAP.0000000000001509DOI Listing
September 2018

The source of ACE during scar formation is from both bone marrow and skin tissue.

FASEB J 2018 09 11;32(9):5199-5208. Epub 2018 May 11.

Department of Plastic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

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.
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http://dx.doi.org/10.1096/fj.201701575RRRDOI Listing
September 2018
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