Bone marrow mesenchymal stem cells alleviate the formation of pathological scars in rats.

Introduction: Although bone marrow-derived mesenchymal stem cells (BMSCs) have attracted increasing attention because of their pivotal functions in the process of wound healing and fibrosis alleviation, the underlying molecular mechanisms have been poorly understood. Moreover, transforming growth factor beta 1 (TGF-ß1) is positively correlated with scar formation, whereas TGF-ß3 inhibits the pathological scar formation process. However, the relation of TGF-ß1, TGF-ß3, and the TGF-ß/Smad signaling pathway with BMSCs is unknown and requires further investigation. Methods: A cell co-culture platform was used to examine the relationship between BMSCs and dermal fibroblasts (DFs). EdU labelling and cell cycle detection were carried out to examine the viability of DF cells. Transwell and wound healing assays were used to test the cell migration of DFs. The expression of TGF-ß pathway components and collagens were determined by RT-qPCR and western blotting. A damaged skin rat model was applied to test the effects of BMSC treatment on skin wound healing. Results: The results showed that BMSC secretion could inhibit the viability and migration of DFs. Moreover, we observed that the TGF-ß-induced expression of TGF-ß1, Smad2, Smad3, COLI and COLIII was attenuated upon BMSC treatment in DFs, while the decrease in TGF-ß3 expression was enhanced by BMSCs. Furthermore, BMSC treatment accelerated wound healing and attenuated skin collagen deposition in a damaged skin rat model, leading to the mitigation of cell proliferation and enhancement of cell apoptosis. In addition, the expression of alpha-smooth muscle actin (α-SMA), COLI, and COLII was alleviated by BMSC treatment. Conclusions: Our results indicate that BMSCs can promote wound healing and inhibit skin collagen deposition, which is associated with the TGF-ß/Smad signaling pathway.

Restoration of forearm supination by combining pronator teres with allogeneic tendon.

BACKGROUND: Many solutions have been proposed in treating of forearm supination. Comparing with other supination function reconstructions, pronator teres rerouting is believed to be less effective due to its insufficient supination strength. The aim of this study is to introduce a modified procedure, and compare its result with two previous approaches. PATIENTS AND METHODS: From 2015 to 2020, 11 patients have restored forearm supination by rerouting of the pronator teres weave sutured with allogeneic tendons. The average follow-up period was 17.5 months (12 to 24). The range of active supination at the final follow-up was recorded. RESULTS: Almost all patients acquired good supination range. The average active post-operative supination was 72.7° (60° to 80°) at the final follow-up. No complication was observed. All patients retained full range of pronation. CONCLUSIONS: This study provides a modified supination function reconstruction with simple operating, fine results, low risks, and no affecting of pronation function. The use of allogeneic tendon makes up for the muscles with insufficient length, making it valuable to reconsider those rebuilding operations that were once considered unpromising by many.

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

Background: Long noncoding RNA (lncRNA) LUADT1 is a known oncogenic lncRNA in lung cancer. This study aimed to explore the roles of LUADT1 in melanoma. Materials and Methods: 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. Results: 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. Conclusions: LUADT1 in melanoma and may sponge miR-28-5p to upregulate RAP1B, thereby promoting cancer cell proliferation.

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

Wound scarring remains a major challenge for plastic surgeons. Transforming growth factor (TGF)-ß plays a key role in the process of scar formation. Previous studies have demonstrated that truncated TGF-ß type II receptor (t-TGF-ßRII) is unable to continue signal transduction but is still capable of binding to TGF-ß, thereby blocking the TGF-ß 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-ßRII 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-ßRII/HGF) into fibroblasts in vitro and in a rat model in vivo was used. The results demonstrated that the expression of t-TGF-ßRII 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-ßRII 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.

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

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.

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

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-ß1 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-ß1 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-ß1 expression. ACEI attenuated the phosphorylation of small mothers against decapentaplegic (Smad2/3) and TGF-ß-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-ß1/Smad and TGF-ß1/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.

Modified Bunnell suture expands the surgical indication of the treatment of Haglund's syndrome heel pain with endoscope.

The aim of the present study was to develop a method which can solve the problem of partial tearing of the Achilles tendon insertion caused by the debridement for Haglund's syndrome using endoscopy-assisted percutaneous repair. Seven patients with Haglund's syndrome were prospectively recruited. All 7 patients (3 female, 4 male) had intratendinous calcifications. Preoperative diagnosis was made according to the clinical symptoms and diagnosis, medical examination results, plain film radiographs, and magnetic resonance imaging. The patients whose average age was 35.2 years, had experienced symptoms and were treated by conservative methods for 12-24 months (average 17.1 months). All 7 cases were treated with debridement of Achilles tendon insertion site with a standard 4.0 mm bur and underwent repair treatment with a modified Bunnell suture method under direct visualization using arthroscopy. The American Orthopaedic Foot and Ankle Society (AOFAS) score and the changes of the patient's parallel pitch lines were used to evaluate and assess the results. The follow-up period averaged 22 months. The lateral X-ray film after operation of all the heels of the patients showed that sufficient osseous planning of all the patients was completed. None of the patients converted to conventional open surgery. The average AOFAS scores of the 7 cases were improved significantly at final follow-up compared to pretherapy (P<0.005). The results of 5 of the 7 cases were excellent, 2, were good, and 0 was fair or poor. None of the cases had permanent nerve injuries, wound infections or Achilles tendon avulsion. Our study is a supplement of endoscopic repairing and strengthening of the Achilles tendon. The advantages and clinical significance of endoscopy during the treatment of Haglunds syndrome under the premise of strict control of operation indications were further verified.

Descriptions of larvae of three species of Hydropsyche (Trichoptera, Hydropsychidae) from China.

Twenty-one individuals of Hydropsyche from An-hui and Zhe-jiang Provinces, China, were examined and their DNA barcode sequences were generated and analyzed. The larvae and males of H. arion, H. columnata, H. simulata, and H. trifora were associated by mtCOI gene sequences. The larvae of H. arion, H. columnata, and H. trifora are described in detail and their diagnostic photographs are provided. Character photographs of the H. simulata larva are also presented. A key to 5th instar larvae of 15 species of Chinese Hydropsyche is provided.

Efficacy of escitalopram oxalate for patients with post-stroke depression.

This retrospective study investigated the efficacy and safety of escitalopram oxalate (ESO) for the treatment of post-stroke depression (PSD).A total of 115 patients with PSD were included in this study. A total of 65 patients underwent ESO (Intervention group). A total of 50 patients received acupressure (Control group). The outcome measurements included Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), and Sheehan Disability Scale (SDS). In addition, we also recorded the adverse events in this study.At the end of 8-week treatment, ESO showed greater efficacy in depression, measured by MADRS (P < .01); anxiety, measured by HAM-A scale (P < .01); and disability, measured by SDS (P < .01), compared to acupressure. Additionally, there were not significant differences regarding adverse events between two groups (P > .05).The present results indicate that ESO can decrease symptoms of patients with PSD.

Descriptions of pupae of two Hydropsyche species from China (Insecta, Trichoptera, Hydropsychidae).

Pupae of two Hydropsyche species collected from Zhe-jiang Province, China, were examined and their barcode sequences were generated and analyzed. The pupae of H. simulata and H. homunculus were associated with their adult males by mtCOI gene sequences, described, illustrated, and diagnosed.

A randomized controlled trial of acupressure as an adjunctive therapy to sodium valproate on the prevention of chronic migraine with aura.

BACKGROUND: The primary objective of the present study was to evaluate the efficacy and safety of using acupressure as an adjunctive therapy to sodium valproate (SV) combined with acupressure (ASV) on the prevention of chronic migraine with aura (CMA). METHODS: A total of 98 patients with CMA were randomly divided into an intervention group and a control group, with 49 patients in each group. The patients in the intervention group received ASV, while the participants in the control group received SV alone. The primary outcome was measured by the numeric rating scale (NRS). The secondary outcomes including frequency of migraine attacks, the times of using analgesics, and quality of life, measured by the short-form 36 Health Survey Scale (SF-36) score. In addition, adverse events (AEs) were also recorded throughout the trial. The outcomes were measured at the end of the 8-week treatment, and 4-week follow-up. RESULTS: After the 8-week treatment and 4-week follow-up, ASV efficacy was not greater than that of SV alone regarding pain relief, as measured using the NRS, and frequency of migraine attacks, consumption of analgesics, and quality of life, as measured using the SF-36. However, ASV can significantly reduce the nausea when compared with SV (P = .04). CONCLUSION: The present results indicate that ASV can decrease migraine-related nausea during treatment, but cannot relieve pain or enhance quality of life in patients with CMA.

The Effectiveness of Topical Anti-scarring Agents and a Novel Combined Process on Cutaneous Scar Management.

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.

Risk Factors for Complications after Reduction Mammoplasty: A Meta-Analysis.

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.

Adiposity and Cardiovascular Risk Factor Variables in Childhood Are Associated With Premature Death From Coronary Heart Disease in Adults: The Bogalusa Heart Study.

BACKGROUND: More than 600 deaths of all causes have been documented over the 40-year duration of the Bogalusa Heart Study. Of these, 97 deaths have been related to cardiovascular events, based on obituaries published in local newspapers, death certificates obtained from the State Health Department, information from the coroner and word of mouth by nursing staff from the community. METHODS: This study was a retrospective longitudinal cohort with several observations of each subject. It consisted of 6 cross-sectional surveys of children aged 5-7 years, conducted between 1973 and 1988, and 4 cross-sectional surveys of previously examined subjects as young adults extending into middle age, conducted between 1988 and 2010. RESULTS: Excluding pulmonary, congenital and noncoronary cardiovascular diseases, 46 deaths (average age at death = 44.7 years, range: 31-55) were considered to have been related to coronary artery disease, that is, myocardial infarction. Cardiovascular risk factor observations, gathered from multiple surveys (average of 4.4 surveys, range: 1-14) since childhood, indicated that body fatness and elevated blood pressure beginning in childhood were more common in subjects who later died of coronary artery disease than in living subjects. CONCLUSIONS: The present findings emphasize that sub-clinical cardiovascular disease begins early in life and that early prevention is vital.

A new species of Stenopsyche, with descriptions of larvae and females of some species associated by gene sequences (Insecta: Trichoptera).

Twenty-seven individuals of Stenopsyche from An-hui, Shan-xi and Si-chuan provinces, China, were examined and their DNA (mtCOI) sequences were extracted and analyzed. The larva, male, and female of a new species, S. huangshanensis sp. nov., associated by mtCOI gene sequences, are described and illustrated. Larvae and adult females of 3 known species, S. angustata Martynov 1930, S. navasi Ulmer 1926, and S. tienmushanensis Hwang 1957, were successfully associated with their identifiable males; the larvae and females of S. navasi and S. tienmushanensis were described and illustrated for the first time, and the larva and female of S. angustata were re-described and re-illustrated. DNA from identifiable males of Stenopsyche lotus Weaver 1987 was also sequenced, but the larva and female of this species remain unknown. An unknown larva, not associated with an identifiable adult, was described and illustrated as Stenopsyche sp. 1. All the sequences were uploaded to GenBank. All specimens are deposited in the Insect Collection of Nanjing Agricultural University.

THz saturable absorption in turbostratic multilayer graphene on silicon carbide.

We investigated the room-temperature Terahertz (THz) response as saturable absorber of turbostratic multilayer graphene grown on the carbon-face of silicon carbide. By employing an open-aperture z-scan method and a 2.9 THz quantum cascade laser as source, a 10% enhancement of transparency is observed. The saturation intensity is several W/cm2, mostly attributed to the Pauli blocking effect in the intrinsic graphene layers. A visible increase of the modulation depth as a function of the number of graphene sheets was recorded as consequence of the low nonsaturable losses. The latter in turn revealed that crystalline disorder is the main limitation to larger modulations, demonstrating that the THz nonlinear absorption properties of turbostratic graphene can be engineered via a proper control of the crystalline disorder and the layers number.

Timing of menarche related to carotid artery intima-media thickness in black and white young adult women: the Bogalusa Heart Study.

PURPOSE: The early onset of menarche is related to the adulthood risk of cardiovascular (CV) disease. This study examines the relation of early onset of menarche to carotid artery intima-media thickness (IMT), which is a surrogate marker of CV disease, among asymptomatic young adult women in a black-white community. METHODS: A cohort of 461 women (31% black, 69% white) aged 24 to 43 years (mean of 35.6 years) were participants in the Bogalusa Heart Study. The age at menarche was retrospectively collected. In addition to CV risk factor variable measurements B-mode ultrasound images of the far walls of carotid artery segments were obtained. The multivariate linear regression model along with mediating effect by Sobel test was applied to analyze menarcheal age effect on carotid artery IMT, adjusting for covariates. RESULTS: Waist to height ratio was significantly greater (P = .01) in early menarcheal age (<11 years) versus menarcheal age (≥11 years) in both black and white women. Homeostasis model assessment of insulin resistance (HOMA-IR) was significantly greater (P = .01) in early menarcheal age (<11 years) versus menarcheal age (≥11 years) in white women and also similar direction in black women. Internal carotid artery IMT was the same in early menarcheal age (<11 years) versus menarcheal age (≥11 years) in white women but higher (P = .02) in black women. Given as previously mentioned these different associations, the mediation analysis by race was performed. The effect of early menarcheal age (<11 years) versus menarcheal age (≥11 years) was mediated by waist to height ratio and HOMA-IR in white women after adjusting for parental education and age. The mediating effect of waist to height ratio (Sobel test = -2.26 and P = .02) and HOMA-IR (Sobel test = -1.85 and P = .06) on internal carotid artery IMT was noted in white women. The direct effect of early menarcheal age (<11 years) versus menarcheal age (≥11 years) on internal carotid artery IMT (ß = -0.150, P = .01) was observed in black women. CONCLUSIONS: The observed deleterious effect of early onset of menarche on carotid artery IMT in asymptomatic black and white younger adult women has biological, social, and public health implications.

The Stenopsyche simplex Species Group from China with descriptions of three new species (Trichoptera: Stenopsychidae).

The Chinese Stenopsyche simplex Group is revised for the first time since Weaver's (1987) revision. The group includes 14 described species and 3 new species. Two diagnostic subgroups were recognized by Schmid (1959). The first subgroup of Chinese species includes S. anaximander Malicky 2011, S. brevata Tian & Zheng 1989, S. chinensis Hwang 1957, S. dentata Navás 1930, S. splendida Martynov 1935, S. dubia Schmid 1965, S. rotundata Schmid 1965, S. simplex Schmid 1959, and S. tienmushanensis Hwang 1957; of these, S. dentata is assigned to this first subgroup for the first time. The second diagnostic subgroup includes S. denticulata Ulmer 1926, S. longispina Ulmer 1926, S. stoetzneri Döhler 1929, S. uniformis Schmid 1965 and S. formosana Kobayashi, 1987. The species newly described here include Stenopsyche ningshanensis sp. nov., from Shaan-xi Province, belonging to the first subgroup, and Stenopsyche acanthoclada sp. nov. and Stenopsyche jinxiuensis sp. nov., both from Guang-xi Province and belonging to the second subgroup. Distribution maps of the two diagnostic subgroups of Chinese species and illustrations of male genitalia of the three new species are provided along with collection data for additional specimens for the previously described species.