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Background and aims Fractional lasers have become increasingly popular for treating atrophic scars, but their effectiveness is limited for deeper scars. We developed a novel technique (manual fractional thermal contraction technology, MFTCT) using an ultra-pulse CO2 laser and evaluated its efficacy and safety for treating atrophic facial scars. Methods A total of 44 patients with atrophic facial scars were treated with MFTCT every 8 weeks for 1-4 times. Overall scar improvement was assessed by photographs taken at baseline and 3 months after the last treatment according to the 4-point global assessment scale (GAS) and ECCA grading scale. Improvements in color, distortion, and texture were assessed by the modified Manchester Scar Scale and scored individually from 1 to 4. Pain degrees and adverse reactions during and after treatment were recorded. Results A total of 44 patients completed the treatment and follow-ups; of them, 89% reported at least 50% overall improvement after the last treatment. The mean ECCA scores fell from 67.50 ± 23.98 to 45.68 ± 18.57 (a 32% improvement), and the change was significant (P = .000). The average score for overall improvement was 3.48. The average scores for color, distortion, and texture were 3.07 ± 0.62, 3.27 ± 0.50, and 3.52 ± 0.51, respectively. Mean pain degree score was 4.27 ± 1.04, and mean erythema duration was 28.43 ± 6.58 days. Some patients developed pigmentation for a few months that resolved with topical treatment. Conclusion Manual fractional thermal contraction technology has definite clinical efficacy in the treatment of atrophic facial scars with fewer adverse reactions and is worth using in the clinical setting.

Reconstruction of defects of nasal ala and dorsum after surgical excision presents a substantial challenge to dermatologic surgeons. Second intention healing is a simple and extremely useful method to optimize cosmesis after skin cancer removal.This study reported the cosmetic outcomes after second intention healing of nasal ala and dorsum defects in Asians, and estimated the time to epithelialization and complete healing.Fifteen defects (1 cm in diameter) of the nasal ala and dorsum in 10 patients were allowed to heal by secondary intention. Cosmetic results were evaluated and the time to epithelialization and complete healing were recorded.Cosmetic outcomes were good to excellent in 80% of the defects; defects of the dorsum showed poorer cosmetic results than defects of the ala. The wounds needed 5-17 days (mean 11.3; SD ± 4.18) to complete epithelialization and 10-24 days (mean 17.7; SD ± 4.85) to heal completely.Second intention healing of small nasal ala and dorsum defects (1 cm in diameter) in Asians produces satisfactory cosmetic results with a low complication rate.

Objective To evaluate the inhibitory effect of fenretinide-loaded liposomes (4-HPR-L) on subcutaneous transplanted malignant melanomas in nude mice. Methods A film-ultrasonic dispersion method was used to prepare 4-HPR-L. BALB/c nude mice were subcutaneously inoculated with A375 melanoma cells in the right axillary fossae to establish malignant melanoma-bearing nude mouse models. Ten nude mouse models were randomly and equally divided into 2 groups to be injected with near-infrared fluorescent cell membrane label (DiR) solution or DiR liposomes (DiR-L) at the same concentration in the caudal vein, and a live imaging system was used to observe the distribution of DiR or DiR-L in nude mice at 6, 12, 24 hours after the injection. Another 30 nude mice were randomly and equally divided into 3 groups to be injected with 5% (mass fraction) glucose solution at a single-dose of 0.2 ml (control group) , 25 mg/kg 4-HPR solution (4-HPR group) and 25 mg/kg 4-HPR-L solution (4-HPR-L group) respectively on days 8, 10, 12, 14, 16, 18, 20 and 22 after the inoculation with A375 cells. The mouse body weight and tumor volume were dynamically monitored in the above groups after the injection, and the survival situation was observed. The nude mice were sacrificed on day 2 after the final injection, and the heart, liver, spleen, lung, kidney and tumor tissues were resected. These tissues were subjected to hematoxylin-eosin staining and immunohistochemical staining to observe the metastasis of melanoma in mice, and terminal deoxyribonucleotidyl transferase-mediated nick end labelling was performed to detect the apoptosis in tumor cells. One-way analysis of variance and independent-sample t test were used to analyze measurement data. Results The live imaging system showed that DiR-L could be retained in melanoma for a long time, and strong fluorescence of DiR-L could be still observed in the tumors at 24 hours after injections. Quantitative fluorescence analysis revealed that the fluorescence intensity of DiR-L (22.85 ± 1.66) was significantly higher than that of DiR in tumor tissues (8.45 ± 0.97, t = 12.957, P < 0.01) . Compared with the control group and 4-HPR group, the resected tumor weight on day 2 after the final injection was significantly decreased in the 4-HPR-L group (F = 27.055, t = 4.768, 6.640, respectively, both P < 0.05) . Hematoxylin-eosin staining showed that liver metastasis occurred in 2 nude mice in the 4-HPR-L group, but in all the nude mice in the control group and 4-HPR group. All the nude mice in the 4-HPR-L group died within 76 days after inoculation, and the mice in the control group and 4-HPR group all died within 56 and 59 days respectively after inoculation. There were significant differences in the apoptotic index among the control group (12.14‰ ± 1.33‰) , 4-HPR group (67.17‰ ± 15.18‰) and 4-HPR-L group (152.73‰ ± 11.27‰; F = 167.588, P < 0.05) , and the apoptotic index was significantly higher in the 4-HPR-L group than in the control group and 4-HPR group (t = 18.162, 11.075 respectively, both P < 0.05) . Conclusion 4-HPR-L can effectively inhibit the growth of subcutaneous melanoma in nude mice and metastasis of melanoma cells, and prolong the survival duration of nude mice. Key words: Nevi and melanomas; Fenretinide; Liposomes; Models, animal; Apoptosis; A375 cells

Recurrence is a common complication observed during cutaneous squamous cell carcinoma (cSCC) treatment; however, biomarkers for predicting recurrence in cSCC remain unknown. The present study aimed to investigate the predictive value of axis inhibition protein 2 (AXIN2) and SNAIL expression in cSCC recurrence. AXIN2 and SNAIL expression was evaluated using immunohistochemistry in 111 cSCC tissue samples obtained from 18 patients who presented recurrence (recurrence interval, 1–91 months) and 93 patients who did not experience recurrence following Mohs micrographic surgery (MMS) during the follow-up period (156 months). Nomogram construction was performed using patients' clinicopathological characteristics and AXIN2 and SNAIL protein expression. The results demonstrated that high AXIN2 (histoscore >100) and SNAIL (histoscore >100) expression was detected in 35 and 44 cSCC tissues, respectively. Furthermore, the expression levels of AXIN2 and SNAIL were significantly associated in patients with cSCC (P=0.001). AXIN2 and SNAIL expression levels were significantly associated with tumor size (P=0.021 and P=0.044, respectively) and recurrence of cSCC (P=0.017 and P=0.042, respectively). In addition, the results of the Kaplan-Meier curve analysis revealed that recurrence-free survival was significantly associated with tumor size (P=0.025), differentiation status (P

Keloids were characterized by excessive growth of fibrous tissues, and shared several pathological characteristics with cancer. They did put physical and emotional stress on patients in that keloids could badly change appearance of patients. N-(4-hydroxyphenyl) retinamide (4HPR) showed cytotoxic activity on a wide variety of invasive-growth cells. Our work was aim to prepare N-(4-hydroxyphenyl) retinamide-loaded lipid microbubbles (4HPR-LM) combined with ultrasound for anti-keloid therapy. 4HPR-loaded liposomes (4HPR-L) were first prepared by film evaporation method, and then 4HPR-LM were manufactured by mixing 4HPR-L and perfluoropentane (PFP) with ultrasonic cavitation method. The mean particle size and entrapment efficiency 4HPR-LM were 113 nm and 95%, respectively. The anti-keloids activity of 4HPR-LM was assessed with BALB/c nude mice bearing subcutaneous xenograft keloids model. 4HPR-LM, combined with ultrasound, could significantly induce apoptosis of keloid fibroblasts in vitro and inhibited growth of keloids in vivo. Thus, 4HPR-LM could be considered as a promising agent for anti-keloids therapy.

Zhouna Li, Zhehu Jin Department of Dermatology, Yanbian University Affiliated hospital, Yanji, Jilin, People’s Republic of China Background: Keloids and hypertrophic scars are the most common types of pathological scarring. Traditionally, keloids have been considered as a result of aberrant wound healing, involving excessive fibroblast participation that is characterized by hyalinized collagen bundles. However, the usefulness of this characterization has been questioned. In recent years, studies have reported the appropriate use of verapamil for keloids and hypertrophic scars.Methods: Searches were conducted on the databases Medline, Embase, Cochrane, PubMed, and China National Knowledge Infrastructure from 2006 to July 2016. State12.0 was used for literature review, data extraction, and meta-analysis. Treatment groups were divided into verapamil and nonverapamil group. Nonverapamil group includes steroids and intense pulsed light (IPL) therapy. Total effective rates include cure rate and effective rate. Cure: skin lesions were completely flattened, became soft and symptoms disappeared. Efficacy: skin lesions subsided, patient significantly reduced symptoms. Inefficient definition of skin was progression free or became worse. Random-effects model was used for the meta-analysis.Results: Six studies that included 331 patients with keloids and hypertrophic scars were analyzed. Analysis of the total effective rate of skin healing was performed. The total effective rates in the two groups were 54.07% (verapamil) and 53.18% (nonverapamil), respectively. The meta-analysis showed that there was no difference between the two groups. We also compared the adverse reactions between the verapamil treatment group and the steroids treatment group in two studies, and the result indicated that the verapamil group showed less adverse reactions.Conclusion: There were no differences between the application of verapamil and nonverapamil group in keloids and hypertrophic scars treatment. Verapamil could act as an effective alternative modality in the prevention and treatment of keloid and hypertrophic scars. A larger number of studies are required to confirm our conclusion. Keywords: keloids, hypertrophic scars, verapamil, steroids, IPL

The aim of the present study was mainly to assess the advantage of docetaxel-loaded PEG-albumin nanoparticles (PEG-DANPs) against non-small cell lung cancer (NSCLC) compared with the commercial product of docetaxel (Aisu®) and docetaxel-albumin nanoparticles (DANPs). We made systematic assessments on these three drugs against NSCLC both in vitro and in vivo. Based on our experiments, PEG-DANPs showed a dose- and time-dependent efficacy in the in vitro cytotoxicity studies; the tumors growth and the metastases in the livers of NSCLC-bearing nude mice in vivo were reduced dmarkedly by PEG-DANPs, and the PEG-DANP-treated mice had a minimum of weight loss; furthermore, the mice which were treated with PEG-DANPs can survive longer than the other groups. In conclusion, the PEG-DANPs have the lowest side-effects, and the highest antitumor and metastases activity of the three drugs, and it may provide an alternative to patients with NSCLC.

Atopic dermatitis (AD) is a chronic recurrent skin disease dominated by T-helper 2 inflammation. Momelotinib (MMB) is a novel JAK1/JAK2 inhibitor suppressing the signal transduction of multiple pro-inflammatory cytokines. Recent studies indicated that JAK inhibitor could play a therapeutic role in AD disease. In this study, we evaluated the efficacy of MMB as a novel JAK1/JAK2 inhibitor in DNCB-induced AD mice and TSLP-activated dendritic cells. Our data showed that topical application of MMB reduced the skin severity scores and total serum IgE levels, and alleviated the histological indexes including epidermal thickness measurement and mast cell number. Also, it was demonstrated that MMB down-regulated the mRNA expression of IL-4, IL-5, IFN-&gamma, and TSLP, and inhibited the phosphorylation of STAT1, STAT3 and STAT5 in skin lesions. Moreover, MMB reduced the expression of CD80, CD86, MHCII and mRNA of OX40L in TSLP-activated dendritic cells. In general, our study suggests that MMB can improve the symptoms of AD and topical application of MMB can become a promising new therapy strategy for AD.

The present study mainly compared the effect of docetaxel-albumin nanoparticles (DANPs) and docetaxel-loaded PEG-albumin nanoparticles (PEG-DANPs) against non-small cell lung cancer (NSCLC). We made systematic assessments on these three drugs against NSCLC both in vitro and in vivo. With the purpose of eliminating side-effects of the commercial formulation (Tween-80) and prolonging the blood circulation time, we used emulsion-evaporation cross-link method to prepare DANPs and PEG-DANPs. The DANPs had an average particle size of 163.4 ± 3.76 nm, a zeta potential of -19.4 ± 0.18 mV, a polydispersity index of 0.143 ± 0.03, a drug loading of 8.71 ± 0.98%, and an encapsulation efficiency of 93.58 ± 0.86%; the average particle size of PEG-DANPs is 169.19 ± 2.36 nm, zeta potential is -18.2 ± 0.21 mV, with a polydispersity index of 1.56 ± 0.05, a drug loading of 8.72 ± 1.05% and an encapsulation efficiency of 95.4 ± 5.5%. PEG-DANPs showed a dose- and time-dependent efficacy in cytotoxicity studies in vitro; the hemolysis test indicated that PEG-DANPs had less hemocytolysis than Aisu® and DANPs; in addition, a more prolonged circulation time and sustained in vitro release behavior were observed in the PEG-DANPs compared with Aisu® and DANPs; the cellular uptake test in vitro demonstrated that PEG-DANPs could be absorbed easier into the nucleus; furthermore, the tumor growth of NSCLC-bearing nude mice in vivo was reduced the most by PEG-DANPs. In conclusion, the PEG-DANPs have the lowest side-effects, the highest antitumor activity with the longest blood circulation time of the three drugs, and it will provide an alternative to patients with NSCLC.

Runt-related transcription factor 3 (RUNX3) has recently been reported to be a possible predictor of sensitivity of cancer cells for photodynamic therapy (PDT), a promising therapeutic modality for keloids. In this study, we aimed to elucidate the implications of RUNX3 for keloid pathogenesis and sensitivity to pheophorbide a-based PDT (Pa-PDT). RUNX3 and proliferating cell nuclear antigen (PCNA) expression were examined in 6 normal skin samples and 32 keloid tissue samples by immunohistochemistry. We found that RUNX3 expression was detected more often in keloid tissues than in dermis of normal skin. In keloid tissues, RUNX3 expression was significantly increased in patients presenting with symptoms of pain or pruritus, and was also significantly related to PCNA expression. The therapeutic effect of Pa-PDT was comparatively investigated in keloid fibroblasts (KFs) with and without RUNX3 expression. Significant differences were found after Pa-PDT between KFs with and without RUNX3 expression in cell viability, proliferative ability, type I collagen expression, generation of reactive oxygen species (ROS), and apoptotic cell death. In addition, RUNX3 expression was significantly decreased after Pa-PDT in KFs, and KFs with downregulation of RUNX3 showed significantly increased cell viability after Pa-PDT. Pa-PDT may be a potential therapeutic modality for keloids, and RUNX3, as a possible contributor to keloid pathogenesis, may improve sensitivity to Pa-PDT in KFs.

Background: Optimal treatment for prostate cancer remains a challenge worldwide. Recently, T cell immunoglobulin mucin-3 (TIM-3) has been implicated in tumor biology but its contribution prostate cancer remains unclear. The aim of this study was to investigate the role of TIM-3 as a prognostic marker in patients with prostate cancer. Methods: TIM-3 protein expression was determined by immunohistochemistry and Western blotting in 137 prostate cancer tumor samples and paired adjacent benign tissue. We also performed cell proliferation assays using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl- 2H tetrazolium bromide (MTT) and cell invasion assays. The effects of small interfering RNA (siRNA)-mediated knockdown of TIM-3 (TIM-3 siRNA) in two human prostate cancer cell lines were also evaluated. Results: TIM-3 expression was higher in prostate cancer tissue than in the adjacent benign tissue (P

Background The beneficial cardiac effects of some Ca(2+) channel blockers have been attributed to blood pressure reduction, but these pleiotropic effects require further investigation. We compared the effects of benidipine, which has beneficial cardiac effects, and nitrendipine, which does not, in an animal model of hypertensive diastolic heart failure (DHF). Methods and results Male Dahl salt-sensitive rats were fed a high-salt diet from age 7 weeks to induce hypertension and were either vehicle or orally administered benidipine (3 mg/kg daily) or nitrendipine (10 mg/kg daily) from age 10 to 18 weeks. Control rats were maintained on a low-salt diet. In vehicle-treated rats, left-ventricular (LV) fractional shortening was preserved but LV end-diastolic pressure was increased, indicative of DHF. Benidipine and nitrendipine had similar antihypertensive effects and reduced both LV weight and cardiomyocyte hypertrophy. Benidipine reduced LV diastolic stiffness and mortality to a greater extent than did nitrendipine. Benidipine, but not nitrendipine, also reduced lung weight. The extent of interstitial fibrosis and the abundance of mRNAs for prohypertrophic, profibrotic, or proinflammatory genes in the left ventricle were reduced by benidipine and nitrendipine. Benidipine, but not nitrendipine, increased capillary density and restored the expression of hypoxia-inducible factor 1alpha, vascular endothelial growth factor, and endothelial nitric oxide synthase in the left ventricle. Conclusions Benidipine reduced LV diastolic stiffness and increased survival, effects likely attributable predominantly to promotion of coronary angiogenesis rather than to attenuation of interstitial fibrosis. Benidipine may thus be more effective than purely L-type Ca(2+) channel blockers in preventing hypertensive DHF.

The forkhead box (FOX) family of transcription factors are considered to have a role in tumorigenesis. FOXJ1 is a member of the FOX family; however, its function in human renal cell carcinoma (RCC) has remained to be elucidated. Therefore, the present study evaluated the expression of FOXJ1 in human clear cell RCC and the effect of FOXJ1 on the proliferative ability of RCC cells. The RCC specimens analyzed in the present study were obtained from 286 patients with RCC who underwent nephrectomy. FOXJ1 mRNA expression levels were determined using reverse transcription-quantitative polymerase chain reaction, and FOXJ1 protein expression levels were determined using immunohistochemistry and western blot analysis. To determine the effect of FOXJ1 on the proliferative ability of RCC cells, the expression of FOXJ1 was decreased using small interfering (si)RNA, and a FOXJ1 vector was stably transfected into RCC cell lines. The proliferative ability of RCC cells was then examined using a WST-1 assay and xenograft experiments with BALB/c nude mice, where the association between FOXJ1 expression and patient survival was determined using Kaplan-Meier analysis. FOXJ1 expression was significantly higher in RCC tissues compared with that of healthy renal tissues. Furthermore, FOXJ1 expression was associated with tumor stage, histologic grade and size. In addition, FOXJ1 significantly enhanced the proliferation of RCC cells in vitro and in vivo. The present study identified that FOXJ1 expression was upregulated in RCC and enhanced the proliferative ability of RCC cells. Therefore, FOXJ1 may serve as an independent prognostic marker and a therapeutic target for the treatment of patients with RCC.

Purpose Several studies have compared the effects of coronary stenting and coronary-artery bypass grafting (CABG) on left main coronary artery (LMCA) disease. However, there are limited data on the long-term outcomes of these two interventions in diabetic patients. Materials and Methods We evaluated 56 patients with LMCA stenosis who underwent drug-eluting stent (DES) implantation and 116 patients who underwent CABG in a single hospital in China between January 2004 and December 2006. We compared long-term major adverse cardiac events (death; a "serious outcome" composite of death, myocardial infarction, or stroke; and target-vessel revascularization). Results In-hospital (30-day) mortality was 0% for the DES group and 3.4% for the CABG group (p=0.31). There was no difference between the two groups in terms of risk of death [hazard ratio for stenting group, 0.49; 95% confidence interval (CI), 0.13-1.63; p=0.55] or risk of serious outcome (hazard ratio for DES group, 1.11; 95% CI, 0.39-1.45; p=0.47). The target-vessel revascularization rate was higher in the DES group than in the CABG group (hazard ratio, 3.67; 95% CI, 1.24-11.06; p=0.018). Conclusion In this cohort of diabetic patients with LMCA stenosis, there was no difference in composite endpoints between patients receiving DESs and those undergoing CABG. However, stenting was associated with higher rates of target-vessel revascularization than CABG. DES implantation in diabetic patients with LMCA disease was found to be at least as safe as CABG.