Facial Injections and Blindness: A Review on Anatomy.

ABSTRACT: With the sudden emergence of new medical aesthetic fillers, the number of fillers injected worldwide has exploded, but there are also worrying risks in the pursuit of beauty. At present, many cases of blindness caused by injection of aesthetic fillers have been reported. Most of the cases are caused by irreversible vascular embolism. This is a rare yet greatly feared complication of using facial cosmetic fillers. This article reviewed and analyzed the literature and summarized the changes in the anatomical structure of facial blood vessels related to blindness during facial injection.

Efficacy of Early Application of 1540 nm Non-ablative Fractional Laser and Silicones to Improve Post-epicanthoplasty Scars.

The combination of epicanthoplasty and blepharoplasty is a popular choice in Asians to acquire a pair of charming big eyes. However, the obvious scarring in the medial canthal area may result in unsatisfactory aesthetic outcomes. Recently, various laser treatments have been used to deal with scars had achieved detectable improvement, but only a few studies investigating the efficacy of lasers used in post-epicanthoplasty scarring were developed. A total of 70 participants who underwent Z-epicanthoplasty were enrolled in this prospective clinical trial and were randomly assigned to the groups of 1540nm non-ablative fractional laser (NAFL) combined with silicones treatment and silicones alone treatment. The NAFL-exposure in the treated group was additionally applied to the medial canthal area on day 21 postoperatively, compared with the participants in the control group who had only been treated with the daily usage of silicone sheets for 12 hours and silicone gels twice for 5 months after scab had fallen from the skin. Scar evolution was performed by patient and observer scar assessment Scales (POSAS) and visual analogue scale (VAS) for 21 days, and 6 months postoperatively. 64 participants have completed the entire follow-up process. The scar recovery was statistically detected in treated group compared with the control group at 6-month postoperatively assessed by POSAS, especially in pliability of scars. Furthermore, the VAS evaluations showed superior satisfaction in treated group. The early treatment of NAFL combined with silicones has improved scar formation in medial canthal region after epicantholplasties efficiently.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Factors Influencing Hypertrophic Scarring after Thyroidectomy.

OBJECTIVE: To identify the risk factors of hypertrophic scarring (HS) after thyroidectomy and construct a risk prediction model. METHODS: From November 2018 to March 2019, the clinical data of patients undergoing thyroidectomy were collected for retrospective analysis. According to the occurrence of HS, the patients were divided into an HS group and a non-HS group. Univariate analysis and binary logistic regression analysis were conducted to explore the independent risk factors for HS. Receiver operating characteristic analysis was also carried out. RESULTS: In this sample, 121 of 385 patients developed HS, an incidence of 31.4%. Univariate analysis showed significant differences in sex, age, postoperative infection, history of abnormal wound healing, history of pathologic scar, family history of pathologic scar, and scar prevention measures between the two groups (P < .05). Binary logistic regression analysis indicated that age 45 years or younger (odds ratio [OR], 1.815), history of abnormal wound healing (OR, 4.247), history of pathologic scarring (OR, 9.840), family history of pathologic scarring (OR, 5.708), and absence of preventive scar measures (OR, 5.566) were independent factors for HS after thyroidectomy. The area under the receiver operating characteristic curve was 0.837. When the optimal diagnostic cutoff value was 0.206, the sensitivity was 0.661, and the specificity was 0.932. CONCLUSIONS: The development of HS after thyroidectomy is related to many factors, and the proposed risk prediction model based on the combined risk factors shows a good predictive value for postoperative HS. When researchers consider the prevention and treatment of scarring in patients at risk, the incidence of HS in different populations can provide theoretical support for clinical decision-making.

Massive Cerebral Infarction Following Facial Fat Injection.

BACKGROUND: Autologous facial fat injection is becoming popular around the world. Semiliquid fat grafts are used for correction of deformities or aesthetic purposes. Fat transfer is a mini-invasive surgical procedure, but causes severe complications occasionally. METHODS: A 30-year-old female patient presented to our hospital with sudden unconsciousness and left limb weakness 8 h after facial fat injection. Brain arteriography (CTA) and venography were performed immediately after her admission. Frontal temporoparietal decompressive craniectomy plus multiple treatments was scheduled for the patient. RESULTS: The patient was diagnosed with extensive cerebral infarction of the right hemisphere. CTA showed that both external and internal carotid arteries were obstructed. A sectional filling defect could be seen at the telecentric segment of the right carotid artery. No development was observed during the full course of the treatment at the carotid bifurcation, external carotid artery, or internal carotid artery. CONCLUSION: Routine cosmetic procedures of facial fat injections could cause devastating and even fatal complications to patients. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A5 online Instructions to Authors www.springer.com/00266.

Application of stems cells in wound healing--an update.

Wound healing is a complex but well-orchestrated tissue repair process composed of a series of molecular and cellular events conducted by various types of cells and extracellular matrix. Despite a variety of therapeutic strategies proposed to accelerate the healing of acute and/or chronic wounds over the past few decades, effective treatment of chronic nonhealing wounds still remains a challenge. Due to the recent advances in stem cell research, a dramatic enthusiasm has been drawn to the application of stem cells in regenerative medicine. Both embryonic and adult stem cells have prolonged self-renewal capacity and are able to differentiate into various tissue types. Nevertheless, use of embryonic stem cells is limited, owing to ethical concerns and legal restrictions. Adult stem cells, which could be isolated from bone marrow, umbilical cord blood, adipose tissue, skin and hair follicles,are being explored extensively to facilitate the healing of both acute and chronic wounds. The current article summarizes recent research on various types of stem cell-based strategies applied to improve wound healing. In addition, future directions of stem cell-based therapy in wound healing have also been discussed. Finally, despite its apparent advantages, limitations and challenges of stem cell therapy are discussed.

Association between SPRY1 and TET3 in skin photoaging and natural aging mechanisms.

BACKGROUND: SPRY1 is associated with the invasiveness and prognosis of various tumors, and TET3 affects aging by regulating gene expression. AIMS: We investigated the roles of SPRY1 and TET3 in natural skin aging, replicative aging, and photoaging, along with the effect of UVA on genome-wide DNA methylation in HaCaT cells. METHODS: TET3 and SPRY1 expression were measured in the skin of patients of different age groups, as well as in vitro human skin, HaCaT cell replicative senescence, and HaCaT and HaCaT-siTET3 cell photoaging models. Senescence was verified using ß-galactosidase staining, and DNA damage was detected using immunofluorescence staining for γ-H2A.X. 5-Methyl cytosine (5-mC) content in the genome was determined using ELISA. RESULTS: SPRY1 expression increased with age, whereas TET3 expression decreased. Similarly, SPRY1 was upregulated and TET3 was downregulated with increasing cell passages. TET3-siRNA upregulated SPRY1 expression in HaCaT cells. UVA irradiation promoted HaCaT cell senescence and induced cellular DNA damage. SPRY1 was upregulated and TET3 was downregulated upon UVA irradiation. Genome-wide 5-mC content increased upon TET3 silencing and UVA irradiation, indicating a surge in overall methylation. CONCLUSIONS: SPRY1 and TET3 are natural skin aging-related genes that counteract to regulate replicative aging and UVA-induced photoaging in HaCaT cells. The cell photoaging model may limit experimental bias caused by different exposure times of skin model samples.

Application of retaining the vessels around the orbicularis oculi muscle in blepharoplasty.

OBJECTIVE: To investigate the effect of retaining the vessels around the orbicularis oculi muscle on reducing local swelling after blepharoplasty. METHODS: A total of 309 patients undergoing blepharoplasty (total incision) were observed and randomly assigned to three groups; (A) conventional operation; (B) preservation of deep vessels; (C) preservation of anterior vessels of orbicularis oculi muscle. The groups were compared based on intraoperative blood loss, operation time, swelling, satisfaction, and complications. RESULTS: Among the 309 patients, 39 were lost to follow-up. c Additionally, A had the shortest operation time, followed by C with slightly longer duration. On the 7th day, 15th day, and 1 month after surgery, both B and C demonstrated significantly lower levels of swelling compared to A. Moreover, patient satisfaction was higher in B and C than in A. CONCLUSION: Retaining either superficial or deep veins of the orbicularis oculi muscle can effectively reduce short-term postoperative swelling. However, when retaining the superficial central group of this muscle during surgery, it is crucial to strictly control the amount of surrounding tissue around vessels.

Dorsal oral mucosa graft urethroplasty for female urethral stricture reconstruction: A narrative review.

Female urethral stricture is currently a challenging situation. In general, urethra dilatation can be selected for treatment, but the complications and high recurrence rate urge doctors to consider other treatments. Recently, dorsal oral mucosa graft urethroplasty is concerned by more and more surgeons, but there are not enough reports so far. A comprehensive search of dorsal oral mucosa graft urethroplasty was performed. According to the existing literature, there are applications of buccal mucosa and lingual mucosa, and compared with other kinds of grafts, the success rate is higher. However, there is a lack of multicenter, large sample and long follow-up studies. And there is still no enough comparative study between different types of oral mucosa. In summary, dorsal oral mucosa graft urethroplasty is an effective option for the management of female urethral stricture. More multicenter and large sample studies with long-term follow-up data are needed.

Comprehensive Analysis of Necroptosis Landscape in Skin Cutaneous Melanoma for Appealing its Implications in Prognosis Estimation and Microenvironment Status.

PURPOSE: Due to poor prognosis and immunotherapy failure of skin cutaneous melanoma (SKCM), this study sought to find necroptosis-related biomarkers to predict prognosis and improve the situation with predicted immunotherapy drugs. EXPERIMENTAL DESIGN: The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression Program (GTEx) database were utilized to recognize the differential necroptosis-related genes (NRGs). Univariate Cox (uni-Cox) and least absolute shrinkage and selection operator (LASSO) Cox analysis were utilized for prognostic signature establishment. The signature was verified in the internal cohort. To assess the signature's prediction performance, the area under the curve (AUC) of receiver operating characteristic (ROC) curves, Kaplan-Meier (K-M) analyses, multivariate Cox (multi-Cox) regression, nomogram, and calibration curves were performed. The molecular and immunological aspects were also reviewed using single-sample gene set enrichment analysis (ssGSEA). Cluster analysis was performed to identify the different types of SKCM. Finally, the expression of the signature gene was verified by immunohistochemical staining. RESULTS: On basis of the 67 NRGs, 4 necroptosis-related genes (FASLG, PLK1, EGFR, and TNFRSF21) were constructed to predict SKCM prognosis. The area's 1-, 3-, and 5-year OS under the AUC curve was 0.673, 0.649, and 0.677, respectively. High-risk individuals had significantly lower overall survival (OS) compared to low-risk patients. Immunological status and tumor cell infiltration in high-risk groups were significantly lower, indicating an immune system that was suppressed. In addition, hot and cold tumors could be obtained by cluster analysis, which is helpful for accurate treatment. Cluster 1 was considered a hot tumor and more susceptible to immunotherapy. Immunohistochemical results were consistent with positive and negative regulation of coefficients in signature. CONCLUSION: The results of this finding supported that NRGs could predict prognosis and help make a distinction between the cold and hot tumors for improving personalized therapy for SKCM.

Cas12a/Guide RNA-Based Platforms for Rapidly and Accurately Identifying Staphylococcus aureus and Methicillin-Resistant S. aureus.

In order to ensure the prevention and control of methicillin-resistant Staphylococcus aureus (MRSA) infection, rapid and accurate detection of pathogens and their resistance phenotypes is a must. Therefore, this study aimed to develop a fast and precise nucleic acid detection platform for identifying S. aureus and MRSA. We initially constructed a CRISPR-Cas12a detection system by designing single guide RNAs (sgRNAs) specifically targeting the thermonuclease (nuc) and mecA genes. To increase the sensitivity of the CRISPR-Cas12a system, we incorporated PCR, loop-mediated isothermal amplification (LAMP), and recombinase polymerase amplification (RPA). Subsequently, we compared the sensitivity and specificity of the three amplification methods paired with the CRISPR-Cas12a system. Finally, the clinical performance of the methods was tested by analyzing the fluorescence readout of 111 clinical isolates. In order to visualize the results, lateral-flow test strip technology, which enables point-of-care testing, was also utilized. After comparing the sensitivity and specificity of three different methods, we determined that the nuc-LAMP-Cas12a and mecA-LAMP-Cas12a methods were the optimal detection methods. The nuc-LAMP-Cas12a platform showed a limit of detection (LOD) of 10 aM (~6 copies µL-1), while the mecA-LAMP-Cas12a platform demonstrated a LOD of 1 aM (~1 copy µL-1). The LOD of both platforms reached 4 × 103 fg/µL of genomic DNA. Critical evaluation of their efficiencies on 111 clinical bacterial isolates showed that they were 100% specific and 100% sensitive with both the fluorescence readout and the lateral-flow readout. Total detection time for the present assay was approximately 80 min (based on fluorescence readout) or 85 min (based on strip readout). These results indicated that the nuc-LAMP-Cas12a and mecA-LAMP-Cas12a platforms are promising tools for the rapid and accurate identification of S. aureus and MRSA. IMPORTANCE The spread of methicillin-resistant Staphylococcus aureus (MRSA) poses a major threat to global health. Isothermal amplification combined with the trans-cleavage activity of Cas12a has been exploited to generate diagnostic platforms for pathogen detection. Here, we describe the design and clinical evaluation of two highly sensitive and specific platforms, nuc-LAMP-Cas12a and mecA-LAMP-Cas12a, for the detection of S. aureus and MRSA in 111 clinical bacterial isolates. With a limit of detection (LOD) of 4 × 103 fg/µL of genomic DNA and a turnaround time of 80 to 85 min, the present assay was 100% specific and 100% sensitive using either fluorescence or the lateral-flow readout. The present assay promises clinical application for rapid and accurate identification of S. aureus and MRSA in limited-resource settings or at the point of care. Beyond S. aureus and MRSA, similar CRISPR diagnostic platforms will find widespread use in the detection of various infectious diseases, malignancies, pharmacogenetics, food contamination, and gene mutations.

[Regulatory effects of bio-intensity electric field on microtubule acetylation in human epidermal cell line HaCaT].

Objective: To investigate the regulatory effects of bio-intensity electric field on directional migration and microtubule acetylation in human epidermal cell line HaCaT, aiming to provide molecular theoretical basis for the clinical treatment of wound repair. Methods: The experimental research methods were used. HaCaT cells were collected and divided into simulated electric field group (n=54) placed in the electric field device without electricity for 3 h and electric field treatment group (n=52) treated with 200 mV/mm electric field for 3 h (the same treatment methods below). The cell movement direction was observed in the living cell workstation and the movement velocity, trajectory velocity, and direction of cosθ of cell movement within 3 h of treatment were calculated. HaCaT cells were divided into simulated electric field group and electric field treatment 1 h group, electric field treatment 2 h group, and electric field treatment 3 h group which were treated with 200 mV/mm electric field for corresponding time. HaCaT cells were divided into simulated electric field group and 100 mV/mm electric field group, 200 mV/mm electric field group, and 300 mV/mm electric field group treated with electric field of corresponding intensities for 3 h. The protein expression of acetylated α-tubulin was detected by Western blotting (n=3). HaCaT cells were divided into simulated electric field group and electric field treatment group, and the protein expression of acetylated α-tubulin was detected and located by immunofluorescence method (n=3). Data were statistically analyzed with Kruskal-Wallis H test,Mann-Whitney U test, Bonferroni correction, one-way analysis of variance, least significant difference test, and independent sample t test. Results: Within 3 h of treatment, compared with that in simulated electric field group, the cells in electric field treatment group had obvious tendency to move directionally, the movement velocity and trajectory velocity were increased significantly (with Z values of -8.53 and -2.05, respectively, P<0.05 or P<0.01), and the directionality was significantly enhanced (Z=-8.65, P<0.01). Compared with (0.80±0.14) in simulated electric field group, the protein expressions of acetylated α-tubulin in electric field treatment 1 h group (1.50±0.08) and electric field treatment 2 h group (1.89±0.06) were not changed obviously (P>0.05), while the protein expression of acetylated α-tubulin of cells in electric field treatment 3 h group (3.37±0.36) was increased significantly (Z=-3.06, P<0.05). After treatment for 3 h, the protein expressions of acetylated α-tubulin of cells in 100 mV/mm electric field group, 200 mV/mm electric field group, and 300 mV/mm electric field group were 1.63±0.05, 2.24±0.08, and 2.00±0.13, respectively, which were significantly more than 0.95±0.27 in simulated electric field group (P<0.01). Compared with that in 100 mV/mm electric field group, the protein expressions of acetylated α-tubulin in 200 mV/mm electric field group and 300 mV/mm electric field group were increased significantly (P<0.01); the protein expression of acetylated α-tubulin of cells in 300 mV/mm electric field group was significantly lower than that in 200 mV/mm electric field group (P<0.05). After treatment for 3 h, compared with that in simulated electric field group, the acetylated α-tubulin of cells had enhanced directional distribution and higher protein expression (t=5.78, P<0.01). Conclusions: Bio-intensity electric field can induce the directional migration of HaCaT cells and obviously up-regulate the level of α-ubulin acetylation after treatment at 200 mV/mm bio-intensity electric field for 3 h.

Roller microneedles transdermal delivery of compound lidocaine cream for enhancing the analgesic effect: A randomized self-controlled trial.

OBJECTIVE: The purpose of this article is to investigate whether the percutaneous delivery of compound lidocaine cream by roller microneedles can shorten the minimal effective onset time of anesthesia, enhance the intensity of anesthesia and prolong the analgesic time, so as to provide a theoretical basis for exploring a comfortable, safe and effective anesthesia method for photoelectric cosmetic surgery. METHODS: A total of 90 healthy volunteers, including 18 male and 72 female, met the criteria and were enrolled in the study from December 2020 to September 2021 in Department of Plastic and Burn Surgery of the First Affiliated Hospital of Chongqing Medical University. This study adopted a two-factor randomized block design of 3 (anesthesia time on the test side: 30, 45, 60 min) × 2 (the test side: the left and right side), and the subjects were divided into group A (n = 30), group B (n = 30), and group C (n = 30). On the test side, the compound lidocaine cream was used for topic anesthesia for 10 min, then the roller microneedle was used to roll on the treatment area, compound lidocaine cream was appropriately supplemented, and the topic anesthesia was kept continued for 20 min (group A), 35 min (group B), and 50 min (group C), respectively. The mirrorsymmetrical area of the test side of the three groups was the control side, and the compound lidocaine cream was used for topic anesthesia for 60 min. Photoelectric therapy was performed after anesthesia was completed. The analgesic effect of the subjects on both sides was comprehensively compared; the scores were obtained using the Kuttner Facial Expression Scale, the Frankl Treatment Compliance Scale, the Houpt Behavior Scale, and the Visual Analog Scale (VAS); the satisfaction with anesthesia was investigated. Before and after treatment the skin temperature, color and adverse reactions of the subjects were recorded. RESULTS: Comparing both sides of the same group, there was no significant difference in terms of the comprehensive evaluation, intraoperative comfort, tolerance, cooperation, pain or satisfaction between the 30-min test side and the routine anesthesia side in group A; the comprehensive evaluation, intraoperative tolerance, cooperation degree, pain degree and satisfaction evaluation of the subjects on the 45-min test side in group B were significantly better than those on the control side; the comprehensive evaluation, intraoperative comfort, tolerance, cooperation, pain and satisfaction of the subjects on the 60-min test side in group C were significantly better than those on the control side. Comparing groups on the control side, there was no significant difference in the comprehensive evaluation, intraoperative comfort, tolerance, cooperation, pain or satisfaction between the three groups of subjects on the control side. Comparing the three groups on the test side, with the prolongation of compound lidocaine cream indwelling time, the subjects' comprehensive evaluation, comfort and pain degree were significantly improved. There was no significant difference in postoperative bruising, swelling, pain, discoloration, redness, or tenderness between the test side and the control side. CONCLUSION: The percutaneous delivery of compound lidocaine cream by roller microneedles can not only shorten the effective time of anesthesia, but also has a good analgesic effect without obvious adverse reactions.

Association between MeCP2 and Smad7 in the pathogenesis and development of pathological scars.

To explore the relationship between methylated binding protein 2 (MeCP2) and mothers against decapentaplegic homolog 7 (Smad7) in the pathogenesis and development of pathological scars. Immunohistochemistry, Western blot and real-time polymerase chain reaction (RT-PCR) were used to detect the expression of MeCP2 in different types of human scars and hypertrophic scars at different growth times. The methylation status of Smad7 gene promoter in different scar tissues was determined by methylation-specific PCR. After transfection with MeCP2-siRNA (small interfering RNA) in human keloid fibroblasts, MTT assay was used to assess the proliferation activity of keloid fibroblasts, while RT-PCR and Western blot assays were used to detect the expression levels of MeCP2, transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), phospho-Smad2 (p-Smad2) and Smad7. MeCP2 was mainly expressed in the nucleus of fibroblasts. The mRNA and protein levels of MeCP2 were significantly higher in keloids than in hypertrophic scars, normal scars and normal skin (p<.05). The expression level of MeCP2 in hypertrophic scars during the growth period of <6 months was markedly higher than that of >6 months (p<.05). The methylation level of Smad7 was significantly higher in keloids compared to normal skin. After MeCP2 silencing, the proliferation rate of human keloid fibroblasts was decreased, the mRNA and protein levels of Smad7 were increased, and the expression levels of TGF-ß1, α-SMA and p-Smad2 were decreased (p<.05). MeCP2 and Smad7 play an important role in formation of pathological scars. During keloid formation, MeCP2 weakens the inhibitory effect of Smad7 on p-Smad2/3 by downregulating the expression of Smad7, which in turn promotes fibrosis and scar hyperplasia.

Transient Receptor Potential Channel Canonical Type 3 Deficiency Antagonizes Myofibroblast Transdifferentiation In Vivo.

OBJECTIVE: Myofibroblast transformation has been shown to be associated with the reactive oxygen species- (ROS-) producing enzyme NADPH oxidase (Nox4). Inhibition of transient receptor potential channel canonical type 3 (TRPC3) attenuates mitochondrial calcium handling and ROS production in the vasculature of hypertensive rats. However, it remains elusive whether TRPC3 regulates mitochondrial calcium and ROS production and participates in myofibroblast transdifferentiation during wound healing. METHODS AND RESULTS: In this study, we demonstrated that activation of TRPC3 by transforming growth factor ß (TGFß (TGFαSMA). Inhibition of TRPC3 with its specific inhibitor, Pyr3, significantly decreased TGFß (TGFαSMA). Inhibition of TRPC3 with its specific inhibitor, Pyr3, significantly decreased TGFß (TGFß (TGFTrpc3-/- mice exhibited significantly attenuated myofibroblast transdifferentiation, as demonstrated by decreased αSMA). Inhibition of TRPC3 with its specific inhibitor, Pyr3, significantly decreased TGFß (TGFß (TGFTrpc3-/- mice exhibited significantly attenuated myofibroblast transdifferentiation, as demonstrated by decreased Trpc3+/+ mice. In addition, Trpc3-/- mice exhibited significantly attenuated myofibroblast transdifferentiation, as demonstrated by decreased. CONCLUSIONS: Our data indicate that TGFß1-mediated activation of TRPC3 enhances mitochondrial calcium and ROS production, which promotes myofibroblast transdifferentiation and HTS formation. Inhibition of the TRPC3-mediated Nox4/pSmad2/3 pathway may be a useful strategy to limit HTS formation after injury.ß (TGF.

High-salt intake increases TRPC3 expression and enhances TRPC3-mediated calcium influx and systolic blood pressure in hypertensive patients.

Enhanced transient receptor potential canonical subtype 3 (TRPC3) expression and TRPC3-mediated calcium influx in monocytes from hypertensive rats and patients are associated with increased blood pressure. Daily salt intake is closely related to hypertension, but the relationship between TRPC3 expression and salt intake has not yet been evaluated in hypertensive patients. Using reverse transcription-polymerase chain reaction, we studied the expression of TRPC3 and TRPC3-related store-operated calcium entry (SOCE) in peripheral blood mononuclear cells (PBMCs) from hypertensive and normotensive control subjects. Measurement of SOCE was performed using the fluorescent dye Fura-2 AM. Participants were divided into a low-salt group (<9 g) and a high-salt group (≥9 g) based on 24-h urinary sodium excretion. Increased TRPC3 mRNA expression levels and SOCE were observed in THP-1 cells after high-NaCl treatment. However, administration of the TRPC3-specific inhibitor Pyr3 significantly decreased the effect. Furthermore, the TRPC3 mRNA expression levels in PBMCs from high-salt intake patients with essential hypertension were significantly higher than those in low-salt intake patients compared with those in normotensive control subjects. We also observed significantly increased TRPC3-mediated SOCE in PBMCs from hypertensive subjects (but not from normotensive control subjects), with calcium concentration correlating with salt intake. More importantly, TRPC3 mRNA levels showed a significant correlation with salt intake and systolic blood pressure in patients with essential hypertension. This study demonstrated, for the first time, that increased TRPC3 mRNA levels are associated with elevated salt intake and systolic blood pressure in hypertensive patients.

Comparison of Efficacy and Complications Between Negative Pressure Wound Therapy and Conventional Mechanical Fixation in Skin Grafts: A Retrospective Analysis.

INTRODUCTION: Graft fixation is critical for the successful survival of a skin graft. Conventional mechanical fixation may induce inappropriate pressure and increase wound complications. Negative pressure wound therapy (NPWT) could be utilized to secure a skin graft and improve drainage. Limited quantitative data exist on the efficacy of NPWT for skin grafting. OBJECTIVE: This retrospective study compares the efficacy and complications between NPWT and conventional mechanical fixation in skin grafts. MATERIALS AND METHODS: Patients who underwent skin graft surgery from January 2015 to December 2016 at a large university hospital in southwest China were retrospectively analyzed. Characteristics, including wound pattern, skin graft type, surgical procedure, survival rate, and postoperative complication, were statistically analyzed by Pearson chi-square or Fisher's exact test. RESULTS: A total of 186 patients were included in the study; 72 received NPWT and 114 received conventional mechanical dressing fixation after skin grafting. Overall survival rate of full-thickness skin grafts was significantly higher in the NPWT group than the dressing group (P ⟨ .01). The NPWT group showed a higher survival rate than the dressing group for each anatomic site, but only patients who had skin grafts of the hand exhibited statistically significant results. CONCLUSIONS: This study reports a quantitative analysis of the efficacy of NPWT on skin graft fixation with NPWT providing consistent pressure and better drainage than conventional mechanical fixation. In addition, the use of NPWT also could increase graft take on the hand region.

Effectiveness of Autologous Stem Cell Therapy for the Treatment of Lower Extremity Ulcers: A Systematic Review and Meta-Analysis.

Primary studies in animal models and humans have suggested the therapeutic potential of autologous stem cell for treating chronic lower extremity ulcers. However, the results of pilot randomized controlled trials (RCTs) in humans have been inconsistent. A meta-analysis of RCTs was performed to evaluate the role of autologous stem cell-based therapy for lower extremity ulcers.Studies were identified during a systematic search of Medline, Embase, Cochrane's library, and references cited in related reviews and studies. Studies were included if they were RCTs published in English, recruited patients with lower extremity ulcers who were assigned to either a group for the topical therapy with autologous stem cells, and reported data regarding the healing of the ulcers.Relative risks (RRs) for healing rate and standardized mean differences (SMDs) for the changes in the mean sizes of ulcers were evaluated with a random-effects model. Overall, autologous stem cell-based therapy was associated with better healing of lower extremity ulcers (12 comparisons, 290 patients, RR for partial healing = 3.07, 95% confidence interval [CI] = 1.14-8.24, P = 0.03; RR for complete healing = 2.26, 95% CI = 1.48-3.16, P < 0.001) with little heterogeneity (I = 0%). Moreover, autologous stem cell-based therapy was associated with a greater reduction in mean ulcer size (SMD = -0.63, 95% CI = -1.03 to -0.22, P = 0.002). Subgroup analyses indicated that stem cells from peripheral blood and bone marrow seemed to exert similar beneficial effects on the healing of ulcers. Stem cell therapy was not associated with any increased risks for adverse events. The optimized sources, amounts, and delivery methods of stem cell -based therapy for patients with chronic lower extremity ulcers need to be determined, and the long-term effects of stem cell-based therapy on clinical outcomes need further exploration.Autologous stem cell-based therapy is effective and safe for improving the healing of chronic lower extremity ulcers and large-scale RCTs are needed to confirm our findings.

Circulating microRNA-196a as a candidate diagnostic biomarker for chronic hepatitis C.

Previous studies have demonstrated the inhibitory effect of microRNA (miR)-196a on hepatitis C virus (HCV) expression in human hepatocytes. However, the clinical implications of aberrant miR-196a expression and the application of circulating miR-196a in the diagnosis and management of chronic hepatitis C (CHC) require further investigation. The present study aimed to examine the possibility of using serum miR-196a as a biomarker for CHC. The Affymetrix miRNA array platform was used for miRNA expression profiling in adenovirus (Ad)-HCV core-infected (HepG2-HCV) and Ad-enhanced green fluorescence protein (EGFP)-infected HepG2 cells (HepG2-control). miR-196a downregulation and levels were analyzed using stem-loop reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis of the sera of 43 patients with CHC and 22 healthy controls. A total of six miRNAs were identified as significantly different (≥ 1.5 fold; P ≤ 0.05) between the two groups. Of note, significant miR-196a downregulation was observed in HepG2-HCV as compared with HepG2­EGFP. Furthermore, as compared with that of the healthy control group, serum miR-196a was demonstrated to be significantly lower in patients with CHC. In addition, analysis of the receiver operating characteristic (ROC) curve for serum miR-196a revealed an area under the ROC curve of 0.849 (95% confidence interval, 0.756-0.941; P<0.001) with 81.8% sensitivity and 76.7% specificity in discriminating chronic HCV infection from healthy controls at a cut-off value of 6.115 x 10(-5), demonstrating significant diagnostic value for CHC. However, no correlation was identified between serum miR-196a and alanine aminotransferase, aspartate aminotransferase or HCV-RNA. In conclusion, the present study identified circulating miR-196a as a specific and noninvasive candidate biomarker for the diagnosis of CHC.

Role of Ran-regulated nuclear-cytoplasmic trafficking of pVHL in the regulation of microtubular stability-mediated HIF-1α in hypoxic cardiomyocytes.

Our previous study suggested that microtubule network alteration affects the process of glycolysis in cardiomyocytes (CMs) via the regulation of hypoxia-inducible factor (HIF)-1α during the early stages of hypoxia. However, little is known regarding the underlying mechanisms of microtubule network alteration-induced changes of HIF-1α. The von Hippel-Lindau tumor suppressor protein (pVHL) has been shown to mediate the ubiquitination of HIF-1α in the nuclear compartment prior to HIF-1α exportation to the cytoplasm, and pVHL dynamic nuclear-cytoplasmic trafficking is indicated to be involved in the process of HIF-1α degradation. In this study, by administering different microtubule-stabilizing and -depolymerizing interventions, we demonstrated that microtubule stabilization promoted pVHL nuclear export and drove the translocation of pVHL to the cytoplasm, while microtubule disruption prevented pVHL nuclear export in hypoxic CMs. Moreover, the ratio between nuclear and cytoplasmic pVHL was associated with HIF-1α regulation. Importantly, microtubule network alteration also affected the subcellular localization of Ran, which was involved in the regulation of pVHL nuclear-cytoplasmic trafficking. The above results suggest that the subcellular translocation of pVHL plays an important role in microtubular structure alteration-induced HIF-1α regulation. Interestingly, Ran is involved in the process of pVHL nuclear-cytoplasmic trafficking following microtubule network alteration in hypoxic CMs.

[Effect of the methylation enzyme inhibitors of 5-aza-2-deoxycytidine on the TGF-beta/smad signal transduction pathway in human keloid fibroblasts].

OBJECTIVE: To investigate the effect of 5-aza-2-deoxycytidine on the TGF-beta/smad signal transduction pathway in human keloid fibroblasts (KFSs). METHODS: Firstly, immunohistochemical method was used to detect the positive expression rate of phospho-smad2 and phospho-smad3 in the specimens of 15 cases of keloid and 15 cases of normal skin. The keloid fibroblasts were cultured in vitro with 5-aza-2-deoxycytidine(experimental group) or with DMEM (control group). The effect of 5-aza-2-deoxycytidine on the cell cycle and apoptosis of fibroblasts was analysed with flow cytometry ( FCM). Transforming growth factor (TGF)-beta1, Smad7, phospho-smad2 and phospho-smad3 were analyzed by Western Blot, and Immunofluorescence. RESULTS: It was found that the positive expression of phospho-smad2 and phospho-smad3 in keloid were higher than those in normal skin. The FCM showed that the proportion of cells in G0/G1 stage was increased, and so does the proportion of apoptosis cells in keloid fibroblasts intervened by 5-aza-2-deoxycytidine. The expression of TGF-beta1, phospho-smad2 and phospho-smad3 protein were significantly suppressed while the expression of smad7 protein increased in keloid fibroblasts with 5-aza-2-deoxycytidine. In addition, 5-aza-2-deoxycytidine reversed phosphorylation and nuclear translocation of smad2 and smad3. CONCLUSIONS: 5-aza-2-deoxycytidine, methylase inhibitors, inhibits cell proliferation and promotes apoptosis of KFSs, which may be associated with the suppression of TGF-beta/smad signal pathway.