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As a p53-regulated gene, Wip1 regulates proliferation, migration, apoptosis, and senescence of several type cells, but its biological functions in keratinocytes and endothelial cells which are involved wound healing are not fully understood. This study aims to reveal the function and underlying mechanism of Wip1 in wound healing using models of transgenic animal, keratinocytes, and endothelial cells. Using Wip1 knockout C57 BL/6 mice, we investigated effect of Wip1 deficiency on wound healing and angiogenesis; And using HaCaT and HUVEC as keratinocytes and endothelial cells, combined using primary keratinocytes from Wip1 knockout mice, we studied the effects of Wip1 knockdown/knockout or overexpression on proliferation, migration, and protein expressions of signaling components in ATM-p53 and mTOR pathway. Wip1 deficiency in mice impaired the wound repair and endothelial angiogenesis, reduced the thickness of granulation tissue, and decreased the number of Ki67-positive cells and CD31 positive vessels in granulation tissue. Knockdown of Wip1 by shRNAs suppressed the proliferation and migration of HaCaT and HUVEC cells and induced notably apoptosis in the two cells. In western blot, Wip1 knockdown enriched p53 and ATM proteins, while decreased activated AKT, mTOR and activated S6 ribosomal protein (pS6) levels in HaCaT and HUVEC cells. Ectopic expression of Wip1 decreased the p53 and ATM proteins, while increased activated AKT, mTOR and pS6 levels in HaCaT and HUVEC cells. And in primary keratinocytes from mice tail skin, Wip1 knockout increased p53 and ATM, while decreased activated AKT, mTOR and pS6 protein levels. Our study directly supports that Wip1 regulated skin wound healing possibly by affecting bioactivities including proliferation, migration and apoptosis of keratinocytes and endothelial cells at least through by modulating ATM-p53 and mTOR signaling. • Wip1 participated in mice wound repair and endothelial angiogenesis. • Wip1 regulated thickness of granulation tissue and the number of Ki67-positive cells and CD31 positive vessels in granulation tissue. • Wip1 affected the proliferation, migration and apoptosis of keratinocytes and endothelial cells by modulating ATM-p53 and mTOR signaling. [ABSTRACT FROM AUTHOR]

Pilomatrixoma is a benign, asymptomatic skin tumor that forms from hair follicle matrix cells. Most are under 3 cm in diameter and occur on the head, face, or neck. Bullous appearance is very rare in pilomatrixoma. In this case report, we present a case of bullous pilomatrixoma of unusual size, region, symptoms, and patient age. It had been misdiagnosed as a keloid and as dermatofibrosarcoma protuberans. Early treatments were ineffective. The patient approached our outpatient facility and underwent excision. He was then diagnosed with pilomatrixoma by pathological examination. The clinical appearance of this case was quite difficult to diagnose, even MRI and B‐ultrasonic examinations provided limited diagnostic evidence. Given the revelations from this case, we reemphasize the importance of performing a biopsy (if patients refused operation or preferred conservative treatment) before any invasive treatment to minimize economic or time loss of patients who have difficulties in diagnosis. [ABSTRACT FROM AUTHOR]

Background: Nipple‐areola complex is a naturally hyperpigmented skin area which can be involved in vitiligo. But limited study focused on the treatment of nipple‐areola complex vitiligo, and few methods were proven to be effective. In this study, we aimed to explore the feasibility and efficacy of ReCell® on vitiligo in the nipple‐areola complex area. Methods: Medical records of patients with vitiligo involving nipple‐areola complex and underwent ReCell® treatment from October 2016 to April 2020 were retrospectively reviewed. The repigmentation rate of the nipple‐areola complex and other breast area were calculated under the Wood's light at each follow‐up. The grade of repigmentation and patient‐reported satisfaction rate were also evaluated to prove the effect of ReCell® on vitiligo of breast and especially in the nipple‐areola complex area. Results: A total of 18 patients were included in this study. No surgical complications were reported. The mean postoperative repigmentation rate in the nipple‐areola complex area (3rd‐month, 78.7 ± 5.8%; 6th‐month, 87.6 ± 5.1%; and 12th‐month, 96.1 ± 3.5%) was significantly higher than that in the other breast treatment area (3rd‐month, 70.4 ± 6.9%; 6th‐month, 84.2 ± 5.7%, and 12th‐month, 93.2 ± 3.6%). All patients showed good or excellent grades at the last follow‐up, and 94.4% of them considered the overall treatment results satisfactory. Conclusions: ReCell® is a feasible and efficient treatment strategy in the nipple‐areola complex vitiligo. [ABSTRACT FROM AUTHOR]

Background: The emergence of COVID‐19 has become a global health emergency. The transmissibility of the disease is of great interest to healthcare workers and scientists alike. The primary route of transmission is via respiratory droplets, but viral RNA has also been found in feces and body fluids such as urine, serum, and semen. So far, there has been no report on whether SARS‐CoV‐2 is present in the exudates of cutaneous lesions. This study was designed to investigate whether SARS‐CoV‐2 can be found in the pressure injury exudates in patients with severe COVID‐19 infections. Methods: 46 critically ill COVID‐19 patients who were admitted to the ICU of the Sino‐French New City Branch of Tongji Hospital in Wuhan between February 4 and April 12 developed pressure injuries. 22 patients with pressure injuries had wound exudates. Wound and pharyngeal swabs of the 22 patients were collected and RT‐PCRs were conducted to detect SARS‐CoV‐2 viral RNA. Results: At the time of pressure injury, 5 patients still tested positive by pharyngeal swabs, the rest of the 17 patients tested negative. However, none of the wound exudate swabs from the participants tested positive for SARS‐CoV‐2 by RT‐PCR. Conclusion: Our study suggests that it is rather unlikely that COVID‐19 can be transmitted via pressure injury exudates, but we still recommend standardized personal protective equipment, face shield and an additional pair of gloves when treating pressure injuries. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin type A (BTA) injection is a widely‐used procedure to correct cosmetic problems caused by muscular hyperactivity. "Cobblestone chin" refers to the appearance of remarkable chin creases caused by mentalis contraction. Aims: The aim of this case report is to raise the awareness of paradoxical bulging after BTA injection in mentalis. Patient/Methods: A 26‐year‐old female asked for cosmetic correction of the "cobblestone chin". BTA injection was performed routinely to the mentalis muscle. However, on the second day after injection, an unusual paradoxical bulging at chin was presented. Results: We speculated that the imbalanced relaxation of mentalis caused by improper injection and uneven diffusion of BTA is responsible for the bulging. After a supplementary injection of BTA in the remaining hyperactive muscle fibers based on the ultrasound examination, the bulging was relieved and chin contour improved significantly. Conclusion: Injection of BTA in mentalis should cover the whole thickness of the muscle to prevent imbalanced paralysis and paradoxical chin bulging, especially in severe mentalis hyperactivity cases. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have been shown to be associated with differentiation, migration and apoptosis in keratinocyte. Although it has been reported that microRNA-26a (miR-26a) plays important roles in tumor cells, its biological functions in keratinocytes are still not well elucidated. In this study, we confirmed expression of miR-26a in human keratinocytes using RT-PCR and further studied the role of miR-26a in cell proliferation and cell migration. Ectopic expression of MiR-26a mimic or inhibitor increased or decreased miR-26a expression respectively in HaCaT cells. Proliferation of HaCaT keratinocyte can be suppressed or promoted by overexpression or down-expression of miR-26a. In scratch wound-healing assay and Boyden chamber cell migration assay, upregulating miR-26a expression blocked cell migration, while downregulating miR-26a expression enhanced the migration. Using quantitative RT-PCR (qRT-PCR) and western blot, we further discovered that both mRNA and protein level of phosphatase and tensin homolog deleted from chromosome 10(PTEN) were regulated by miR-26a in HaCaT cells. Meanwhile the level of active form of AKT was also regulated by the miR-26a. In rescue experiment, knockdown of PTEN in the miR-26a mimic transduced cells recovered the migration ability of HaCaT cells. Together these results suggest that miR-26a modulates the proliferation and migration of keratinocytes via regulating PTEN/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Although the application of Q-switched lasers on nevus of Ota (OTA) is well demonstrated, debates about clinical option between Q-switched alexandrite laser (QSA) and Q-switched Nd:YAG laser (QSNY) still remain. This systematic review and meta-analysis estimated the overall successful rate of OTA pigment clearance and complication rate of QSA and QSNY and evaluated which laser could produce a better result. English articles evaluating pigment clearance and complications of QSA and/or QSNY on OTA were screened through predetermined inclusion and exclusion criteria and analyzed. The successful rate of pigment clearance and complication rate of QSA and QSNY were respectively calculated using a random-effects or fixed-effects model, depending on the heterogeneity of the included studies. The successful rate and complication rate of QSA and QSNY were compared statistically. Of the 140 articles searched, 13 met inclusion criteria. Totally, 2153 OTA patients treated by QSA and 316 patients treated by QSNY were analyzed. In QSA and QSNY groups, respectively, the successful rate of OTA pigment clearance was 48.3% (95% confidence interval (CI) 19.9-76.8%) and 41% (95% CI 9.7-72.2%), while the complication rate was 8.0% (95% CI 3.9-12.2%) and 13.4% (95% CI 7.7-19.0%). When compared with QSNY, QSA had a significantly higher successful rate (P = 0.017), and a lower complication rate (P = 0.000). According to this review, QSA may surpass QSNY in treatment for OTA as it had a superior successful rate of pigment clearance and a lower complication rate than QSNY did. [ABSTRACT FROM AUTHOR]

Background: Merkel cell carcinoma (MCC) is a rare and highly aggressive form of skin cancer. However, there is limited research on the clinicopathological features of early‐onset MCC (EOMCC) and the differences between EOMCC and late‐onset MCC (LOMCC). Our objective was to evaluate the clinicopathological features and cancer‐specific survival (CSS) of EOMCC. Methods: Our cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2018, to December 31, 2020. Data from 1941 patients who were diagnosed with primary cutaneous MCC were included. We then divided the patients with MCC into two groups: those with EOMCC (526 patients) and those with LOMCC (1415 patients). CSS is used as the primary outcome. Results: The EOMCC group exhibited trends toward advanced tumor progression, an expanded surgical scope, increased lymph node retrieval, intensified radiotherapy, greater utilization of systemic therapy, and a better prognosis. Multivariate analysis revealed that LOMCC (HR 3.305 [2.002–5.456], P < 0.001), advanced T stage (HR 1.430 [1.139–1.797], P = 0.002), advanced N stage (HR 1.522 [1.221–1.897], P < 0.001), M1 stage (HR 2.587 [1.480–4.521], P < 0.001), and radiation (HR 0.586 [0.410–0.837], P = 0.003) were significantly associated with CSS. Among these factors, EOMCC/LOMCC was most strongly associated with CSS, indicating that LOMCC is an independent risk factor for CSS. Interestingly, we found that regional EOMCC and localized or in situ LOMCC had almost completely overlapping survival curves (Plog‐rank = 0.620). Additionally, we observed that the TNM staging + age model was a more accurate predictor of CSS among MCC patients than using TNM staging alone. Conclusions: We found that EOMCC has distinct clinicopathological features compared to LOMCC. EOMCC is associated with better CSS. The combination of TNM staging and age was more accurate for predicting patient outcomes than TNM staging alone. [ABSTRACT FROM AUTHOR]

Background: The inframammary approach is one of the most commonly used incisions in breast augmentation. There are many suture methods for inframammary incisions; however, no one method has proven optimal. We modified the traditional three‐layer suture method according to the inframammary fold (IMF) cadaver dissection results. This study aims to investigate whether using a modified suture method can improve postoperative outcomes. Methods: Cadaver dissections were performed in order to clarify the anatomy of the IMF. From June 2013 to December 2017, a retrospective study of primary breast augmentation patients subjected to the inframammary approach was conducted. Patients were divided into two cohorts: the traditional suture method and the modified suture method. The patient's demographics, specifics of breast augmentation procedures, complications, and scar assessment were analyzed. Univariate and multivariable analyses were used to determine differences between the two cohorts. Results: One hundred eighty‐four patients were included: 75 patients were subjected to the traditional suture method, and 109 patients were subjected to the modified suture method. Wound‐related adverse events (p = 0.026) and IMF‐indented scarring (p = 0.014) were significantly different between the two groups. Multivariable analysis showed that the suture method was the most influential factor related to IMF‐indented scarring (OR = 16.9), followed by BMI (OR = 2.9). Conclusions: We defined a new suture method for the inframammary incision in primary breast augmentation. This modified suture method reduces the occurrence of wound‐related adverse events and IMF‐indented scarring. [ABSTRACT FROM AUTHOR]

This review aims to assess the efficacy and safety of laser therapy in managing scars resulting from cleft lip and/or palate (CL/P) repair surgeries, as well as to determine the optimal timing for intervention. A systematic search was conducted across four databases using a predefined search strategy. Studies included were randomized controlled trials, non-randomized studies, and case series focusing on laser therapy for CL/P scars. Data extraction and analysis were performed using Revman Software. A total of two randomized controlled trials, four non-randomized studies, and three case series were included in the analysis. The fractional CO2 laser was the most commonly utilized type of laser. Following laser therapy, there was a significant decrease in Vancouver Scar Scale (VSS) scores by 4.05 (95% CI, 2.10–5.99). Meta-analysis revealed that laser treatment groups exhibited a significantly lower mean VSS score (1.3; 95% CI, 0.02–2.67) compared to control groups. Moreover, initiating laser therapy intervention at one month postoperatively resulted in a significantly lower VSS score compared to initiation at three months postoperatively (difference of 1.70; 95% CI, 1.33–2.08). No severe complications were reported. Laser therapy demonstrates effectiveness and safety in improving CL/P scars, with earlier intervention yielding greater benefits. [ABSTRACT FROM AUTHOR]

Background: Polynucleotides (PDRN) have gained attention in aesthetic and regenerative medicine for their potential to enhance tissue regeneration, improve skin quality, and deliver superior aesthetic outcomes. However, the transition from theoretical benefits to proven clinical outcomes faces challenges due to inconsistencies and methodological shortcomings in the existing evidence base. This systematic review aims to critically evaluate the scientific basis and empirical evidence supporting the use of PDRN in aesthetic and regenerative medicine, highlighting the quality, reproducibility, and reliability of existing research, and identifying gaps and inconsistencies within the current literature. Methods: Adhering to PRISMA guidelines and registered with PROSPERO, this review formulated a research question using the PICO framework to assess the efficacy of PDRN applications. A comprehensive literature search across PubMed–MEDLINE, EMBASE, and Web of Science was conducted. The inclusion criteria focused on clinical studies applying PDRN in regenerative or aesthetic medicine with clear outcome measures. Quality assessment utilized Cochrane Risk of Bias tool, ROBINS-I, and Newcastle Ottawa Scale. Data synthesis was qualitative due to anticipated heterogeneity. Results: From 360 identified studies, 16 clinical trials met the inclusion criteria, encompassing various study designs and a total of 750 participants. The studies investigated PDRN's efficacy across different conditions and applications. Findings revealed a lack of specificity in PDRN sequencing, molecular targets, and dosage details, with a noted variability in source and manufacturing standards. Most studies demonstrated a low risk of bias, suggesting methodological rigor, yet the absence of comprehensive reporting on sequencing, targeted mechanisms, and molecular length was evident. The review underscores the embryonic stage of PDRN research and the necessity for more rigorous studies to validate clinical outcomes. Conclusions: The potential of PDRN in aesthetic and regenerative medicine is significant, yet the current state of evidence necessitates a cautious and evidence-based approach to their clinical integration. Future research should focus on overcoming the highlighted gaps and inconsistencies, ensuring that the innovation in treatments does not compromise patient safety and efficacy. Regulatory frameworks must evolve to address the unique challenges presented by PDRN technologies, ensuring their safe and ethical application. Level of evidence: Level I, Therapeutic. [ABSTRACT FROM AUTHOR]

Keloid scars occur as a result of abnormal wound healing caused by trauma or inflammation of the skin. The progression of keloids is dependent on genetic and environmental influences. The incidence is more prevalent in people with darker skin tones (African, Asian and Hispanic origin). Studies have demonstrated that transforming growth factor (TGF) β/Smad signalling has an essential function in keloid as well as that USP11 could modulate the activation of TGFβ/Smad signalling and impact the progression of the fibrotic disease. Nonetheless, the potential mechanisms of USP11 in keloid were still unclear. The authors postulated that USP11 up-regulates and augments the ability of proliferation, invasion, migration and collagen deposition of keloid-derived fibroblasts (KFBs) through deubiquitinating TGF-β receptor II (TβRII). Fibroblast cells were isolated from keloid scars in vitro. Lentivirus infection was utilized to knockdown and over-express the USP11 in KFBs. Influence of USP11 on proliferation, invasion and migration of KFBs, and expression level of TβRII, Smad2, Smad3, α-SMA, collagen1 and collagen3 were assayed by CCK8, scratching, transwell, Western blot and real-time quantitative polymerase chain reaction. The interactions between USP11 and TβRII were examined using ubiquitination assays and co-immunoprecipitation. To further confirm the role of USP11 in keloid growth, we performed animal experiments. Results show that down-regulated USP11 markedly suppressed the ability of proliferation, invasion and migration of keloid derived-fibroblasts in vitro and reduce the expression of TβRII, Smad2, Smad3, αSMA, collagen1 and collagen3. In addition, over-expression of USP11 demonstrated the contrary tendency. Ubiquitination experiments and co-immunoprecipitation demonstrated that USP11 was interacting with TβRII and deubiquitinated TβRII. Interferences with USP11 inhibited growth of keloid in vivo. Additionally, we have verified that knockdown of USP11 has no significant effect on normal skin fibroblasts. USP11 elevates the ability of proliferation, collagen deposition, invasion and migration of keloid–derived fibroblasts by deubiquitinating TβRII. Comparing with normal skin derived fibroblasts, USP11 is elevated in keloid–derived fibroblasts. USP11 elevates the ability of proliferation, collagen deposition, invasion and migration of keloid–derived fibroblasts. Down-regulated USP11 markedly reduced the expression of TβRII, Smad2, Smad3, αSMA, collagen1 and collagen3. USP11 was interacting with TβRII and deubiquitinated the protein level of TβRII. [ABSTRACT FROM AUTHOR]

Background: Full lips are beauty standards. Botulinum toxin A (BTA) paralyzes the orbicularis oris muscle to achieve the eversion of the lip, and thus makes the lip look plump. Aims: This study presents three cases of BTA injection to the lip and evaluates the possible changes in the labial morphology and the lip surface area. Methods: Three patients received a total of 4U BTA injection at the vermilion border of the upper lip. Vectra® H1 3D imaging system was used to capture 3D photographs of the lips before injection and two weeks after injection. Eight linear distances and the upper lip surface area were measured. Anthropometric measurements before and after injection were compared. Results: Patients displayed a larger upper vermillion height (P =.038) and a smaller cutaneous upper lip height (P =.024). There was a trend for a larger upper lip surface area, but not statistically significant (P =.109). Symptoms of slight perioral muscular palsy and mouth incompetence lasted about one month in three patients. Conclusion: BTA helps to enlarge the upper lip and shorten the philtrum. The BTA injection can be an option for lip enhancement with caution. [ABSTRACT FROM AUTHOR]

Background: Vulvar migration is a rare complication of filler injection for breast augmentation, generally presenting as repeated pain and fever. We will report a case of woman with polyacrylamide hydrogel breast injection develops vulvar abscess. Case presentation: A woman with a history of polyacrylamide hydrogel breast injection was noted to have vulvar abscess due to migration of filler materials. Filler removal surgery and vacuum sealing drainage was performed for this patient. The patient was discharged from the hospital with no further complications. After a review of pertinent literature, only four previous case reports are found. Local inflammatory response, infection, large volume injections, inframammary fold destruction, hematogenous or lymphatic migrate, trauma, gravity and external pressure could play essential parts in the migration of injected filler. Conclusion: Polyacrylamide hydrogel migration poses a worldwide challenge, necessitating personalized solutions. Our case study underscores the importance of comprehensive examinations for individuals with a history of filler breast injection when suspecting vulvar filler migration. [ABSTRACT FROM AUTHOR]

Under visual observation, keloids are more rough than normal skin. This roughness may be used to assess the activity and severity of keloids but lacks the support of objective and accurate evidence. The purpose of this study was to verify the role of roughness in the development of keloids and to clarify the advantage of roughness in the comprehensive assessment of keloids. Patients with keloids who attended Peking Union Medical College Hospital were recruited. Keloids were classified into progressive, stable, and atrophic stages based on the change in size over the past year and blood perfusion. The keloids were evaluated using the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). The roughnesses of the keloid and normal skin were measured using the Phaseshift Rapid In vivo Measurement Of the Skin (PRIMOS), and blood perfusion was measured using laser speckle contrast imaging (LSCI). Thirty-three patients with a total of 81 keloids were included. The surface roughness values Sa, Sq, and Sz of the keloid region were 243.70 (143.85–328.05), 316.20 (179.85–475.20), and 1708.20 (1098.30–4087.20), respectively, which were 4.87, 4.80, and 3.08 times higher than those of normal skin. There were significant differences in roughness among the different keloid stages. A significantly strong correlation between roughness and other assessed indices was found. Roughness as a morphological characteristic is of great value in the evaluation of keloids. It is recommended as an important examination for keloids. • The roughness of keloid was higher than normal skin. There were differences in keloid roughness among different stages. • A significantly strong correlation between roughness and other assessed indices was found. • Roughness is of great value in the evaluation of keloids, and it is recommended as an important examination for keloids. [ABSTRACT FROM AUTHOR]

There is a need for a specialist pathway or progression in esthetic medicine for esthetic physicians. A structured program for specialized training in nonsurgical facial esthetics to empower physicians is the need of the hour. The pharmaceutical companies currently provide training sessions, taking considerable initiatives to train esthetic professionals. "Leaders of the future" is a global thought leadership program by the Allergan Aesthetics. The program was designed to support and nurture the next generation of leaders by focusing on science and evidence. It aimed to help practitioners grow, evolve, learn, share, and connect with leading international experts. The sessions were focused on the importance of science and sensibility in esthetic medicine, as well as critical thinking and leadership skills. Mentorship is one of the most effective approaches for transforming the lives of young esthetic practitioners and, in turn, future patients. In addition, the importance of in-depth knowledge of injection anatomy for safe practice was emphasized. As esthetic surgeons and physicians, we must commit to incorporating evidence-based medicine into our life-long practice. "Leaders of the Future" program aims to build a solid foundation for esthetic surgeons and physicians to grow and evolve as thought leaders. The program would also aid in the pursuit of a best esthetic practice that incorporates professional identity formation, clinical competence, and evidence-based management in nonsurgical esthetics. [ABSTRACT FROM AUTHOR]

Background: Regenerative Epithelial Suspension can lead to the restoration of wound and repigmentation, which can be gained by ReCell medical device to treat scar and depigmentation diseases. Objectives: To report the effectivity of ReCell combined with microdermabrasion in scar and depigmentation diseases and review the literature of this new technology. Methods: We gave a differential donor⁄recipient ratio of about 1:20‐30 with vitiligo, 1:40 with postburn construction, 1:80 with acne scar, and 1:120 with adult congenital melanocytic nevus, 1:80 with pediatrics, respectively. Photographs of patients before treatment and 3 months following the last treatment session were used to evaluate the effectivity. Results: A total of 8 patients including vitiligo vulgaris, postburn reconstruction, acne scars, and congenital melanocytic nevi treated by ReCell technology combined with microdermabrasion showed significant improvement in skin texture and color. And 17 studies of the research on ReCell technology were totally included in the systematic review. Conclusion: Our investigation showed that Regenerative Epithelial Suspension gained by ReCell technology combined with microdermabrasion may improve scar and depigmentation diseases. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Promoting epidermal cell survival in an oxidative stress microenvironment is vital for skin regeneration after burns and/or wounds. However, few studies have explored the mediators related to epidermal cell apoptosis in an oxidative stress microenvironment. Cellular viability was determined using the MTT assay, TUNEL staining, western blot analysis and LDH release assay. Two independent siRNAs were transfected into HaCaT cell to repress INF2 and/or HIF1 in the presence of H 2 O 2. Mitochondrial function was determined using JC-1 staining, mitochondrial ROS staining, immunofluorescence staining and western blotting. In the present study, our data demonstrated that the expression of inverted formin-2 (INF2) increased rapidly when the cells were exposed to H 2 O 2. Interestingly, INF2 knockdown promoted HaCaT cell survival via reducing H 2 O 2 -mediated cell apoptosis. Molecular investigations demonstrated that INF2 deletion attenuated mitochondrial ROS overloading, restored the cellular redox balance, sustained the mitochondrial membrane potential, improved mitochondrial respiratory function and corrected the mitochondrial dynamics disorder in an H 2 O 2 -mimicking oxidative stress microenvironment. In addition, INF2 deletion upregulated the expression of HIF1. Interestingly, the inhibition of HIF1 increased cell death and caused mitochondrial stress despite the deletion of INF2, suggesting that the HIF1 signaling pathway is required for INF2 deletion-mediated HaCaT cell survival and mitochondrial protection. Altogether, our results identified INF2 as a novel apoptotic mediator for oxidative stress-mediated HaCaT cell death via modulating mitochondrial stress and repressing the HIF1 signaling pathway. This finding provides evidence to support the critical role played by the INF2-HIF1 axis in regulating mitochondrial stress and epidermal cell viability in an oxidative stress microenvironment. [ABSTRACT FROM AUTHOR]

Inflammation and fibrosis of the skin are characteristics of localized scleroderma (LS). Emerging evidence has demonstrated that exosomes from human adipose tissue–derived mesenchymal stem cells (ADSC-Exo) could alleviate skin fibrosis. The impact and potential mechanism of ADSC-Exo on LS fibrosis was examined. ADSC-Exo was isolated and identified. The effects of ADSC-Exo on the abilities of proliferation and migration of LS-derived fibroblasts (LSFs) were assessed by CCK-8 and scratch assays, respectively. qRT-PCR, western blot, and immunofluorescence were conducted to detect LSFs stimulated with ADSC-Exo, ADSC-ExoAnti-let−7a−5p, let-7a-5p mimic/TGF-βR1 shRNA virus, and negative controls. The impact of ADSC-Exo on C57BL/6j LS mice was evaluated by photographic morphology, hematoxylin-eosin (H&E), Masson's trichrome, and immunohistochemical staining. The verified ADSC-Exo limited the proliferation and migration of LSFs and reduced the expression of COL1, COL3, α-SMA, TGF-βR1, and p-Smad2/ 3 in vitro and in vivo. TGF-βR1 knockdown and let-7a-5p mimic in LSFs reduced the expression of COL1, COL3, α-SMA, and p-Smad2/3. However, compared with the ADSC-ExoNC group, the dermal thickness was increased, collagen arrangement was disordered, and α-SMA and TGF-βR1 levels were increased after exposure to ADSC-ExoAnti-let−7a−5p. In this study, it might show that ADSC-Exo may successfully prevent LSF bioactivity, collagen deposition, and myofibroblast trans-differentiation. Additionally, we confirmed that let-7a-5p in ADSC-Exo could directly target TGF-R1 to control the Smad pathway and reduce fibrosis in LSFs. Our work offered a brand-new therapeutic approach and clarified the unique mechanism for the clinical management of LS. • Exosomes from human adipose–derived mesenchymal stem cells attenuate localized scleroderma fibrosis. • Let-7a-5p directly targeted TGF-βR1 to control LS fibrosis. • TGF-βR1 was overexpressed in the LS animal model, and TGF-βR1 silencing decreased the expression of collagen and α-SMA in LSFs. • Let-7a-5p in ADSC-Exo could directly target TGF-R1 to control the Smad pathway and reduce fibrosis in LSFs. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin type A (BoNT‐A) can not only reduce the dynamic wrinkles but also improve the skin quality. This study aims to quantitaively and comprehensively assess the improvement of dynamic wrinkles and skin quality following BoNT‐A treatment on the upper face. Methods: Patients were recruited to receive BoNT‐A treatment of the glabellar, frontal, and lateral periorbital wrinkles. Antera 3D camera was used to evaluate the skin quality and dynamic wrinkle severity. Follow‐up visits were at 1 week, 1 month, 3 months, and 6 months after treatment. Different filters were utilized to quantitatively detect the severity of fine wrinkles (FWS), the volume of pores (PV), the roughness of skin texture (STR), and the severity of dynamic wrinkles (DWS). Results: Twenty‐four participants (average 30.5 ± 7.2 years) were recruited. The significant improvement of PV, FWS, and STR in different areas usually maintained from 1 to 6 months after injections but of DWS only existed within 3 months. For each area, the improvement rates of FWS, PV, and STR peaked at 3 months or 6 months after treatment while the maximal improvement of DWS was observed at 1 month posttreatment. Conclusion: After BoNT‐A treatment for dynamic wrinkles on the upper face, the skin quality of target regions can also be ameliorated. The improvement of skin quality and dynamic wrinkles presented unparallel patterns. The former is with a slower onset but longer duration while the latter exhibits a more rapid onset but shorter duration. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin type A (BoNT‐A) injection is a popular cosmetic procedure in East Asian countries, and there are multiple types of toxins on the market. Whether different toxin types induce different changes in the masseter has not been studied. Objective: We aimed to investigate and compare the changes induced by injection of different types of BoNT‐A in the masseter. Methods: Upon retrospective review of clinical records and routine ultrasound examination results of patients who underwent BoNT‐A injection, four groups were set for comparison: unapproved toxin, OnabotulinumtoxinA, LanbotulinumtoxinA, and non‐injected. Clinical records and ultrasound images were collected. Ultrasound images were taken in both horizontal and coronal planes. Elasticity of the masseter muscle was also investigated by measuring the surface wave speed. Results: A total of 24 patients were included (six patients per group). All patients were young females. For the non‐injected group, the deep inferior tendon was clear and the muscle bundles were arranged, with little fibrous content. Patients who received unapproved toxin injection showed highly disarranged muscle and fiber bundles, with much fiber content present. The changes in OnabotulinumtoxinA and LanbotulinumtoxinA groups were in between those in the non‐injected and unapproved toxin groups. Muscle rigidity was the highest in the unapproved toxin group, and generally higher in injected groups compared with the non‐injected group. Conclusion: Different types of BoNT‐A may induce different changes in the masseter. [ABSTRACT FROM AUTHOR]

Background: Large calves are considered unattractive. Botulinum toxin type A (BoNT‐A), acting as a neurotoxin that reduces muscle contraction, is widely used in calf contouring. However, there lacks detailed anatomical data to guide clinical injection. Objectives: This study aims to use ultrasonography to provide depth information of the calf muscles and determine the morphological types of the gastrocnemius muscle. Methods: Ultrasound scanning was performed at six sites on 40 Chinese adults. A real‐time ultrasound scannerwas used to detect the depth of the gastrocnemius muscle and the soleus muscle. Results: The thickness of the gastrocnemius muscle and the soleus muscle was measured. The depth from the skin to the surface, the middle, and the bottom of the gastrocnemius muscle was measured. The morphology of gastrocnemius muscle was classified into four different types under ultrasound according to the muscle bulge pattern. Conclusion: This study took ultrasonic measurements of Asian calves to guide accurate and effective BoNT‐A injection in real clinical practice. [ABSTRACT FROM AUTHOR]

A keloid results from abnormal wound healing, which has different blood perfusion and growth states among patients. Active monitoring and treatment of actively growing keloids at the initial stage can effectively inhibit keloid enlargement and has important medical and aesthetic implications. LSCI (laser speckle contrast imaging) has been developed to obtain the blood perfusion of the keloid and shows a high relationship with the severity and prognosis. However, the LSCI-based method requires manual annotation and evaluation of the keloid, which is time consuming. Although many studies have designed deep-learning networks for the detection and classification of skin lesions, there are still challenges to the assessment of keloid growth status, especially based on small samples. This retrospective study included 150 untreated keloid patients, intensity images, and blood perfusion images obtained from LSCI. A newly proposed workflow based on cascaded vision transformer architecture was proposed, reaching a dice coefficient value of 0.895 for keloid segmentation by 2% improvement, an error of 8.6 ± 5.4 perfusion units, and a relative error of 7.8% ± 6.6% for blood calculation, and an accuracy of 0.927 for growth state prediction by 1.4% improvement than baseline. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to observe the effects of marrow mesenchymal stem cell (MSCs) arterial perfusion on vascular repair and angiogenesis in osteonecrosis of the femoral head (ONFH). Methods: Twelve healthy male adult Beagle dogs were randomly divided into two groups: group A (the control group) and group B (the MSCs arterial perfusion group). ONFH animal models were established by hip dislocation and liquid nitrogen. At the same time, MSCs were obtained, cultured and proliferated. After three weeks, arterial perfusion was performed in all animals. Group B was given 1 ml MSCs (5 × 10-1 × 10/ml), while 0.9 % normal saline was used in group A. After four weeks or eight weeks, the dogs were put to death. The changes of main arteries, the expression of vascular endothelial growth factor (VEGF), VEGF mRNA and microvessel density (MVD) of ONFH were observed. All the data were analysed by SPSS13.0. Results: In digital subtraction angiography (DSA), after four or eight weeks of treatment, the quantity and diameter of the main arteries of the femoral head in group B were improved, compared to group A ( P < 0.05, P < 0.01). Concerning histology and immunohistochemistry, after four or eight weeks of treatment, the expression of VEGF and MVD were significantly higher than that of group A ( P < 0.05, P < 0.01). For real-time quantitative polymerase chain reaction (RT-PCR), after four or eight weeks of treatment, the expression of VEGF mRNA in group B was significantly higher than that of group A ( P < 0.05, P < 0.01), and after eight weeks of treatment, the expression of VEGF mRNA were significantly higher than that of four-weeks treatment in group A ( P <0.01). Conclusions: MSCs arterial perfusion can promote vascular repair and angiogenesis and then improve blood supply and repair of femoral head. [ABSTRACT FROM AUTHOR]

Background: Botulinum neurotoxin A injection is a popular noninvasive alternative for the treatment of masseter hypertrophy. This study was conducted to identify a safe injection volume to avoid sunken lateral cheek after botulinum neurotoxin A injection in the masseter muscle. Methods: One milliliter or 0.5 ml of indocyanine green was randomly injected into either side of the masseter muscles of 18 fresh cadaver heads. The bilateral spreads of indocyanine green within the masseter were observed by a fluorescence imager. The masseters were then dissected, and the spreading distance was measured. Results: Dye spreading showed an oval shape parallel to the long axis of the masseter muscle. The lower edges of the masseters were all stained with indocyanine green. The upward spreading exceeded the mouth corner‐tragus line in 94.44% (17/18) of the masseters on the 1‐ml side, and 11.11% (2/18) of the masseters on the 0.5‐ml side. The spreading area and upward spreading distance on the 1‐ml side (9.95 ± 0.48 cm2, 3.18 ± 0.31 cm) were significantly larger than the 0.5‐ml side (7.13 ± 0.80 cm2, 2.08 ± 0.32 cm). Conclusions: The spread of indocyanine green within the masseter occurs in direct proportion to its volume. A bolus of 1 ml easily exceeded the mouth corner‐tragus line and cause sunken cheek. [ABSTRACT FROM AUTHOR]

To study the reliability and validity of the Chinese version of the Lymphedema Quality of Life Questionnaire (LYMQOL) in lymphedema patients. LYMQOL was translated into Chinese. The Chinese version of the LYMQOL was distributed with the official Wechat account "Lymphedema Channel" to lymphedema patients who were recruited from October 28th, 2020 to February 23rd, 2021. Patients with upper limb lymphedema and lower limb lymphedema completed the LYMQOL-ARM subscale and the LYMQOL-LEG subscale separately, at enrollment, 1 week later, and 1 month later. Reliability, validity, feasibility, responsiveness and average time required for completing the questionnaire were assessed. A total of 195 patients participated in the study. The Chinese questionnaire showed high reliability with Cronbach's a coefficients of 0.849-0.902 for the LYMQOL-ARM and intraclass correlation coefficient (ICC) of 0.848-0.884 and Cronbach's a coefficients of 0.726-0.902 for the LYMQOL-LEG and ICC of 0.863-0.900. The LYMQOL showed moderate to good correlations with the EQ-5D (0.4

Background: No reports of the potential areas of surgeons' aesthetics in blepharoplasty. Aims: To explore the association between the surgeons' own double eyelid morphology and their aesthetics and surgical outcome. Methods: An investigation of 1605 patients was carried collecting the data of double eyelid shape, based on which to propose a preliminary double eyelid classification for analyzing the aesthetics of surgeons. Ten double eyelid surgical cases were randomly collected from each surgeon according to the inclusion criteria, whose double eyelid shape, ideal shape, the selection tendency of surgical approach, most cared factor during surgery, and design concept of eyelid shape were collected. Structural equation modeling (SEM) was performed to assess the association between participants' double eyelid shape, aesthetics, and blepharoplasty outcome. Results: Fifty‐three double eyelid surgeons were enrolled for study, whose double eyelids shapes mostly were obviously fan‐shaped (37.74%) and low‐parallel eyelid (26.42%), and the ideal shapes were obviously fan‐shaped (41.51%) and high‐parallel eyelid (24.53%). 54.72% of the subjects preferred to use the full‐incisional method. 45.28% cared for long‐term outcome most. Regarding blepharoplasty outcome style, 49.06% of the subjects preferred obviously fan‐shaped type and 24.53% for high‐parallel type. SEM showed that aesthetics rank increased by 0.692 points for surgeons' shape (P <.001), and surgical outcome rank increased by 0.861 points for aesthetics (P <.001). However, their eyelid shape had no direct contribution to surgical outcome (P =.96). Conclusions: The findings indicated that surgeons' double eyelid shape positively affected their aesthetics, which affected their surgical outcomes further, but their double eyelid shape failed to affect the surgical outcomes directly. [ABSTRACT FROM AUTHOR]

Objective: We retrospectively evaluated the efficacy and safety of keystone‐designed perforator island flaps for chest keloid reconstruction. Methods: We reviewed consecutive patients who received keystone flap reconstruction after chest keloid resection between January 2017 and February 2018. The patient demographic data, defect size, flap size, complications, and recurrence were recorded. Results: Thirty‐eight patients were evaluated in this retrospective case series. After keloid resection, dimension of wound defects was 5.5‐9.5 cm × 9.5‐12.5 cm, with an average dimension of 7.3 cm × 10.7 cm. The dimension of keystone flaps was between 6‐10 cm × 20‐34.5 cm, with an average dimension of 7.5 cm × 25.5 cm. The flaps healed smoothly without any complication. There was no keloid recurrence with 15 months of follow‐up. 89.4% of the patients had good outcome with no apparent scarring, and 10.6% patients had satisfactory outcome with localized scarring. Conclusions: Keystone‐designed perforator island flap is an effective and reliable method for reconstruction following chest keloid resection. [ABSTRACT FROM AUTHOR]

Background: The lip is of important aesthetic value and highly subjected to aging. Collecting anthropometric baseline data and understanding age‐related changes of labial morphology can help with diagnosis of deformity, assessment of aging, and planning of cosmetic procedures. Many studies have focused on Caucasians, while there is a lack of anthropometric data on Chinese women. Methods: A total of 169 women were enrolled in this cross‐sectional study and divided into four consecutive age groups. Linear distances, angles, and surface area data were obtained via stereophotogrammetry. Intergroup comparisons between different age groups were performed to find age‐related differences. Results: Lip width significantly increased with age while philtrum width seemed to show no obvious change. Cutaneous upper and lower lip height increased, lengthening the lip in the vertical dimension. Decrease of upper vermilion height and changes in angles indicated that aging process shortened the upper vermilion and flattened the vermilion border. Surface area also showed age‐related changes. Intergroup comparison showed no statistical significance in most variables between 20s and 30s or 30s and 40s, while age‐related changes in some variables were significant between 40s and 50s. Conclusion: This study provided anthropometric data of labial morphology across a wide age range. Aging process affected a variety of labial anthropometric variables. Age‐related changes accelerated after 40 among Chinese women. [ABSTRACT FROM AUTHOR]

Background: Due to the relatively higher tendency of postsurgery scars, insufficient cartilage support, and low surgical acceptability, nasal defect repair with forehead flap in Asian patients needs further study. Objective: We aim to determine the necessity of tissue expansion, timing of pedicle division, and the importance of cartilage scaffold reinforcement and scar prevention at the donor site during nasal reconstruction in Asian patients with paramedian forehead flap. Methods: A retrospective analysis was performed on patients who underwent nasal reconstruction with forehead flap at our hospital from January 2013 to January 2018. The demographical information, surgery details, and postoperative complications of all patients were recorded. The reconstructed nose, scars, and eyebrow deformities were evaluated by digital photographs, and the overall satisfaction of the patients was documented. Results: The study included 15 patients (7 males and 8 females). All nasal defects involved at least two aesthetic units and included seven full‐thickness defects. Only one patient underwent two revision operations. Complications like hematoma, infection, and necrosis were not detected, except in one patient with partial necrosis of the flap. All patients were satisfied with the reconstructed nose and did not report any respiratory dysfunction. No obvious scars or eyebrow deformities were observed. Conclusion: Three‐stage full‐thickness forehead flap should be used to repair nasal defects in Asian patients, with immediate cartilage scaffold reconstruction at stage one and reinforcement at stage two. Botox injection into the forehead can refine the scar. [ABSTRACT FROM AUTHOR]

Background: The repair and reconstruction of the upper lip defects should focus on the important anatomical landmarks of the upper lip. In this investigation, double V‐Y advancement flaps were used to simultaneously repair the cutaneous and mucosal defects of the upper lip. It was especially suitable for young patients with tight skin and high‐risk scar hyperplasia in the donor sites. Objective: The objective was to examine the surgical outcomes following the simultaneous repairation of upper lip mucocutaneous defects using double V‐Y advancement flaps. Methods: A retrospective review of all patients with defects near the vermilion border who underwent double V‐Y flaps repair from July 2014 to November 2018 was performed. Transverse V‐Y advancement flaps were used to repair the cutaneous defects and longitudinal V‐Y advancement flaps to repair the mucosal defects. Results: Fifteen patients (six males, nine females) were retrospectively reviewed. Defects spanning the vermilion border ranged from 0.8 × 0.5 to 2.5 × 1.5 cm2. Follow‐up was for 3 months or longer. There were no perioperative complications or visible postoperative scars, and major anatomic landmarks were preserved and reconstructed. All patients were satisfied with the aesthetic outcome. Conclusion: Double V‐Y advancement flaps are suitable for the repair of superficial mucocutaneous defects smaller than 50% of the lateral upper lip, especially for younger patients with tight skin. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of a scar-free surgical approach, the modified McIndoe technique, in cases of vaginal agenesis.Materials and Methods: Seven patients with Mayer-Rokitansky-Kuster-Hauser syndrome underwent vaginoplasty with the modified McIndoe technique. Mucosa grafts harvested from the vulva were minced into small particles and transplanted to the neovagina.Results: Epithelization in the neovagina is approximately 20 times in size than that in the mucosa harvested from the donor site. An adequate vaginal length was obtained in all cases, with a minimal change in genital appearance and invisible scars. All 4 sex-active patients reported satisfactory sexual experiences, with spontaneous lubrication during intercourse.Conclusion: With the modified McIndoe technique, using an autologous micromucosa graft harvested from the vulva and the buccal cavity, we can physiologically reconstruct a new mucosa-lined vagina with minimal sacrifice. [ABSTRACT FROM AUTHOR]

The key to treating steroid-induced necrosis of femoral heads (SINFH) is early diagnosis. Dramatic improvements in diagnosis could be made if the pathogenesis of SINFH was more fully understood; however, the underlying mechanism of this disease is currently unknown. To explore the potential mechanism of SINFH, we performed gene array analysis on a rat model of the disease and compare the expression profile with that of normal rats. A quantitative RT-PCR and immunohistochemistry (IHC) assays were used to confirm the microarray results. Compared to the control group, 190 genes in the experimental group were differentially expressed, with 52 up-regulated and 138 down-regulated. Of these genes, 102 are known (deposited in GenBank), while 88 of them are unknown. The known genes can be divided into several families according to their biological functions, such as oxidative stress, apoptosis, signal transduction, angiogenesis, extracellular matrix, lipid metabolism, and transcription related genes. The results of quantitative RT-PCR and IHC were consistent with gene chip results. Our findings indicate that many genes involved in diverse signaling pathways were differentially expressed between SINFH rats and normal rats. Furthermore, our findings suggest that the development of SINFH is a complicated and dynamic process affected by multiple factors and signaling pathways and regulated by various genes. [ABSTRACT FROM AUTHOR]

Skin undergoes constant self-renewal, and its functional decline is a visible consequence of aging. Understanding human skin aging requires in-depth knowledge of the molecular and functional properties of various skin cell types. We performed single-cell RNA sequencing of human eyelid skin from healthy individuals across different ages and identified eleven canonical cell types, as well as six subpopulations of basal cells. Further analysis revealed progressive accumulation of photoaging-related changes and increased chronic inflammation with age. Transcriptional factors involved in the developmental process underwent early-onset decline during aging. Furthermore, inhibition of key transcription factors HES1 in fibroblasts and KLF6 in keratinocytes not only compromised cell proliferation, but also increased inflammation and cellular senescence during aging. Lastly, we found that genetic activation of HES1 or pharmacological treatment with quercetin alleviated cellular senescence of dermal fibroblasts. These findings provide a single-cell molecular framework of human skin aging, providing a rich resource for developing therapeutic strategies against aging-related skin disorders. • Single-cell transcriptional landscapes of human skin aging • Dysregulation of cell-type-specific transcriptional networks during skin aging • Cell-type-specific downregulation of HES1 or KLF6 accelerates senescence • Quercetin promotes the rejuvenation of aged dermal fibroblasts Zou et al. performed a single-cell transcriptomic analysis of human skin from donors of different ages and identified cell-type-specific aging-associated downregulation of growth-controlling transcription factors including HES1 in fibroblasts and KLF6 in basal cells. [ABSTRACT FROM AUTHOR]

Background: Human adipose-derived stem cells (hADSCs) are an important source of cells for regenerative medicine. Evidence of extensive interactions with the surrounding microenvironment has led researchers to focus more on hADSCs as activating agents of regenerative pathways, rather than simply replacing damaged cells. Several studies have found that functional miRNAs can be packaged into exosomes and transferred from donor cells into recipient cells, indicating that transported miRNAs may be a new class of cell-to-cell regulatory species. The aim of the present study was to evaluate whether the exosome-derived miRNAs secreted by hADSCs are capable of influencing angiogenesis, a key step in tissue regeneration. Methods: Exosomes were purified from hADSCs followed by the characterization of their phenotype and angiogenic potential in vitro. RNA sequencing was performed to detect the miRNAs that were enriched in the hADSC-derived exosomes. A miRNA-mimic experiment was used to detect the key miRNAs in the proangiogenic activity of hADSC-derived exosomes. Results: Exosomes isolated from hADSCs were characterized as round membrane vesicles with a size of approximately 100 nm and were positive for CD9 and flotillin. The exosomes were internalized by primary human umbilical vein endothelial cells (HUVECs) and stimulated HUVEC proliferation and migration. Remarkably, the exosomes promoted vessel-like formation by HUVECs in a dose-dependent manner, and their maximum activity (10 μg/mL) was comparable with that of 5% FBS. The RNA-seq bioinformatics analysis predicted 1119 gene targets of the top 30 exosomal miRNAs in Gene Ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the pathway involved in the angiogenesis was among the top KEGG pathways. Moreover, intact miR-423-5p was further demonstrated to be transferred into HUVECs via exosomes and to exert its angiogenic function by targeting Sufu. Conclusions: Exosomal miR-423-5p mediated the proangiogenic activity of hADSCs by targeting Sufu, which may contribute to the exploitation of exosomes from hADSCs as a therapeutic tool for regenerative medicine. [ABSTRACT FROM AUTHOR]