Background: Immediate breast reconstruction helps breast cancer patients regain physical and emotional confidence, but the risk of skin flap necrosis can lead to reconstruction failure. Laser speckle contrast imaging (LSCI) has emerged as an innovative technique for predicting necrosis. This study prospectively compared the effectiveness of indocyanine green (ICG) fluorescence imaging with LSCI in predicting the risk of necrosis after direct-to-implant reconstruction. Methods: This study included 87 patients undergoing mastectomy and immediate reconstruction from December of 2022 to January of 2024. Perfusion of the 195 measurement units, including nipple-areola complex and peri-incision skin flaps, was assessed by both LSCI and ICG imaging intraoperatively and postoperatively. Results: A total of 195 measurement units were analyzed, showing significant differences in perfusion values between surviving and necrotic flaps. LSCI demonstrated superior sensitivity (87.10% versus 81.82%), with a perfusion threshold of 37.93% intraoperatively and 22.84% postoperatively. ICG imaging showed higher specificity (80.42% versus 71.60%) but was limited to a single intraoperative use. Conclusions: Both LSCI and ICG were superior predictors of postoperative flap necrosis. LSCI offers the advantage of repeated measurements, making it a versatile tool for ongoing assessment. While the 2 methods showed consistent differences in measured values, LSCI may serve as a viable alternative to ICG in evaluating tissue viability.

Amid the global trend toward smooth implants' use, implant stability has become a progressively significant concern for augmentation mammaplasty. During the dual-plane augmentation via the inframammary fold (IMF) approach, IMF fixation suture-suturing the Scarpa's fascia to the deep fascia-is routinely adopted by surgeons to minimize inferior implant displacement. However, this approach of maintaining implant stability demonstrates inconsistent reliability, particularly with smooth implants. Excluding suboptimal technical factors, the fundamental cause of implant malposition lies in inadequate inferior or lateral support structure. Based on pectoralis major's anatomical foundation and the access characteristics of the IMF incision, the authors introduce an innovative technical refinement-the modified bi-muscular flap (BMF) technique. The procedure involves an L-shaped muscle release that preserves the lateral long-head origins of the muscle, creating an inferior support structure for the implant. A preliminary outcome compared with the dual-plane technique using fixation suture suggests that this new technique may represent a promising alternative for reducing smooth implant malposition and improving long-term stability.

BACKGROUND:Localized scleroderma (LoS) is a fibrotic skin disorder characterized by excessive collagen deposition, leading to functional and cosmetic impairments. Mesenchymal stromal cells (MSCs) offer therapeutic potential through immunomodulation and tissue repair, but their clinical use is limited by donor variability and replicative senescence. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) present a promising alternative owing to their scalable production and rejuvenated phenotype. METHODS:We generated adipose-derived iMSCs (AD-iMSCs) from reprogrammed adipose-derived stem cells (ADSCs) and compared their therapeutic efficacy to primary ADSCs in vitro and in vivo. Functional assays including transcriptomic profiling, conditioned medium (CM) effects on fibrosis markers (α-SMA, TGF-β/Smad), and angiogenesis were conducted. A bleomycin-induced murine LoS model was employed to assess AD-iMSC engraftment, collagen deposition, and microvascularization. RESULTS:AD-iMSCs exhibited rejuvenated-like phenotype, with reduced senescence markers and enhanced proliferative capacity. AD-iMSC-derived conditioned medium (AD-iMSCs-CM) outperformed ADSC-derived conditioned medium (ADSC-CM) in promoting angiogenesis in vitro. In vivo, AD-iMSCs demonstrated superior persistence and therapeutic efficacy, notably decreasing dermal thickness and collagen density while promoting vascularization. Mechanistically, AD-iMSCs more effectively suppressed the TGF-β/Smad2/3 signaling and extracellular matrix (ECM) remodeling pathways compared to ADSCs. CONCLUSION:In conclusion, our findings provide a robust preliminary proof-of-concept demonstrating that iPSC-mediated reprogramming yields iMSCs with rejuvenated-like phenotype and a potent anti-fibrotic secretome. These data offer a valuable molecular and functional rationale for the prospective development of iMSC-based platforms to circumvent the expansion limitations and donor variability inherent to primary MSC therapies for fibrotic skin disorders.

Recent research has underscored the significant role of skin fungi in human health and disease. The advent of next-generation sequencing has facilitated the identification of previously unrecognized fungi; however, a standardized sampling method for the skin mycobiome has yet to be established. Given that fungi are distributed across all layers of the skin, this study aimed to establish and compare the fungal profiles obtained from paired skin swabs (skin surface) and tissue specimens (skin dermis), utilizing ITS rRNA gene sequencing. Fungal diversity and composition varied between swabs and tissue specimens from the same individual. Tissue specimens exhibited greater fungal diversity relative to skin swabs, as indicated by the Chao1 estimator (P=0.028) and Shannon index (P=0.0136). Notably, Malassezia species was more abundant in swabs (P=0.002), whereas Trichoderma species was more prevalent in tissue samples (P=0.0001). Compared to swabs, tissue sampling also demonstrated superior sensitivity in detecting non-Malassezia species. These findings suggest that skin swabs and tissue specimens provide different views of the skin mycobiome: Swabs are effective for studies targeting surface-dwelling fungi, while tissue sampling remains necessary when investigating deeper skin fungi and potential systemic infections. Future research should carefully consider appropriate sampling method based on target fungal location to mitigate procedural artifacts. Level of Evidence III 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 .

Meige syndrome is a rare segmental dystonia characterized by blepharospasm and oromandibular dystonia, often leading to significant functional and aesthetic impairment. This report details a 59-year-old female patient with a 16-year history whose symptoms were refractory to prior drug therapies. An individualized botulinum toxin type A (BTX-A) injection protocol was devised based on detailed facial muscle mapping and plastic surgery principles of muscle balance. Following treatment, the patient showed marked improvement in facial spasms within 1 week, with resolution of nocturnal headaches and notable correction of aesthetic concerns arising from dystonia, including facial asymmetry and the involuntary "gummy smile". The gingival exposure during dystonic contraction was reduced from >4 mm (classified as severe gingival smile) to 1 mm. Social and eating functions were restored. This case suggests that a BTX-A treatment strategy guided by plastic surgery principles, which addresses both functional symptoms and aesthetic disharmony, may provide an effective and safe office-based treatment option for Meige syndrome. Further studies with larger cohorts are warranted to validate this protocol.

Collagenous fibroma (CF), also known as desmoplastic fibroblastoma, is a rare benign fibroblastic/myofibroblastic tumor characterized by FOSL1/FOS rearrangements. CF typically presents as a solitary, slow-growing mass in middle-aged adults. This case presents three extraordinarily rare features: pediatric onset at age 5, chronic multifocal disease over 46 years, and rapid post-surgical growth at a sternotomy site. Surgical excision is the preferred treatment. We report a 51-year-old male with chronic, multifocal CF beginning at age 5 and persisting over 46 years, predominantly affecting the right side. In 2022, a rapidly enlarging mass (25 × 7 cm) developed at a pericardial window incision site within 2–3 years post-procedure. Core needle biopsy at an outside institution showed overlapping features with desmoid fibromatosis. Following an unsuccessful trial of imatinib, comprehensive immunohistochemical analysis at our institution definitively established the diagnosis of CF. Marginal excision with local flap reconstruction resulted in R1 margins. MRI demonstrated T1 isointensity and low T2 signal. Histopathology revealed sparsely cellular spindle-cell proliferation in dense collagenous stroma. Immunohistochemistry showed cytoplasmic/membranous β-catenin expression without nuclear accumulation, low Ki-67 index, and nuclear FOSL1 positivity. The postoperative course was uneventful, with no new lesions at 5-month follow-up. This case presents an extraordinary constellation of three rare features: (1) pediatric onset at age 5; (2) chronic multifocal disease persisting over 46 years; and (3) rapid post-surgical growth suggesting trauma-associated tumorigenesis. These features justify comprehensive molecular analysis and long-term surveillance.

Frequent coexistence of sunken upper eyelid and tear trough deformities presents a common esthetic concern, yet little attention has been paid to concurrent surgical management of the two conditions. A single-institution retrospective study was conducted on patients who underwent tear trough deformity correction combined with upper eyelid surgery, performed either with isolated orbital fat release or orbital fat release combined with lower eyelid fat transfer. Park’s grading and Hirmand classification systems were employed to assess the severity of deformities. The FACE-Q questionnaire was utilized to evaluate changes in patient satisfaction regarding periorbital appearance, psychological well-being, and social function. A total of 37 female patients were included: 13 in the fat release group and 24 in the fat release with transfer group. The loss to follow-up rate was low (10.8 www.springer.com/00266 .

As cellular energy metabolic hubs, mitochondria undergo dynamic fusion-fission cycles and autophagy that enable rapid adaptation to cellular energy demands and stress conditions. In addition to their role in energy metabolism, mitochondria are integral to cellular homeostasis and regulate cell cycle progression, differentiation, and apoptosis pathways. In recent years, the importance of mitochondrial function in skin health and disease has garnered increasing attention. Mitochondrial dysfunction has been implicated in a spectrum of skin disorders, including skin aging, psoriasis, vitiligo, keloids, scleroderma, and skin cancer. The pathogenesis of these conditions is closely linked to mitochondrial deoxyribonucleic acid (mtDNA) damage, excessive reactive oxygen species (ROS) production, and alterations in mitochondrial metabolic pathways. In terms of therapeutic strategies, this review summarizes a range of mitochondrion-targeted interventions. These treatments include the activation of the PGC-1α pathway to increase mitochondrial adenosine triphosphate synthesis, the use of antioxidants to mitigate mitochondrial ROS production, and the application of bioactive compounds and drugs to protect mitochondria or promote mtDNA repair. These approaches not only contribute to improved skin health but also provide novel insights for the treatment of skin diseases. Additionally, mitochondrial transplantation technology has shown considerable promise in skin regeneration and wound healing and is emerging as a new frontier for skin tissue repair.

Upper blepharoplasty is the most common cosmetic procedure in East Asia. A natural Asian double eyelid features specific crease characteristics. AI advancements, such as UNet and PointRend, enhance medical image segmentation, aiding in post-blepharoplasty evaluation. This study applies deep neural networks to analyze facial images, providing morphological parameters to assist surgeons in assessing outcomes and planning revisions. This study included 102 eyes from 51 patients seeking for revisional blepharoplasty and 100 eyes from 50 volunteers with inborn double eyelid. Standardized images and videos were collected. The deep learning-based image analysis automatically evaluated four eyelid morphological parameters, including pre-tarsal show, corneal visibility ratio, dynamic value, and crease depth. Analysis was done on the agreement between the automated measures and the manual measurements. The parameters of the patients’ and volunteers’ eyelids were compared. FACE-Q surveys were used to measure patient-reported esthetic outcomes. The intraclass correlation coefficients between manual measures and automated measurements of pre-tarsal show, corneal visibility ratio, and dynamic value were 0.973, 0.975, and 0.965. At the long-term follow-up, the pre-tarsal show and crease depth decreased significantly, whereas the corneal visibility ratio and dynamic value increased significantly. FACE-Q scores demonstrated a high level of patient satisfaction for facial appearance (87.6) and were negatively correlated with pre-tarsal show (r = − 0.814, p = 0.000). The deep neural network technique automatically measured the eyelid morphology with excellent precision and reproducibility, enabling an objective evaluation of the surgical outcomes for blepharoplasty. 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 .

The study aimed to use eye-tracking technology objectively quantifying changes in visual attention patterns in observers viewing faces of patients with facial localized scleroderma (LoS) before and after autologous fat transplantation (AFT). In this retrospective observational study, preoperative and postoperative standardized photographs of 30 patients with facial localized scleroderma (LoS) were presented to 50 observers. Gaze data were recorded using an eye tracker. Fixation proportions were analyzed for all affected regions and for specific facial subunits. A total of 30,266 fixation points were recorded. Postoperatively, the fixation proportion on the affected hemiface significantly decreased by 4.92 www.springer.com/00266 .

BACKGROUND:Drooping oral commissures can impart a displeased appearance, negatively affecting psychosocial interactions and well-being. Botulinum toxin type A (BTX-A) is an efficacious treatment for mouth corner lift. However, the optimal injection strategy is controversial. Therefore, this study aims to compare the efficacy and safety of BTX-A injection at different sites of depressor anguli oris (DAO) muscle and to assess the added benefit of BTX-A injection into the platysma (PLT). METHODS:This two-stage, single-center prospective study included a randomized, double-blind randomized trial (stage 1) and a non-randomized prospective study (stage 2). Primary outcomes were oral commissure position (OCDA, OCLA) and lip asymmetry (DSL) using three-dimensional photogrammetry. Secondary outcomes included patient satisfaction, pain, and side effects. RESULTS:Both methods improved OCDA and OCLA across all time points, with lower DAO injection showing greater effects than the upper site. DAO+PLT further improved OCLA at 1 month and OCDA at 6 months. Satisfaction was higher with DAO+PLT (P < 0.05). DSL differences were <1 mm. No severe adverse events occurred. CONCLUSION:Lower DAO injection is more effective in inhibiting DAO movement. DAO+PLT yields superior commissure lifting with minimal side effects.

Background:Correction of moderate-to-severe nasolabial folds (NLFs) is a key concern in aesthetic medicine. Poly-L-lactic acid (PLLA) microspheres, with biostimulatory properties, potentially offer longer-lasting results compared with hyaluronic acid (HA), the current standard of care. Objectives:The aim of this study was to evaluate the efficacy and safety of PLLA microspheres vs HA for the correction of moderate-to-severe NLFs. Methods:In this multicenter, randomized, double-blind, parallel-controlled trial, 252 participants were enrolled across 8 centers in China and assigned to receive either PLLA or HA filler. The primary endpoint was the effective correction ratio of the Wrinkle Severity Rating Scale (WSRS) at 48 weeks, assessed by blinded independent reviewers. Secondary endpoints included WSRS change, Global Aesthetic Improvement Scale (GAIS) scores (investigator- and participant-assessed), treatment frequency, and safety outcomes. Results:At 48 weeks, PLLA demonstrated a significantly higher effective correction ratio than HA (92.4% vs 59.3%; difference, 33.1% [95% CI, 23.1-43.2]; P < .0001). HA outperformed PLLA at Week 4, reflecting its immediate effect, whereas PLLA showed superior outcomes from Week 36 onward with sustained improvement confirmed by WSRS and GAIS. PLLA required more frequent early treatments, whereas HA generally achieved correction with fewer sessions. Adverse events were mild and transient, with no serious complications in either group. Conclusions:Under current protocols, HA offers rapid improvement, whereas PLLA requires multiple early sessions but yields more durable correction up to 48 weeks with similar safety. Filler selection should be individualized according to patient priorities. Level of Evidence 2 Therapeutic:

BackgroundThe expansion of plastic and aesthetic industries is heavily market-driven. With socioeconomic advancement, the plastic and aesthetic industries have experienced extraordinarily rapid growth over the past several decades, exhibiting distinct patterns between public and private hospitals.MethodsWe collected national data from public and private hospitals across mainland China through the National Clinical Information System (NCIS) and the National Medical Quality Control Platform (NMQCP) for Plastic and Aesthetic Major. Data encompassed hospital profiles, practitioner demographics, inpatient clinical case mix, ambulatory therapeutic modalities, and the consultation rate for aesthetic injection complications.ResultsAmong public hospitals offering plastic/aesthetic services, 99.20% were general hospitals, while 80.60% of private hospitals were specialized in plastic and aesthetic procedures. We also found significant differences between public and private hospitals regarding physician qualifications, professional backgrounds, inpatient case mix, and ambulatory therapeutic modalities. The consultation rate for aesthetic injection complications was additionally higher in public hospitals relative to private hospitals.ConclusionBoth public and private hospitals have established plastic and aesthetic specialties with distinct scale characteristics. Driven by greater operational autonomy and their market-driven nature, private hospitals exhibited greater flexibility in development within this specialty and demonstrated a stronger preference for minimally invasive treatments. However, despite their perceived minimal invasiveness, aesthetic injections carried significant complication risks; and particularly, severe cases resulted in substantial physical trauma and financial burdens for aesthetic patients. We recommend that government authorities formulate tailored quality-control measures based on the divergent developmental paths of public and private hospitals to safeguard patient safety.Level of Evidence IIIThis 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.

BACKGROUND:Temple hollowing represents a prevalent aesthetic concern traditionally addressed with autologous fat grafting or hyaluronic acid fillers. Poly-L-lactic acid (PLLA) offers gradual, collagen-mediated volumization and is increasingly utilized for soft tissue augmentation. Nevertheless, to date, no approved study has evaluated its use for temporal augmentation. OBJECTIVES:The aim of this study was to evaluate the efficacy and safety of a PLLA facial filler for the augmentation of temple hollowing. METHODS:This randomized, no-treatment control, evaluator-blinded, multicenter clinical trial enrolled 174 participants with moderate to severe temple hollowing, randomized 2:1 to the treatment or control group. The treatment group received 2 to 3 sessions of PLLA bilateral temporal injections with 12-month follow-up, and the control group received no treatment within 6 months after randomization. Efficacy was assessed with the Allergan Temple Hollowing Scale (ATHS), Global Aesthetic Improvement Scale (GAIS), 3-dimensional (3D) volume change of temples, and participant-reported satisfaction. Safety evaluations included adverse events (AEs), injection-site reactions, vital signs, and laboratory tests. RESULTS:At Month 6, 96.5% of participants in the treatment group achieved an at least 1-grade improvement on the ATHS, in contrast to 0% in the control group (P < .0001). Consistent and significant improvements were observed across all secondary endpoints, including ATHS efficacy rates assessed by both blinded evaluators and injection investigators at all follow-up visits up to 12 months, GAIS improvement rates, and temporal volume measured by 3D imaging. Aesthetic improvement and participant satisfaction were rated highly at all follow-up visits. PLLA was safe and well tolerated, with no therapy-related adverse events reported. CONCLUSIONS:PLLA facial filler effectively improved temple hollowing and achieved aesthetic enhancement for up to 12 months, with an excellent safety profile. LEVEL OF EVIDENCE: 1:(Therapeutic)For image description, please refer to the figure legend and surrounding text.

Objective To assess the current status of early surgical site infections following prosthetic implantation in plastic surgery across four provincial-level administrative regions in China,and to explore the effectiveness of standardized training for infection prevention and control.Methods From January to May 2025,an online questionnaire survey was conducted to perform a baseline investigation in medical institutions performing plastic and aesthetic prosthetic implant surgeries in Chongqing,Shaanxi,Jiangxi,and Guizhou provinces.Data were collected on the volume of various types of prosthetic implant surgeries and the correspond-ing incidence of early surgical site infections.Improvement strategies for the prevention and control of early sur-gical site infections in prosthetic implant surgeries were jointly developed by the National Medical Quality Con-trol Center for Plastic and Aesthetic Surgery and the National Medical Quality Control Center for Hospital Infec-tion Management,followed by promotion and training.Subsequently,post-implementation data from June to Oc-tober 2025 were collected from the above regions,and comparisons were made between pre-and post-implemen-tation periods across different regions and surgical categories.Results A total of 209 medical institutions were included in the baseline period,with a questionnaire response rate of 99.52%and a total of 7475 prosthetic im-plantation surgeries.In the post-implementation period,624 medical institutions were included,with a response rate of 96.00%and a total of 4813 surgeries.The combined proportion of breast prosthesis implantation and na-sal/nasal base prosthesis implantation surgeries consistently exceeded 80%across all regions and periods.Re-garding the distribution of infection cases,among different types of prosthetic implant surgeries,nasal/nasal base prostheses accounted for the highest proportion,with 57.50%(23/40)at baseline and 62.86%22/35)post-implementation.The proportion of breast prosthesis infections decreased from 40.00%(16/40)at baseline to 17.14%(6/35)post-implementation.Across different regions,infection cases in Jiangxi(post-im-plementation)(100%),Guizhou[both baseline(100%)and post-implementation(100%)]were all concentrated in nasal/nasal base prostheses.Shaanxi reported four cases of chin prosthesis infections(22.22%)during the post-implementation period,and Chongqing reported three cases of metal-related infec-tions(27.27%)during the post-implementation period.In terms of infection rates,Chongqing(0.55%vs.0.26%)and the overall combined regions(0.73%vs.0.54%)showed higher infection rates post-implementa-tion compared to baseline,while Shaanxi(0.93%vs.1.05%),Jiangxi(0.29%vs.1.38%),and Guizhou(0.91%vs.1.22%)showed lower infection rates post-implementation;none of these differences reached sta-tistical significance(all P＞0.05).The infection rate for metal-related prostheses increased significantly in Chongqing(1.43%vs.0,P=0.04)and in the overall combined regions(1.22%vs.0,P=0.04),while no significant differences were observed for other surgical categories within the same regions(all P＞0.05).Conclusions Breast prostheses and nasal/nasal base prostheses currently represent the main types of implants used in prosthetic implantation surgeries.The improvement strategies implemented in this study were associated with decreased early surgical site infection rates in multiple regions,suggesting that these strategies provide clinical insights for the prevention and control of early infections following prosthetic implantation surgeries in China.

Traumatic masses can present a diagnostic challenge, often encompassing both neoplastic and nonneoplastic lesions. This article reports a unique case of a 51-year-old woman with a recurrent subcutaneous mass initially diagnosed as fibrolipoma through multiple surgical excisions. Despite previous histopathologic analyses, the definitive diagnosis was established as a posttraumatic hemangioma with clear traumatic etiology. The patient had a history of a penetrating slingshot injury that went unnoticed until retrospective examination following surgical intervention revealed retained foreign bodies contributing to mass recurrence. Imaging studies indicated irregular nodular formations suggestive of vascular anomalies. This case highlights the importance of considering traumatic factors in the differential diagnosis for plastic surgeons managing soft-tissue masses, and the need for comprehensive surgical excision with intraoperative assessment to prevent misdiagnosis, particularly in recurrent benign tumors. The findings underscored the potential for persistent irritative factors and the limitations of preoperative biopsies in accurately diagnosing complex lesions.

Adipose precursor cells (APCs), present within the stromal vascular fraction (SVF) of adipose tissue, play an important role in adipose biology. However, its regulatory functions in adipogenesis and tissue homeostasis remain incompletely characterized. Here, we isolated APC from the subcutaneous adipose tissue of Prx1-Cre; Rosa26-tdTomato mice and confirmed that APC has a high adipogenic differentiation efficiency. Next, RNA sequencing analysis indicates that APC may have dual effects of promoting adipogenesis and anti-inflammatory effects. Subsequent in vivo studies identified clusterin (Clu) as a key secretory factor through which APC exerts its regulatory functions. By utilizing gene regulation and APC/adipocyte co-culture, we further demonstrated that APC-derived Clu promotes its own adipogenic differentiation and improves local resistance to oxidative stress. Collectively, data from conditional Clu knockout mice establish its key function in preserving adipose tissue homeostasis. These findings highlight Clu as a potential therapeutic target for interventions aimed at adipose tissue homeostasis and regeneration.

Advanced primary lymphedema is challenging to treat and imposes physical and psychosociological burdens on patients. Currently, vascularized lymph node transfer and modified Charles procedures are recommended for late-stage patients due to the limited functional superficial lymphatics required for conventional lymphovenous bypass. However, the reconstruction involves radical resection of tissue and changes in lymphatic flow, resulting in prolonged recovery time, high complication rates, and emotional and economic burdens on the patients. The authors proposed a novel alternative for treating stage II primary lymphedema using a duo-plane lymphovenous bypass. The innovation involves anastomosing the collecting lymphatics in the deeper subcutaneous tissue to superficial venules. The technique benefits from accessing functional lymphatics with preserved architecture, a larger vessel diameter, and a well-defined anatomical location to optimize drainage and prevent venous backflow using the Venturi effect. The duo-plane lymphovenous bypass procedure warrants significant volume reduction, faster recovery, and minimal scarring, thus providing a less-invasive treatment option for patients with advanced primary lymphedema.

BACKGROUND:YY001 (Retoxin ®), the first global recombinant botulinum toxin type A (rBoNT/A) tested in humans, contains a pure 150-kDa core neurotoxin identical to natural BoNT/A (nBoNT/A). This study aimed to evaluate the safety and preliminary efficacy of YY001 in humans for moderate-to-severe glabellar lines. METHODS:Preclinical assessments comprised homology modeling, biochemical and pharmacological evaluation, and multispecies toxicology. In this phase I multicenter double-blind, randomized, dose-ranging, vehicle- and active- controlled trial, participants (n=50) with moderate-to-severe glabellar lines were randomized 1:1:1:1:1 to receive intramuscular injection of YY001 at 10, 20 and 30 U, Botox ® at 20 U, or vehicle. The primary endpoint encompassed the incidence of adverse events (AEs), serious AEs, injection site reactions and clinically significant laboratory changes within 28 days post-injection, with exploratory follow-up to 168 days. RESULTS:The YY001's structure and biological activities are highly consistent with those of nBoNT/A. In this trial, no drug-related AEs were observed in the tested 10-30 U of YY001. At day 28, the response rate by investigator's live assessment was 60% for 10 U of YY001, 80% for 20 U of YY001, 90% for 30 U of YY001, 70% for 20 U of Botox ®, and 0% for the vehicle, while the proportion of subjects with none or mild glabellar lines at maximum frown was 80%, 90%, 100%, 80%, and 0%, respectively. CONCLUSIONS:The first rBoNT/A (YY001) in human study demonstrated a favorable safety and tolerability profile (dose-independent) at doses of 10, 20 and 30 U in Chinese subjects with moderate-to-severe glabellar lines. It also showed dose-dependent efficacy benefit.Trial Registration: ChinaDrugTrials.org.cn identifier: CTR20221419.