"Comparative study of adipose-derived stem cells from localized scleroderma patients and healthy donors in treating skin fibrosis".

BACKGROUND: Localized scleroderma (LoS) is an autoimmune disease characterized by fibrosis of the skin and atrophy of the subcutaneous fat tissue. Adipose-derived mesenchymal stem cells (ASCs) is a promising treatment approach for LoS. However, ASCs from scleroderma patients (LoS-ASCs) have been shown to exhibit altered characteristics compared to ASCs from healthy donors (healthy-ASCs). This study aimed to compare the abilities of LoS-ASCs and healthy-ASCs in treating skin fibrosis. METHODS: The paracrine ability of ASCs was tested with cytokine array. Bleomycin-challenged mice models received subcutaneous injection of LoS-ASCs and healthy-ASCs. Pathological staining and western blotting of COL1, α-SMA was performed. Fibroblasts derived from LoS lesions (LoS-FB) was co-cultured with ASCs, and subjected to RNA sequencing to further explore the similarities and differences in the treatment mechanism. RESULTS: In vivo comparison revealed that healthy ASCs had a stronger proliferation ability and secreted higher levels of growth factors and cytokines, including VEGFA, PDGFB, and IL-10. Pathological staining of the skin in mice models treated with ASCs demonstrated that healthy ASCs were more effective in reducing dermal thickness and collagen deposition, while increasing microvessel density and the proportion of M2 macrophages. Co-culture with both healthy-ASCs and LoS-ASCs reduced the proliferation and migration abilities of LoS-FB, as well as the protein expression of α-SMA and COL1. RNA sequencing and validation revealed potential difference in the canonical Wnt pathway. CONCLUSIONS: Healthy-ASCs exhibited stronger proliferation, paracrine, anti-fibrosis, pro-angiogenesis, and immunomodulation abilities in treating skin fibrosis in scleroderma mouse models. CLINICAL RELEVANCE STATEMENT: Allogenic ASCs obtained from healthy donors are more efficient in treating skin fibrosis, and could serve as a potential alternative for patients who are not suitable candidates for liposuction surgery in the future.

Deciphering Depressor Anguli Oris for Lower Face Rejuvenation: A Prospective Ultrasound-based Investigation.

BACKGROUND: The depressor anguli oris muscle (DAO) is a pivotal treatment target when creating a harmonic jawline. However, evidence of its live morphology remains scarce. OBJECTIVES: In this study we aimed to reevaluate the DAO with a facile ultrasound analysis and thereby guide safer and more effective botulinum toxin type A (BTX-A) injection. METHODS: A prospective ultrasound assessment was conducted in 41 patients. Morphology of the DAO and its relative position to neighboring structures were appraised at the ubiquitous facial landmark, the labiomandibular fold (LMF). Three-dimensional images were captured before and after the patient received the BTX-A injection based on sonographic evidence. RESULTS: The skin-to-muscle depths of the DAO on average (measured from the medial to lateral border) were 5.26, 5.61, and 8.42 mm. The DAO becomes thinner and wider from zone 1 to zone 3 (P < .001). Overlapping lengths of the DAO and the depressor labii inferioris increased from zone 1 to zone 3: 4.74, 9.68, 14.54 mm (P < .001). The medial border of the DAO was located at 4.33, 6.12, 8.90 mm medial to the LMF (zone 1-3), and no muscle fibers of the DAO were observed in zone 1 or zone 2 in nearly one-third of patients. Improvement of the mouth corner downturn angle upon receiving BTX-A injection at zones 2 and 3 were 88.3%, 32.3%, and 14.7% for the neutral, maximum smile, and down-turning mouth corner expressions. CONCLUSIONS: This work established an informative ultrasound portrait of the DAO and structures in the perioral region, which suggested the LMF as a convenient landmark for locating the DAO. Injection at the middle and lower thirds of the LMF at a 4- to 5-mm depth is recommended.

Exosomes from human adipose-derived mesenchymal stem cells attenuate localized scleroderma fibrosis by the let-7a-5p/TGF-ßR1/Smad axis.

BACKGROUND: 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. OBJECTIVE: The impact and potential mechanism of ADSC-Exo on LS fibrosis was examined. METHODS: 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-ßR1 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. RESULTS: The verified ADSC-Exo limited the proliferation and migration of LSFs and reduced the expression of COL1, COL3, α-SMA, TGF-ßR1, and p-Smad2/ 3 in vitro and in vivo. TGF-ßR1 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-ßR1 levels were increased after exposure to ADSC-ExoAnti-let-7a-5p. CONCLUSIONS: 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.

Fat Grafting Reduces Skin Hyperpigmentation of Localized Scleroderma Patients: A Prospective Self-controlled Study.

BACKGROUND: Localized scleroderma (LS) is characterized by skin fibrosis, hyperpigmentation and soft tissue atrophy. Fat grafting has been widely used to correct LS deformity. OBJECTIVE: To investigate the effect of fat grafting on the skin pigmentation of LS lesions. METHODS: A prospective self-controlled study was conducted. Skin melanin and erythema indexes were measured by Mexameter® MX18 before and 3 months after surgery. Differences between lesions and contralateral normal sites were compared to evaluate changes induced by fat grafting. Localized Scleroderma Cutaneous Assessment Tool and PUMC Localized Scleroderma Facial Aesthetic Index were used for clinical evaluation. RESULTS: Fourteen frontal linear LS patients participated in the study. Before surgery, the melanin index of the lesions was significantly higher than the contralateral sites (p = 0.023), while the erythema indexes were not significantly different (p = 0.426). Three months post-operation, the melanin index of the lesions significantly decreased (p = 0.008). There was no significant change in the erythema index of the lesions before and after fat grafting (p = 0.322). The LoSCAT and PUMC LSFAI scores demonstrated improved disease condition and facial esthetics after surgery. CONCLUSION: Fat grafting could alleviate skin hyperpigmentation and skin damage of LS lesions while having little effect on skin erythema and disease activity. 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 .

Wip1 regulates wound healing by affecting activities of keratinocytes and endothelial cells through ATM-p53 and mTOR signaling.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

What factors will influence patients when choosing plastic surgeons? A behaviour analysis of Chinese patients.

PURPOSE: To analyze the factors that patients consider when choosing plastic surgeons and investigate patients' attitudes toward physicians' aesthetic ability and their adherence toward same-gender physicians. METHODS: A cross-sectional study was conducted. All patients who presented for evaluation and management between January and April 2022 were eligible for study enrolment. Data collected include demographical information and specific questions related to choosing plastic surgeons, including physician's education, surgical ability, research, title, appearance, dress, age, aesthetics, the patient's preference for physicians' gender, and the way of learning about physicians. RESULTS: 1006 valid respondents participated, and the average age was 46.44 ±â€¯15.51 years old (participation rate 99.60%). 72.5% were female. Plastic surgery history (OR 3.242, 95%CI: 1.664-6.317, p = 0.001), education (OR 1.895, 95%CI: 1.064-3.375, p = 0.030), income (OR 1.340, 95%CI: 1.026-1.750, p = 0.032), sexual orientation (OR 1.662, 95%CI: 1.066-2.589, p = 0.025), and concern for the physicians' appearance (OR 1.564, 95%CI: 1.160-2.107, p = 0.003) were significantly associated with patients' tendency to value physicians' aesthetic ability. Marital status (OR 0.766, 95% CI: 0.616-0.951, p = 0.016), income (OR 0.896,95% CI: 0.811-0.990, p = 0.031), the attention to physicians' age (OR 1.191,95% CI: 1.031-1.375, p = 0.017), and the attention to physicians' aesthetic ability (OR 0.775,95% CI: 0.666-0.901, p = 0.001) were significantly associated with the respondents' same-gender adherence degree. CONCLUSION: These findings suggest that patients with plastic surgery history, higher income, higher education background, and more diverse sexual orientation paid more attention to physicians' aesthetic ability. Marriage and income would affect the same-gender adherence degree, which would further influence patients' attention to the doctor's age and aesthetic ability.

2-Methoxyestradiol inhibits the proliferation level in keloid fibroblasts through p38 in the MAPK/Erk signaling pathway.

BACKGROUND: The MAPK/Erk signaling pathway is a classic pathway in cell proliferation. Our former study showed that keloid tissue revealed a higher proliferation level than physiological scars and normal skin. As a natural metabolite of estradiol, 2-methoxyestradiol (2ME2) showed an inhibition proliferation effect on tumor cells. AIM: In this study, the treatment effect of 2ME2 and its potential mechanisms are explored. METHODS: Six keloid patients and six non-keloid patients were randomly selected from the Department of Plastic Surgery at our hospital during June 2021 to December 2021. Six groups were established: normal skin fibroblasts (N); keloid fibroblasts (K); keloid fibroblasts treated with 2ME2 (K + 2ME2); keloid fibroblasts treated with dimethyl sulfoxide (DMSO) (K + DMSO); keloid fibroblasts treated with doramapimod (K + IN); keloid fibroblasts treated with doramapimod (p38 inhibitor) and 2ME2 (K + IN+2ME2). The fibroblast activity and key factor expression of the MAPK/Erk signaling pathway were measured. RESULTS: In the results, 2ME2 significantly inhibited keloid fibroblast activity and key factor expression (except STAT1). CONCLUSION: The proliferation levels were reduced by both the p38 inhibitor and 2ME2, indicating 2ME2 may achieve an antiproliferation effect by targeting p38 in keloid fibroblasts.

Does injection pattern matter in upper face BoNT-A application? A prospective split-face andomized trial comparing linear and spot technique.

BACKGROUND: Although the efficacy of botulinum toxin type A (BoNT-A) has been shown to vary depending on injection layer, reconstitution volumes, and BoNT-A formulations, the impact of injection patterns has been rarely mentioned. This article compared the therapeutic effects in patients treated with BoNT-A with retrograde linear and traditional spot injection techniques. METHODS: Twenty-eight participants were enrolled in a split-face, patient-blinded randomized clinical trial. Each patient received BoNT-A injected with linear injection technique on one side and with spot injection technique on the other side. Outcomes included the wrinkle improvement rates (WIR) of the two injection techniques determined by the wrinkle scores derived from Antera 3D camera, the muscle activity assessed via ultrasound, and patient-reported pain rating on a numeric pain rating scale (NRS). RESULTS: All participants completed the study. For forehead wrinkles, WIR on the linear side was significantly larger than that on the spot side at 1 week and 1 month (p<0.02). For glabellar wrinkles, WIR on the linear injection side was significantly larger than that on the spot side at 1 week (p=0.04). However, for periorbital wrinkles, WIR on the spot side was significantly larger than that on the linear side at 1 week (p<0.03). No significant difference was observed between the injection patterns in terms of muscle contraction and NRS scores. CONCLUSIONS: Compared with the traditional spot injection, the retrograde linear injection shows to be superior in reducing forehead lines and glabellar lines, but less effective in reducing periorbital lines when identical dosages were injected. TRIAL REGISTRATION: chictr.org.cn: ChiCTR2100046880.

Intrathyroid thymic carcinoma: clinicopathological features and whole exome sequencing analysis.

Intrathyroid thymic carcinoma (ITC) is a rare malignant tumour. We present nine cases of ITC that were analysed by immunohistochemical staining, of which five were analysed using whole exome sequencing (WES). These cases included six women and three men with an age range of 31-66 years. The average postoperative follow-up term was 37.8 months (range, 7-95 months), and all patients survived well except for one case with lung metastasis. Microscopically, ITC showed solid islands of tumour cells separated by fibrous connective tissue containing lymphocytes and other inflammatory cells. Tumour cells strongly expressed Ckpan (AE1/AE3), P63, and CD117. And all cases but one were positive for CD5. The median value of Ki-67 was 32% (range 10-60%). We observed partial positivity of Syn and CgA in only one case. ITC shares morphological and immunohistochemical similarities with thymic squamous cell carcinoma. In situ hybridization of EBER showed negative results. All cases were microsatellite stable, and the tumour mutational burden of the 5 cases was all < 1 mutations/Mb. WES showed higher mutation rates for N4BP1 (2/5), and many genetic alterations were related to the NF-kB signalling pathway, which is crucial for insight into the molecular mechanisms of the occurrence and development of ITC.

Temporal and periorbital depressions identified by 3D images are correlated with malnutrition phenotypes in cancer patients: A pilot study.

Background: Prompt diagnosis of malnutrition and appropriate interventions can substantially improve the prognosis of patients with cancer; however, it is difficult to unify the tools for screening malnutrition risk. 3D imaging technology has been emerging as an approach to assisting in the diagnosis of diseases, and we designed this study to explore its application value in identifying the malnutrition phenotype and evaluating nutrition status. Methods: Hospitalized patients treating with maintenance chemotherapy for advanced malignant tumor of digestive system were recruited from the Department of Oncology, whose NRS 2002 score > 3. Physical examination and body composition data of patients at risk for malnutrition were analyzed by physicians trained to complete a subjective global assessment. The facial depression index was recognized using the Antera 3D® system, temporal and periorbital depression indexes were acquired using the companion software Antera Pro. This software captures quantitative data of depression volume, affected area, and maximum depth of temporal and periorbital concave areas. Results: A total of 53 inpatients with malnutrition-related indicators were included. The volume of temporal depression was significantly negatively correlated with upper arm circumference (r = -0.293, p = 0.033) and calf circumference (r = -0.285, p = 0.038). The volume and affected area of periorbital depression were significantly negatively correlated with fat mass index (r = -0.273, p = 0.048 and r = -0.304, p = 0.026, respectively) and percent body fat (r = -0.317, p = 0.021 and r = -0.364, p = 0.007, respectively). The volume and affected area of temporal depression in patients with muscle loss phenotype (low arm circumference/low calf circumference/low handgrip strength/low fat-free mass index) were significantly higher than those in patients without muscle loss. Moreover, patients with fat mass loss phenotype (low fat mass index) showed a significant increase in the volume and affected area of periorbital depression. Conclusion: The facial temporal region, and periorbital depression indicators extracted by 3D image recognition technology were significantly associated with the phenotype of malnutrition-related muscle and fat loss and showed a trend of grade changes in the population of different subjective global assessment nutritional classifications.

The Dorsal Nasal Complex in Asians: Anatomical Variations and Injection Guide for Botulinum Toxin Type A.

BACKGROUND: Multiple muscles contribute to the formation of dorsal nasal lines (DNLs) and affect nasal aesthetics. Few attempts have been made to explore the range of distribution of DNLs in relation to injection planning. OBJECTIVES: The aim of this study was to classify the distribution types of DNLs and propose a refined injection technique validated by clinical study and cadaver dissection. METHODS: Patients were classified into 4 types according to their DNL distribution type. Botulinum toxin type A injections were administered at 6 regular points and 2 optional points. The effect on wrinkle reduction was assessed. Patient satisfaction was recorded. Cadaver dissection was conducted to explore the anatomical evidence of DNL variation. RESULTS: The study included 349 treatments in 320 patients (269 females and 51 males), whose DNLs were classified into complex type, horizontal type, oblique type, and vertical type. The severity of DNLs was significantly reduced after treatment. Most patients were satisfied. From the cadaver study, connecting muscular fibers were clearly observed among the muscles involved in the formation of DNLs, and these muscles were collectively named the dorsal nasal complex (DNC) by the authors. Four anatomical variations of the DNC were discovered, corroborating the DNL classification system. CONCLUSIONS: A novel anatomical concept, the DNC, and a classification system for DNLs were proposed. Each of the 4 distribution types of DNLs corresponds to a specific anatomical variation of the DNC. A refined injection technique for DNLs was developed, and its efficacy and safety were demonstrated.

Vaginal Rejuvenation with Acellular Dermal Matrix.

Female genital cosmetic surgery consists of multiple procedures, usually including labiaplasty, clitoral prepuce reduction, labia majora augmentation, and vaginoplasty. The reasons for women to undergo these surgeries can be categorized as functional and aesthetic ones. In this study, we introduced the modified vaginoplasty with acellular dermal matrix (ADM) and briefly reviewed our experience in the combination of multiple procedures to achieve the optimal effect.

The 100 Most-Cited Manuscripts on Blepharoptosis: A Bibliometric analysis.

BACKGROUND: We conducted a bibliometric analysis of blepharoptosis, obtained the top 100 most-cited articles, and then researched the characteristics of every article. MATERIALS AND METHODS: The Web of Science Citation Index was utilized to identify articles related to blepharoptosis written in English published from 1900 to 2021 using predefined search terms. Then, the returned results were screened, and the top 100 most-cited articles were individually classified based on publication year, country of publication, source journal, total citations, authors' specialty, level of evidence, main subject, and type of study. RESULTS: The 100 most-cited articles were published between 1948 and 2014. The number of citations/articles ranged from 49 to 743. Ophthalmology journals made the greatest contributions to landmark literature (n=61). The primary focus of these 100 studies was the surgical technique (n=41). The majority of them (n=52) only achieved level 4 evidence, as a high proportion of these articles were case series (n=52). The most common country of publication was the United States (n=59). CONCLUSIONS: Our bibliometric analysis provides insight into the citation frequency of the most-cited articles on blepharoptosis. The landmark, highly cited articles that have shaped the landscape of blepharoptosis were identified. The results from these top 100 cited articles are helpful for present current surgical decision-making.

New Method for Genital Aesthetic Surgery: An Easy-to-Learn 2-Step Approach With Acellular Dermal Matrix.

BACKGROUND: Vaginal laxity, usually accompanied with prolapse symptoms, affects women's sexual satisfaction and quality of life. Vaginal tightening surgery aims to reinforce perivaginal muscle strength and restore normal vaginal anatomy. OBJECTIVES: The aim of this study was to introduce a new surgical approach to vaginal tightening that uses acellular dermal matrix. METHODS: In this retrospective study, data from 80 patients with vaginal laxity who underwent surgery between April 2017 and April 2021 were analyzed. Three-dimensional transvaginal ultrasound was performed and the Female Sexual Function Index was evaluated. RESULTS: The mean age of the patients was 44.6 years. The mean patient follow-up was 13.2 months. No infection, rectovaginal fistula, or implant explantation occurred. Transvaginal ultrasound examination demonstrated a significant reduction of introital diameter on a maximum Valsalva maneuver (2.3 cm vs 4.1 cm; P < 0.05) and the reconstruction of acute vaginal angulation. The Female Sexual Function Index orgasm subscore increased significantly. CONCLUSIONS: Vaginal tightening with acellular dermal matrix is a minimally invasive surgery that offers a safe and effective treatment for patients with vaginal laxity.

The Novel Role of Cytomorphology from Ultrasound-Guided Fine Needle Aspiration Cytology in Evaluating the Status of Prognostic Factors including Estrogen Receptor, Progesterone Receptor and HER2 in Breast Cancer.

It is well established that estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) could be regarded as prognostic factors in breast cancer. Ultrasound-guided fine needle aspiration cytology (FNAC) has revolutionized the management of cancers, providing less invasive and quick diagnostic method. There are hardly any studies on the correlation between cytomorphology and prognostic biomarkers. We retrospectively analyzed the immunohistochemistry and the fluorescence in situ hybridization of breast cancer specimens from 252 patients, who have been diagnosed as breast cancer at our hospital. Morphological features of cytology smears were scored. The relationship between cytological features and three biomarkers were analyzed. Based on this, we developed a system to predict the status of biomarkers. The results indicated that some cytological parameters, especially the features of nucleoli, were distinctively related to the makers' expression. In the novel scoring system, a cutoff of 12.0 provided a statistical discrimination for cytological grading. We concluded that cytomorphological features were associated with prognostic factors. The HR+ neoplasms showed scattered micronucleoli, while HER2+ neoplasms demonstrated centered macronucleoli. We summarized a scoring system to predict the status of three factors. This may help us to broaden the application of breast cancer cytology.

Fused Lateral Clitoral Hood and Labia Minora: New Classification Based on Anatomic Variation of the Clitoral Hood-Labia Minora Complex and Simple Surgical Management.

BACKGROUND: Existing classifications of the clitoral hood-labia minora complex (CLC) have neglected its integrity and anatomic variation, resulting in failure to optimize approaches tailored to individuals. OBJECTIVES: The aim of this study was to present a new classification system for comprehensive evaluation of variations of the CLC and to introduce a simple surgical approach for the fused type. METHODS: Anatomic variations of the CLC were classified into 3 types: isolated labia minora or lateral clitoral hood hypertrophy (Type 1); conventional combined hypertrophy (Type 2); and fused lateral clitoral hood and labia minora (Type 3). A modified procedure for the fused type was performed in 4 steps: the anterior border of labia minora was defined first, then the hypertrophic lateral clitoral hood and labia minora were each removed separately, and finally the junction region was trimmed. Satisfaction questionnaires were administered during follow-ups. RESULTS: Among all 301 patients (602 sides), Type 2 was the most common variation (285 sides, 47.3%). Type 3 variations in 67 patients (105 sides, 17.5%) were identified, and 77.6% of these patients answered the questionnaires 3 months after surgery. For patients with type 3 variations, the satisfaction rate in the 4-step excision group was 91.7%, which was significantly higher than that in the wedge excision group (56.3%) (P = 0.01). The complication rate of the 4-step excision was 2.5%. CONCLUSIONS: Preoperative evaluation based on the new classification facilitated recognition of variations of the CLC, especially of the fused type. The 4-step excision is a simple, effective, and safe approach to treat the fused variation with high satisfaction.

Pivotal role of injection volume on sunken cheek prevention in masseter muscle BoNT-A injection: A cadaver study.

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.

Nuclear Morphological Characteristics in Breast Cancer: Correlation with Hormone Receptor and Human Epidermal Growth Factor Receptor 2.

BACKGROUND: Hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) are the common diagnostic/prognostic markers in breast cancer. Few articles have recently reported the correlation between cytology and molecular subtypes. We combined nuclear morphological characteristics with HR and HER2 status to observe the relationship and provide ideas for machine learning. METHODS: We reanalyzed fine-needle aspiration cytology samples and core-needle puncture histological specimens from 142 patients with invasive breast cancer between March 2019 and December 2019, and the findings were compared with the two groups (HR+/HER2- and HR-/HER2+) following nuclear cytomorphological features: nuclear/cytoplasmic ratio, difference of nuclear size, nuclear pleomorphism, chromatin feature, nuclear membrane and nucleoli, and Nottingham grading. RESULTS: Two groups were significantly associated with the difference of nuclear size, nuclear pleomorphism, and nucleoli (P < 0.001) and consistent with histological grading (P < 0.001). Moreover, nucleolar characteristics of size and number had obviously statistical significance (P < 0.001). Multiple micro-nucleoli were frequently seen in the HR+/HER2- group compared with the HR-/HER2+ group which mostly were observed centered medium-large nucleoli. We described four interesting nuclear morphologies in the experiment. CONCLUSIONS: There were significant differences in nuclear characteristics between two groups. HR and HER2 status not only might be predicted in cytological samples, but some specific nuclear morphological features might have potential value to help us understand molecular function and predict more information.

Gene Expression Profiling for Differential Diagnosis of Liver Metastases: A Multicenter, Retrospective Cohort Study.

BACKGROUND: Liver metastases (LM) are the most common tumors encountered in the liver and continue to be a significant cause of morbidity and mortality. Identification of the primary tumor of any LM is crucial for the implementation of effective and tailored treatment approaches, which still represents a difficult problem in clinical practice. METHODS: The resection or biopsy specimens and associated clinicopathologic data were archived from seven independent centers between January 2017 and December 2020. The primary tumor sites of liver tumors were verified through evaluation of available medical records, pathological and imaging information. The performance of a 90-gene expression assay for the determination of the site of tumor origin was assessed. RESULT: A total of 130 LM covering 15 tumor types and 16 primary liver tumor specimens that met all quality control criteria were analyzed by the 90-gene expression assay. Among 130 LM cases, tumors were most frequently located in the colorectum, ovary and breast. Overall, the analysis of the 90-gene signature showed 93.1% and 100% agreement rates with the reference diagnosis in LM and primary liver tumor, respectively. For the common primary tumor types, the concordance rate was 100%, 95.7%, 100%, 93.8%, 87.5% for classifying the LM from the ovary, colorectum, breast, neuroendocrine, and pancreas, respectively. CONCLUSION: The overall accuracy of 93.8% demonstrates encouraging performance of the 90-gene expression assay in identifying the primary sites of liver tumors. Future incorporation of the 90-gene expression assay in clinical diagnosis will aid oncologists in applying precise treatments, leading to improved care and outcomes for LM patients.

Two updates on oesophagogastric junction adenocarcinoma from the fifth WHO classification: Alteration of definition and emphasis on HER2 test.

INTRODUCTION: The incidence of oesophagogastric junction adenocarcinoma has increased rapidly but remains controversial over the last decades. There are two crucial updates of the fifth World Health Organization (WHO) classification, including the alteration of its definition and the emphasis on the human epidermal growth factor receptor 2 (HER2) test. METHODS: A total of 566 clinicopathological samples from patients who were diagnosed with gastric adenocarcinoma were retrospectively analyzed. We comprehensively compared the clinicopathological features of oesophagogastric junction adenocarcinoma between the fourth (V4.0) and fifth (V5.0) WHO versions. The clinicalpathological features among oesophagogastric junction, proximal and distal gastric tumors with fourth and fifth edition were also compared, respectively. Also, we discuss the correlation of HER2-expression with clinicopathological features according to the V5.0. RESULTS: The results showed that the difference was mainly between oesophagogastric junction and distal adenocarcinoma in V4.0, while some were found between proximal and distal adenocarcinoma in V5.0. Tumors invading the oesophagus more than 3cm were still mainly oesophagogastric junction tumors. The expression of HER2 in oesophagogastric junction and proximal gastric adenocarcinoma was still higher than that in gastric body and distal sites. CONCLUSIONS: The clinicopathological parameters of the oesophagogastric junction tumors changed to some extent in the updated WHO version. The proximal gastric tumors tended to be more invasive, more than those located in oesophagogastric junction. But the latter with oesophageal invasion required additional management. The HER2-expression of oesophagogastric junction adenocarcinoma is the highest. The classification of V5.0 is reasonable and worth recommendation.