Thyroid Hormone Suppresses Medulloblastoma Progression Through Promoting Terminal Differentiation of Tumor Cells.

Hypothyroidism is commonly detected in patients with medulloblastoma (MB). A possible link between thyroid hormone (TH) signaling and MB pathogenicity has not been reported. Here, we find that TH plays a critical role in promoting tumor cell differentiation. Reduction in TH levels frees the TH receptor, TRα1, to bind to EZH2 and repress expression of NeuroD1, a transcription factor that drives tumor cell differentiation. Increased TH reverses EZH2-mediated repression of NeuroD1 by abrogating the binding of EZH2 and TRα1, thereby stimulating tumor cell differentiation and reducing MB growth. Importantly, TH-induced differentiation of tumor cells is not restricted by the molecular subgroup of MB. These findings establish an unprecedented association between TH signaling and MB pathogenicity, providing solid evidence for TH as a promising modality for MB treatment.

Outer Fascia of Orbicularis Oculi Muscle (OFOOM)-Orbicularis (OOM)-Aponeurosis Fixation Approach in Double-Eyelid Blepharoplasty Revision.

BACKGROUND: Incisional double-eyelid blepharoplasty is the main surgical technique to obtain an artificial crease. Postoperative complications decrease patients' satisfaction, and patients with prominent depressed groove and persistent pretarsal swelling (sausage phenomenon) usually need revision surgery. To resolve the sausage phenomenon after blepharoplasty, we adopt Outer Fascia of Orbicularis Oculi Muscle (OFOOM)-Orbicularis (OOM)-Aponeurosis Fixation Approach to create natural double eyelids. METHODS: We included 68 patients in the study. The inclusion criteria for revision surgery were as follows: (1) pretarsal OOM remained after primary surgery, (2) prominent depressed surgical scar/groove and persistent pretarsal bulge (sausage phenomenon), (3) postsurgical abnormally wide crease. The surgical procedure involved releasing the pretarsal OOM, forming OFOOM-OOM flap, and OFOOM-OOM flap fixed with aponeurosis. Outcome observations were assessed using the FACE-Q questionnaire, and the follow-up period ranged from 6 to 36 months (mean=18 months). RESULTS: The depressed groove and pretarsal bulge showed significant improvements, and FACE-Q scores of the 68 patients before surgery (mean scores=66) compared with those after surgery (mean scores=90) were significantly different (P<0.01). Four patients with palpebral fold asymmetry and two patients with shallow eyelids received revision surgery, and patients were satisfied with the secondary surgery effects. Six patients presented with unnatural curves of folds and revision surgery alleviated these situations. CONCLUSIONS: Outer Fascia of Orbicularis Oculi Muscle (OFOOM)-Orbicularis (OOM)-Aponeurosis Fixation Approach is an effective way to resolve the sausage phenomenon. The OFOOM-OOM flap is a reliable and flexible structure to create natural double eyelids. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Immune checkpoint inhibitors (ICIs) have been widely used to treat various tumors and have changed the landscape of tumor management, but the data from real-world studies of ICIs for TNBC treatment remain limited. The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real-world setting and to explore possible correlates. Methods: The clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army (PLA) General Hospital were collected. Treatment responses, outcomes and adverse events (AEs) were assessed. Results: Eighty-one patients were included in the study. The confirmed objective response rate (ORR) was 32.1%, and the disease control rate (DCR) was 64.2%. The median progression-free survival (PFS) was 4.2 months, and the median overall survival (OS) was 11.0 months. PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later-line ICIs and higher levels of inflammation; specifically, patients with higher TILs had longer PFS. Overall AEs were tolerable. Conclusions: ICIs are effective in the treatment of advanced TNBC, and the adverse reactions are tolerable. A panel of biomarkers including LDH, ALP, and bNLR were identified to predict the efficacies of ICIs in TNBC treatment.

Generating a mouse model for relapsed Sonic Hedgehog medulloblastoma.

Tumor relapse is the leading adverse prognostic factor in medulloblastoma (MB). However, there is still no established mouse model for MB relapse, impeding our efforts to develop strategies to treat relapsed MB. We present a protocol for generating a mouse model for relapsed MB using irradiation by optimizing mouse breeding and age, as well as irradiation dosage and timing. We then detail procedures for determining tumor relapse based on tumor cell trans-differentiation in MB tissue, immunohistochemistry, and tumor cell isolation. For complete details on the use and execution of this protocol, please refer to Guo et al. (2021).1.

PDLIM3 supports hedgehog signaling in medulloblastoma by facilitating cilia formation.

Elevated levels of PDLIM3 expression are frequently detected in sonic hedgehog (SHH) group of medulloblastoma (MB). However, the possible role of PDLIM3 in MB tumorigenesis is still unknown. Here, we found that PDLIM3 expression is necessary for hedgehog (Hh) pathway activation in MB cells. PDLIM3 is present in primary cilia of MB cells and fibroblasts, and such cilia localization is mediated by the PDZ domain of PDLIM3 protein. Deletion of PDLIM3 significantly compromised cilia formation and interfered the Hh signaling transduction in MB cells, suggesting that PDLIM3 promotes the Hh signaling through supporting the ciliogenesis. PDLIM3 protein physically interacts with cholesterol, a critical molecule for cilia formation and hedgehog signaling. The disruption of cilia formation and Hh signaling in PDLIM3 null MB cells or fibroblasts, was significantly rescued by treatment with exogenous cholesterol, demonstrating that PDLIM3 facilitates the ciliogenesis through cholesterol provision. Finally, deletion of PDLIM3 in MB cells significantly inhibited their proliferation and repressed tumor growth, suggesting that PDLIM3 is necessary for MB tumorigenesis. Our studies elucidate the critical functions of PDLIM3 in the ciliogenesis and Hh signaling transduction in SHH-MB cells, supporting to utilize PDLIM3 as a molecular marker for defining SHH group of MB in clinics.

Aesthetic Sideburn Reconstruction Using an Expanded Hair Bearing Skin Flap With Natural Hairline.

BACKGROUND: Hairline is the marginal line of hair growth on the scalp. Patients with sideburn defects, caused by tumor resection, severe infection, or burns, might have low self-esteem and mental stress. The purpose of this article was to explore a surgical method of applying the expanded scalp flap with natural hairline for cosmetic reconstruction of hairline, so as to provide reference for future clinical work. METHODS: In this study, a retrospective analysis was conducted on 23 patients in the plastic surgery ward of the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences from January 2015 to December 2018, who underwent expanded scalp flap cosmetic reconstruction of the sideburns with natural hairline (14 males and 9 females; average age, 18.7 ± 13.7 years). The follow-up time was 8 to 44 months. RESULTS: Patient satisfaction rate (scored 4 or more) was 95.7%, with an average score of 4.59. A total of 16 patients were very satisfied, and 6 were satisfied. There were 21 patients who had good flap survival, and 2 patients who had venous congestion at the distal end of the flap. One case relieved voluntarily 3 days postsurgery, and the other case had partial skin necrosis at the distal end, healing phase II. These 2 cases were classified as grade I according to the Clavien-Dindo classification. In 9 of the patients, the reconstructed sideburn presented a natural look with good hair angle and great size and shape, with average scores of 4.61, 4.52, and 4.48. The scars at the donor site were inconspicuous, and there were no complaints (average score, 4.61). The rest of the patients received satisfactory appearances after surgery. CONCLUSION: In conclusion, the technique described above presented a fine method for sideburn reconstruction. Based on the achieved aesthetic scores of our study, as well as the high patient satisfaction rate (95.7%), the aforementioned technique is acceptable for both surgeons and patients.

A New Technique for Chondrolaryngoplasty in Patients Assigned Female at Birth.

BACKGROUND: Chondrolaryngoplasty is a classical facial feminization surgery for transgender women. In recent years, however, an increasing number of patients assigned female at birth are seeking chondrolaryngoplasty for esthetic purposes. Traditional chondrolaryngoplasty can no longer cope with problems of the growing group whose leading cause of laryngeal prominence differs from the transgender population. METHODS: A modified technique is designed as a supplement to the classical procedure. After the cartilage reduction process, paired platysma flaps are raised and advanced successively, resulting in an overlapped area over the thyroid notch, to further camouflage the thyroid prominence. To evaluate the efficiency of the new technique, a retrospective survey of 34 patients (5 men and 29 women) who underwent the surgery from 2016 to 2021 was performed, via a 5-point Likert scale including 7 questions. Physician assessment was also accomplished to provide an extra estimation. Complications were followed up and analyzed to evaluate the safety of modified surgery as well. RESULTS: Although only half of the patients graded prominence changes more than "moderately changed," as many as 75.0% of them still expressed "completely satisfied" or "satisfied very much" with the outcome. Similarly, physician assessment indicated a satisfactory result in appearance improvement. No severe and irreversible complications occurred after surgery, but lasting scar-related issues were reported by 4 patients and should be paid more attention to. CONCLUSIONS: Generally speaking, the new technique is both safe, efficient, and satisfying for most patients, especially ones assigned females at birth with esthetic demand.

Three-Dimensional Z-Epicanthoplasty Retains the Depth of the Medial Canthus With Scars That Are Less Visible.

BACKGROUND: Traditional coronal Z-epicanthoplasty usually generates visible scars, and V-Y advancement or skin redraping can damage the normal shape of the lower eyelid. In addition, these methods usually lead to loss of the medial canthus depth, which is important for the natural appearance of East Asians. This report aims to describe a 3-dimensional Z-epicanthoplasty that can maintain the depth of the medial canthus with fewer visible scars. METHODS: Patients who underwent 3-dimensional Z-epicanthoplasty from January 2016 to December 2019 were included. In our method, excess skin in the horizontal direction was first rotated to the vertical position and then turned inward from a coronal to a sagittal orientation to supplement the skin deficiency of the medial canthus in the sagittal orientation. The skin flap turned in the sagittal orientation and maintained the depth of the medial canthus and the natural appearance of the eye. RESULTS: In total, 138 patients were included, and the follow-up interval ranged from 6 to 36 months. After the surgery, the epicanthi were removed, and the shapes of the patients' eyes were significantly improved and appeared natural. The surgical scars were hidden in the sagittal orientation rather than in the coronal orientation, which cannot be seen easily. The depth of the medial canthus was well preserved without any lower eyelid destruction. Patients were satisfied with the natural appearance of the medial canthus. CONCLUSIONS: This method could not only correct the epicanthal fold effectively with scars that are less visible but also maintain the depth of the medial canthus and make the appearance of the eye look more natural.

Inhibiting Warburg Effect Can Suppress the Biological Activity and Secretion Function of Keloid Fibroblasts.

BACKGROUND: Keloids have always been a difficult problem in the clinic. In our previous study, we demonstrated a Warburg effect in keloid fibroblasts (KFs), like tumors. In this study, we aimed to investigate the effects of the suppression of the Warburg effect on the biological activity and function of KFs. METHODS: KFs were isolated and cultured with different concentrations of oxamate, a classical competitive lactate dehydrogenase A (LDHA) inhibitor. First, the suppression effect of oxamate on the Warburg effect in KFs was verified. After treatment with oxamate, a scratch wound assay, real-time PCR, flow cytometry, CCK8 kit, and western blotting were used to detect the migration ability, collagen production, apoptosis, cell proliferation, cell cycle distribution, and related molecular mechanisms in KFs. RESULTS: As expected, oxamate inhibited the Warburg effect in KFs in a dose-dependent manner. After the inhibition of the Warburg effect in KFs, the cell migration rate decreased significantly, the mRNA transcription levels of type I collagen and α-SMA were significantly lower, the cell apoptosis rate increased significantly, the cell proliferation activity decreased significantly, and G0/G1 phase cells in KFs increased significantly. The expression of cyclin D1 and its upstream regulatory factors, Akt protein and GSK3 ß (phospho S9), decreased significantly. CONCLUSION: Inhibiting the Warburg effect in KFs significantly suppressed cell proliferation, enhanced cell apoptosis, inhibited cell migration ability, reduced collagen secretion, and induced G0/G1 arrest through the Akt-GSK3ß-Cyclin D1 pathway. Therefore, inhibiting the Warburg effect in KFs may provide a new option for the prevention and treatment of keloids. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Warburg effect in keloids: A unique feature different from other types of scars.

Keloid fibroblasts (KFs) undergo reprogramming of the metabolic phenotype from oxidative phosphorylation to the Warburg effect. However, more studies are needed to demonstrate whether there is a Warburg effect in KFs and to determine whether there is a similar phenomenon in other types of scars or in the proliferative stage of scars. In our study, the mRNA and protein expression of key glycolytic enzymes, glucose consumption and lactate production in KFs, normal skin fibroblasts (NFs), atrophic scar fibroblasts (ASFs), proliferative stage scar fibroblasts (PSSFs), and hypertrophic scar fibroblasts (HSFs) were detected. In addition, the effects of 2-deoxy-d-glucose (2-DG, a glycolysis inhibitor) on cell proliferation in KFs and NFs were studied. We found that the mRNA and protein expression of key glycolytic enzymes in KFs were significantly upregulated compared with those in NFs. Glucose consumption and lactate production in KFs were also higher than that in NFs. However, we found no similar phenomenon in ASFs, PSSFs, or HSFs. When treated with 2mmol/l 2-DG, the cell viability of KFs decreased more than that of NFs. What's more, treatment with increasing concentrations of 2-DG could inhibit cell viability and migration of KFs in a dose-dependent manner. In conclusion, the Warburg effect in KFs is a feature different from ASFs, PSSFs, or HSFs. Keloids are essentially different from other types of scars in terms of energy metabolism. This characteristic of KFs could provide new hope for the early diagnosis and treatment of keloids.

Infraeyebrow Blepharoplasty Using Dynamic Suspension Technique Between Dermis-Fascia Flap and Frontalis in Upper Eyelid Lifting and Eyebrow Augmentation.

OBJECTIVE: Upper eyelid laxity affects facial aesthetics and the eyebrow arch in the East Asian population is generally low. The authors developed infraeyebrow blepharoplasty using a dynamic suspension technique between the dermis-fascia flap and frontalis for upper eyelid lifting and eyebrow augmentation. METHODS: A retrospective study was performed on 43 female patients with upper eyelid laxity from August 2015 to October 2019. The epidermis and superficial dermis of the infraeyebrow was removed from the surgical marking area with the deep dermis and fascia preserved. The eyebrow skin flap was separated from the frontalis surface which fully exposed the area around eyebrow arch. The preserved dermis-fascia flap was folded and suspended to frontalis in the superior margin of eyebrow arch. RESULTS: Forty-three patients (median age 54 years [range, 38-70]) underwent this operation. Mean follow-up was 25 months (range, 8-42) was assessed. All incisions healed well and were almost invisible. The eyebrow area improved with upper eyelid skin lift and eyebrow augmentation; 40 cases were "very satisfied" with their appearance. Three cases were "not very satisfied," including 1 case with numbness in surgical area. 2 cases had slight bilateral asymmetry of the upper eyelids. CONCLUSIONS: The dynamic suspension technique is worthy of clinical application because it can correct upper eyelid laxity, augment the low eyebrow arch, and obtain an invisible scar by reducing the incision tension.

Different Transfer Forms of the Expanded Forehead Flap Pedicled With Superficial Temporal Vessels to Treat Chin and Submental Scar Deformities.

BACKGROUND: The chin and submental regions are located at the junction of the face and neck. Its function and aesthetic appearance can be seriously affected when scar deformities cause the cervico-mental angle to disappear. The expanded forehead flap pedicled with superficial temporal vessel(s) is a surgical treatment for chin and submental scar deformities. Different transfer types have developed for this flap based on individual situations. At present, there is no unified treatment strategy for applying this forehead flap to treat different regions and ranges of chin and submental scar deformities. METHODS: Ninety one cases were collected from patients with chin and submental scar deformities that were treated using the expanded forehead flap pedicled with superficial temporal vessels from January 2008 to December 2018. The authors divided the chin and submental scar deformities into 4 types according to different regions and ranges, and summarized flap survival and complications of 5 different transfer forms used to treat scars for creating feasible treatment strategies. We followed up 76 cases, investigating the satisfaction of appearance and texture of the flaps, improvement of neck movement, and scar recurrence. RESULTS: Expanded forehead flaps were used to repair 91 cases of chin and submental scar deformities. According to the postoperative flap survival and complications of flap blood supply, the treatment strategies are as follows: Bilateral cutaneous and subcutaneous pedicled forehead flaps are applied to treat scars in bilaterally symmetrical large-scale scars in Zone LCL. Unilateral pedicled forehead flaps are applied to treat small-scale scars in Zone C and Zone L. Unilateral pedicled plus contralateral vascular anastomosis and unilateral pedicled plus contralateral super thin forehead flaps are applied to treat the moderate-scale scars of Zone LC. Mean follow-up period was 81 months (range 28-131), 93.4% (71/76) was satisfied with appearance and texture of the flaps, 97.4% (74/ 76) was satisfied with the improvement of neck movement, and 2.6% (2/76) occurred scar recurrence. CONCLUSIONS: Five different types of expanded forehead flaps pedicled with superficial temporal vessels can be used to repair differential scar deformities of the chin and submental regions and achieve good therapeutic effects.

The application of a retrograde postauricular island flap in reconstructing periorbital region defects.

BACKGROUND: Reconstruction of periorbital region defects is thought to be one of the most challenging areas in reconstructive plastic surgery. This paper describes our experiences with the application of retrograde postauricular island flaps in reconstructing periorbital region defects. METHODS: Between November 2008 and June 2019, 16 patients with periorbital region defects underwent treatment using a retrograde postauricular island flap. The flap is designed with two portions: 1) the pedicle segment only with the superficial temporal fascia and 2) the flap segment in the posterior auricular region with non-hair-bearing full-thickness tissue. Intraoperatively, the vascular networks between the postauricular and the superficial temporal vessels were preserved. The flap was then transferred to the receipt area after passing through a subcutaneous tunnel. The donor site was directly closed in the postauricular sulcus by advancing the posterior scalp flap. RESULTS: All the periorbital region defects were reconstructed in one-stage surgery. All the flaps survived without venous congestion. The size of the harvested flaps varied from 5.0 × 2.5 cm to 7.5 × 5 cm. The colour of the transferred flaps matched the surroundings of the receipt region, and the eyelids functioned well. CONCLUSION: A retrograde postauricular island flap is a good choice for the reconstruction of periorbital region defects. The flap can be useful for the reconstruction of the periorbital region, since it uses similar colours and textures. In addition, it permits a "one-stage" reconstruction with less conspicuous donor site scars behind the auricle.

Aesthetic Design of Expanded Bilateral Superficial Temporal Vascular Fascial Pedicled Flap for Repairing Maxillocervical Scars.

BACKGROUND: Large-scale maxillocervical scars impair face and neck function and damage appearance. The forehead expanded bilateral superficial temporal pedicled flap is a good treatment strategy for this area; however, the traditional cutaneous pedicled flap damages the temporal hair area. This impairs aesthetics and causes alopecia; furthermore, requires an additional pedicle-cut operation. METHODS: A retrospective study was performed on 7 patients with large-scale maxillocervical scars from January 2014 to August 2018. Forehead expanders were implanted in the first-stage operation for all patients. After the injection and rest period, patients were treated using the forehead expanded bilateral superficial temporal vascular fascial pedicled flap. Superficial temporal vascular fascia pedicles were carefully harvested. The use of an intralesional or hidden retrotragus incision was determined by the presence of a preauricular scar. Patient satisfaction with postoperative neck activity and the incision scar was evaluated. RESULTS: Intralesional and retrovagus incisions were used in 4 and 3 cases, respectively. One flap developed hematoma, which recovered completely after conservative treatment; all other cases had no complications. All flaps healed well. The neck mobility of the patients was significantly improved with no visible scar in the temporal region. Six cases reported being "very satisfied" and one was "relatively satisfied" with their improvement in neck mobility. All cases reported being "very satisfied" with frontotemporal morphology. CONCLUSIONS: The forehead expanded bilateral superficial temporal vascular fascial pedicled flap is a good choice for patients with large-scale maxillocervical scars. This technique can maintain the aesthetics of temporal hair and reduce patients extra surgical injury.

Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse.

Astrocytes, a major glial cell type in the brain, play a critical role in supporting the progression of medulloblastoma (MB), the most common malignant pediatric brain tumor. Through lineage tracing analyses and single-cell RNA sequencing, we demonstrate that astrocytes are predominantly derived from the transdifferentiation of tumor cells in relapsed MB (but not in primary MB), although MB cells are generally believed to be neuronal-lineage committed. Such transdifferentiation of MB cells relies on Sox9, a transcription factor critical for gliogenesis. Our studies further reveal that bone morphogenetic proteins (BMPs) stimulate the transdifferentiation of MB cells by inducing the phosphorylation of Sox9. Pharmacological inhibition of BMP signaling represses MB cell transdifferentiation into astrocytes and suppresses tumor relapse. Our studies establish the distinct cellular sources of astrocytes in primary and relapsed MB and provide an avenue to prevent and treat MB relapse by targeting tumor cell transdifferentiation.

Nestin Is Required for Spindle Assembly and Cell-Cycle Progression in Glioblastoma Cells.

Nestin, a class IV intermediate filament protein, is generally considered as a putative marker of neural stem and progenitor cells in the central nervous system. Glioma is a common type of adult brain tumors, and glioblastoma (GBM) represents the most aggressive form of glioma. Here, we report that Nestin expression is significantly upregulated in human GBM, compared with other types of glioma. Nestin knockdown or deletion in U251 cells and tumor cells from GBM patients derived xenografts resulted in G2-M arrest, finally leading to apoptosis in tumor cells. Using proximity-dependent biotin identification method, we identified ßII-tubulin as an interacting protein of Nestin in U251 cells. Nestin stabilized ßII-tubulin in U251 cells through physical interaction. Knockdown of Nestin or ßII-tubulin disrupted spindle morphology in tumor cells. Our studies further revealed that Nestin deficiency in U251 cells and GBM PDX cells repressed tumor growth upon transplantation. Finally, we found that Nestin deficiency sensitized GBM cells to microtubule-destabilizing drugs such as vinblastine and vincristine. Our studies demonstrate the essential functions and underlying mechanisms of Nestin in the growth and drug response of GBM cells. IMPLICATIONS: Through interaction with ßII-tubulin, Nestin facilitates cell-cycle progression and spindle assembly of tumor cells in glioblastoma.

Purification of differentiated tumor cells from medulloblastoma for transplantation into mouse cerebellum.

This protocol provides the procedures for isolating differentiated tumor cells from medulloblastoma (MB) in mice. Procedures for transplantation into cerebella are also included to examine the tumorigenesis of differentiated MB cells. This protocol outlines the detailed steps required for (1) isolation of tumor cells from mouse MB, (2) purification of differentiated tumor cells by fluorescence-activated cell sorting, and (3) transplantation of tumor cells into cerebella. This protocol is useful to purify differentiated tumor cells for investigating mechanisms underlying MB progression. For complete details on the use and execution of this protocol, please refer to Cheng et. al. (2020).

Statins repress hedgehog signaling in medulloblastoma with no bone toxicities.

The Hedgehog (Hh) pathway plays an indispensable role in bone development and genetic activation of the pathway results in medulloblastoma (MB), the most common malignant brain tumor in children. Inhibitors of Hh pathway (such as vismodegib and sonedigib), which are used to treat MB, cause irreversible defects in bone growth in young children. Cholesterol is required for the activation of the Hh pathway, and statins, inhibitors of cholesterol biosynthesis, suppress MB growth by repressing Hh signaling in tumor cells. Here, we investigate the role of cholesterol biosynthesis in the proliferation and Hh signaling in chondrocytes, and examine the bone development in mice after statin treatment. Statins significantly inhibited MB growth in young mice, but caused no defects in bone development. Conditional deletion of NADP steroid dehydrogenase-like (NSDHL), an enzyme necessary for cholesterol biosynthesis, suppressed cholesterol synthesis in chondrocytes, and disrupted the growth plate in mouse femur and tibia, indicating the important function of intracellular cholesterol in bone development. Hh pathway activation and the proliferation of chondrocytes were inhibited by statin treatment in vitro; however, statins did not impair bone growth in vivo due to insufficient penetration into the bone. Our studies reveal a critical role of cholesterol in bone development, and support the utilization of statins for treatment of MB as well as other Hh pathway-associated malignancies.

Nanofat Injection for the Treatment of Depressed Facial Scars.

BACKGROUND: Patients with depressed facial scars complain of their negative effects. However, the efficacy of optional treatment techniques is never completely adequate. This study aimed to assess the efficacy of nanofat injection in the improvement of depressed facial scars. METHODS: This retrospective study included patients who underwent depressed facial scar filling with nanofat between November 2017 and January 2020. The FACE-Q scale was sent to patients for feedback regarding satisfaction. Evaluations of the results were also performed by three plastic surgeons. RESULTS: Among the 52 included patients, 44 patients (29 women and 15 men) completed the questionnaire. Obvious and stable effects were usually acquired 3 months after surgery. Temporary erythema appeared at the injection site to varying degrees, lasting 2 to 3 weeks in 93% of the patients. No other serious postoperative complications were observed in the injection area. The FACE-Q outcomes showed that patients who completed injection therapy more than 1 year prior were significantly more satisfied with the decision to undergo this therapy than those who completed the treatment less than 1 year prior. Furthermore, according to the physicians' evaluations, 91% of patients experienced improvement in scar appearance after treatment. CONCLUSIONS: The low rate of injection-site complications and the safety of this procedure both support the current implementation of nanofat in the treatment of depressed facial scars. The results of the physicians' evaluations and patient satisfaction surveys confirmed the stable effect of nanofat injection in the treatment of depressed facial scars. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.