Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled

Objective:This study aimed to explore the safety and feasibility of gasless transoral vestibular robotic resection of thyroglossal duct cysts. Methods:The clinical data of patients who underwent gasless transoral vestibular robotic resection of thyroglossal duct cysts at the Department of otolaryngology, Sun Yat-sen Memorial Hospital, Sun yat-sen university from September 2020 to May 2022 were analyzed. The operative time, blood loss, postoperative complications, postoperative pain score, postoperative aesthetic score, and recurrence were prospectively evaluated. Results:All patients completed the operation successfully and no case conversed to an open operation. The operation time was 104.00（95.00, 131.25） minutes, and the surgical blood loss was 15.00（10.00, 16.25） mL. The drainage volume was（59.71±9.20） mL. Postoperative pathology was consistent with thyroglossal duct cysts. There was no local reswelling, subcutaneous hematoma, emphysema, skin flap necrosis, infection and other complications. The postoperative hospital stay was 3.00（2.00, 3.00） days. Six patients had mild sensory abnormalities of the lower lip 3 months after surgery, and all patients were satisfied with the cosmetic outcomes. No recurrence was found during the 5-26 months follow-up. Conclusion:gasless transoral vestibular robotic resection of thyroglossal duct cysts is safe and feasible, with hidden postoperative scars and good cosmetic outcomes. It can provide a new choice for patients with thyroglossal duct cysts.
Humans ; Robotic Surgical Procedures ; Thyroglossal Cyst/pathology* ; Postoperative Complications ; Cicatrix/pathology* ; Pain, Postoperative

Objective: To investigate the clinicopathological features and possible mechanisms of burned-out testicular germ cell tumors. Methods: The clinical and imaging data, histology and immunophenotypic characteristics of three cases of burned-out testicular germ cell tumors diagnosed at the Ruijin Hospital, Medical College of the Shanghai Jiaotong University, from 2016 to 2020 were retrospectively analyzed. The relevant literature was reviewed. Results: The mean age of the three patients was 32 years. Case 1 had an elevated preoperative alpha-fetoprotein level (810.18 μg/L) and underwent "radical pancreaticoduodenectomy and retroperitoneal lesion resection" for a retroperitoneal mass. Postoperative pathology showed embryonal carcinoma, which needed to exclude gonadal metastasis. Color Doppler ultrasound showed a solid mass of the right testis, with hypoechoic lesion and scattered calcification in some areas. Case 2 was a "right supraclavicular lymph node biopsy specimen." Chest X-ray showed multiple metastases in both lungs. The biopsy showed metastatic embryonic carcinoma and bilateral testicular color Doppler ultrasound revealed abnormal calcifications in the right testicle. Case 3 showed a cystic mass of the right testis with calcification and solid areas. All 3 patients underwent radical right orchiectomy. Grossly, borders of the testicular scar areas were well defined. Cross sectioning of the tumors showed a gray-brown cut surface and single focus or multiple foci of the tumor. The tumor maximum diameter was 0.6-1.5 cm. Microscopically, lymphocytes, plasma cells infiltration, tubular hyalinization, clustered vascular hyperplasia and hemosiderin laden macrophages were found in the scar. Atrophic and sclerotic seminiferous tubules, proliferation of clustered Leydig cells and small or coarse granular calcifications in seminiferous tubules were present around the scar. Seminoma and germ cell neoplasia in situ were seen in case 1, germ cell neoplasia in situ was seen in case 2 and germ cells with atypical hyperplasia were seen in case 3. Immunohistochemistry showed that embryonic carcinoma expressed SALL4, CKpan(AE1/AE3) and CD30, seminoma and germ cell tumor in situ expressed OCT3/4, SALL4 and CD117, and spermatogenic cells with atypical hyperplasia expressed CD99 and SALL4. The Ki-67 positive index was about 20%, while OCT3/4 and CD117 were both negative. Conclusions: Burned-out testicular germ cell tumors are rare. The possibility of gonad testicular metastasis should be considered first for extragonadal germ cell tumor. If fibrous scar is found in testis, it must be determined whether it is a burned-out testicular germ cell tumor. The burned-out mechanisms may be related to the microenvironment of tumor immune-mediated and local ischemic injury.
Male ; Humans ; Adult ; Seminoma/secondary* ; Cicatrix/pathology* ; Hyperplasia ; Retrospective Studies ; China ; Testicular Neoplasms/pathology* ; Neoplasms, Germ Cell and Embryonal/surgery* ; Calcinosis ; Carcinoma ; Tumor Microenvironment

The wound healing time, tension of wound edge, proliferation of fibroblast, and extracellular matrix deposition are the important factors of scar formation, and botulinum toxin type A can regulate the above. Prevention and treatment of scar with botulinum toxin type A is one of the hot topics of clinical research in recent years. This paper briefly reviews researches by scholars at home and abroad on the mechanism, clinical application, complications, and adverse effects of botulinum toxin type A in scar prevention and treatment.
Botulinum Toxins, Type A/therapeutic use* ; Cicatrix/prevention & control* ; Extracellular Matrix/pathology* ; Fibroblasts/drug effects* ; Humans ; Wound Healing/drug effects*

Objective: To assess the current situation of early treatment of partial-thickness burn wounds by professional burn medical staff in China, and to further promote the standardized early clinical treatment of partial-thickness burn wounds. Methods: A cross-sectional investigation was conducted. From November 2020 to February 2021, the self-designed questionnaire for the early treatment of partial-thickness burn wounds was published through the "questionnaire star" website and shared through WeChat to conduct a convenient sampling survey of domestic medical staff engaged in burn specialty who met the inclusion criteria. The number, region, and grade of the affiliated hospital, the age, gender, occupation, and seniority of the respondents were recorded. The respondents were divided into physician group and nurse group, senior group and junior group, eastern region group and non-eastern region group, primary and secondary hospital group and tertiary hospital group. Then the seniority, grade of the affiliated hospital, region of the affiliated hospital of the respondents in physician group and nurse group, conventional treatment of partial-thickness burn blisters, reasons for retaining vesicular skin, reasons for removing vesicular skin, and the conventional selection and optimal solution recommendation of topical drugs or dressings for partial-thickness burn wounds in the early stage of respondents in each of all the groups were recorded. Data were statistically analyzed with chi-square test. Results: The survey covered 31 provinces, municipalities, and autonomous regions in China (except for Hong Kong, Macau, and Taiwan regions). A total of 979 questionnaires were recovered, which were all valid. The 979 respondents came from 449 hospitals across the country, including 203 hospitals in the eastern region, 116 hospitals in the western region, 99 hospitals in the central region, and 31 hospitals in the northeast region, 348 tertiary hospitals, 79 secondary hospitals, and 22 primary hospitals. The age of the respondents was (39±10) years. There were 543 males and 436 females, 656 physicians and 323 nurses, 473 juniors and 506 seniors, 460 in the eastern regions and 519 in the non-eastern regions, 818 in tertiary hospitals and 161 in primary and secondary hospitals. There were statistically significant differences in the composition of different seniority in the respondents between physician group and nurse group (χ²=44.32, P<0.01), while there were no statistically significant differences in grade or region of the affiliated hospital of the respondents between physician group and nurse group (P>0.05). There were no statistically significant differences in the conventional treatment of partial-thickness burn blisters among respondents between different occupational groups, seniority groups, and region of the affiliated hospital groups (P>0.05).The respondents in different grade of the affiliated hospital groups differed significantly in the conventional treatment of partial-thickness burn blisters (χ²=6.24, P<0.05). Compared with respondents in nurse group, larger percentage of respondents in physician group chose to retain vesicular skin for protecting the wounds and providing a moist environment, and alleviating the pain of dressing change (with χ² values of 21.22 and 19.96, respectively, P values below 0.01), and smaller percentage of respondents in physician group chose to retain vesicular skin for prevention of wound infection (χ²=23.55, P<0.01). The reasons for retaining vesicular skin of respondents between physician group and nurse group were similar in accelerating wound healing, alleviating pigmentation and scar hyperplasia post wound healing (P>0.05). Compared with respondents in junior group, larger percentage of respondents in senior group chose to retain vesicular skin for protecting the wounds and providing a moist environment and alleviating the pain of dressing change (with χ² values of 10.36 and 4.60, respectively, P<0.05 or P<0.01), and smaller percentage of respondents in senior group chose to retain vesicular skin for prevention of wound infection (χ²=8.20, P<0.01). The reasons for retaining vesicular skin of respondents in senior group and junior group were similar in accelerating wound healing, alleviating pigmentation and scar hyperplasia post wound healing (P>0.05). The 5 reasons for the respondents between eastern region group and non-eastern region group, primary and secondary hospital group and tertiary hospital group chose to retain vesicular skin were all similar (P>0.05). Compared with those in physician group, significantly higher percentage of respondents in nurse group were in favor of the following 6 reasons for removing the vesicular skin, including convenience for using more ideal dressings to protect the wounds, prevention of wound infection, facilitating the effect of topical drugs on the wounds, the likely rupture of blisters and wound contamination, accelerating wound healing, and alleviating pigmentation and scar hyperplasia post wound healing (with χ² values of 4.35, 25.59, 11.83, 16.76, 46.31, and 17.54, respectively, P<0.05 or P<0.01). Compared with respondents in senior group, larger percentage of respondents in junior group chose to remove vesicular skin for the reasons such as the likely blister rupture and wound contamination, preventing wound infection, accelerating wound healing, and alleviating pigmentation and scar hyperplasia post wound healing (with χ² values of 17.25, 18.63, 14.83, and 10.23, respectively, P values below 0.01). Compared with respondents in non-eastern region group, larger percentage of respondents in eastern region group chose to remove vesicular skin for preventing wound infection and the likely rupture of blisters and wound contamination (with χ² values of 9.30 and 8.65, respectively, P values below 0.01). The 6 reasons for the respondents between tertiary hospital group and primary and secondary hospital group choose to remove vesicular skin were similar (P>0.05). Compared with respondents in physician group, larger percentage of respondents in nurse group chose to use moisturizing materials for partial-thickness burn wounds in the early stage (χ²=6.18, P<0.05), and smaller percentage of respondents in nurse group chose other topical drugs or dressings (χ²=5.20, P<0.05). Compared with respondents in junior group, larger percentage of respondents in senior group chose to use moisturizing materials and other topical drugs or dressings for partial-thickness burn wounds in the early stage (with χ² values of 4.97 and 21.80, respectively, P<0.05 or P<0.01). Compared with respondents in non-eastern region group, larger percentage of respondents in eastern region group chose to use topical antimicrobial drugs for partial-thickness burn wounds in the early stage (χ²=4.09, P<0.05), and smaller percentage of respondents in eastern region group chose to use other topical drugs or dressings for the partial-thickness burn wounds in the early stage (χ²=5.63, P<0.05). Compared with respondents in primary and secondary hospital group, larger percentage of respondents in tertiary hospital group chose to use biological dressings for partial-thickness burn wounds in the early stage (χ²=9.38, P<0.01). The optimal solution recommendation of topical drugs or dressings for partial-thickness burn wounds in the early stage varied significantly among the respondents between different occupational groups and seniority groups (with χ² values of 39.58 and 19.93, respectively, P values below 0.01). There were no statistically significant differences between eastern and non-eastern region groups, tertiary hospital group and primary and secondary hospital groups in optimal solution recommendation of topical drugs or dressings for partial-thickness burn wounds in the early stage (P>0.05). Conclusions: The conventional treatment measures of partial-thickness burn blisters and reasons for preserving blister skin by professional burn medical staff in China are relatively consistent, but there are great differences in the selection of reasons for removing blister skin, the conventional selection and optimal solution recommendation of topical drugs or dressings for partial-thickness burn wounds in the early stage. Therefore, it is urgent to establish a clinical treatment standard for partial-thickness burn wounds.
Adult ; Blister ; Burns/drug therapy* ; Cicatrix/pathology* ; Cross-Sectional Studies ; Female ; Humans ; Hyperplasia ; Male ; Medical Staff ; Middle Aged ; Occupations ; Pain ; Soft Tissue Injuries ; Wound Infection

Acne is a common chronic inflammatory disease of the skin that often occurs on the face, and acne scars are often secondary to the healing process of acne, which often leads to impaired appearance and psychological disorders of patients. The current treatment for acne scars is extremely difficult. With the development of regenerative medicine, stem cell transplantation has become a new treatment for acne scars. In recent years, it has been reported that stem cells and their derivatives can effectively antagonize the formation of acne scars. Therefore, this paper briefly reviews the basic and clinical researches on the treatment of acne scars with various mesenchymal stem cells and their derivatives, aiming to provide theoretical basis and reference for the stem cell therapy of acne scars.
Acne Vulgaris/pathology* ; Cicatrix/pathology* ; Humans ; Mesenchymal Stem Cells ; Skin/pathology* ; Stem Cell Transplantation

Objective: To investigate the effects of compound analgesia on ultra-pulsed fractional carbon dioxide laser (UFCL) treatment of post-burn hypertrophic s in children. Methods: A prospective randomized controlled study was conducted. From April 2018 to March 2020, 169 pediatric patients with post-burn hypertrophic s admitted to the First Affiliated Hospital of Air Force Medical University were randomly divided into general anesthesia alone group (39 cases, 19 males and 20 females, aged 35 (21, 48) months), general anesthesia+lidocaine group (41 cases, 23 males and 18 females, aged 42 (22, 68) months), general anesthesia+ibuprofen suppository group (41 cases, 25 males and 16 females, aged 38 (26, 52) months), and three-drug combination group with general anesthesia + lidocaine+ibuprofen suppository (48 cases, 25 males and 23 females, aged 42 (25, 60) months), and the pediatric patients in each group were treated with corresponding analgesic regimens when UFCL was used to treat s, and the pediatric patients were given comprehensive care throughout the treatment process. The pain degree of pediatric patients scar was evaluated by facial expression,legs,activity,cry,and consolability (FLACC) of children's pain behavior scale at 0 (immediately), 1, 2, and 4 h after awakening from the first anesthesia, respectively. At 4 h after awakening from the first anesthesia of postoperative pain assessment, the self-made analgesia satisfaction questionnaire was used to evaluate the satisfaction for the analgesic effect of the pediatric patients or their families, and the satisfaction rate was calculated. Within 2 h after the first operation, the occurrences of adverse reactions of the pediatric patients, such as nausea and vomiting, headache, dizziness, drowsiness, etc, were observed and recorded. Before the first treatment and 1 month after the last treatment, the Vancouver scar scale (VSS) was used to evaluate the pediatric patients scar, and the difference value between the two was calculated. Data were statistically analyzed with least significant difference test, Kruskal-Wallis H test, chi-square test and Fisher's exact probability test. Results: At 0 h after awakening from the first anesthesia, the FLACC scores of pediatric patients in general anesthesia+lidocaine group, general anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than those in general anesthesia alone group (P<0.01). The FLACC scores of the pediatric patients in anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than that in general anesthesia+lidocaine group (P<0.01), and the FLACC score of the pediatric patients in three-drug combination group was significantly lower than that in general anesthesia+ibuprofen suppository group (P<0.01). At 1 and 2 h after awakening from the first anesthesia, the FLACC scores of pediatric patients in general anesthesia+ibuprofen suppository group and three-drug combination group were both significantly lower than those in general anesthesia alone group and general anesthesia+lidocaine group (P<0.01), and the FLACC score of the pediatric patients in three-drug combination group was significantly lower than that in general anesthesia+ibuprofen suppository group (P<0.01). At 4 h after awakening from the first anesthesia, the FLACC scores of the pediatric patients in general anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than those in general anesthesia alone group and general anesthesia+lidocaine group (P<0.01). At 4 h after awakening from the first anesthesia, the satisfactions rate with the analgesic effect in the four groups of pediatric patients or their families were 79.49% (31/39), 85.37% (35/41), 87.80% (36/41), and 97.92% (47/48), respectively. The satisfaction rate of the pediatric patients in three-drug combination group was significantly higher than those in general anesthesia alone group, general anesthesia+lidocaine group, general anesthesia+ibuprofen suppository group. Within 2 h after the first operation, there was no significant difference in the overall comparison of adverse reactions such as nausea and vomiting, headache, dizziness, and drowsiness of pediatric patients among the 4 groups (P>0.05). The VSS scores of pediatric patients before the first treatment, 1 month after the last treatment, and and the difference value between the two in the 4 groups were not significantly different (P>0.05). Conclusions: Three-drug combination for analgesia has a good effect in the treatment of hypertrophic scars after burn in pediatric patients with UFCL. Pediatric patients or their families are highly satisfied with the effect, and the treatment effect and incidence of adverse reactions are similar to other analgesic regimens, so it is recommended to be promoted in clinical practice.
Analgesia ; Analgesics ; Child ; Cicatrix, Hypertrophic/pathology* ; Dizziness/drug therapy* ; Female ; Headache/drug therapy* ; Humans ; Ibuprofen/therapeutic use* ; Lasers, Gas/therapeutic use* ; Lidocaine ; Male ; Nausea/drug therapy* ; Pain/drug therapy* ; Prospective Studies ; Treatment Outcome ; Vomiting/drug therapy*

Objective To study the influence of recombinant bovine basic fibroblast growth factor as an adjuvant therapy on scar alleviation and inflammatory cytokines in patients with atrophic acne scar. Methods The random number table was employed to randomly assign 120 patients with atrophic acne scar into a test group and a control group.Both groups of patients were treated with CO₂ lattice laser.After the operation,the control group was routinely smeared with erythromycin ointment and the test group was coated with recombinant bovine basic fibroblast growth factor gel.The clinical efficacy,clinical indicators,scar alleviation,and inflammatory cytokine levels before and after treatment were compared,and adverse reactions were counted. Results The test group had higher total effective rate(P=0.040) and lower total incidence of adverse reactions(P=0.028) than the control group.Compared with the control group,the test group showcased short erythema duration after treatment(P=0.025),early scab forming(P=0.002),and early edema regression(P<0.001).After treatment,the proportion of grade 1 scars graded by Goodman and Baron's acne scar grading system in the test group and control group increased(P=0.001,P=0.027),and the proportion of grade 4 scars decreased(P<0.001,P=0.034).Moreover,the proportion of grade 1 scars in the test group was higher than that in the control group(P=0.031) after treatment,and the proportion of grade 4 scars presented an opposite trend(P=0.031).After treatment,the levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in both groups declined(all P<0.001),and the test group had lower TNF-α and IL-1β levels than the control group(all P<0.001). Conclusion The recombinant bovine basic fibroblast growth factor gel as an adjuvant therapy of CO₂ lattice laser can effectively alleviate the atrophic acne scar,relieve local inflammatory reaction,and has good curative effect and less adverse reactions.
Acne Vulgaris/drug therapy* ; Animals ; Atrophy/complications* ; Carbon Dioxide ; Cattle ; Cicatrix/pathology* ; Fibroblast Growth Factor 2/therapeutic use* ; Humans ; Treatment Outcome ; Tumor Necrosis Factor-alpha

Complete wound regeneration preserves skin structure and physiological functions, including sensation and perception of stimuli, whereas incomplete wound regeneration results in fibrosis and scarring. Amniotic fluid stem cells (AFSCs) would be a kind of cell population with self-renewing and non-immunogenic ability that have a considerable role in wound generation. They are easy to harvest, culture, and store; moreover, they are non-tumorigenic and not subject to ethical restrictions. They can differentiate into different kinds of cells that replenish the skin, subcutaneous tissues, and accessory organs. Additionally, AFSCs independently produce paracrine effectors and secrete them in exosomes, thereby modulating local immune cell activity. They demonstrate anti-inflammatory and immunomodulatory properties, regulate the physicochemical microenvironment of the wound, and promote full wound regeneration. Thus, AFSCs are potential resources in stem cell therapy, especially in scar-free wound healing. This review describes the biological characteristics and clinical applications of AFSCs in treating wounds and provide new ideas for the treatment of wound healing.
Humans ; Amniotic Fluid ; Wound Healing/physiology* ; Regeneration/physiology* ; Skin/pathology* ; Cicatrix ; Stem Cells

OBJECTIVES: Steroidal anti-inflammatory drugs have certain side effects in the treatment of hypertrophic scar, and the scar recurrence is easy after withdrawal of steroid anti-inflammatory drugs. Finding reliable alternative drugs is an effective means to improve this defect. Aspirin, a traditional non-steroidal anti-inflammatory drug, is safe for topical use and has anti-inflammatory effects similar to those of steroidal anti-inflammatory drugs, which may have similar effects on the treatment of hypertrophic scar. This study aims to investigate the inhibitory effect of aspirin on the proliferation of hypertrophic scar in rabbit ears and the underlying mechanism. METHODS: The rabbit ear hypertrophic scar models were prepared. The rabbits were randomly divided into a normal skin group (group A), a blank control group (group B), a 0.9% NaCl group (group C), a 0.2% aspirin group (group D), a 0.5% aspirin group (group E), a 2% aspirin group (group F), and a triamcinolone acetonide group (group G). Macroscopic observation of hyperplasia was performed 8 weeks after local injection of the scar, followed by collecting the scar tissue samples for HE staining, Masson staining, and immunohistochemistry, respectively to assess the proliferation of fibroblasts and collagen fibers, and calculate the hypertrophic index, microvessel density, and immunohistochemical score. RESULTS: All rabbit ear hypertrophic scar models were successfully constructed. In groups B and C, the hypertrophic scar edge was irregular, with reddish protruding epidermis, significant contracture and hard touch. In group D, E, and F, with the increase of aspirin administration concentration, the scar became thinner and gradually flat, the proliferation of fibrocytes and collagen fibers was weakened, and the hypertrophic index was gradually decreased (P<0.05). Immunohistochemistry showed that the expression of β-catenin was decreased in the group D, E and F in turn, and the immunohistochemical score was gradually decreased (P<0.05). There was no significant difference in hypertrophic index, microvessel density, and immunohistochemical score (all P>0.05). CONCLUSIONS Local injection of aspirin can reduce the generation of hypertrophic scar in a dose-dependent manner within a certain concentration range; aspirin inhibits the growth of hypertrophic scar in rabbit ears by inhibiting Wnt/β-catenin signal pathway; 2% aspirin and 40 mg/mL triamcinolone acetonide have similar curative efficacy on hypertrophic scar.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; Aspirin/therapeutic use* ; Cicatrix, Hypertrophic/pathology* ; Collagen ; Rabbits ; Signal Transduction ; Triamcinolone Acetonide/therapeutic use* ; beta Catenin/metabolism*