RESUMEN
Breast Cancer Type 1 Susceptibility Protein (BRCA1) is a tumor-suppressor protein that regulates various cellular pathways, including those that are essential for preserving genome stability. One essential mechanism involves a BRCA1-A complex that is recruited to double-strand breaks (DSBs) by RAP80 before initiating DNA damage repair (DDR). How RAP80 itself is recruited to DNA damage sites, however, is unclear. Here, we demonstrate an intrinsic correlation between a methyltransferase DOT1L-mediated RAP80 methylation and BRCA1-A complex chromatin recruitment that occurs during cancer cell radiotherapy resistance. Mechanistically, DOT1L is quickly recruited onto chromatin and methylates RAP80 at multiple lysines in response to DNA damage. Methylated RAP80 is then indispensable for binding to ubiquitinated H2A and subsequently triggering BRCA1-A complex recruitment onto DSBs. Importantly, DOT1L-catalyzed RAP80 methylation and recruitment of BRCA1 have clinical relevance, as inhibition of DOT1L or RAP80 methylation seems to enhance the radiosensitivity of cancer cells both in vivo and in vitro. These data reveal a crucial role for DOT1L in DDR through initiating recruitment of RAP80 and BRCA1 onto chromatin and underscore a therapeutic strategy based on targeting DOT1L to overcome tumor radiotherapy resistance.
Asunto(s)
Proteína BRCA1 , Reparación del ADN , Chaperonas de Histonas , N-Metiltransferasa de Histona-Lisina , Humanos , Proteína BRCA1/metabolismo , Proteína BRCA1/genética , Chaperonas de Histonas/metabolismo , Chaperonas de Histonas/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Metilación , Línea Celular Tumoral , Roturas del ADN de Doble Cadena , Cromatina/metabolismo , Metiltransferasas/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Animales , Femenino , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Ratones , Tolerancia a Radiación/genética , Metilación de ADNRESUMEN
BACKGROUND: Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients. METHODS: This study analyzed the expression of DOT1L in PARPi-resistant cell lines compared to sensitive ones and correlated it with clinical outcomes in OC patients. Comprehensive in vitro and in vivo functional experiments were conducted using cellular and mouse models. Molecular investigations, including RNA sequencing, chromatin immunoprecipitation (ChIP) and Cleavage Under Targets and Tagmentation (CUT&Tag) assays, were employed to unravel the molecular mechanisms of DOT1L-mediated PARPi resistance. RESULTS: Our investigation revealed a robust correlation between DOT1L expression and clinical PARPi resistance in non-BRCA mutated OC cells. Upregulated DOT1L expression in PARPi-resistant tissues was associated with diminished survival in OC patients. Mechanistically, we identified that PARP1 directly binds to the DOT1L gene promoter, promoting transcription independently of its enzyme activity. PARP1 trapping induced by PARPi treatment amplified this binding, enhancing DOT1L transcription and contributing to drug resistance. Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. Furthermore, we discovered that combining a DOT1L inhibitor with PARPi demonstrated a synergistic effect in both cell line-derived xenograft mouse models (CDXs) and patient-derived organoids (PDOs). CONCLUSIONS: Our results demonstrate that DOT1L is an independent prognostic marker for OC patients. The PARP1-DOT1L/H3K79me2-PLCG2/ABCB1 axis is identified as a pivotal contributor to PARPi resistance. Targeted inhibition of DOT1L emerges as a promising therapeutic strategy for enhancing PARPi treatment outcomes in OC patients.
Asunto(s)
Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Neoplasias Ováricas , Poli(ADP-Ribosa) Polimerasa-1 , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Femenino , Resistencia a Antineoplásicos/genética , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Animales , Ratones , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Pronóstico , N-Metiltransferasa de Histona-LisinaRESUMEN
BACKGROUND: Radioresistance is the leading cause of death in advanced cervical cancer (CC). Dysregulation of RNA modification has recently emerged as a regulatory mechanism in radiation and drug resistance. We aimed to explore the biological function and clinical significance of 5-methylcytosine (m5C) in cervical cancer radiosensitivity. METHODS: The abundance of RNA modification in radiotherapy-resistant and sensitive CC specimens was quantified by liquid chromatography-tandem mass spectrometry. The essential RNA modification-related genes involved in CC radiosensitivity were screened via RNA sequencing. The effect of NSUN6 on radiosensitivity was verified in CC cell lines, cell-derived xenograft (CDX), and 3D bioprinted patient-derived organoid (PDO). The mechanisms of NSUN6 in regulating CC radiosensitivity were investigated by integrative m5C sequencing, mRNA sequencing, and RNA immunoprecipitation. RESULTS: We found a higher abundance of m5C modification in resistant CC samples, and NSUN6 was the essential m5C-regulating gene concerning radiosensitivity. NSUN6 overexpression was clinically correlated with radioresistance and poor prognosis in cervical cancer. Functionally, higher NSUN6 expression was associated with radioresistance in the 3D PDO model of cervical cancer. Moreover, silencing NSUN6 increased CC radiosensitivity in vivo and in vitro. Mechanistically, NDRG1 was one of the downstream target genes of NSUN6 identified by integrated m5C-seq, mRNA-seq, and functional validation. NSUN6 promoted the m5C modification of NDRG1 mRNA, and the m5C reader ALYREF bound explicitly to the m5C-labeled NDRG1 mRNA and enhanced NDRG1 mRNA stability. NDRG1 overexpression promoted homologous recombination-mediated DNA repair, which in turn led to radioresistance in cervical cancer. CONCLUSIONS: Aberrant m5C hypermethylation and NSUN6 overexpression drive resistance to radiotherapy in cervical cancer. Elevated NSUN6 expression promotes radioresistance in cervical cancer by activating the NSUN6/ALYREF-m5C-NDRG1 pathway. The low expression of NSUN6 in cervical cancer indicates sensitivity to radiotherapy and a better prognosis.
Asunto(s)
5-Metilcitosina , Proteínas de Ciclo Celular , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular , ARN Mensajero , Tolerancia a Radiación , Neoplasias del Cuello Uterino , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/patología , Humanos , Femenino , Tolerancia a Radiación/genética , 5-Metilcitosina/metabolismo , 5-Metilcitosina/análogos & derivados , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Animales , Ratones , ARN Mensajero/genética , ARN Mensajero/metabolismo , Línea Celular Tumoral , Pronóstico , Ensayos Antitumor por Modelo de Xenoinjerto , Metiltransferasas/genética , Metiltransferasas/metabolismoRESUMEN
BACKGROUND: Lagophthalmos, a common complication after blepharoptosis correction, has plagued oculoplastic surgeons. The goal of this study was to investigate the effect of tape eyelid closure on reducing the occurrence of lagophthalmos after blepharoptosis correction. METHODS: From April 2020 to June 2021, a total of 112 patients with severe congenital ptosis received corrective surgery at the Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University. Of these, 48 underwent frontalis muscle advancement technique and 64 underwent conjoint fascial sheath suspension. Preoperative data collected included demographics, levator function, Bell's phenomenon, and marginal reflex distance 1 (MRD1). Postoperative data included surgery type, MRD1, eyelid closure function, aesthetic outcomes (including eyelid contour, eyelid symmetry, and eyelid crease), keratitis, and other complications. RESULTS: Frontalis muscle advancement technique group: the median of safe eye closure time was 7.3 months (positive Bell's phenomenon; interquartile range [IQR], 3.8-10.8 months) and 13.9 months (poor Bell's phenomenon; IQR, 11.6-16.1 months). There was a significant improvement between the preoperative and postoperative MRD1 (-1.52 ± 0.82 vs 3.85 ± 0.58 mm, P < 0.05). Conjoint fascial sheath suspension group: the median of safe eye closure time was 5.7 months (positive Bell's phenomenon; IQR, 2.9-8.5 months) and 12.4 months (poor Bell's phenomenon; IQR, 8.1-16.7 months). There was a significant improvement between the preoperative and postoperative MRD1 (-1.02 ± 0.91 vs 4.15 ± 1.03 mm, P < 0.05). All patients/guardians were satisfied with the aesthetic outcomes. CONCLUSIONS: Tape tarsorrhaphy is a safe, easy-to-learn method for treating lagophthalmos with a good aesthetic outcome.
Asunto(s)
Blefaroplastia , Blefaroptosis , Lagoftalmos , Humanos , Blefaroptosis/cirugía , Blefaroptosis/congénito , Músculos Oculomotores/cirugía , Párpados/cirugía , Blefaroplastia/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Severe congenital ptosis is a common ocular deformity in pediatric patients that can significantly impact visual development and aesthetic appearance, leading to negative psychosocial outcomes. The frontalis muscle advancement technique is a well-established surgical treatment for severe congenital ptosis. Aesthetic changes of the brow-eye continuum often plays an important role in ptosis surgery. METHODS: We conducted a single-center retrospective case series study of patients with severe congenital ptosis who underwent the frontalis muscle advancement technique at the Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University between April 2020 and June 2021. The study aimed to evaluate the aesthetic changes of the eyebrow-eyelid continuum after surgery. The main outcome measurements included marginal reflex distance 1, palpebral fissure height, eyebrow position, upper eyelid to lower eyebrow distance, lower eyelid to upper eyebrow distance, and nasal base to lower eyelid distance. RESULTS: The study included 48 patients (66 eyelids), with 30 unilateral and 18 bilateral patients. Our analysis found that eyebrow height decreased by an average of 4.8% postoperatively relative to preoperatively in all patients. CONCLUSIONS: The frontalis muscle advancement technique has demonstrated effectiveness in achieving aesthetically pleasing outcomes in children with severe ptosis. It is crucial to pay careful attention to the brow-eye continuum during the correction process, as its harmony can greatly impact the final result.
Asunto(s)
Blefaroplastia , Blefaroptosis , Humanos , Niño , Blefaroplastia/métodos , Estudios Retrospectivos , Blefaroptosis/cirugía , Blefaroptosis/congénito , Estética , Músculos/cirugía , Músculos Oculomotores/cirugíaRESUMEN
BACKGROUND: Poor Bell's phenomenon is often considered a relative contraindication for ptosis surgery, as it increases the risk of corneal exposure and dry eye symptoms after surgery. However, the Bell's phenomenon may vary in different individuals and sleep stages, making it inaccurate to predict the position of the eye during sleep based on awake examination. This study aimed to investigate the role of Bell's phenomenon in ptosis surgery and the management of nocturnal lagophthalmos. METHODS: We conducted a retrospective case series of 23 patients with ptosis and poor Bell's phenomenon who underwent different surgical techniques at Xijing Hospital from April 2020 to June 2021. We assessed Bell's phenomenon at different stages of sleep and collected data on ptosis degree, surgical approach, lagophthalmos, complications, and outcomes. RESULTS: Of the total 23 patients originally considered for study, 9 with frontalis muscle advancement technique, 8 with conjoint fascial sheath suspension, 4 with levator resection technique, and 2 with levator aponeurosis plication technique. All patients achieved satisfactory correction of ptosis. One patient had prolonged lagophthalmos and underwent reoperation to lower the eyelid height. Other complications were minor and resolved with conservative treatment. CONCLUSION: We conclude that poor Bell's phenomenon is not a relative contraindication for ptosis surgery. Nocturnal lagophthalmos should be monitored after ptosis surgery regardless of the Bell's phenomenon results. Tape eyelid closure can be an effective solution to protect the corneal surface during nocturnal lagophthalmos. 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 Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Asunto(s)
Blefaroplastia , Blefaroptosis , Lagoftalmos , Humanos , Estudios Retrospectivos , Músculos Oculomotores/cirugía , Blefaroptosis/cirugía , Blefaroplastia/métodos , Párpados/cirugíaRESUMEN
OBJECTIVE: To introduce the surgical procedures and experiences in restoration of lower facial esthetics for a male and a female patients who suffered from burn injuries. The difference of surgical methods which varied from sexes were discussed. MATERIALS AND METHODS: The clinical data of the patients was collected and retrospectively analyzed. The cervical contracture was repaired by pre-expanded free scapular flaps with sufficient pliable tissue for large defects. Moreover, for the male patient, prefabricated double pedicle scalp flap was applied to rebuild the beard region. The patients were followed up for 2 years. Surgical procedures and outcomes were detailed in the article. RESULTS: All the flaps were survived well. The facial hair-bearing area of the man was recovered with natural appearance. The reconstructed mental cervical angels and mandibular margins were clear. The neck extension mobility was improved. The 2 patients were satisfied with the outcomes of the treatments. CONCLUSION: The treatments of facial and neck scar varied from sexes and different requirements. For male patient, the combination of scalp and scapular flaps was a feasible method to achieve natural beard and cervical appearance. For female patient, bilateral expanded scapular flaps could meet the demands of large tissue supply and a relative hidden donor site.
Asunto(s)
Estética Dental , Cuero Cabelludo , Humanos , Masculino , Femenino , Estudios Retrospectivos , Colgajos Quirúrgicos , CuelloRESUMEN
BACKGROUND: As an exposure region, the face is susceptible to burn injuries, which often lead to physical and psychological problems. For facial scar reconstruction, the subclavicular region has the advantages of matched color, similar texture, and thin and pliable tissue supply. The island or pedicled subclavicular flap, which is nourished by the thoracic branch of supraclavicular artery (TBSA) had been reported to cover cervical facial defects and achieved good outcomes. However, the main restriction is the limitation of the pedicle length. Therefore, the authors applied preexpanded TBSA free flap transplantation for treatments of upper and contralateral facial scars to overcome the pedicle limitation. METHODS: Three patients were treated with preexpanded TBSA flaps to repair the facial defects after scar resections. Two of them were combined with forearm or deltopectoral flaps according to different purposes. The patients were followed up for 2 to 7 years. The clinical data and surgical techniques were recorded and analyzed. The scars were scored by Vancouver Scar Scale. RESULTS: Two of the TBSA flaps survived well without complication. Partial flap necrosis in the distal end was healed by dressing changes, and mild contracture in the left medial canthus was corrected by Z plasty in case 1. The scars around transferred flaps and donor sites were scored 3 to 4 by Vancouver Scar Scale. The patients were satisfied with the outcomes. All the donor sites were closed primarily. CONCLUSION: A preexpanded TBSA-free flap could overcome the restriction of pedicle length for reconstruction procedures. The method is a feasible alternative of thoracic flaps to repair facial defects beyond pedicle limitation.
Asunto(s)
Colgajos Tisulares Libres , Procedimientos de Cirugía Plástica , Humanos , Cicatriz/cirugía , Trasplante de Piel/métodos , Colgajos Tisulares Libres/cirugía , Arterias/cirugíaRESUMEN
BACKGROUND: Loss of beard in adult male caused by severe burn may cause cosmetic and psychological problems for these patients. Reconstruction of the beard with hair-bearing skin flaps in similar color and texture of the surrounding tissues remains a challenge. METHODS: Eight male patients suffered from submental postburn scar and beard loss were treated by using the hair-bearing expanded scalp flap. A 1000 mL nephroid tissue expander was first implanted under the frontal and mid scalp. After a 3 to 4-month tissue expansion, the expanded hair-bearing scalp flap based on bilateral superficial temporal vessels were raised and transferred for beard reconstruction, and the cutaneous pedicles were curled into tubes. Delay and division of the pedicles were performed 3 to 4 weeks after flap transfer. RESULTS: Eight male patients with postburn scar and beard loss were successfully treated with no major complication. One patient suffered from edge necrosis at distal end of the flap and healed after daily dressing change. Chin and submental areas were repaired by expanded scalp flap and total beard was reconstructed at the same time. All donor sites were closed directly without skin grafting. CONCLUSIONS: The modified expanded bipedicled scalp flap provides an easy and reliable way for total beard reconstruction and large-scale submental scars repairment.
Asunto(s)
Cicatriz , Cuero Cabelludo , Adulto , Humanos , Masculino , Cicatriz/cirugía , Cuero Cabelludo/cirugía , Mentón , Colgajos Quirúrgicos/trasplante , CabelloRESUMEN
BACKGROUND: For moderate ptosis associated with fair levator function (LF), the levator resection is the most commonly used procedure. However, the levator resection technique still has some disadvantages, such as residual lagophthalmos (RL), undercorrection, conjunctival prolapse, and eyelid contour abnormality. To solve the above problems, our team have made modifications to the levator resection technique in three aspects: releasing the levator muscle sufficiently, preserving the supporting structure of the conjunctiva, and placing multiple suture sites. METHODS: Fifty-seven patients (81 eyes) underwent the modified levator resection technique and were enrolled in the study. Preoperative data collected included age, sex, margin reflex distance 1 (MRD1), and LF. Postoperative data collected included MRD1, RL, patient satisfaction, complications, and length of follow-up. RESULTS: Mean MRD1 significantly increased from 1.45 ± 0.65 mm preoperatively to 3.57 ± 0.51 mm postoperatively. Mean LF significantly increased from 6.49 ± 1.12 mm preoperatively to 9.48 ± 1.39 mm postoperatively. Successful correction was obtained in 77 eyes (95.1%). Mean RL was 1.09 ± 0.57 and 72 eyes (88.9%) showed excellent or good eyelid closure function. Fifty-four patients (94.7%) were completely satisfied with the final result. Complications such as hematoma, infection, conjunctival prolapse, suture exposure, corneal abrasion, and keratitis were not found in any cases during follow-up. CONCLUSION: This modified levator resection technique introduced in this study is effective in correcting moderate congenital blepharoptosis, while minimizing RL, undercorrection, conjunctival prolapse, eyelid contour abnormality by releasing the levator muscle sufficiently, preserving the supporting structure of the conjunctiva, and placing multiple suture sites. LEVEL OF EVIDENCE IV: This journal requires that authors 42 assign a level of evidence to each article. For a full 43 description of these Evidence-Based Medicine ratings, 44 please refer to the Table of Contents or the online 45 Instructions to Authors www.springer.com/00266 .
Asunto(s)
Blefaroplastia , Blefaroptosis , Lagoftalmos , Humanos , Blefaroptosis/cirugía , Blefaroptosis/congénito , Párpados/anomalías , Estudios Retrospectivos , Blefaroplastia/métodos , Músculos Oculomotores/cirugía , Prolapso , Resultado del TratamientoRESUMEN
BACKGROUND: Fifty percent of Asians are born without a supratarsal fold (also called single eyelid), and double eyelid blepharoplasty is one of the most commonly performed and most popular facial cosmetic surgeries in the Asian population. However, patients with single eyelid frequently present with concomitant mild blepharoptosis (degree of ptosis, ≤2 mm), which often fails to cause the attention of surgeons and misses correction. METHODS: A retrospective study of all patients who underwent double eyelid blepharoplasty and blepharoptosis correction simultaneously with the modified levator aponeurosis plication technique was performed from June of 2017 to June of 2020. RESULTS: A total of 108 patients (155 eyelids) underwent double eyelid blepharoplasty and blepharoptosis correction simultaneously with the modified levator aponeurosis plication technique and were enrolled in the study. The average follow-up period was 11.8 ± 4.5 months. There was a statistically significant difference between the preoperative margin reflex distance 1 (MRD1) and postoperative MRD1 (2.93 ± 0.37 vs 4.21 ± 0.39 mm, P = 0.000), and the mean MRD1 improvement was 1.28 ± 0.50 mm. Sufficient correction was obtained in 148 eyelids (95.5%), whereas undercorrection was observed in 5 eyelids (3.2%) and overcorrection was observed in 2 eyelids (1.3%). One hundred two patients (94.4%) were completely satisfied with the final result.All patients had smooth and elegant upper eyelid margin curve, and no patients complained of distortion of the eyelid margin contour and foreign body sensation.There were no cases of hematoma, infection, suture exposure, corneal abrasion, and keratitis in any patient. CONCLUSIONS: This modified levator aponeurosis plication introduced in this study is a simple and effective method for creating double-eyelid crease and correcting mild blepharoptosis simultaneously, and provides a satisfactory outcome. As such, we recommend this method in treating patients with both single eyelid and mild blepharoptosis.
Asunto(s)
Blefaroplastia , Blefaroptosis , Aponeurosis/cirugía , Blefaroplastia/métodos , Blefaroptosis/cirugía , Párpados/cirugía , Femenino , Humanos , Músculos Oculomotores/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Blepharoptosis is defined as an abnormally low-positioned upper eyelid margin in the primary gaze position, which results in cosmetic discomfort and functional visual dysfunction. Recurrence is one of the common complications after ptosis correction and requires further revision. Conjoint fascial sheath (CFS) suspension has become increasingly popular for ptosis. In this article, we described our experience of CFS suspension in the treatment of recurrent blepharoptosis and evaluated the postoperative outcomes so as to guide the clinical application of CFS suspension. METHODS: Thirty-eight patients (48 eyelids) who had recurrent blepharoptosis and received CFS suspension were included in this study. Before the surgery, the degree of ptosis and levator function were assessed. The postoperative evaluation consisted of the correction effect, eyelid symmetry, protective closure function of eyelid, and surgical complications. RESULTS: At the final follow-up, 46 eyelids (95.8%) showed an ideal correction, of which 24 eyelids (50%) showed sufficient correction and 22 eyelids (45.8%) showed normal correction. The remaining 2 eyelids (4.2%) showed under-correction. Among all 38 patients, 26 patients (68.4%) achieved good symmetry, and 10 patients (26.3%) achieved fair symmetry, while only 2 patients (5.3%) showed poor symmetry. Recovery time of eyelid protective closure function was 3.9 ± 1.04 months (range, 2.5-6 months). There were no complications except residual lagophthalmos (9 eyelids) residual conjunctival prolapse (10 eyelids). CONCLUSION: CFS suspension is an effective method for the correction of recurrent blepharoptosis due to its sufficient correction effect, recovery of eyelid protective closure function, and less complication rate. 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 .
Asunto(s)
Blefaroplastia , Blefaroptosis , Blefaroplastia/métodos , Blefaroptosis/cirugía , Humanos , Músculos Oculomotores/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: As periorbital aesthetic commonly improved in blepharoptosis patients after correction surgery, the aim of this study was to elaborate the brow-eyelid continuum changes in moderate-severe ptosis patients who underwent conjoint fascial sheath suspension systematically. METHODS: Patients with moderate-severe ptosis who underwent conjoint fascial sheath suspension were assessed by using pre- and post-operative digital photographs in the primary gaze position of the eye. The main outcome measurements included marginal reflex distance1 (MRD1), palpebral fissure height (PFH), eyebrow position, the symmetry of face and the horizontal forehead lines condition. RESULTS: There were 43 patients (53 eyelids) in our study, including 33 unilateral and 10 bilateral patients. The mean levator function was 3.00 ± 1.07 mm. Before surgery, the mean MRD1 and PFH were 0.60 ± 1.14 mm and 6.75 ± 1.71 mm, respectively. The mean eyebrow height at medial, center, lateral position was 33.16 ± 3.95 mm, 35.99 ± 4.02 mm and 34.35 ± 4.80 mm, respectively. It was found that MRD1 and PFH symmetry both were 23.26% and eyebrow symmetry was 62.79%. For forehead wrinkles, 48.84% of the patients was mild, 34.88% was moderate, and 16.28% was severe. The average follow-up was 12.78 months (ranged from 12 to 18 months). One month after surgery, the mean MRD1 and PFH were 5.68 ± 0.86 mm, 11.61 ± 0.97 mm, respectively, both of which improved significantly (P < 0.0001). The mean eyebrow height at medial, center, lateral position descended to 28.22 ± 4.77 mm (P = 0.017), 31.41 ± 4.58 mm (P = 0.033) and 30.28 ± 3.41 mm (P = 0.018), respectively. The result showed that the rate of patients with MRD1 symmetry was 32.56%, PFH symmetry was 30.23%, and eyebrow symmetry was 90.7%. For forehead wrinkles, 69.77% was mild and 30.23% was moderate. Then, patients' eyebrow gradually elevated, while their upper eyelid dropped. At the last follow-up, the mean MRD1 and PFH were 3.83 ± 0.98 mm and 9.84 ± 1.56 mm, respectively. The mean eyebrow height at medial, center, lateral position improved to 30.52 ± 4.59 mm (P = 0.031), 32.40 ± 4.68 mm (P = 0.033), 31.19 ± 4.16 mm (P = 0.028), respectively. The patients with MRD1 symmetry accounted for 86.05%, PFH symmetry 86.05%, and eyebrow symmetry 90.7%. For forehead wrinkles, 67.44% was mild and 32.56% was moderate. CONCLUSION: CFS suspension can effectively reconstruct moderate-severe ptosis patients' aesthetics of the brow-eyelid continuum by descending elevated eyebrow, improving facial symmetry and reducing forehead rhytids. 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 .
RESUMEN
Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeutics. In response to DNA double-strand breaks (DSBs), G9a is phosphorylated at serine 211 by casein kinase 2 (CK2) and recruited to chromatin. The chromatin-enriched G9a can then directly interact with replication protein A (RPA) and promote loading of the RPA and Rad51 recombinase to DSBs. This mechanism facilitates homologous recombination (HR) and cell survival. We confirmed the interaction between RPA and G9a to be critical for RPA foci formation and HR upon DNA damage. Collectively, our findings demonstrate a regulatory pathway based on CK2-G9a-RPA that permits HR in cancer cells and provide further rationale for the use of G9a inhibitors as a cancer therapeutic.
Asunto(s)
Antígenos de Histocompatibilidad/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , Reparación del ADN por Recombinación , Proteína de Replicación A/metabolismo , Quinasa de la Caseína II/metabolismo , Supervivencia Celular , Roturas del ADN de Doble Cadena , Células HCT116 , Humanos , Recombinasa Rad51/metabolismoRESUMEN
Titanium mesh was widely used for cranium defect repair but associated with high complication rates. In this study, the authors describe a method using latissimus dorsi-myocutaneous flap in the repair of titanium mesh exposure and scalp defect after cranioplasty, and the plate retaining is also achieved. Fifteen patients from April 2012 to May 2016 underwent this procedure, the age ranged from 32 to 62 years and 47 years old on average, and all the patient had plate exposure combined with surgical site infection and variation of scalp defect. All the patients had fully flap survive, and follow up ranged from 6 months to 24 months, 1 patient had titanium mesh re-expose and received additional operation to remove the plate. The free latissimus dorsi musculocutaneous flap could supply large size of bulky tissue coverage with good blood supply and strong anti-infection ability. This method was an option for retaining the titanium mesh and repairing the exposure for the mild infection with small size scalp defect patient.
Asunto(s)
Colgajo Miocutáneo/cirugía , Cuero Cabelludo/cirugía , Músculos Superficiales de la Espalda/cirugía , Mallas Quirúrgicas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cráneo/cirugía , Titanio , Resultado del TratamientoRESUMEN
Skin grafting is often the first choice for closing forehead defects. However, the aesthetics of skin grafting-reconstructed forehead defects are still not accepted by a large number of patients. With the technological advancement of laser hair removal, scalp flaps have been considered as donors for reconstruction of forehead defects. We evaluated 10 cases of forehead defect reconstructions with expanded scalp flaps followed by hair removal by an 800 nm diode laser. All flaps survived uneventfully and underwent 4-6 laser treatments for hair removal. The appearances of the reconstructed foreheads were similar to that of the adjacent skin, and all patients were satisfied with the treatment outcomes during the 6-24 months of follow-up. It is concluded that the combined treatments of expanded scalp flaps and diode laser hair removal are effective for repairing forehead defects.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 .
Asunto(s)
Frente/cirugía , Remoción del Cabello/métodos , Láseres de Semiconductores/uso terapéutico , Cuero Cabelludo/cirugía , Colgajos Quirúrgicos , Expansión de Tejido , Adulto , Preescolar , Terapia Combinada , Femenino , Humanos , Masculino , Procedimientos de Cirugía Plástica/métodos , Estudios RetrospectivosRESUMEN
The facial-cervical scars bring the suffering to the patients both physically and mentally. Choosing a proper donor soft tissue is always one of the critical issues, especially to Asian patients. Among the common used donor sites, the deltopectoral site was conceived as the most suitable donor tissue for the reconstruction in face and neck for its adjacent site and match in color and texture. There were 220 patients with facial-cervical scars reconstructed by the pedicled expanded deltopectoral flap between 2007 through 2015 in the authors' hospital. There are 4 stages, including tissue expansion, flap pedicled transfer, pedicle delaying, and pedicle division, for the reconstruction of the facial-cervical scars using the pedicled expanded deltopectoral flap. Good skin compliance, normal contours, and emotional expression were noted in all the patients after the reconstruction. However, there were complications including expander exposure, stretch marks, flap tip necrosis, and mild postoperative hypertrophic scars. The unpleasant skin wound or color caused by the complications was repaired by further treatments such as skin grafting and laser. In conclusion, the pedicled expanded deltopectoral flap is a reliable and excellent option for the reconstruction of the facial-cervical scars.
Asunto(s)
Cicatriz , Cara , Cuello , Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos/cirugía , Cicatriz/patología , Cicatriz/cirugía , Cara/patología , Cara/cirugía , Humanos , Cuello/patología , Cuello/cirugía , Hombro/cirugíaRESUMEN
The scars of face and scalp caused by burning often show as 1 large facial-scalp scar. The deltopectoral flap was recognized as one of the first choices for the facial scar reconstruction. However, this flap cannot cross the level of zygomatic arch traditionally when it was transferred with pedicle. When the flap reconstructed the facial-scalp scars with expanded random scalp flap, another flap was often needed to reconstruct the remaining temple and forehead scars. The authors reviewed 24 patients of large facial-scalp scars reconstructed by expanded pedicled deltopectoral flap and scalp flap with several technique improvements. The seaming scar between the deltopectoral flap and scalp flap in the temple region formed the new hairline. The technique improvements included ligation of the perforating branches of the transverse cervical artery and thoracoacromial artery when dissecting the pocket, the partial bolster compressive dressing to the distal part of the flap and dividing the pedicle partly as a delaying procedure before dividing the pedicle completely. Good skin compliance, normal contours, and emotional expression were noted. There were complications including expander exposure in 3 patients, stretch marks in 5 patients, flap tip necrosis in 2 patients, and mild postoperative hypertrophic scars in 3 patients. In conclusion, the expanded pedicled deltopectoral flap can enlarge the reconstructive territory in face successfully with the technique improvements. The combination of the expanded pedicled deltopectoral flap and scalp flap is a reliable and excellent reconstructive option for large postburn facial-scalp scars.
Asunto(s)
Quemaduras/complicaciones , Cicatriz , Cara/cirugía , Procedimientos de Cirugía Plástica/métodos , Cuero Cabelludo/cirugía , Colgajos Quirúrgicos/cirugía , Cicatriz/etiología , Cicatriz/cirugía , Estudios de Cohortes , HumanosRESUMEN
BACKGROUND: Compared to the traditional transcutaneous approach, a safe and effective lower eyelid blepharoplasty has been recognized. In 2007, Sadove first reported a series of patients treated with transconjunctival septal suturing, but the inferior orbitopalpebral sulcus was not totally improved. PURPOSE: Orbital septal fat release and preservation through the transconjunctival approach was used to treat 20 young patients with bulging bags and inferior orbitopalpebral sulcus. METHOD: The orbital septal fat was released and transferred to infraorbital rim to be a base for the inferior orbitopalpebral sulcus. RESULT: Obvious bulging fat was released, and the orbitopalpebral sulcus was flattened by released and excessive orbital septal fat. Satisfactory results were achieved. CONCLUSION: The results achieved from this series of patients indicate that orbital septal fat release and preservation through the transconjunctival approach for reducing the orbitopalpebral sulcus is a safe and effective treatment for bulging fat and orbitopalpebral sulcus in young patients. 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 .