Combined Blepharoplasty and Brow Fat Pad Transfer for the Correction of Dermatochalasis and Sunken Upper Eyelids.

BACKGROUND: Women commonly experience upper eyelid dermatochalasis and upper eyelid depression with advancing age. Blepharoplasty is a suitable method for treating dermatochalasis, but not sunken eyelid. This study proposed a novel technique for eyelid rejuvenation by simultaneously correcting dermatochalasis and sunken upper eyelids in middle-aged women. METHODS: Forty patients underwent subbrow blepharoplasty combined with brow fat pad transfer. Ellipse-shaped skin and subcutaneous tissue underneath the eyebrow were measured, demarcated, and excised. The orbicularis oculi muscle beneath the subcutaneous tissue was exposed and dissected in the upper-third area. The brow fat pad was turned downward using the lower edge as the pedicle and was fixed in the layer of retro-orbicularis oculi fat to fill the depressed area in the upper eyelid. The lower muscle flap was fixed to the supraorbital rim periosteum and upper musculocutaneous flaps, thereby forming a cross flap for interlocking fixation. The surgical outcomes were evaluated using a three-dimensional imaging device and the Global Aesthetic Improvement Scale. RESULTS: The depth and volume of upper eyelid depression decreased significantly 3 months after the surgery and stabilized within 6 months. Global Aesthetic Improvement Scale scores significantly improved after the surgery, and the postoperative outcomes were acceptable. CONCLUSIONS: The novel technique is simple and effective for simultaneously correcting dermatochalasis and sunken upper eyelids in middle-aged women. The surgical outcomes are predictable and acceptable to most patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Comparison of Postoperative Scarring in Asian Women After Supra-brow and Sub-brow Blepharoplasty: A Retrospective Study.

BACKGROUND: Supra-brow and sub-brow blepharoplasty are two types of upper eyelid blepharoplasties that are commonly performed in middle-aged Asian women to correct skin laxity of the upper eyelid; the postoperative scar formation of the two procedures may be different. Therefore, we designed this retrospective study to explore the differences in postoperative scarring between patients receiving supra- or sub-brow blepharoplasty. METHODS: We identified 52 patients who underwent supra-brow blepharoplasty and 54 patients who underwent sub-brow blepharoplasty. For each patient, the scar quality was assessed using photographs, the Observer Scar Assessment Scale (OSAS), and the Patient Scar Assessment Scale (PSAS) 1 year following surgery. RESULTS: For OSAS, higher scores for pigmentation, thickness, relief, pliability, surface, and overall opinion were observed in patients who underwent supra-brow blepharoplasty (p < 0.05) except for the "vascular score" (p = 0.148). The average overall opinion scores of the supra- and sub-brow blepharoplasty were 3.90 ± 0.41 and 2.33 ± 0.48, respectively, indicating that acceptance of postoperative scars in patients who underwent supra-brow blepharoplasty was worse than that in patients who underwent sub-brow blepharoplasty. Significantly higher scores were observed in all items of PSAS items for patients with supra-brow blepharoplasty (p < 0.05). CONCLUSIONS: The postoperative scars in patients who underwent supra-brow blepharoplasty were more obvious than those in sub-brow blepharoplasty. From the perspective of postoperative scar formation, sub-brow blepharoplasty may be a more suitable choice for patients. LEVEL OF EVIDENCE V: 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 .

CTRP3 promotes TNF-α-induced apoptosis and barrier dysfunction in salivary epithelial cells.

BACKGROUND: C1q/tumour necrosis factor-related protein 3 (CTRP3) plays important roles in metabolism and inflammatory responses in various cells and tissues. However, the expression and function of CTRP3 in salivary glands have not been explored. METHODS: The expression and distribution of CTRP3 were detected by western blot, polymerase chain reaction, immunohistochemical and immunofluorescence staining. The effects of CTRP3 on tumour necrosis factor (TNF)-α-induced apoptosis and barrier dysfunction were detected by flow cytometry, western blot, co-immunoprecipitation, and measurement of transepithelial resistance and paracellular tracer flux. RESULTS: CTRP3 was distributed in both acinar and ductal cells of human submandibular gland (SMG) and was primarily located in the ducts of rat and mouse SMGs. TNF-α increased the apoptotic rate, elevated expression of cleaved caspase 3 and cytochrome C, and reduced B cell lymphoma-2 (Bcl-2) levels in cultured human SMG tissue and SMG-C6 cells, and CTRP3 further enhanced TNF-α-induced apoptosis response. Additionally, CTRP3 aggravated TNF-α-increased paracellular permeability. Mechanistically, CTRP3 promoted TNF-α-enhanced TNF type I receptor (TNFR1) expression, inhibited the expression of cellular Fas-associated death domain (FADD)-like interleukin-1ß converting enzyme inhibitory protein (c-FLIP), and increased the recruitment of FADD with receptor-interacting protein kinase 1 and caspase 8. Moreover, CTRP3 was significantly increased in the labial gland of Sjögren's syndrome patients and in the serum and SMG of nonobese diabetic mice. CONCLUSIONS: These findings suggest that the salivary glands are a novel source of CTRP3 synthesis and secretion. CTRP3 might promote TNF-α-induced cell apoptosis through the TNFR1-mediated complex II pathway.

C1q/tumor necrosis factor-related protein-6 attenuates TNF-α-induced apoptosis in salivary acinar cells via AMPK/SIRT1-modulated miR-34a-5p expression.

C1q/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified adipokine involved in diverse biological processes. However, its role in salivary glands remains unknown. Here, we demonstrated that CTRP6 was mainly distributed in the nuclei, apicolateral membranes, and cytoplasm of human submandibular glands (SMGs), serous cells of parotid glands, and ducts and apicolateral membranes of serous cells in rats and mice. CTRP6 inhibited the apoptosis rate and reversed the increased levels of cleaved caspase 3, caspase 8, caspase 9, and cytochrome C and the decreased Bcl-2 expression induced by tumor necrosis factor (TNF)-α in both SMG-C6 cells and cultured human SMG tissues. Microarray analysis identified 43 differentially expressed microRNAs (miRNAs) in the SMGs of nonobese diabetic mice. miR-34a-5p was selected due to its upregulation by TNF-α, which was abolished by CTRP6. The miR-34a-5p inhibitor promoted whereas the miR-34a-5p mimic suppressed the effects of CTRP6 on TNF-α-induced apoptosis. CTRP6 increased AMP-activated protein kinase (AMPK) phosphorylation and reversed TNF-α-induced SIRT1 downregulation in salivary cells. AraA, an AMPK inhibitor, reversed the effects of CTRP6 on TNF-α-induced alterations in the levels of SIRT1, miR-34a-5p, Bcl-2, and cleaved caspase 3 in vitro and ex vivo, whereas activating AMPK by AICAR reversed the decrease in SIRT1 expression and increase in miR-34a-5p expression induced by TNF-α. Inhibition of SIRT1 by EX527 suppressed the effects of CTRP6 on TNF-α-induced changes in miR-34a-5p and apoptosis-related proteins. Our findings indicate that salivary glands are novel sites for CTRP6 synthesis and secretion. CTRP6 protects acinar cells against TNF-α-induced apoptosis via AMPK/SIRT1-modulated miR-34a-5p expression.

Comparative efficacy and safety of radiotherapy/cetuximab versus radiotherapy/chemotherapy for locally advanced head and neck squamous cell carcinoma patients: a systematic review of published, primarily non-randomized, data.

BACKGROUND: Cetuximab (CTX) has been approved to be administered concurrently with radiotherapy (RT) to treat locally advanced head and neck squamous cell carcinoma (HNSCC). The aim of this study was to assess the efficacy and safety of concurrent CTX with RT (ExRT). METHOD: The PubMed, Cochrane Library, EMBASE databases were systematically searched to find relevant articles. The combined hazard ratio (HR), risk ratio (RR) and 95% confidence interval were calculated to assess the efficacy and safety of ExRT in contrast to concurrent platinum-based chemotherapy with RT (ChRT). RESULTS: In total, 32 articles with 4556 patients were included. The pooled HRs indicated that ExRT achieved an unfavorable overall survival (HR: 1.86, p < 0.0001), disease-specific survival (HR: 2.58, p = 0.002), locoregional control (HR: 1.94, p < 0.00001), and progression-free survival (HR: 2.04, p = 0.003) compared with ChRT for locally advanced HNSCC patients. In human papillomavirus-positive patient subgroups, ExRT showed inferior disease-specific survival (HR: 2.55, p = 0.009) and locoregional control (HR: 2.27, p < 0.0001) in contrast to ChRT. Additionally, ExRT increased the occurrence of mucositis (RR: 1.17, p < 0.005), skin toxicity (RR: 6.26, p < 0.00001), and infection (RR: 2.27, p = 0.04) compared with non-CTX groups (ChRT and RT), and was associated with lower incidence of anemia (RR: 0.35, p = 0.009), leukocytopenia (RR: 0.17, p < 0.0001), neutropenia (RR: 0.06, p < 0.0001), nausea/vomiting (RR: 0.23, p < 0.0001), and renal toxicity (RR: 0.14, p = 0.007). CONCLUSION: ChRT should remain the standard treatment for locally advanced HNSCC patients. ExRT was recognized as an effective alternative treatment for locally advanced HNSCC patients who experienced unbearable toxicities caused by non-CTX treatments.

Parasympathectomy increases resting secretion of the submandibular gland in minipigs in the long term.

Parasympathectomy leads to retrogressive alteration and dysfunction of the submandibular gland (SMG) within 1 month, but its long-term effect is unclear. Excessive secretion is observed in half of the patients 4-6 months after SMG transplantation, which completely denervates the gland. Here, we investigated the long-term effect of parasympathectomy on the secretion of SMGs in minipigs. The results showed that the resting salivary secretion of SMGs decreased by 82.9% of that in control at 2 months after denervation, but increased by 156% at 6 months. Although experiencing an atrophic period, the denervated glands regained their normal morphology by 6 months. The expression of the function-related proteins, including muscarinic acetylcholine receptor (mAChR) 3, aquaporin 5 (AQP5), tight junction protein claudin-3, and claudin-4 was decreased at 2 months after denervation. Meanwhile, the protein expression of stem cell markers, including sex-determining region Y-box 2 and octamer-binding transcription factor 4, and the number of Ki67+ cells were significantly increased. However, at 6 months after denervation, the expression of mAChR3, AQP5, claudin-1, claudin-3, and claudin-4 was significantly raised, and the membrane distribution of these proteins was increased accordingly. The autonomic axonal area of the glands was reduced at 2 months after denervation but returned to the control level at 6 months, suggesting that reinnervation took place in the long term. In summary, parasympathectomy increases resting secretion of the SMGs in the long term with a possible mechanism involving improved transepithelial fluid transport. This finding may provide a new strategy for xerostomia treatment.

Expression patterns of tight junction proteins in porcine major salivary glands: a comparison study with human and murine glands.

Tight junction (TJ) proteins play a dynamic role in paracellular fluid transport in salivary gland epithelia. Most TJ studies are carried out in mice and rats. However, the morphology of rodent salivary glands differs from that of human glands. This study aimed to compare the histological features and the expression pattern of TJ proteins in porcine salivary glands with those of human and mouse. The results showed that porcine parotid glands were pure serous glands. Submandibular glands (SMGs) were serous acinar cell-predominated mixed glands, whereas sublingual glands were mucous acinar cell-predominated. Human SMGs were mixed glands containing fewer mucous cells than porcine SMGs, whereas the acinar cells of murine SMGs are seromucous. The histological features of the duct system in the porcine and human SMGs were similar and included intercalated, striated and excretory ducts, but the murine SMG contained a specific structure, the granular convoluted tubule. TJ proteins, including claudin-1 to claudin-12, occludin and zonula occludin-1 (ZO-1), were detected in the porcine major salivary glands and human SMGs by RT-PCR; however, claudin-6, claudin-9 and claudin-11 were not detected in the murine SMG. As shown by immunofluorescence, claudin-1, claudin-3, claudin-4, occludin and ZO-1 were distributed in both acinar and ductal cells in the porcine and human SMGs, whereas claudin-1 and claudin-3 were mainly present in acinar cells, and claudin-4 was mainly distributed in ductal cells in the murine SMG. In addition, 3D images showed that the TJ proteins arranged in a honeycomb-like structure on the luminal surface of the ducts, whereas their arrangements in acini were irregular in porcine SMGs. In summary, the expression pattern of TJ proteins in salivary glands is similar between human and miniature pig, which may be a candidate animal for studies on salivary gland TJ function.