One-Step Construction of 1,3,4-Oxadiazoles with Anticancer Activity from Tertiary Amines via a Sequential Copper(I)-Catalyzed Oxidative Ugi/aza-Wittig Reaction.

An unparalleled copper(I)-catalyzed synthesis of 1,3,4-oxadiazoles from tertiary amines in one step has been described. The one-pot reactions involving (N-isocyanimine)triphenylphosphorane, tertiary amines, and carboxylic acids resulted in the formation of 1,3,4-oxadiazoles in moderate to good yields through a consecutive oxidative Ugi/aza-Wittig reaction, enabling the direct functionalization of sp3 C-H bonds adjacent to the nitrogen atom. This method offered several notable advantages, including ligands-free, exceptional productivity and a high functional group tolerance. The preliminary biological evaluation demonstrated that compound 4f inhibited hepatoma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.

Correction of Primary Multiple Upper Eyelid Folds by Three Mini-Incision Upper Blepharoplasty and Simultaneous Orbital Fat Pad Repositioning in East Asians.

BACKGROUND: This study aims to assess the feasibility and efficacy of a three mini-incision upper blepharoplasty combined with simultaneous orbital fat pad repositioning for correcting primary multiple upper eyelid folds in East Asians. METHODS: A retrospective analysis of 75 patients who underwent three mini-incision double-eyelid blepharoplasty in conjunction with orbital fat pad repositioning for the correction of multiple upper eyelid folds between January 2018 and January 2022 was conducted. During the surgery, the lateral extension of the central upper eyelid fat mass was anchored medially to the upper medial eyelid via three small skin incisions. Postoperative follow-up was carried out to evaluate the improvement in multiple upper eyelid folds, and patient satisfaction was measured. RESULTS: The follow-up period ranged from 6 to 36 months, with an average of 12 months. Post-surgery, the multiple fold lines were completely resolved in 71 patients (95%), while relapse occurred in 4 patients (5%). The overall satisfaction rate was 88%. CONCLUSIONS: The three mini-incision double-eyelid blepharoplasty combined with simultaneous orbital fat repositioning is an effective method for correcting primary multiple upper eyelid folds. This technique presents a novel alternative for patients with primary multiple eyelid folds, particularly those who are hesitant to undergo a full-incision double-eyelid procedure. 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 .

Use of the Acellular Dermal Matrix (ADM) to Reconstruct Full-thickness Eyelid Defects.

This study aimed to introduce the use of an acellular dermal matrix (ADM) as a posterior lamellar substitution for full-thickness eyelid reconstruction after malignant tumor excision. After resection of the malignant eyelid tumors, anterior lamellar defects were repaired using direct sutures and pedicled flaps in 20 patients (15 men and 5 women). ADM was used to replace the tarsal plate and the conjunctiva. All patients were followed up for 6 months or more to assess the functional and esthetic outcomes of the procedure. The flaps survived in all but 2 cases, wherein they necrosed due to insufficient blood supply. The functionality and esthetic outcomes were excellent in 10 and 9 patients, respectively. There were no changes in visual acuity or corneal epithelial damage after the surgery. The eyeball movement was good. Corneal irritation no longer appeared, and patient comfort was maintained. Furthermore, no tumor recurrence occurred in any patient. ADM is a valuable posterior lamellar material for the full-thickness reconstruction of eyelid defects after the resection of malignant tumors on the eyelids.

Skin-redraping epicanthoplasty combined with the modified Hotz procedure to treat recurrent trichiasis in adults caused by congenital entropion.

OBJECTIVE: To report the efficacy of skin-redraping epicanthoplasty combined with the modified Hotz procedure for the management of recurrent trichiasis in adults caused by congenital entropion. METHODS: A retrospective chart review of nine recurrent trichiasis patients caused by congenital entropion was performed. All the patients were adults, and the follow-up period lasted more than 6 months. Success was defined as no recurrence of the trichiasis. RESULTS: The mean age of the patients was 22.7 ± 2.83 years, and the mean period of follow-up was 10.8 ± 4.15 months. The complete correction of trichiasis was observed in all patients, and there was no recurrence during the follow-up period. The ratio of the medial sclera area to the cornea area was enhanced from 0.25 ± 0.08 to 0.37 ± 0.11. Preoperatively, five patients were categorized as grade 2, and four patients were categorized as grade 3 of the Taylor classification, and all the patients were categorized as grade 0 after surgery. The preoperative severity of keratopathy was grade 3 in six patients and grade 2 in three patients. The preoperative lower lid horizontal skin fold heights were class 4 in six patients and class 3 in three patients. All the patients were grade 0 and class 1 after surgery. CONCLUSION: Skin-redraping epicanthoplasty combined with the modified Hotz procedure is reasonably successful in managing recurrent trichiasis in adults.

Full-thickness lower eyelid defect reconstruction using a pedicle rotation temporal flap and Acellular Human Dermis Graft (Alloderm).

The aim of this research was to prospectively examine the combination of a pedicled temporal rotation flap with an acellular human dermal graft technique for intermediate-sized lower eyelid defect reconstruction. Pedicled temporal rotation flaps based on the orbicularis oculi muscle were used to reconstruct the anterior lamella of lower eyelid defects in six patients (five males and one female) while the posterior lamella was reconstructed using an acellular human dermis graft (Alloderm). Flap survival at 6 months was 100%. The functionality and cosmetic results of the technique were evaluated, and corneal protection was achieved. The texture and color of the reconstructed eyelid matched the surrounding skin, and neither pain nor corneal irritation was reported. The donor site scar healed well and was inconspicuous in all cases. Furthermore, no recurrence of malignancy was observed. The combination of a temporal rotational flap with an acellular human dermal graft is the key points. This technique could be ideal for the reconstruction of intermediate-sized full-thickness lower eyelid defects.

Aesthetic Analysis of Alteration of Eyebrow and Forehead Position After Endoscopic Eyebrow lift.

BACKGROUND: Some of the surgeons performing endoscopic brow lift believe that this technique does not lead to clinically significant enlargement of the forehead. PURPOSE: The goal of this study is to determine the change in eyebrow and forehead height after endoscopic brow lift and to assess the durability of the result over time. METHODS: The pre- and postoperative photographs of 97 patients who underwent endoscopic brow lift from January 2016 to July 2020 were standardized and analyzed. The distance between median hairline and upper edge of eyebrow, the distance between upper edge of the eyebrow and edge of the lower eyelid and the distance between edge of the lower eyelid and the nasal base were measured, and the change in the upper face proportion was measured and analyzed. RESULTS: There was statistically significant brow elevation after endoscopic brow lift in all three time periods (less than 1 month, 1-6 months and greater than 6 months). Forehead height did not change to a significant degree, while eyebrow height was increased statistically significant. A longitudinal study on 14 patients for whom multiple follow-up data were available showed that the increase in periorbital height appears to be sustained over time, whereas the change in the forehead height is not as readily apparent, resulting in a bigger relative change in the periorbital compared to the forehead height. CONCLUSIONS: The brow height increased more than the forehead height, corroborating the fact that most of our patients have not complained about forehead becoming larger. 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 .

Aesthetic Analysis of Alteration of Eyebrow Position After Double Eyelidplasty.

BACKGROUND: There is an anecdotal belief among some surgeons performing Asian eyelid surgery that double eyelid surgery itself decreases eyebrow position. However, the exact amount of descent and the specific changes in the proportion of facial aesthetics are unknown. PURPOSE: The goal of this study is to determine whether there indeed is a change in brow position after double eyelidplasty and to quantify the proportional differences associated with the change. The three-point double eyelids surgery method was used so that the change in the brow position is solely attributed to the surgery itself and not to the excision of redundant skin. METHODS: From January 2016 to December 2017, double eyelid surgery using the three-point technique was performed on 204 patients who did not require skin excision. Their pre- and postoperative photographs were standardized and analyzed. The ratio of the length between the upper edge of the eyebrow and the edge of the lower eyelid (A) and the length between the edge of the lower eyelid and the nasal base (B) as well as the subsequent change in the midfacial proportion was measured and analyzed. RESULTS: There was a statistically significant brow descent after double eyelidplasty. The average preoperative A/B was 0.71 and the average postoperative A/B was 0.67 (P < 0.001). Although the eyebrow distance did not change in 32.5% of patients, the remaining cohort showed average brow descent of 5.6%. And in this cohort that showed descent, linear regression showed that there was a correlation between the ratio of pre- and postoperative eyebrow distance CONCLUSION: Double eyelid surgery can lower the eyebrow in patients with foldless eyelids. This is in accordance with clinical observation in Asian blepharoplasty. In addition, there are associated changes in the proportion of midfacial aesthetics after the surgery. Such knowledge can be helpful in preoperative consulting with patients as well as in predicting postoperative results. 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.

Use of phosphodiesterase type 5 inhibitors and risk of melanoma: a meta-analysis of observational studies.

BACKGROUND: Phosphodiesterase type 5 inhibitor (PE5i) administration may stimulate the proliferation and survival of melanocytes. However, discrepancies remain regarding the association between PDE5i use and melanoma risk in observational studies in humans. AIM: To evaluate the association between PDE5i use and melanoma in a meta-analysis. MATERIALS AND METHODS: Studies were identified by searching the PubMed and Embase databases. A random-effects model was applied to synthesize the data. A stratified study was performed to evaluate the influence of study characteristics on outcomes. RESULTS: Four prospective cohort studies and three case-control studies with 1,534,615 male participants and 16,053 melanoma cases were incorporated. Patients who received a PDE5i had a significantly increased risk for melanoma (adjusted risk ratio [RR] =1.12, 95% CI =1.03-1.33, P=0.008) with moderate heterogeneity (I2=54%). Cohort studies (adjusted RR =1.22, 95% CI =1.02-1.46, P=0.03) largely contributed to this result rather than case-control studies. Subsequent stratified analyses revealed that sildenafil was associated with an increased risk of melanoma (adjusted RR =1.26, 95% CI =1.07-1.50, P=0.007), but tadalafil and vardenafil were not. Also, PDE5i use was associated with a significantly increased risk of in situ melanoma (adjusted RR =1.31, 95% CI =1.01-1.69, P=0.04), but not of localized or nonlocalized melanoma. CONCLUSION: PDE5i use may be associated with a significantly increased risk for melanoma in men. However, further research is needed to determine whether the association is causative.

Chaetocin induces apoptosis in human melanoma cells through the generation of reactive oxygen species and the intrinsic mitochondrial pathway, and exerts its anti-tumor activity in vivo.

Chaetocin is a small-molecule natural product produced by Chaetomium species fungi, and it has a potent anti-proliferative pharmacological activity on various cancer cells. However, the effect of chaetocin on anti-melanoma pharmacological role has not been investigated. Therefore, in this study, we explored the effect of chaetocin on cell proliferation in the human melanoma Sk-Mel-28 and A375 cells and the growth of tumor xenografts in nude mice. The results indicated that chaetocin treatment significantly suppressed cell proliferation and induced apoptosis in the Sk-Mel-28 and A375 cells in a dose- and time-dependent manner. Furthermore, chaetocin treatment resulted in an increased level of cellular reactive oxygen species (ROS), and pre-incubation of cells with N-acetylcysteine (NAC) significantly abrogated chaetocin-induced apoptosis in the melanoma cells. A significant reduction of mitochondrial membrane potential and the release of cytochrome c were observed after chaetocin treatment. Additionally, chaetocin treatment significantly up-regulated the protein levels of Bax, cleaved caspase-9/-3, simultaneously down-regulated the protein levels of Bcl-2, procaspase-9/-3, and activated caspase-9/-3 activity in the melanoma cells. The in vivo data demonstrated that chaetocin treatment significantly inhibited the growth of melanoma tumor xenografts in nude mice, which was closely associated with apoptosis induction, a reduced level of PCNA (proliferating cell nuclear antigen) expression, and activation of capase-9/-3 in tumor xenografts. These are the first data to demonstrate that chaetocin exerts a proapoptotic activity on human melanoma cells through ROS generation and the intrinsic mitochondrial pathway. Therefore, chaetocin might represent an effective candidate for melanoma chemotherapy.

[Advanced orbicularis oculi muscle flap for eyelid defect].

OBJECTIVE: To investigate the application and therapeutic effect of advanced orbicularis oculi muscle (OOM ) flap for eyelid defect. METHODS: Uni-pedicle or bi-pedicle advanced OOM flaps were designed according to the location, depth and size of the eyelid defects. The resulted wounds in the donor sites were closed directly. The flap size ranged from 1.5 cm x 0.5 cm - 6.0 cm x 3.5 cm. RESULTS: 120 cases were treated. All the flaps survived except for 3 flaps with epidermis necrosis at the end of flaps, which healed after dressing. The patients were followed up for 3 -36 months with inconspicious scar in donor sites. The flap color, texture had a good match with surrounding skin. CONCLUSIONS: The OOM flap is ideal for eyelid defect with reliable blood supply, satisfied color and texture. The wound at donor site can be closed directly with less morbidity.

Introduction of an easy technique for purification and injection of autogenous free fat parcels in correcting of facial contour deformities.

BACKGROUND: Facial contour deformities usually result from congenital abnormalities, trauma, and the aging process. All depressions in the face, including glabella wrinkles and mild retrogression of chins, fall in this category. Local injection of autogenous fat parcels has been introduced for correction of these facial deformities for almost 20 years. METHOD: Using common materials (gauzes and cotton sticks), a simple technique was used by us to purify syringe-suctioned fat parcels followed by a multilayered injection of the purified fat tissue into implantation sites to treat the facial contour deformities in 152 sites of 50 cases with successful outcomes. RESULTS: Thirty-nine sites in 17 cases were followed up from 13 months to 37 months (average, 22.8 months). The injected fat parcels deposited successfully and the increasing volume maintained well. The impact factors on the successful deposit of the injected fat parcels included the extent of mechanical injuries to the fat cells during liposuction and lipoinjection, application of the purification procedure, and postsurgery immobilization as well as the blood-nourishing situation of recipient sites. Postoperative complications included undercorrection, overcorrection, small fat mass, unevenness, or irregularity. CONCLUSION: The introduced purification and injection techniques provided a comparative simple and reliable method in facial recontouring treatment. The local volume could be increased successfully by means of controlling the influencing factors of fat parcel deposit.