Strategy of Out-Fold Double Eyelid Corrected Into In-Fold: Low Position Design, Direction Control Suture, and Fat Transfer.

BACKGROUND: Double eyelid surgery is a common but delicate cosmetic procedure in Asia. Because of the precise requirements and technical reasons, patients who received blepharoplasty may not satisfied with their out-fold crease. Some patients are born with unsatisfied out-fold double eyelids. The medial creases of double eyelid were higher than should be. OBJECTIVES: In this study, the authors developed a strategy to correct out-fold crease of double eyelid to in-fold to satisfy patients' requirements. METHODS: From January 2022 to May 2024, 102 patients (96 females and 6 males) were included in this retrospective analysis. Patients with out-fold double-eyelid inborn or obtained. The patients were divided into 3 groups: inborn out-fold double-eyelid, obtained double-eyelid with epicanthus, and obtained double-eyelid without epicanthus. The surgical strategy contained low position design, direction control suture, and fat transfer. Preoperative and postoperative images were collected, and patients' satisfaction and complications were evaluated. RESULTS: In total, 102 consecutive patients were included in this study, with an average follow-up of 11.9 months. Eleven patients had inborn out-fold creases, and 83 patients had out-fold creases with epicanthus after primitive blepharoplasty, and 8 patients had out-fold creases without epicanthus after primitive blepharoplasty. Ninety-six (94.12%) patients were satisfied with their results. Complications included narrow double eyelid width (n =1, 0.98%), asymmetric creases (n=2, 1.96%), incompletely in-fold creases (n=3, 2.94%), and subtle fork in medial creases (n=4, 3.92%). CONCLUSIONS: The surgical strategy, which contained low-position design, direction control suture, and fat transfer, could correct out-fold creases of double-eyelid into in-fold effectively.

Dopaminergic and anti-estrogenic responses in juvenile steelhead (Oncorhynchus mykiss) exposed to bifenthrin.

The frequency of detection and concentrations of bifenthrin, a pyrethroid insecticide, in the waterways inhabited by the endangered species, steelhead trout (Oncorhynchus mykiss), has become a significant concern for regulatory agencies. Endocrine disruption has been observed with estrogenic and anti-estrogenic responses in fish species at different life stages. Since several studies have indicated alterations in dopaminergic signaling associated with endocrine responses, juvenile steelhead were exposed to environmentally relevant concentrations of 60 or 120 ng/L bifenthrin for two weeks. Fish brains were assessed for dopamine levels and the expression of genes involved in dopaminergic and estrogenic processes, such as catechol-o-methyltransferase (comt) and monoamine oxidase (mao). Vitellogenin (vtg) and estrogenic receptors (ERα1, ERß1, and ERß2) were also evaluated in livers of the animals. Dopamine concentrations were significantly higher in fish brains following bifenthrin exposure. Consistent with a reduction in dopamine clearance, there was a significant decrease in the mRNA expression of comt with increased bifenthrin concentration. Hepatic expression of ERα1 and ERß2 mRNA was significantly decreased with increased bifenthrin concentration. These data support the possible mechanism of bifenthrin altering the dopaminergic pathway at low ng/L concentrations, in juvenile steelhead, which could interfere with endocrine feedback loops. These findings support the need for and importance of identifying species and life stage differences in pesticide modes of action to reduce uncertainties in risk assessments.

N-nitrosamines induced gender-dimorphic effects on infant rats at environmental levels.

The safety of drinking water has always been a concern for people all over the world. N-nitrosamines (NAs), a kind of nitrogenous disinfection by-products (N-DBPs), are generally detected as a mixture in drinking water at home and abroad. Studies have shown that individual NAs posed strong carcinogenicity at high concentrations. However, health risks of NAs at environmental levels (concentrations in drinking water) are still unclear. Therefore, the potential health risks of environmentally relevant NAs exposure in drinking water needs to be conducted. In this study, blood biochemical analysis and metabolomics based on nuclear magnetic resonance (NMR) were performed to comprehensively investigate NAs induced metabolic disturbance in infant rats at environmental levels. Results of blood biochemical indices analysis indicated that AST in the serum of male rats in NAs-treated group exhibited a significant gender-specific difference. Multivariate statistics showed that two and eight significantly disturbed metabolic pathways were identified in the serum samples of NAs-treated male and female rats, respectively. In the urine samples of NAs-treated female rats, glycine, serine, and threonine metabolism pathway was significantly disturbed; while three significantly disturbed metabolic pathways were found in the urine of NAs-treated male rats. Finally, results of spearman correlation coefficients suggested that the disturbances of metabolism profile in serum and urine were correlated with changes in the gut microbiota (data derived from our published paper). Data presented here aimed to generate new health risk data of NAs mixture exposure at environmental levels and provide theoretical support for drinking water safety management. ENVIRONMENTAL IMPLICATION: N-nitrosamines (NAs) are a kind of nitrogenous disinfection by-products (N-DBPs) generated during drinking water disinfection processes. Herein, health risks of NAs at environmental levels (concentrations in drinking water) are investigated using blood biochemical analysis and nuclear magnetic resonance (NMR)-based metabolomics. Results confirmed NAs induced gender-specific on the metabolism in rat and the disturbances of metabolism profile in serum and urine were correlated with changes in the gut microbiota. Data presented here aimed to generate new health risk data of NAs mixture exposure at environmental levels and provide theoretical support for drinking water safety management.

Comparing the enantioselective toxicity on cell cycle and apoptosis of DL-glufosinate and L-glufosinate to SH-SY5Y cells.

Glufosinate (Glu), a broad-spectrum and highly effective non-selective herbicide, behaves in typical chiral features to target organisms. However, the information on the enantioselective toxicity of DL-Glu and L-Glu against non-target organisms is still limited especially at environmental concentrations. In this study, we investigated the potential mechanism accounting for the enantioselective cytotoxicity of Glu based on cell cycle and apoptosis. Results showed that DL-Glu and L-Glu had no suppression on cell viability at 10-5 M, however, SH-SY5Y cells were significantly arrested at G1/G0 phase after L-Glu exposure compared with DL-Glu. The apoptosis assay exhibited an increase in late apoptosis cells and a decrease in viable cells for DL-Glu and L-Glu treatment. The bioinformatics analysis demonstrated that alterations in transcription translation and signal transduction including "calcium signaling pathway", "Wnt signaling pathway", "FoxO signaling pathway" were the possible pathways responsible for Glu-induced enantioselectivity in cell cycle and apoptosis. Interestingly, the Gene Set Enrichment Analysis (GSEA) also revealed the probable association between DL-Glu exposure and degenerative diseases. These findings serve as a reminder that caution should be exercised not only when using pesticide racemates but also when promoting or applying single- or enriched-isomer pesticides.

Quantifying stiffness and forces of tumor colonies and embryos using a magnetic microrobot.

Stiffness and forces are two fundamental quantities essential to living cells and tissues. However, it has been a challenge to quantify both 3D traction forces and stiffness (or modulus) using the same probe in vivo. Here, we describe an approach that overcomes this challenge by creating a magnetic microrobot probe with controllable functionality. Biocompatible ferromagnetic cobalt-platinum microcrosses were fabricated, and each microcross (about 30 micrometers) was trapped inside an arginine-glycine-apartic acid-conjugated stiff poly(ethylene glycol) (PEG) round microgel (about 50 micrometers) using a microfluidic device. The stiff magnetic microrobot was seeded inside a cell colony and acted as a stiffness probe by rigidly rotating in response to an oscillatory magnetic field. Then, brief episodes of ultraviolet light exposure were applied to dynamically photodegrade and soften the fluorescent nanoparticle-embedded PEG microgel, whose deformation and 3D traction forces were quantified. Using the microrobot probe, we show that malignant tumor-repopulating cell colonies altered their modulus but not traction forces in response to different 3D substrate elasticities. Stiffness and 3D traction forces were measured, and both normal and shear traction force oscillations were observed in zebrafish embryos from blastula to gastrula. Mouse embryos generated larger tensile and compressive traction force oscillations than shear traction force oscillations during blastocyst. The microrobot probe with controllable functionality via magnetic fields could potentially be useful for studying the mechanoregulation of cells, tissues, and embryos.

Enantioselectivity in the toxicological effects of chiral pesticides: A review.

As a special category of pesticides, chiral pesticides have increased the difficulty in investigating pesticide toxicity. Based on their usage, chiral pesticides can be divided into insecticides, herbicides, and fungicides. Over the past decades, great efforts have been made on elucidating their toxicological effects. However, no literature has reviewed the enantioselective toxicity of chiral pesticides since 2014. In recent years, more chiral pesticides have been registered for application. As such, huge research progresses have been achieved in enantioselective toxicity of chiral pesticides. Generally, more researches have remedied the knowledge gap in toxicological effects of old and new chiral pesticides. And the toxicological endpoints being evaluated have become more specific rather than centering on basic toxicity and target organisms. Besides, the underlying mechanisms accounting for the enantioselectivity in toxicological effects of chiral pesticides have been discussed as well. All in all, this review provides the critical knowledge for risk assessments, and help to drive the green-technology of single- or enriched-enantiomer pesticides and formulation of relevant laws and regulations.

Triticonazole enantiomers induced enantioselective metabolic phenotypes in Fusarium graminearum and HepG2 cells.

The management of Fusarium head blight relies heavily on triazole fungicides. Most of triazole fungicides are chiral, and their enantioselective effects on metabolic phenotypes are poorly understood. Herein, we analyzed the bioactivity of triticonazole against Fusarium graminearum, and 1H-nuclear magnetic resonance-based metabolomics was used to assess the metabolic disturbances of triticonazole enantiomers in Fusarium graminearum and human hepatocarcinoma cells. Results indicated that the bioactivity of R-triticonazole was 4.28-fold higher than its antipode since it bound stronger with fungal CYP51B and induced more abnormal metabolic processes of Fusarium graminearum, including lipid metabolism, glycolysis, and amino acid metabolism. In human hepatocarcinoma cells, pathways of "alanine, aspartic acid and glutamate metabolism" and "pyruvate metabolism" were disturbed significantly by R-triticonazole; "phenylalanine metabolism" and "taurine-hypotaurine metabolism" were abnormal in the exposure of S-triticonazole. These results suggested that R- and S-triticonazole could affect different metabolic pathways of human hepatocarcinoma cells, and the massively use of inefficient S-triticonazole should be avoided. Our data will help to better understand the enantioselectivity of chiral pesticides and provide a reference for the development of green pesticides.

Ear Reconstruction with the Combination of Expanded Skin Flap and Medpor Framework: 20 Years of Experience in a Single Center.

BACKGROUND: In ear reconstruction, the difficulty lies in reestablishing the ear's bionic form with adequate skin coverage and an appropriate framework. Skin expansion and a porous polyethylene (i.e., Medpor) framework are often used for ear reconstruction. However, a long-term review of the combined application of the expanded skin and Medpor framework has not been reported. This article reviews ear reconstruction combining these two factors over the past 20 years in the authors' center to summarize the surgical technique and analyze the postoperative results and complications. METHODS: A retrospective review was performed that included all patients who underwent ear reconstruction with expanded skin and Medpor framework in the authors' center between 1998 and 2018. RESULTS: A total of 68 patients with microtia who were admitted to the authors' center for surgical ear reconstruction were included, and 70 ears were reconstructed. Fifty-seven of the patients (83.82 percent) felt satisfied with their reconstructed ear, five patients (7.35 percent) were not satisfied with the reconstructed ear, and six patients (8.82 percent) had the frameworks removed. Fifteen patients (22.06 percent) developed complications, including framework exposure (13.24 percent), infection (4.41 percent), scar hypertrophy (4.41 percent), and hematoma (2.94 percent). CONCLUSIONS: Framework exposure limits the combined application of expanded skin flap and Medpor framework when reconstructing the ear without additional fascial interposition. Using a temporoparietal fascia or postauricular fascia flap during the operation is effective to decrease the exposure rate; however, this complication cannot be completely avoided. Using postauricular fascia and skin graft may lead to scar hypertrophy; thus, these techniques should be used with caution. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Four cypermethrin isomers induced stereoselective metabolism in H295R cells.

Cypermethrin (CP) is widely used for controlling agricultural and indoor vermin. Previous studies have reported the stereoselective difference of CP in biological activities. However, little is known about their potential mechanisms between metabolic phenotypes and endocrine-disrupting effects. Herein, nuclear magnetic resonance (NMR)-based metabolomics combining metabolite identification and pathway analysis were applied to evaluate the stereoselective metabolic cdisorders induced by CP isomers in human adrenocortical carcinoma cells (H295R) culture medium. Then, gene expression levels related to disturbed metabolic pathways were assessed to verify according to metabolic phenotypes. Metabolomics profiles showed that [(S)-cyano(3-phenoxyphenyl)methyl](1R,3R)-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate [(1R,3R,αS)-CP] induced the most significant changes in metabolic phenotypes than did the other stereoisomers. There are 10 differential metabolites (isoleucine, valine, leucine, ethanol, alanine, acetate, aspartate, arginine, lactate, and glucose) as well as two significantly disturbed pathways, including "pyruvate metabolism" and "alanine, aspartate, and glutamate metabolism," that were confirmed in H295R cells culture medium of (1R,3R,αS)-CP compared with other stereoisomers. Polymerase chain reaction (PCR) array also confirmed the results of metabolomics. Our results can help to understand the potential mechanisms between the isomer selectivity in metabolic phenotypes and endocrine-disrupting effects. Data provided here not only lend authenticity to the cautions issued by the scientists and researchers but also offer a solution for the balance between environment and political regulations.

Assessment of endocrine-disrupting effects of emerging polyhalogenated carbazoles (PHCZs): In vitro, in silico, and in vivo evidence.

Polyhalogenated carbazoles (PHCZs) are an emerging class of persistent, bioaccumulative compounds that are structurally and chemically related to dioxins. They have been detected widely in sediment, river, and soil samples, but their environmental risks are largely unknown. Therefore, seven common PHCZs were tested for their endocrine disrupting potential in silico, in vitro, and in vivo. A dual-luciferase reporter gene assay was used to detect receptor-mediated (agonist or antagonistic) activity (concentration range: 10-9-10-5 M) against the estrogen receptor α (ERα), glucocorticoid receptor α (GRα), and mineralocorticoid receptor (MR). The alterations in the steroidogenesis pathway were investigated in H295R cells. Antagonistic effects against GRα were observed with five PHCZs, along with an increase in the cortisol levels of H295R cells. The most common effect observed was that of the agonistic activity of ERα, with the molecular docking analysis further indicating that hydrogen bonding and hydrophobic interactions may stabilize the interaction between PHCZs and the estrogen receptor binding pocket. In addition, a seven-day exposure of young female rats to three PHCZs (27-BCZ, 3-BCZ, and 36-BCZ) resulted in changes in serum E2 levels, uterine epithelium cell heights, and relative uterus weights. In conclusion, endocrine-disrupting effects, especially the estrogenic effects, were observed for the tested PHCZs. Such adverse effects of PHCZs on humans and wildlife warrant further thorough investigation.

Metabolomic modulations of HepG2 cells exposed to bisphenol analogues.

Bisphenol analogues including bisphenol A (BPA), bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS) share similar chemical structures and endocrine disrupting effects. Their effects on metabolisms, however, are so far only marginally understood. In this study, NMR-based metabonomic profiles of HepG2 cell culture media and PCR array were used to assess the metabolomics disturbances and gene expression levels of HepG2 in response to four BPs (BPA, BPAF, BPF, and BPS). The results indicated that BP analogues resulted in disturbances in 7-15 metabolites that were classified as amino acid (alanine, glutamine, glutamate), intermediates and end-products in the glycolysis (pyruvate) and the tricarboxylic acid cycle (acetate, lactate). Their rank in order according to the number of metabolites and pathways was BPF > BPA > BPAF > BPS. The common disrupted pathways (pyruvate metabolism; alanine, aspartate, and glutamate metabolism) indicated enhanced glycolysis. The following glucometabolic PCR array analysis suggested that although four BPs shared the capability of disrupting glucose metabolism, they may act through different mechanisms: BPAF has increased the pyruvate kinase (PKLR) expression level, which implied enhanced glycolysis that was agreed with NMR results. The other three BP analogues, however, decreased the expression level of glucokinase (GCK) that indicated glucose sensing impairment. Our results demonstrated the potential for using metabolomic and PCR array to understand the underlying action of mechanisms and identify the potential targets for future targeted risk assessment.

Enantioselectivity in endocrine disrupting effects of four cypermethrin enantiomers based on in vitro models.

Cypermethrin (CP) is a kind of chiral pesticides that has been defined as endocrine disrupting chemical. The diversity in bioactivity, toxicity, metabolism, bioaccumulation, and degradation behaviors of CP enantiomers as well as the research deficiency had made the risk assessment of CP enantiomers very complicated. Herein, four CP enantiomers were separated as target chemicals to investigate their enantioselective endocrine disrupting effects. Firstly, dual-luciferase reporter gene assays were adopted to investigate their potential endocrine disrupting effects via various receptors. The expression levels of steroid hormones related genes and hormone secretion levels in H295R cell were measured to verify the results. Results from the reporter gene assay showed that 1R-cis-αS-CP (CP11) exhibited glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and thyroid receptor (TR) antagonistic activity with the RIC20 values of 9.22 × 10-7, 3.33 × 10-7, and 4.47 × 10-7 M, respectively; 1R-trans-αS-CP (CP21) also showed androgen receptor (AR) agonist activity and estrogen receptor (ER) antagonistic activity with the REC20 and RIC20 values were 1.07 × 10-4 M and 4.78 × 10-6 M, respectively. Results of qRT-PCR and hormone measurement also showed that CP11 and CP21 could disturb the expression of steroid hormones related genes and hormone secretion accordingly. Results provided here can help to understand the enantioselective ecological and health risks of CP enantiomers comprehensively and provide constructive guidance for the safe use of chiral pesticides and the invention of green pesticides.

Reconstruction of a Giant Wound Induced by Advanced Penile Carcinoma with Bilateral Anteromedial Thigh Flap and Left Deep Circumflex Iliac Artery Flaps.

A 39-year-old male patient presented with an extensive putrescent ulceration of abdominoperineal region infiltrated by advanced penile squamous cell carcinoma. To our knowledge, it is the largest defect after aggressive palliative resection of penile squamous cell carcinoma (pSCC) in the literature, which was 36×23 cm. The defect was divided into three sub-defects, and was repaired by bilateral anteromedial thigh (AMT) and left deep circumflex iliac artery (DCIA) flaps. The postoperative course was uneventful and no flap necrosis occurred. The symptom relief was excellent.

The Aesthetic Analyzing of Midface Ratio After Folding Aponeurosis of Levator Palpebrae Superioris Muscle in the Ptosis Correction.

BACKGROUND: Some fordless-eyelid patients with moderate upper lid ptosis characterize in a higher eyebrow position which leads to an increased midfacial ratio. Apart from performing blepharoplasty to create dynamic folds, additional procedures such as folding aponeurosis of levator palpebrae superioris muscle were effective to revise the enlarged ratio of midface through lowering eyebrow, which gains good aesthetic results. However, the specific changes in the proportion of facial aesthetics and the importance of these change were serious lack in the literature as far as the authors know. PURPOSE: To measure the ratio of the length between upper edge of eyebrow and edge of lower eyelid (L1)/the length between edge of lower eyelid and nasal base (L2) in the fordless-eyelid and upper lid ptosis patients who received levator aponeurosis folding surgery, and to analyze the change in the proportion of midfacial aesthetics. METHOD: From December 2015 to October 2016, the pre- and postoperative photographs from 21 cases of patients with foldless eyelid and upper lid ptosis who underwent the levator aponeurosis folding procedures in the authors' department were collected as study group. Additional full-face pictures of 20 Chinese female movie stars were prepared as control group. The ratios of L1/ L2 (J) were measured via Adobe Photoshop CS6. The statistical significance was analyzed and the change of midfacial proportion was evaluated. RESULT: In the study group, the mean value of preoperative L1/L2 (J1) is 0.746, and (J2) 0.657 postoperatively. In the control group, the mean value of L1/L2 (J3) is 0.667. Statistical differences showed between the pre- and postoperative samples and between preoperative samples and control group. There was no statistical difference between postoperative samples and control group samples. The ratios between L1 and L2 in postoperative samples are close to those in the control group, which are closer to the golden radio. CONCLUSION: Levator aponeurosis folding can effectively lower eyebrow in patients with upper lid ptosis, shortening the length between eyebrow and lower eyelid, and therefore harvesting a more appropriate and harmonious ratio of L1/ L2 according to the golden section theory. The changes in the proportion of midfacial aesthetics after operation could be used as a key point in the preoperative communication and postoperative effect evaluation, besides the size of palpebral fissure and corneal exposure rate.

A comparative study of surgical outcomes using a Colorado microdissection needle versus standard-size needle electrocautery in one-stage hypospadias repair using a transverse preputial island flap.

BACKGROUND: The purpose of this study was to compare the surgical outcomes of a Colorado microdissection needle (CMN) with that of a standard-size electrocautery needle in one-stage hypospadias repair using a transverse preputial island flap (TPIF). METHODS: The records of patients who received hypospadias repair from September 2012 to October 2013 were retrospectively reviewed. Patients were divided into a group that received repair using a CMN and those in which a standard-size electrocautery needle was used. Data collected and compared included age, types of hypospadias, duration of surgery, intraoperative blood loss, and postoperative edema and complications. RESULTS: There were 51 patients in the CMN group and 44 in the standard needle group, and the groups were similar with respect to age and type of hypospadias. The median surgery time for the CMN group was significantly shorter than that of the standard group (15.7 minutes vs. 20.6 minutes, respectively, P<0.001). At postoperative day 7 and day 30, the CMN group had significantly less patients with edema than the standard needle group (31.4% vs. 65.9%, P<0.01; and 37.3% vs. 79.5%, P<0.001, respectively). The overall complication rate has no significant difference between two groups. CONCLUSIONS: The use of CMN for tissue dissection and separation in hypospadias repair can facilitate foreskin degloving, shape the flap in a more efficient way, and help maintain adequate blood supply for the new urethra and its skin coverage.

Multiple pedicled flaps cover for large defects following resection of malignant tumors with partition concept.

Large defects after skin malignant tumors resection were difficult to repair. We introduced a partition concept, in which the large defects were divided into several subunits, and each subunit was repaired by a certain pedicled flap to achieve a complete coverage.Between May 2012 and Oct 2016, 8 patients with skin malignant tumors underwent radical resection. Prior to surgery, the dimension of the potential defect after tumor ablation was estimated and outlined. After evaluation, the partition concept was applied and the defects were divided into several subunits. Also, the rationality of the choice of pedicled flap was evaluated. Each flap was used to cover its specific subunits defect.After excision, the defect areas were from 13 × 17 cm to 36 × 23 cm. Each subunit was designed to be repaired with a pedicled flap, which included local random flap, superficial iliac artery flap, transverse rectus abdominis myocutaneous (TRAM) flap, lateral thoracic advanced island flap, anterolateral thigh (ALT) flap, anteromedial thigh (AMT) flap, and deep circumflex iliac artery (DCIA) flap. Primary closure of both donor and recipient sites was achieved in all patients. All the flaps survived. Flap necrosis was not observed.Reconstruction of large defects following resection of malignant tumors with multiple pedicled flaps was a reliable method. The partition concept is useful in the reconstruction of large tumor wounds in 1-stage operation.

Application for MEDPOR Surgical Implant in Modified Penile Elongation: Review of 19 Cases.

OBJECTIVE: To investigate the application of MEDPOR surgical implant in modified penile elongation. METHODS: The suspensory ligaments were divided, and cavernous bodies of crus were partially mobilized, so as to release part of the cavernous bodies from inferior ramus of pubis. Then, the penis was elongated sufficiently. MEDPOR surgical implants (MEDPOR; high-density porous polyethylene, Howmedica Osteonics Corp. Newnan, Ga) were inserted between the cavernous bodies and pubic symphysis. Local fat flap was transposed to fill the front space of pubis to make sure of the effective elongation of penis and improve the appearance of mons pubis. RESULTS: Nineteen cases of micropenis were treated. The average length of the penis was 5.23 cm in the static state and 7.83 cm in erectile state before operation. After the operation, it increased to 8.63 cm in the static state and 11.36 cm in erectile state. CONCLUSIONS: Application for MEDPOR surgical implant in modified penile elongation can make sure of the effective elongation of penis and improve the appearance of mons pubis.

The identification of the metabolites of chlorothalonil in zebrafish (Danio rerio) and their embryo toxicity and endocrine effects at environmentally relevant levels.

Chlorothalonil is a broad spectrum fungicide with high annual production and environmental contamination. Despite its high consumption, studies regarding the potential ecological risks of chlorothalonil, especially its metabolites, to aquatic organisms are still limited. In this study, we selected the zebrafish (Danio rerio) as the in vivo model and first identified the metabolite (4-hydroxychlorothalonil) of chlorothalonil in zebrafish by tandem quadrupole/orthogonal-acceleration time-of-flight (Q-TOF). Then, the in vivo and in vitro models were applied to comprehensively estimate the embryo toxicity and potential endocrine effect of chlorothalonil and 4-hydroxychlorothalonil. The data from zebrafish embryo toxicity showed that the lowest observed effect concentrations of both chlorothalonil and 4-hydroxychlorothalonil were 50 µg/L after 96 h of exposure. The mortality rate of the 4-hydroxychlorothalonil was 2.6-fold higher than that of the parent compound at the concentration of 50 µg/L. Dual-luciferase reporter gene assays indicated that both chlorothalonil and 4-hydroxychlorothalonil exerted estrogen receptor α (ERα) agonist activity with REC20 values of 2.4 × 10-8 M and 3.6 × 10-8 M, respectively. However, only 4-hydroxychlorothalonil exhibited both thyroid receptor ß (TRß) agonistic and antagonistic activities. Lastly, we employed molecular docking to predict the binding affinity of chlorothalonil and 4-hydroxychlorothalonil with ERα or TRß. The results revealed that the potential endocrine effect of chlorothalonil and 4-hydroxychlorothaloni might be attributed to the different binding affinities with the receptors. In conclusion, our studies revealed that 4-hydroxychlorothalonil exhibited potent endocrine-disrupting effects compared to its parent compound, chlorothalonil. The results provided here remind us that the assessment of the potential ecological and health risks of the metabolites of fungicides in addition to their parent compounds should arouse great concerns.

Treatment of nasal ala nodular congenital melanocytic naevus with carbon dioxide laser and Q-switched Nd:YAG laser.

Total excision of congenital melanocytic nevi (CMN) is not always feasible. We here present our experience of using carbon dioxide laser and Q-switched neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser to treat nodular CMN of the nasal ala. Q-switched Nd:YAG laser and/or carbon dioxide laser were used to treat eight cases of nasal ala nodular CMN. Carbon dioxide laser was utilized to ablate all visible melanocytic tissue within one session. Ablation was performed so as to reproduce the original anatomical contours as closely as possible. Recurrences were treated in the same way. Q-switched Nd:YAG laser was also used to irradiate all target lesions to achieve the desired end point within one session. The intervals between treatments were at least 8 weeks. Recurrence of melanocytic tissue, scar formation, pigmentation, depigmentation, and the degree of patient satisfaction were recorded at every visit. Two of the eight patients were treated with Q-switched Nd:YAG laser. Although, the lesion lightened in one of them, the hyperplastic tissue persisted. Eventually, these two patients, along with the remaining six patients, were successfully treated with a carbon dioxide laser. We recommend carbon dioxide laser treatment for nodular nasal CMN. This simple treatment does not involve skin flap transplantation and has good cosmetic outcomes. Although Q-switched Nd:YAG laser does lighten some nasal nodular CMNs, it does not eradicate the hyperplastic tissue, and is therefore not an effective treatment for nodular nasal CMN.

Surgical Repair of Mid-shaft Hypospadias Using a Transverse Preputial Island Flap and Pedicled Dartos Flap Around Urethral Orifice.

OBJECT: To evaluate the effects, particularly the incidence of anastomotic fistula, of a pedicled dartos flap around the urethral orifice in the treatment of urethroplasty of mid-shaft hypospadias. METHODS: A total of 46 cases of congenital mid-shaft hypospadias were included in this study. The patients ranged in age from 0.7 to 25.4 years and the average was 5.8 years. The patients received penis chordee correction. A transverse preputial island flap was developed for urethral reconstruction. The proximal dartos of the urethral orifice was used to develop a pedicled dartos flap, which was transposed to cover and strengthen neourethral anastomosis. The ventral penile skin defect was repaired by another flap. RESULTS: The 46 patients were examined during follow-up visits for 6 months to 3 years. An anastomotic fistula was observed in one case (2.2 %). Scar healing without fistula was observed in another patient due to poor blood supply to part of the ventral penile skin. No other incidences of fistula, urethral rupture, flap necrosis, wound infections, urinary tract (meatal) stenosis, or urethral diverticulum were observed in the patients. CONCLUSION: A pedicled dartos flap around the urethral orifice can take advantage of well-vascularized local tissue to add a protective layer to the proximal aspect of the neourethral anastomosis for reducing the incidence of anastomotic fistula in mid-shaft hypospadias repair using a transverse preputial island flap. 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 .