Treatment of Facial Artery Embolization Caused by Polycaprolactone-based Dermal Filler with a Regimen Including 5-Fluorouracil.

Polycaprolactone-based fillers are commonly used in plastic surgery to improve facial aging. However, adverse vascular events following these injections have been reported. An arterial embolism is a rare but serious complication associated with injectable filler procedures. We report a case of arterial embolism in a 35-year-old woman who received a polycaprolactone-based dermal filler at the nasal base and was treated with a regimen containing 5-fluorouracil. We discuss the potential causes of the patient's condition and assess the superiority of our method over conventional approaches. Before treatment, ultrasound detected a decreased flow velocity in the patient's right medial canthus artery with distal hypoperfusion, which improved significantly posttreatment. Long-term follow-up revealed near-disappearance of facial scarring. Our treatment effectively addressed facial artery embolism without any reported adverse reactions.

Factors Influencing Bone Resorption after Augmentation Mentoplasty with Implants: A Retrospective Study Using Three-Dimensional Imaging.

BACKGROUND: Augmentation mentoplasty with implants is an extremely rewarding procedure. Bone resorption is almost unavoidable. The high-risk factors for chin bone resorption have not been explored in the past. This study aimed to analyze and evaluate the factors influencing bone resorption after augmentation mentoplasty with implants using three-dimensional imaging. METHODS: We retrospectively analyzed preoperative craniofacial Computed Tomography scan data from 105 patients who underwent mandibular implantation surgery and 108 patients who did not. We also examined the extent to which different factors influenced the occurrence of bone resorption in the chin area. RESULTS: Patients with silicone gel implants are more prone to bone resorption than those with Medpor implants. Patients who experienced bone resorption had thicker mentalis muscles than those who did not experience bone resorption (6.35 ± 1. mm vs. 5.73 ± 1.25 mm, P < 0.05), and thinner cortical bone (3.25 ± 1.65 mm vs. 5.22 ± 2.04 mm, P < 0.05). Additionally, implants placed above the mandibular bone were more likely to induce bone resorption than those placed below it. CONCLUSIONS: This study is the first to systematically reveal the impact of implant type, placement position, mentalis muscle thickness, and cortical bone thickness on bone resorption after chin augmentation surgery. For patients with thicker mentalis muscles and thinner cortical bones, greater attention should be paid to the occurrence of bone resorption. Choosing silicone implants or placing the implants higher on the mandible can help reduce the occurrence of bone resorption. This study can assist clinicians in selecting appropriate treatment methods, thereby reducing post-implantation bone resorption. LEVEL OF EVIDENCE III: 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.

Evaluation of the effect of chin prosthesis implantation on mentalis muscles based on three-dimensional imaging technology.

BACKGROUND: Chin prosthesis implantation, a cosmetic procedure to correct chin asymmetry, depression, or retraction, is generally safe and simple. However, its long-term effects on surrounding tissues are a concern. This study aimed to use three-dimensional (3D) scanning to classify the mentalis muscle shapes and assess the impact of prosthesis implantation on these muscles. METHOD: This study evaluated 450 eligible female participants. Using three-dimensional imaging, data on the types, thickness, width, and length of the left and right mentalis muscles were collected and summarized. The impact of chin prosthesis on these muscle dimensions was assessed using analysis of variance, and the effect on muscle type was determined using χ2 test. RESULTS: Chin implant placement affected the mentalis muscles, resulting in increased length, thickness, and width. The subjects' mentalis muscles were categorized into 3 types and divided into 7 subtypes. χ2 test results indicated that implantation influences the classification of these muscles. CONCLUSION: Recognizing how implant placement affects the mentalis muscle can guide the development of treatments to mitigate these changes. Additionally, understanding the muscle's morphology enables more precise treatment approaches for patients.

Glycopeptide-based multifunctional nanofibrous hydrogel that facilitates the healing of diabetic wounds infected with methicillin-resistant Staphylococcus aureus.

Diabetic wound management remains a significant challenge in clinical care due to bacterial infections, excessive inflammation, presence of excessive reactive oxygen species (ROS), and impaired angiogenesis. The use of multifunctional wound dressings has several advantages in diabetic wound healing. Moreover, the balance of macrophage polarization plays a crucial role in promoting skin regeneration. However, few studies have focused on the development of multifunctional wound dressings that can regulate the inflammatory microenvironment and promote diabetic wound healing. In this study, an extracellular matrix-inspired glycopeptide hydrogel composed of glucomannan and polypeptide was proposed for regulating the local microenvironment of diabetic wound sites. The hydrogel network, which was formed via Schiff base and hydrogen bonding interactions, effectively inhibited inflammation and promoted angiogenesis during wound healing. The hydrogels exhibited sufficient self-healing ability and had the potential to scavenge ROS and to activate the mannose receptor (MR), thereby inducing macrophage polarization toward the M2 phenotype. The experimental results confirm that the glycopeptide hydrogel is an effective tool for managing diabetic wounds by showing antibacterial, ROS scavenging, and anti-inflammatory effects, and promoting angiogenesis to facilitate wound repair and skin regeneration in vivo. STATEMENT OF SIGNIFICANCE: •The designed wound dressing combines the advantage of natural polysaccharide and polypeptide. •The hydrogel promotes M2-polarized macrophages, antibacterial, scavenges ROS, and angiogenesis. •The multifunctional glycopeptide hydrogel dressing could accelerating diabetic wound healing in vivo.

The Effects of Radial Cartilage Incision on the Growth of Rabbit Ear.

OBJECTIVES: Recently, radial cartilage incision (first-stage) at an early age combined with free auricular composite tissue grafting (second-stage) can effectively correct the concha-type microtia with the moderate or severe folded cartilage in the middle and upper third auricle, but radial cartilage incision's effects on the growth of the ear remain to be determined. The authors aimed to evaluate the effects of radial cartilage incision in young rabbits model. METHODS: Ten New Zealand white rabbits were included in our experiment. Two ears of each rabbit were divided randomly into two groups. The experimental group was operated with radial cartilage incision, and no intervention was given to the control group. The ear width, length, and perimeter were noted every two weeks. Auricular surface area was noted at 4 and 22 weeks old. The repeated measures ANOVA was used to describe ears' growth trend. A paired-sample's t test is conducted to test whether there are significant differences among the variables through the SPSS25.0 software. RESULTS: The growth tendencies of the ear length, width, and perimeter were observed and analyzed. The growth curves of the experimental ears were similar to that of the control. There was no significant difference in the increased ratio of surface area among the two groups. The cartilage of the experimental ears showed no change in biomechanical properties compared to that of control group. CONCLUSION: This study shows that radial cartilage incision at an early age does not influence the growth of rabbit ear length, width, perimeter, and surface area and also does not change the biomechanical properties of the cartilage. LEVEL OF EVIDENCE I: 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 .

Patient-specific iPSC-derived cardiomyocytes reveal variable phenotypic severity of Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is a cardiac channelopathy that can result in sudden cardiac death (SCD). SCN5A is the most frequent gene linked to BrS, but the genotype-phenotype correlations are not completely matched. Clinical phenotypes of a particular SCN5A variant may range from asymptomatic to SCD. Here, we used comparison of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) derived from a SCN5A mutation-positive (D356Y) BrS family with severely affected proband, asymptomatic mutation carriers (AMCs) and healthy controls to investigate this variation. METHODS: 26 iPSC lines were generated from skin fibroblasts using nonintegrated Sendai virus. The generated iPSCs were differentiated into cardiomyocytes using a monolayer-based differentiation protocol. FINDINGS: D356Y iPSC-CMs exhibited increased beat interval variability, slower depolarization, cardiac arrhythmias, defects of Na+ channel function and irregular Ca2+ signaling, when compared to controls. Importantly, the phenotype severity observed in AMC iPSC-CMs was milder than that of proband iPSC-CMs, an observation exacerbated by flecainide. Interestingly, the iPSC-CMs of the proband exhibited markedly decreased Ca2+ currents in comparison with control and AMC iPSC-CMs. CRISPR/Cas9-mediated genome editing to correct D356Y in proband iPSC-CMs effectively rescued the arrhythmic phenotype and restored Na+ and Ca2+ currents. Moreover, drug screening using established BrS iPSC-CM models demonstrated that quinidine and sotalol possessed antiarrhythmic effects in an individual-dependent manner. Clinically, venous and oral administration of calcium partially reduced the malignant arrhythmic events of the proband in mid-term follow-up. INTERPRETATION: Patient-specific and genome-edited iPSC-CMs can recapitulate the varying phenotypic severity of BrS. Our findings suggest that preservation of the Ca2+ currents might be a compensatory mechanism to resist arrhythmogenesis in BrS AMCs. FUNDING: National Key R&D Program of China (2017YFA0103700), National Natural Science Foundation of China (81922006, 81870175), Natural Science Foundation of Zhejiang Province (LD21H020001, LR15H020001), National Natural Science Foundation of China (81970269), Key Research and Development Program of Zhejiang Province (2019C03022) and Natural Science Foundation of Zhejiang Province (LY16H020002).

Generation of an induced pluripotent stem cell line (ZJULLi003-A) from a hypertrophic cardiomyopathy patient carrying MYH7/c.4384G > A mutation.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited cardiovascular disease characterized by left ventricular hypertrophy and cardiomyocyte disarray. In this study, a skin biopsy was obtained from a HCM patient, who carried a missense mutation (c.4384G > A; p.E1462K) in the myosin heavy chain 7 (MYH7) gene. The skin fibroblasts were subsequently reprogrammed with a non-integrated Sendai viral method to generate a patient-specific induced pluripotent stem cell (iPSC) line. The generated iPSC line showed typical morphology and normal karyotype, expressed pluripotency markers, and was capable to differentiate into three germ layers.

Generation of an induced pluripotent stem cell line from a long QT syndrome patient carrying KCNH2/1956C > A mutation.

Long QT syndrome (LQT) is an inherited primary arrhythmic disorder characterized by prolonged QT interval on the surface electrocardiogram and life-threatening arrhythmia. In this study, a skin biopsy was obtained from an LQT type 2 (LQT2) patient, who carried a nonsense mutation (c.1956C > A; p.Y652X) in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. The skin fibroblasts were reprogrammed by non-integrated Sendai viral method to generate a patient-specific induced pluripotent stem cell (iPSC) line. The generated iPSC line showed typical embryonic stem cell-like morphology, exhibited normal karyotype, expressed pluripotency markers, and was capable to differentiate into three germ layers.

[Research progress of clinical therapy for concha-type microtia].

OBJECTIVE: To summarize the current progress of clinical therapy for concha-type microtia. METHODS: The domestic and overseas literature about the treatment of concha-type microtia was reviewed and the contents of operative timing, operation selection, and complications were analyzed. RESULTS: The unified therapeutic schedule of the concha-type microtia has not yet been determined due to its complicated various therapeutic methods and unknown etiology. The operation methods commonly used in clinic are partial ear reconstruction with autologous costal cartilage framework and free composite tissue transplantation. The timing of the partial ear reconstruction depends on the development of costal cartilage and children's psychological healthy. The timing of free composite tissue transplantation depends on the severity. It is recommended to perform the operation at about 10 years old for mild patients. For moderate patients, ear cartilage stretching should be performed at 1-2 years old and free composite tissue transplantation would be performed at about 10 years old. The complications of partial ear reconstruction with autologous costal cartilage framework for concha-type microtia mainly include framework exposure, deformation, infection, cartilage absorption, and skin necrosis. The complications of free composite tissue transplantation have not been reported. CONCLUSION: Etiology and elaborated classifications with individualized treatment are the future research directions.

Human induced pluripotent stem cell-derived cardiomyocytes reveal abnormal TGFß signaling in type 2 diabetes mellitus.

Diabetes mellitus is a serious metabolic condition associated with a multitude of cardiovascular complications. Moreover, the prevalence of diabetes in heart failure populations is higher than that in control populations. However, the role of cardiomyocyte alterations in type 2 diabetes mellitus (T2DM) has not been well characterized and the underlying mechanisms remain elusive. In this study, two patients who were diagnosed as T2DM were recruited and patient-specific induced pluripotent stem cells (iPSCs) were generated from urine epithelial cells using nonintegrated Sendai virus. The iPSC lines derived from five healthy subjects were used as controls. All iPSCs were differentiated into cardiomyocytes (iPSC-CMs) using the monolayer-based differentiation protocol. T2DM iPSC-CMs exhibited various disease phenotypes, including cellular hypertrophy and lipid accumulation. Moreover, T2DM iPSC-CMs exhibited higher susceptibility to high-glucose/high-lipid challenge than control iPSC-CMs, manifesting an increase in apoptosis. RNA-Sequencing analysis revealed a differential transcriptome profile and abnormal activation of TGFß signaling pathway in T2DM iPSC-CMs. We went on to show that inhibition of TGFß significantly rescued the hypertrophic phenotype in T2DM iPSC-CMs. In conclusion, we demonstrate that the iPSC-CM model is able to recapitulate cellular phenotype of T2DM. Our results indicate that iPSC-CMs can therefore serve as a suitable model for investigating molecular mechanisms underlying diabetic cardiomyopathies and for screening therapeutic drugs.

[Anthropometric measurements of moderate concha-type microtia after auricular cartilage unfolding].

OBJECTIVE: To explore the anthropometric changes of the auricle after auricular cartilage unfolding in moderate concha-type microtia patients, so as to provide the basis to help evaluate surgical timing and prognostic. METHODS: A total of 33 children with moderate concha-type microtia, who were treated with auricular cartilage unfolding between October 2016 and September 2018 and met the inclusive criteria, were included in the study. There were 24 boys and 9 girls with an average age of 1.4 years (range, 1-3 years). Sixteen cases were left ears and 17 cases were right ears. The follow-up time was 12-23 months (mean, 17.5 months). The affected auricular detailed structures were observed and quantitatively analyzed before operation and at immediate after operation. The width, length, and perimeter of auricle before operation and at immediate after operation and at last follow-up were noted with three dimensional-scanning technology. The normal auricle was noted as control. RESULTS: There were (7.5±1.0) and (11.3±0.8) structures of the affected auricle at pre- and post-operation, respectively, showing significant difference between pre- and post-operation ( t=23.279, P=0.000). The length, width, and perimeter of the affected auricle constantly increased after operation, and there were significant differences between pre-operation and immediately after operation and between immediately after operation and last follow-up ( P<0.05). The differences of length, width, and perimeter of the affected auricle between immediately after operation and last follow-up were (3.13±1.44), (2.44±0.92), and (8.50±3.76) mm, respectively. And the differences of length, width, and perimeter of the normal auricle between pre-operation and last follow-up were (3.16±1.54), (2.35±0.86), and (9.79±4.60) mm, respectively. There was no significant difference in the differences of length, width, and perimeter between the affected auricle and the normal auricle ( P>0.05). CONCLUSION: The auricular cartilage unfolding in treatment of the moderate concha-type microtia can receive more ear structures and increase auricle sizes, which make it possible for free composite tissue transplantation. In addition, the affected and the contralateral normal auricles have a very similar growth rate and it offers the theoretical foundation for the early treatment for moderate concha-type microtia.

Classification of the concha-type microtia and their new suitable treatment strategies without autogenous costal cartilage grafting.

OBJECTIVE: Numerous corrective methods have been successfully applied in concha-type microtia reconstruction over the past several decades, and autogenous rib cartilage grafting has become a routine technique in a two or three-stage operation. However, it still remains a challenge due to the effective use of the large volume of the remnant cartilage and skin involved. The objective of this study was to clarify how this remnant cartilage and skin could be manipulated for new suitable treatment strategies without autogenous costal cartilage grafting. METHODS: A total of 424 patients with concha-type microtia operated at our Center from January of 2012 to June of 2019 have been reviewed and analyzed cases. At the same time, a classification system for grading the severity of concha-type microtia was created on the basis of anatomical findings and ear size. RESULTS: A total of 436 ear cases (involving 424 patients), showing concha-type microtia, were included in our study and reviewed through medical records, photographs, analysis of surgical methods, and postoperative outcomes. The concha-type microtia were classified into four graded types: Grade I (n = 151), Grade II (n = 101), Grade III (n = 93), and Grade IV (n = 79). A total of 352 ears in 345 patients with Grade I to III concha-type microtia were followed up for 1 month to 7 years (average, 14.7 months). 329 patients (95.4%) were satisfied with the aesthetic outcomes of the corrected ear. CONCLUSIONS: Individual corrective methods and aesthetic outcomes for patients with Grade I to III of deformity were described in this study. The authors present new suitable approaches according to a progressive classification system which provide conservative and individualized methods of treatment in early stages of life.

[Preliminary study on microdissection needle-assisted ear cartilage reshaping in vivo rabbit models].

OBJECTIVE: To preliminarily investigate morghological changes of rabbits reshaping ear cartilage assisted by microdissection needle and explore feasibility of new therapy for ear deformity. METHODS: The bilateral ears of 5 male New Zealand rabbits (aged, 5-6 months) were fixed maintaining the curvature and randomly divided into 2 groups (5 ears in each group). The ears were stimulated by microdissection needle in experimental group and were not treated with stimulation in control group. The skin reaction in the experimental group was observed immediately and at 4 weeks after stimulation. Then, the fixtures were removed at 4 weeks, and the shapes of the ears were observed. The cartilages were harvested from the ears to examined morphological changes after HE staining, and measured the chondrocyte layer thickness. RESULTS: All rabbits survived until the end of the experiment. The skin has healed completely after 4 weeks in experimental group. After removing fixtures, the ears in the two groups all maintained certain forms momentarily; while 24 hours later, the ears in the control group mostly recovered original form, and the ears in the experimental group still maintained certain molding form until 8 weeks. HE staining showed there were smooth cartilage and uniform distribution of cells in the control group; the matrix staining was basically consistent; and the skin was normal appearance with epidermis, dermis, and cartilage of normal aspect. But the proliferation of chondrocyte with more layers of cells were observed in the experimental group. In addition, there were degeneration and injury of cartilage cells and connective tissue with necrotic cells and inflammatory cells at needle insertion sites. The chondrocyte layer thickness was (385.714±2.027) µm in the control group and (1 594.732±1.872) µm in the experimental group, there was significant difference between the two groups ( t=-759.059, P=0.000). CONCLUSION: Rabbit ear cartilage can be effectively reshaped by microdissection needle. Proliferation of chondrocyte and changes in matrix can be found during the reshaping process.

Preliminary Analysis on Characteristics of Rib Cartilage Calcification in Patients With Congenital Microtia.

Autogenous rib cartilage graft procedure for microtia reconstruction has been adopted as the most standardized current method. But calcification would make it difficult for cartilage harvesting and ear framework sculpting. The objective of this study was to explore the rate, degree, and pattern of rib cartilage calcification in microtia and to guide rib cartilage harvesting and the optimal timing of auricular reconstruction. A retrospective study was performed with the imaging data from 320 consecutive patients who received a preoperative 3-dimensional chest computed tomography (CT). Overall, calcification rate of cartilages in female patients was higher than male's (P < 0.05). In 6 to 15 years group, calcification rates of male and female had a similar rate, while female's were higher than male's in other 3 groups. Furthermore, the moderate-to-severe calcification rate was higher in female than in male patients (P < 0.001). Therefore, girls who are over 15 years should be paid more attention regarding the possibility of moderate-to-severe calcification; these patients should take CT examinations if necessary. Calcification rate of the youngest group (6-15 years) was the lowest of all groups, while other 3 groups showed no statistical significance (P > 0.05). So merely the age increasing is not the contradiction for cartilage harvesting, as long as the authors effectively evaluate the condition of rib cartilage before operation. Rib cartilages serve as the key material in auricular framework sculpting and determine the feasibility and outcomes of the surgery. So CT examinations for preoperative evaluation of rib cartilage could be a useful method for planning microtia reconstruction.

The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins.

Metabolism of most endogenous and exogenous compounds is usually produced by the oxidation of cytochrome P450. Due to drug-drug interactions caused by the inhibition or induction of cytochrome P450 enzymes, changes in drug metabolism are the major causes of drug toxicity, CYP3A4 is one of the key isozymes, and involved in the metabolism of over 60% of clinical drugs. Human ether-a-go-go related genes (hERG) potassium channel is the most important target of many drugs and plays an important role in cardiac repolarization. Blockade of this channel may lead to long QT syndrome (LQTS), leading to sudden cardiac death. Therefore, it is necessary to evaluate the inhibitory properties of drugs on cytochrome P450 enzymes and hERG channel. We primarily evaluate the safety of berberine in combination with statins. Based on these findings, berberine in combination with statins has a greater inhibitory effect on CYP3A4 activity and CYP3A4 protein and mRNA expression than berberine alone. Simvastatin and atorvastatin reduce hERG current by accelerating channel inactivation. At the same time, the inhibitory effect of berberine and statin combination increased on hERG current by reducing the time constant of inactivation than the single drug alone. These results indicate that berberine in combination with statins can increase cardiotoxicity by inhibiting CYP3A4 and hERG channel.

[Current progress of laser-assisted cartilage reshaping for prominent ear].

Objective: To summarize the current progress of laser-assisted cartilage reshaping (LACR) for prominent ear. Methods: The domestic and abroad article concerning the LACR in treatment of prominent ear was reviewed and analyzed. Results: As a new technique, there were three types of LACR therapies that been used for prominent ear. LACR with the 1 064 nm Nd/YAG laser is painful and the penetration depth of the 1 064 nm Nd/YAG laser is greater than that of the 1540 nm Er/Glass laser which is caused more tissue injury. LACR with the 1 540 nm Er/Glass laser has high absorption by the ear cartilage and produce less injury to the surrounding tissue. Use of the CO 2 laser permitted cartilage reshaping combined with both vaporization and incisions, which complicates the technique, although, with low recurrence rate and definite effect. Insisting on wearing ear mold is the key to get satisfactory effectiveness for postoperative patients. The complications of LACR for prominent ear, such as the dermatitis, perforation of the skin, hematoma, or infection, should be noticed. Conclusion: Application of LACR for prominent ear just has a short period of time, limited number of cases, and few relevant literature reports. Its effectiveness needs to be further studied and clarified.

Two single mutations in the fusion protein of Newcastle disease virus confer hemagglutinin-neuraminidase independent fusion promotion and attenuate the pathogenicity in chickens.

The fusion (F) protein of Newcastle disease virus (NDV) affects viral infection and pathogenicity through mediating membrane fusion. Previously, we found NDV with increased fusogenic activity in which contained T458D or G459D mutation in the F protein. Here, we investigated the effects of these two mutations on viral infection, fusogenicity and pathogenicity. Syncytium formation assays indicated that T458D or G459D increased the F protein cleavage activity and enhanced cell fusion with or without the presence of HN protein. The T458D- or G459D-mutated NDV resulted in a decrease in virus replication or release from cells. The animal study showed that the pathogenicity of the mutated NDVs was attenuated in chickens. These results indicate that these two single mutations in F altered or diminished the requirement of HN for promoting membrane fusion. The increased fusogenic activity may disrupt the cellular machinery and consequently decrease the virus replication and pathogenicity in chickens.

The enhancement of cardiac toxicity by concomitant administration of Berberine and macrolides.

As is well-known, hERG plays an essential role in phase III repolarization of cardiac action potentials. Blocking of hERG channels can lead to LQTS. Inhibition of the metabolism of CYPs activities may elevate plasma levels, to further increase accumulation of drug on cardiac. The elevated serum levels may however elicit unexpected toxicities. Therefore, the inhibition tests of hERG and CYP are central to the preclinical studies because they may lead to severe cardiac toxicity. Berberine is widely used as an antibacterial agent and often combined with macrolides to treat gastropathy. Our objective was to assess cardiac toxicity during the combined use of Berberine with macrolides. (1) Azithromycin reduced hERG currents by accelerated channel inactivation. (2) The combination of Berberine with Azithromycin reduced hERG currents, producing an inhibitive effect stronger than use of a single drug alone, due to the high binding affinity for the onset of inactivation. (3) When cells were perfused concomitantly with Berberine and Clarithromycin, they showed a stronger inhibitive effect on hERG currents by decreasing the time constant for the onset of inactivation. (4) The combined administration of Berberine with Clarithromycin had a powerful inhibitive effect on CYP3A activities than use of a single drug alone. Collectively, these results demonstrated that concomitant use of Berberine with macrolides may require close monitoring because of potential drug toxicities, especially cardiac toxicity.

[CURRENT PROGRESS OF CLINICAL THERAPY FOR HEMIFACIAL MICROSOMIA].

OBJECTIVE: To summarize the current progress of clinical therapy for hemifacial microsomia (HFM). METHODS: The domestic and overseas articles concerning the treatment of HFM were reviewed and analyzed. RESULTS: The unified therapeutic schedule of HFM has not yet been determined due to its variable clinical manifestation. Therapies mainly include: correction of bone deformity, which attain high effectiveness by adopting distraction osteogenesis or the improvement approach based on it; repair of the hypoplasia of facial soft tissue using graft of free tissue or autologous fat, augmentation of prosthesis materials. Autologous fat is becoming a hot research area and is widely used in recent years. For the aspect of treatment of microtia, different methods are adopted according to the severity of the malformation. CONCLUSION: The uniform clinical diagnosis and therapy of HFM are not determined for its complicated classification and unknown etiology. The research of etiology and tissue engineering may provide the therapy of HFM.

The rescuable function and mechanism of resveratrol on As2O3-induced hERG K⁺ channel deficiency.

Arsenic trioxide (As2O3) is used to treat acute promyelocytic leukemia. However, the cardiotoxicity of long QT syndrome restricts its clinical application. Previous studies showed that As2O3 can damage the human ether-a-go-go-related gene (hERG) current via disturbing its trafficking to cellular membrane. This study aimed to investigate whether the As2O3-insulted hERG channel can be rescued by resveratrol, a recognized cardioprotective agent. The whole-cell patch clamp technique was used to record the hERG current and action potential duration. Co-immunoprecipitation and Western blot assay were applied to determine the function of hERG-Hsp70/Hsp90 chaperone complexes and the expression alteration of protein-folding-related proteins, respectively. Compared with treatment of As2O3 alone, co-treatment with resveratrol successfully restored the current and surface expression of hERG and obviously shortened action potential duration in guinea pig ventricular myocytes. Further experiments demonstrate that resveratrol relieved As2O3-caused endoplasmic reticulum (ER) stress by restoring the function of hERG-Hsp70/Hsp90 chaperone complexes and downregulating the protein expression of ER chaperone proteins (calnexin and calreticulin) and activating transcription factor 6. In conclusion, resveratrol was able to rescue the trafficking deficiency and relieve the ER stress (ERS). Our findings suggest that resveratrol has a potential effect to alleviate the adverse effect of As2O3 on cardiotoxicity.