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The transcription factor STAT3 is a promising target for the treatment of non-small cell lung cancer (NSCLC). STAT3 activity is mainly dependent on phosphorylation at tyrosine 705 (pSTAT3-Y705), but the modulation on pSTAT3-Y705 is elusive. By screening a library of deubiquitinases (Dubs), we found that the Otub1 increases STAT3 transcriptional activity. As a Dub, Otub1 binds to pSTAT3-Y705 and specifically abolishes its K48-linked ubiquitination, therefore preventing its degradation and promoting NSCLC cell survival. The Otub1/pSTAT3-Y705 axis could be a potential target for the treatment of NSCLC. To explore this concept, we screen libraries of FDA-approved drugs and natural products based on STAT3-recognition element-driven luciferase assay, from which crizotinib is found to block pSTAT3-Y705 deubiquitination and promotes its degradation. Different from its known action to induce ALK positive NSCLC cell apoptosis, crizotinib suppresses ALK-intact NSCLC cell proliferation and colony formation but not apoptosis. Furthermore, crizotinib also suppresses NSCLC xenograft growth in mice. Taken together, these findings identify Otub1 as the first deubiquitinase of pSTAT3-Y705 and provide that the Otub1/pSTAT3-Y705 axis is a promising target for the treatment of NSCLC., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: To analyze the complications related to deep brain stimulation(DBS) surgery in Parkinson's disease(PD) patients and to determine whether there is a learning curve effect in terms of complications. Methods: Retrospective analysis of the DBS surgical data of 822 PD patients performed by the same surgeon at the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital) from December 2012 to December 2022. The complications related to DBS were evaluated and analyzed the complications of every 100 DBS surgery were further analyzed. Results: A total of 822 PD patients, 453 males and 369 females, aged 31-80 years old, were included. The minimum follow-up period after DBS surgery is 6 months. Surgical related complications occurred in 55 patients (6.69%), including 5 patients (0.61%) with slight bleeding around the electrode, 1 patient (0.12%) with cerebral infarction, 4 patients (0.49%) with postoperative epilepsy, 42 patients (5.11%) with postoperative delirium, 2 patients (0.24%) with respiratory distress, and 1 patient (0.12%) with acute cardiac insufficiency. There were 16 cases (1.94%) of hardware related complications in DBS, of which 4 cases (0.48%) had infection, 1 case (0.12%) had a broken angle at the connection between the pulse generator and the extension wire, 8 cases (0.97%) had an excessively tight extension wire, and 3 cases (0.36%) had an IPG bag hematoma. In the infected cases, 2 patients removed IPG and extension wires. There were 7 cases (0.85%) of stimulus related complications, including 4 cases (0.61%) with programmed sensory abnormalities, 1 case (0.12%) with postoperative abnormal movements and dance like movements, and 2 cases (0.24%) with psychiatric symptoms. A comprehensive analysis was conducted on the above complications, among which 8 cases (0.97%) were relatively serious complications. After active treatment, satisfactory results were achieved, and none of them affected the patient's DBS treatment effect and no patients died. For every 100 cases of DBS surgery complications were analyzed, the percentage of complications decreased significantly from 14.50% (58 cases) in the first 400 cases to 4.73% (20 cases) in the last 400 cases ( P <0.001). Conclusion: DBS surgery is safe and has an acceptable low incidence of complications. The incidence of complications also decreases with the accumulation of experience, showing a learning curve effect.

Objective: Lumbar spinal stenosis is the most common spinal degenerative disease in patients over 60 years, and the unilateral biportal endoscopic (UBE) spine surgery treatment of lumbar spinal stenosis (LSS) has achieved preliminary clinical results. This systematic review and meta-analysis aimed to reveal the clinical efficacy of UBE for LSS and provide evidence for clinical practice., Materials and Methods: PubMed, Embase, Web of Science, and Cochrane databases were searched for literature. The papers selected were those published from inception till October 2021. The selected pieces of literature were graded for evidence using the Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). Outcomes measures were operation time, blood loss, complication rate, admission period, Visual Analogue Scale (VAS)-back, VAS-leg, and Oswestry Disability Index (ODI) score, and radiological outcomes. The mean comparisons were based on VAS and ODI scores., Results: A total of 823 patients with a single LSS segment were included from the selected nine studies. There were nine studies comparing UBE clinical outcomes and micro-endoscopic unilateral laminotomy for bilateral decompression (M-ULBD). The meta-analysis revealed that the UBE group had better VAS-leg and -back scores in the first week postoperatively [total: mean difference (MD) = -0.96, 95% confidence interval (CI): -1.19, -0.74, p < 0.00001; total: MD = -1.69, 95% CI: -1.93, -1.45, p < 0.00001], 1st month postoperatively (total: MD = -0.35, 95% CI: -0.61, -0.08, p = 0.01; total: MD = -0.40, 95% CI: -0.68, -0.12, p = 0.005), 6th month postoperatively (total: MD = -0.22, 95% CI: -0.35, -0.08, p = 0.002; total: MD = -0.24, 95% CI: -0.40, -0.07, p = 0.005), and UBE group also performed better in ODI score at 1st month postoperatively (total: MD = -3.36, 95% CI: -4.26, -2.46, p < 0.00001). There was no significant difference in VAS-leg and -back scores between both groups at the 3rd and 12th month postoperatively, and ODI scores did not significantly differ between both groups at 3, 6, and 12 months postoperatively (all p > 0.05)., Conclusions: UBE has achieved good preliminary clinical results and may be a minimally invasive alternative surgery for patients with single segmental LSS.

Objective: The aim of this study was to explore the influences of micro ribonucleic acid (miR)-150 on the proliferation and apoptosis of mantle-cell lymphoma (MCL) cells and to investigate the potential underlying mechanism., Patients and Methods: Differentially expressed miRNAs in MCL tissues were excavated via microarray analysis of miRNA expression profiles. Subsequently, the expression of miRNAs were verified by quantitative Reverse Transcription-Polymerase Chain Reaction (RT-qPCR). The influence of miRNA expression on the survival of patients was detected based on clinical data. Besides, the potential targets of miRNAs were determined using Luciferase reporter gene assay combined with qRT-PCR and Western blotting. Primary tumor cells were extracted, and the influences of miR-150 expression on cell proliferation were detected via Cell Counting Kit (CCK)-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) staining assay. Finally, Western blotting and flow cytometry were performed to explore the impact of miR-150 on the apoptosis of primary tumor cells., Results: Microarray analysis of miRNA expression profiles and RT-qPCR verified that the expression levels of hsa-miR-486, hsa-miR-4746, and hsa-miR-3158 rose considerably in MCL tissues, while those of hsa-miR-29b-3p, hsa-miR-150, and hsa-miR-142-5p remarkably declined. According to the results of survival analysis, the survival time was notably prolonged in patients with higher expression levels of miR-150 and miR-486, especially in those with higher expression level of miR-150. Luciferase reporter gene assay and RT-qPCR and Western blotting results demonstrated that miR-150 negatively regulated the expression level of MET. Subsequent CCK-8 assay and EdU staining results revealed that up-regulation of miR-150 significantly suppressed the proliferation of primary MCL cells. Finally, Western blotting and flow cytometry found that increased expression of MET remarkably facilitated the apoptosis of primary MCL cells., Conclusions: MiR-150 inhibits the proliferation and promotes the apoptosis of MCL cells by negatively regulating MET expression.

Objective: The purpose of the present study was to construct a nomogram for postoperative delirium (POD) after deep brain stimulation (DBS) surgery in patients with Parkinson's disease (PD)., Methods: The present study retrospectively enrolled 165 patients with PD who had undergone DBS surgery. The patients were assessed using the Confusion Assessment Method for the Intensive Care Unit and were divided into 2 groups: the delirium group and nondelirium group. The nomogram for POD after DBS surgery was constructed from the results of univariate analysis and multivariate logistic analysis of the influencing factors for POD after DBS surgery., Results: Univariate analysis revealed that the preoperative length of stay and the presence of preoperative brain atrophy, preoperative pulmonary inflammation, and postoperative cerebral edema were statistically significant. The results from the nonmotor symptoms scale for PD, mini-mental state examination, PD sleep scale, and unified PD rating scale III were also statistically significant (P < 0.05). Multivariate logistic regression analysis showed that the unified PD rating scale III (odds ratio [OR], 2.284; 95% confidence interval [CI], 1.614-3.232), nonmotor symptoms scale for PD (OR, 8.191; 95% CI, 5.629-11.917), PD sleep scale (OR, 0.058; 95% CI, 0.05-0.067), preoperative length of stay (OR, 1.230; 95% CI, 1.053-1.437), and preoperative brain atrophy (OR, 3.912; 95% CI, 3.5-4.255) were independent factors that influenced the occurrence of POD after DBS surgery. A nomogram model was constructed using these indicators. The model predicted an area under the receiver operating characteristic curve after DBS surgery of 0.870 (95% CI, 0.808-0.918), sensitivity of 74.19%, and specificity of 91.54%., Conclusions: The present study has presented a reliable and useful nomogram that can accurately predict the occurrence of POD after DBS surgery in patients with PD. This tool is easy to use and could assist physicians during the therapeutic decision-making process., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Spigelian hernia (SH) is rare and constitutes less than 2% of all hernias. It is reported that more than 90% of SHs lie in the "Spigelian belt", but SH in the upper abdominal wall is extremely uncommon. Here, we report a case of SH in the right upper quadrant of abdomen., Case Presentation: A 38-year-old female was admitted to hospital with complaints of abdominal pain and right upper quadrant mass for 10 days. Contrast-enhanced computed tomography (CECT) of abdomen revealed the dilated small intestine between the swelling ventral muscles in the right upper abdominal wall which suggested a ventral hernia. The surgeons considered it was a spontaneous hernia because there was no history of surgery or trauma in the upper abdomen. About two hours later, the patient underwent emergency surgery. According to laparotomy, a diagnosis of SH with ileum herniation in the right upper abdominal wall was confirmed. The necrotic ileum segment was resected. Meanwhile the abdominal wall defect was repaired by suturing the internal oblique and transverse muscles to the rectus sheath. The patient had a favorable outcome for 1 year without recurrence., Conclusion: A mass and pain in the upper abdominal wall may suggest an atypical SH. SH occurring in the upper abdominal wall is a rare condition with possibility of dire outcome if not managed early.

Objective: To summarize the principles of ear reconstruction after rupture of postauricular expanded flap., Methods: The rupture of the postauricular expanded flap was graded as I-IV degree. For flap rupture of I and II degree, the ear reconstruction was performed immediately with autogenous cartilage framework. For flap rupture of III degree, topical and systemic treatment should be done to relieve the redness and swelling. Then the ear reconstruction was performed. For flap rupture of IV degree, the expanded postauricular flap was smoothened. Ear reconstruction was performed 3 months later., Results: There were 67 cases with flap rupture, including 43 cases as I and II degree, 17 cases as III degree and 7 cases as IV degree. Ear reconstruction with autogenous cartilage framework was performed in 43 cases, with Medpor framework in 17 cases. Flap smoothing and secondary ear reconstruction with autogenous cartilage framework was performed in 7 cases. The results were satisfactory with complications in 4 cases (7%), which resolved after treatment. Primary healing was achieved in all the patients., Conclusions: Good result could be achieved in ear reconstruction, even after flap rupture. Proper treatment should be adopted according to the rupture degree.

Background: The auditory complex of the chick, like that of humans, is made of intimate and highly ordered connections between the inner ear, the middle ear, and the outer ear. Unlike mammals, the middle ear of chick has only one ossicle, known as the columella. The independent lineages of the two suggest that some mechanism must exist that ensures the connectivity between the inner ear and the columella; however, the basis of integration is not known., Results: Using quail-chick chimeras, we demonstrate that columella development depends on signaling interactions. Specifically, both pharyngeal endoderm and cranial paraxial mesoderm can alter the morphology of the columella. Only a discrete region of pharyngeal endoderm exerts this patterning activity, and this region is specified by the overlying paraxial mesoderm., Conclusions: Paraxial mesoderm is also used in the induction of the inner ear, thus we propose that this overlapping source of signalling cues in both middle and inner ear development may underlie the integration of these structures., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: To screen for abnormal methylation in CpG islands and CpG sites through whole genome of congenital microtia to identify their associated genes. To discuss the relationship between abnormal methylation level of genes and the etiology of congenital microtia., Methods: Residual ear cartilage of 50 patients with microtia was collected with ear cartilage of 34 patients without ear malformations as control. Nimblegen CpG promoter array was chosen to screen the 28,226 CpG islands in the whole genome of both experimental and control groups. The genes with differential methylated CpG islands were selected. SpectroCHIP array was chosen to detect the methylation level of each CpG site in abnormal methyletion CpG islands of both experimental and control groups. The CpG sites with differential methylation level were selected., Results: There were 36 CpG islands with differential methylated level in whole genome between experimental group and control group, among which 29 CpG islands were connected with 29 named genes. In the abnormal methylated CpG islands of COL18A1, MYH14, RBMY1A1 and ZIC3, 6 differentially methylated CpG sites were found with statistical significance. The methylation level of these 6 CpG sites in experimental group and control group were COL18A1&#95;2&#95;CpG&#95;170.9783 +/- 0.0235 and 0.9526 +/- 0.0589; MYH14&#95;CpG&#95;170.9600 +/- 0.0414 and 0.9284 +/- 0.0655; RBMY1A1&#95;1&#95;CpG&#95;3.40.9966 +/- 0.0055 and 0.9914 +/- 0.0069; RBMY1A1&#95;1&#95;CpG&#95;130.9648 +/- 0.0118 and 0.9757 +/- 0.0127; ZIC3&#95;3&#95;CpG&#95;150.0867 +/- 0.0212 and 0.0543 +/- 0.0399; ZIC3&#95;2&#95;CpG&#95;270.3775 +/- 0.1816 and 0.472 3 +/- 0.0439., Conclusions: The DNA methylation profile of the entire genome is initially established. The abnormal methylated CpG islands of COL18A1, MYH14, RBMY1A1 and ZIC3 might be related to the pathogenesis of microtia.

Objective: To analyze the sectional anatomical features of auricular and middle ear malformation in patients with microtia so as to improve the clinical classification and the instruction of surgery., Methods: From Jun. to Dec. 2009, 36 cases with microtia were selected in the center of auricular reconstruction in Plastic Surgery Hospital, including 22 cases of unilateral microtia and 14 cases of bilateral microtia. 22 patients with unilateral microtia were studied with the contralateral healthy ears as controls. Spiral CT was performed for high-resolution scan of the temporal bone. The coronal, sagittal and 3D reconstruction images were created with Mimic software. Several distances and degrees were measured., Results: The patients were classified by Max classification. The anteroposterior diameter and the vertical diameter of tympanic cavity were (7.75 +/- 1.92) mm and (14.66 +/- 4.75) mm for type I; (6.17 +/- 2.56) mm and(14.35 +/- 5.12) mm for type II; (6.31 +/- 3.40) mm and (9.97 +/- 4.36) mm for type III (P = 0.001). The mastoid pneumatization degree for type I, II, III were 13.33%, 13.64%, 30.77% in sclerotic type, 13.33%, 18.18%, 7.69% in diploe type, 0, 9.09%, 38.46% in composite type, 73.33%, 59.09%, 23.08% in pneumatic type (chi2 = 24.11, P = 0.002). The cover of fenestra vestibuli by facial nerve was 21.43%, 47.62%, 54.55% (chi2 = 23.44, P = 0.002) for type I, II, III. There was a statistical difference between the microtia group and the control group., Conclusions: According to the Max classification, the middle ear malformation changed along the auricular malformation. The anatomical variations was complicated in type II microtia, which should be sub-classified.

Objective: To investigate the therapeutic effect of bi-pedicled frontal expanded flap for cervical cicatricial contracture., Methods: Tissue expanders were implanted under frontal muscle. After expansion, the frontal flaps were designed based on bilateral superficial temporal vessels and were transferred to the neck wound. The cervical spine movement and the mento-cervical angle was measured and analyzed by SPSS16.0 and t test., Results: From September 2006 to May 2010, 7 patients were treated by this method. The range of active cervical movement was improved in all direction. The mento-cervical angle decreased from (152.7 +/- 1.9) to (90.7 +/- 2.2) degrees after operation. The patients were followed up for 5 months to 3 years with satisfactory result and no contracture recurrence., Conclusions: The bi-pedicled expanded frontal flap has a reliable blood supply and is very suitable for cervical cicatricial contracture with good functional and esthetic results, leaving less morbidity at donor site.

Objective: To explore the methylation of CpG islands in promoter of eye absent gene 1 (EYA1) in microtia., Methods: The methylation of CpG islands in EYA1 gene in 64 microtias and 36 healthy controls were measured using the technique of matrix-assisted laser desorption/ionization-time of flight., Results: The methylation of CpG&#95;Unit3 and CpG&#95;Unit5 of EYA1 gene in microtia were 0.09258 +/- 0.033846 and 0.0922 +/- 0.02379, respectively, which were significantly lower than those in control., Conclusions: Hypomethylation in microtia may be related to the pathogenesis of the disease.

Objective: To explore the surgical treatment and pathologic mechanism of polyotia., Methods: The operative methods for polyotia were flexible. The main procedures were aimed at the remodeling of tragus with the redundant tissue. Tissue transplantation was used to correct the depression deformity. Compound auricular tissue transplantation and Z-plasty were used for correction of the malformation at the posterior part of polyotia., Results: From 2003 to 2008, 9 patients with polyotia were treated. The tragus was reconstructed after resection of redundant tissue. The depression deformity was corrected with tissue infilling in 6 cases. The compound auricular tissue transplantation was performed in 4 cases. Z-plasty at the lower ear lobe was performed in 2 cases. The appearance and the location of the reconstructed ears looked symmetric to the healthy ear., Conclusions: Natural and symmetric appearance of reconstructed ear can be achieved in polyotia. The abnormal migration of neural crest cell might be the pathologic mechanism of polyotia.

Objective: To explore the application of tissue expander in ear reconstruction and to deal with the complications., Methods: 50 ml kidney-shape tissue expanders were implanted subcutaneously in the mastoid area. The drainage tube was removed 3 days after operation. The suture was removed 10 days later. Since 7 days after operation, 5 ml NS was injected into the expander every time, three times a week. The total injection volume was about 60 ml. After that, the expander was maintained for one month., Results: From January 1992 to December 2006, 5,248 patients of microtia were treated with 6,252 expander. After the maintaining period, the expanded skin was thin and well-vascularized. The complication rate was 7.79%, including hematoma, malunion and infection., Conclusions: The quantitative tissue expansion is easily manipulated with few complications. It can provide hairless, thin skin with reliable blood supply for ear reconstruction.

Objective: To explore the application of the remnant in repairing the reconstructed ear in microtia., Methods: From October 2000 to July 2006, 1,823 patients with reconstructed ear underwent the second operation for repairing. The remnants were used to reconstruct tragus, antitragus, crus of helix, concha cavum, or relax the adhesion between the reconstructed auricle and cranio wall, or insert into the reconstructed lobule or under the basement of the costal cartilage frame to restore the cranio-auricular angle or to the preauricular subcutaneous to correct the facial local depression., Results: In 1,823 cases, the tragus, antitragus and concha cavum was reconstructeded by remnant auricle in 1,180 cases; helix crus was repaired by remnant auricle in 743 cases; the wound was repaired by remnant auricle flap resulted from relaxing the adhesion between the reconstructed auricle and cranial wall in 68 cases; Subcutaneous and cartilage flap was formed and transferred in 95 cases, and among them the flap was transferred under the basement of the frame to restore the cranio-auricular angle in 77 cases and was transferred to the preauricular subcutaneous to correct the facial local depression in 18 cases; the skin flap was formed by remnant auricle to repair the lobule in 37 cases. All flaps survived completely. The appearance of reconstructed ear was satisfied., Conclusion: The remnant is very useful in repairing the reconstructed ear in microtia. It should be preserved propriately in auricular reconstruction.

Objective: To explore the fabrication and application of three-dimensional autogenous cartilage framework in auricular reconstruction., Methods: The process of fabrication of three-dimensional cartilage framework consisted of cartilage harvesting, carving and assembling the cartilage. The rib cartilage was harvested separately. The three-dimensional framework was composed of three main parts:the helix, the base and the pad, at different layer. The framework was fabricated according to the development of rib cartilage and contour and height of the reconstructed ear., Results: From January 1992 to December 2006, 5,248 patients of microtia were treated with 6,252 autogenous cartilage frameworks., Conclusions: The three-dimensional framework is easily manipulated. The reconstructed ears look natural and had an erect contour. This method can effectively use the cartilage.

Objective: To study the difference of histologic examination and type II collagen expression in the rib cartilage of patients at different age., Methods: The patients were divided into three groups, as children group (5 to 10 years old), teenager group (11 to 17 years old), and adult group (18 to 29 years old). Histologic examination of rib cartilage and quantitative analysis of type II collagen with immunohistochemical stain were carried out in the three groups. Motic Med 6.0 A system was used to quantitate immunohistochemical image through measurement of mean photodensity. The results were statistically analyzed., Results: Among the three groups, the children's rib cartilage had the most blood vessels, the most chondrocytes, well-distributed stain of matrixes, and the type II collagen was expressed actively and highest in photodensity. The rib cartilage of teenager group had less blood vessels, unhomogeny distributed stain of matrixes, the enlarged and separated cartilage lacunae. The rib cartilage in adult group showed the least blood vessels, the least chondrocytes, the hyalinization of perichondrium, the most deposition of calcium salt, and the type II collagen was expressed at the lowest level in photodensity. Statistical analysis showed significant differences among the three groups (P < 0.01)., Conclusions: Histologic structure in human rib cartilage changes during the aging process and the type II collagen is decreased with the increase of age.

Objective: To investigate the chest contour deformities after harvesting of costal cartilage for total ear reconstruction, so as to prevent donor site morbidity., Methods: 107 cases of microtia who underwent ear reconstruction with costal cartilage during the period from 1994 to 2003, were retrospectively studied. Both the chest depression deformity and the costal arch deformity were evaluated. The possible related factors to the chest contour deformities were analyzed statistically with Stata software., Results: The incidence of chest depression was 54.55% (48/88), including 35 cases of mild depression (39.77%) and 13 cases of severe depression (14.77% ). The incidence of costal arch deformity was 52.77% (46/88), including 33 cases of mild deformity (37.50%) and 13 cases of severe deformity (14.77%). The incidence of both deformities was significantly different at different age (P < 0.01), but not at different follow-up period (P = 0.294 and P = 0.225, respectively). Gender was related to the incidence of chest depression (P < 0.01), but not to the costal arch contour deformity (P = 0.619). Comparing resection of the 6th and 7th rib cartilage with resection of 7th and 8th rib cartilage, the incidence of costal arch deformity was significantly different (P < 0.01), but the incidence of depression deformity was not (P = 0.657)., Conclusions: The incidence of chest deformities increases with early operation time (< 13 years old). The male patients have higher incidence of depression deformity than female. The arch deformity is higher when the 6th and 7th rib cartilage were resected. The follow-up period is not related to the chest deformities.

Objective: To investigate the effect of postauricular tube flap for repairing traumatic partial helical defect., Methods: The tube flaps were designed according to the site and size of helical defects. The length of tube flaps was 1.2 - 1.5 times as the length of the defects. The length-to-width ratio of tube flap was 3 - 4:1. The procedures required three stages for completion: (1) fabrication of tube flap; (2) 2 - 3 weeks later, division of one pedicle and insetting the flap; (3) 2 - 3 weeks later, complete division of pedicle and repairing the defects., Results: From January 1998 to June 2006, 47 cases of traumatic partial helical defects were treated with postauricular tube flaps. All the tube flaps survived completely with no vascular disturbance, infection or necrosis. The patients were followed up for 2 months to five years with satisfactory results., Conclusions: Postauricular tube flap is a reliable and simple procedure for traumatic partial helical defects with good cosmetic result and less donor site morbidity.

Objective: To introduce the design and application of the expanded transposition skin flap in the treatment of cheek skin defects., Methods: The expanded transposition flaps were divided into three types: the regular expanded transposition flap (ERT flap), the expanded transposition-advancement-transposition flap (TAT flap) and the expanded rotation-advancement-transposition flap (RAT flap). 135 cases of cheek skin defects resulted from hemangioma, scar and naevi were treated with these three types of flaps. Delay surgery was needed when the ratio of length to width was bigger than 2 : 1., Results: There were 139 expanded transposition flaps, including 17 ERT flaps, 69 TAT flaps, 53 RAT flaps. Blood supply disturbance was happened at the end of the flaps in 6 cases, including 2 ERT flaps and 4 other flaps. Other flaps had no complication. The results were satisfactory., Conclusions: The expanded transposition skin flap is a reliable method to repair the cheek skin defect. The preoperative flap design is very important for successful reconstruction.

Objective: To investigate the indication and results of three methods for total ear reconstruction., Methods: 960 cases of total ear defect were treated with skin expansion and autogenous rib cartilage framework (n = 786), or skin expansion and Medpor framework (n = 150), or ear prosthesis (n = 24). The indication and results of the three methods were analysed., Results: Good cosmetic results were achieved with all three methods. Autogenous rib cartilage framework was suitable for patients under 30 years old with unaffected skin at mastoid region. Medpor framework was good for grown-up, especially over 30 years old, or with mild infection at mastoid region. Patients with severe skin injury at mastoid region or unwilling to accept surgery should choose ear prosthesis., Conclusions: Satisfactory results can be achieved with suitable methods for total ear reconstruction.

Objective: To investigate the age-related change in biomechanical properties of the costal cartilage and its relevance to the timing of ear reconstruction with costal cartilage framework., Methods: The patients of 5 to 25 years old were divided into three groups according to their age. The biomechanical properties of costal cartilage harvested from these patients during ear reconstruction were tested, including stree-strain relationship, stress relaxation and creep, tensile strength. All the results were analyzed statistically., Results: The costal cartilage from children group had the best biomechanical properties, while the costal cartilage from the adolescent group had the worst. The difference had a statistically significance (P < 0.05)., Conclusions: The biomechanical properties of costal cartilage are age-related. So it is recommended that ear reconstruction with costal cartilage framework should be performed in childhood when the costal cartilage has the best biomechanical properties.

Objective: To classify the blood vessel distribution of the expanded skin in the mastoid region and its relevance to reasonable and reliable design of the expanded flap for auricular reconstruction in congenital microtia., Methods: The blood vessel distribution of the expanded skin in the mastoid region was observed by light permeation test. The expanded flaps with different ratio of length to width were designed according to their blood vessel distribution types., Results: The vascular distribution of the expanded skin in 403 cases was divided into five types. All the flaps survived completely., Conclusions: The blood vessel distribution type of the expanded skin in mastoid region has great significance for the design of post-auricular expanded flap in auricular reconstruction.

Conclusions: Improved appearance and hearing and increased efficiency are achievable for congenital microbia with defects of external auditory meatus (EAM) and middle ear. First the site of the external auditory meatus (EAM) orifice must be located according to the results of the temporal CT scan, then the auricle can be reconstructed employing the three-stage method. At the third stage, the EAM and middle ear can be reconstructed at the same time., Objective: To select the best approach for reconstruction of congenital microtia with defects of the EAM and middle ear., Patients and Methods: This study analyzed 498 cases (528 ears) of auricle reconstruction by the three-stage method and 77 cases (91 ears operation/120 ears) of EAM and middle ear reconstruction., Results: For auricular reconstructions, the effects of reconstructed auricles were classified into four grades according to their structure verisimilitude and the bilateral symmetry. The majority of patients/families were satisfied. For 52 ears with normal movement of stapes, reconstructions of EAM and middle ear improved hearing by 15-50 dB, but long-term improvement was not ideal. In bilateral patients, 20 of 24 ears with reconstructed EAMs exhibited relapse of stenosis or atresia. For patients whose EAMs were reconstructed first, scar developed around the orifice and affected the skin flap and later auricle reconstruction, while reconstructing the auricle first sometimes resulted in the location of the EAM orifice deviating from an ideal position.

Objective: To investigate the alternation of biological characteristics of residual ear chondrocytes when proliferating in vitro, and study the effects of CDMP-1 on proliferation and differentiation of residual ear chondrocytes., Methods: Residual ear chondrocytes were cultured in vitro. Then we observed the effect of CDMP-1 on differentiation by immunohistochemistry of collagen type II and dyeing with toluidine blue, investigated proliferation effects of CDMP-1 by method of MIT, and analysis cell cycle changes by flow cytometry., Results: The quantity of GAG gradually decreased along with the increase of the doubling time of chondrocytes in vitro. The quantity of chondrocytes with positive expression of collagen type II were significantly more in the experimental group used with CDMP-1 than the contrast. And the most efficient concentration of CDMP-1 was 100 ng/ml., Conclusions: CDMP-1 had a good effect on proliferating and could maintain morphology of the residual ear chondrocytes of microtia cultured in vitro.

Objective: To explore surgical procedure for the treatment of acquired ear defect., Methods: The ear reconstruction was carried out by using soft tissue skin expander and autogenous rib cartilage framework, Medpor framework, auricular prosthesis, and so on., Results: The long-term follow-ups showed that the flap of reconstructed ear was ruddy, soft, with normal sensory function. The cartilage framework had no degeneration, absorption and deformation. The Medpor framework had no deformation. The contour of auricular prosthesis was vivid and the implant system was stable. In addition, the reconstructed ears were coincidence with the normal side on location, form and dimension., Conclusions: It may be a major method for traumatic ear reconstruction that the soft tissue skin expander with autogenous rib cartilage framework could be applied at present time. In some special circumstances, the soft tissue skin expander with Medpor framework and auricular prosthesis may be other helpful choices.

Objective: To investigate the psychologic status of congenital microtia patients and related influential factors., Methods: In a cross-sectional survey for congenital microtia, 410 patients, 314 males and 96 females, aged 12 +/- 6 (5 - 37), underwent psychological survey with the symptom checklist-90 (SCL-90) or Achenbach child behavior checklist (CBCL), centering on the 3 main psychological problems: depression, interpersonal sensitivity or social difficulties, and hostility or aggression. A questionnaire was designed to investigate the influencing factors, such as the patients' own factors, and psychological factors of the patients' families Chi square test and logistic regression analysis were performed to find the factors contributing to those psychological problems., Results: Psychological status of congenital microtia patients were depression existed in 83 patients (20.2%), interpersonal sensitivity or social difficulties existed in 150 patients (36.6%), and hostility or aggression existed in 108 patients (26.3%). The factors, such as age (OR = 1.75), microtia grade (OR = 2.77), mother's education (OR = 2.49), having been subjected to ridicule (OR = 2.58), pressure of family affection (OR = 1.96), family attitude to patient (OR = 2.45), and deficiency of family harmony (OR = 2.57) were risk factors contributing to depression of patients. The factors, such as age (OR = 1.62), having been subjected to ridicule (OR = 3.34), and pressure of family affection (OR = 1.89) were risk factors contributing to interpersonal sensitivity or social difficulties of the patient. The factors, such as having been subjected to ridicule (OR = 2.47), and pressure of family affection (OR = 1.80) were risk factors contributing to hostility or aggression of the patient., Conclusion: Having been subjected to ridicule, deficiency of family harmony, and pressure of family affection are mainly risk factors of psychological problems of congenital microtia patients. Early education and early operation for the patients are necessary.

Objective: To explore an ideal method for repairing the skin-soft tissue defects according to the different anatomical units of cheek, and find reasonable design principles to transfer the expanded flaps., Methods: According to the location of the defect, we placed 1-3 appropriate expanders nearby, when the flap expanded enough we adopted advanced skin flaps, rotation-advanced skin flaps or transposition skin flaps to repair the defect. In this group of 269 cases, the defects were secondary to hemangioma, various scars, nevus or nevus excision., Results: In all 269 cheek defects, 305 expanded flaps were developed which included 145 rotation-advanced flaps, 121 advanced skin flaps and 39 transposition skin flaps. 52 of them generated complications, including blood circulation disorder of the distal part of flaps, hematoma, infection, injection, lower eyelid ectropion, expander extrusion and capsule contracture. Mostly, these complications didn't affect the final results., Conclusions: The principles presented in this article are the guidelines to treat the skin-soft tissue defect of check with tissue expansion. The satisfied results come from the reasonable flap designs.

Objective: To investigate the possibility of external ear reconstruction using expanded postauricular scar flap and Medpor framework in burn cases., Methods: External ear reconstruction using expanded postauricular scar flap in combination with Medpor framework was performed in 17 cases whose ear had burn injury., Results: Of the 17 cases, 15 cases achieved success; 2 cases experienced partial exposure of the framework due to inadequate wrapping of the subcutaneous fascia flap and later injury. The longest follow-up was three years, and the final result was satisfactory., Conclusions: External ear reconstruction using expanded postauricular scar flap in combination with Medpor framework is a reliable method for adult (over 25 years) who has ear defect from burn injury.

Objective: To classify and repair "Butterfly Ear" deformity which presents characters of dysplasia of inferior auricle of ear and congenital bat ear., Method: The repairment procedures include: type I: auricular cartilage flap inversion folding technique. type II: local ear skin flap. type III: soft tissue expander autogenous, rib cartilage framework., Results: The method was used in 19 cases from October 2001 to March 2005. Postoperative follow-up showed satisfactory results in all cases., Conclusion: According to "Butterfly Ear" deformity classification, different technique could be applied.

Objective: To further explore the effects of substance P on the proliferation and apoptosis of fibroblasts obtained from pathological scars in vitro., Methods: Fibroblasts from keloid (KSF) , hypertrophic scar (HSF) and normal dermis (NDF) of 12 burn patients were cultured in vitro and divided into control, SP (with 1 x 10 (-6) mol/L SP added to the culture medium) , and SP + spantide( with 1 x 10 (-6) mol/L SP and 3 x 10 (-5) mol/L spantide added to the culture medium) groups. MTT method or flow cytometry assay was used for the determination of the proliferative activities or apoptotic rate of fibroblasts obtained from KSF, HSF and NDF with SP or Spantide. And then the fibroblasts in SP group were subdivided into 1 x 10( -9) -1 x 10 (-5) mol/L groups to examine the time-or dose-effect of SP to fibroblasts from different sources., Results: In control group, different types of fibroblasts exhibited similar proliferative activities and apoptotic rates. But there was significant difference in these indices between control and SP group (the proliferative activity of KSF, HSF, NDF was 0. 656+/-0. 071, 0. 525 +/-0. 064, 0. 404+/-0. 063, respectively; and the apoptotic rate of KSF, HSF, NDF was [( 1.5+/-0.3) % , (4.0+/-0.5) % , (5.5+/-0.7) % , respectively],( P < 0. 05). SP had stronger effect on KSF than it did to HSF, as well as it had stronger effect on HSF than it did to NDF. In SP + spantide group, the effect of SP on KSF was partially inhibited, while it was completely inhibited in cultures of HSF and NDF. KSF was more sensitive to SP and the effect was longer when compared with HSF., Conclusion: SP may play an important role in the process of pathological scar formation due to its diverse effects on fibroblasts from different sources.

Objective: To explore surgical procedure of congenital microtia., Methods: Ear reconstruction was made using soft tissue skin expander and autogenous rib cartilage framework., Results: Long time follow-up showed that the flap of reconstructed ear was ruddy, soft, with normal sensory function; cartilage framework had no degeneration, absorption and deformation. In addition, the reconstructed ears were coincidence with the normal side on location, form and dimension., Conclusions: It was a good method for congenital microtia to use soft tissue skin expander together with autogenous rib cartilage framework at present time.

Objective: To identify the risk factors associated with congenital microtia., Methods: A case-control, retrospective study was performed. A total of 207 cases of congenital microtia and 209 age-frequently-matched controls were interviewed individually according to the uniform questionnaire. The questionnaire included: (1) Essential information about patients and their parents. (2) First trimester diseases and medication of mother. (3) Past gestation history of mother. (4) Family history and life style of the parent. The available data were analyzed by chi-square test and multivariate Logistic regression model., Results: The factors, such as gender (OR = 5.893), first trimester disease of mother (OR = 34.49) and medication (OR = 4.299), excessive drinking and smoking of father (OR = 4. 347, OR = 4.304), non-primiparous parity (OR = 9.524), abortion (spontaneous and induced, OR = 1.723), low-education of mother (OR = 2.275) were risk factors contributing to microtia in multivariate study. The factors, such as tea (OR = 0.179) were protective factors in multivariate study., Conclusions: Multi-risks factors are contributing to microtia. Preventive measures according to risk factors should be put forward.

Objective: To evaluate a technique for closing the cleft of nasal aspect at the junction of the hard and soft palate and ensuring the wound healing well during the procedures of repairing broad cleft palate., Methods: A inferior turbinate mucoperiosteal flap based posterior is designed and transposed to the junction of the hard and soft palate for decreasing the tension effectively and closing the cleft easily., Results: All of the patients showed wound healing well and no distinct scars or palatal fistula., Conclusions: It is a simple and effective technique to decrease the tension and close the cleft of nasal aspect at the junction of the hard and soft palate with inferior turbinate mucoperiosteal flap.

Objective: To investigate the effects of L-arginine on the microcirculation and survival of rat island skin flaps after ischemia-reperfusion., Method: A right lower abdominal island flap was created in SD rats and the microcirculatory blood flow in these flaps measured with laser Doppler velocimetry following L-arginine injection via the contralateral femoral artery. Both NO and malondialdehyde (MDA) levels in the flaps were assayed and the survival of the flaps replanted in situ was evaluated 1 week later., Results: L-arginine treatment caused increase in the microcirculatory blood flow of the flaps and elevation of NO while and decrease of MDA levels. The survival rate of the flaps with L-arginine treatment was significantly higher than the flaps from saline-treated and normal rats., Conclusion: L-arginine can improve the survival of island flap through increasing the microcirculatory blood flow and lessening ischemia-reperfusion injury of the flaps.

Objective: To study the psychologic status and their influencing factors in congenital microtia patients and their families., Methods: Totally one hundred and two congenital microtia patients (79 men, 23 women, mean age 13.62 +/- 7.2 years) were enrolled. The patients and their families answered the questionnaire written by ourselves to identify the psychosocial problems., Results: (1) 23.5% patients were found to have severe psychosocial problems, such as lack of self-confidence, close and fear and so on. (2) With the growth of age, psychosocial problems of the patients were rated high (P < 0.05). (3) For patients who found their deformations early, psychosocial problems also were rated low. (4) For patients who found their deformations by themselves, psychosocial problems also were rated low. (5) The education and psychosocial impact for parents all affected patients deeply., Conclusions: To prevent psychosocial problems, we should operate for patients as early as possible. And correct guidance is very important for youngsters.

Objective: To explore the relationship between neuropeptide substance P (SP) and wound healing in scalded rats., Methods: (1) Scalded rats with different degrees of scald injury were employed as the experimental model and were sacrificed at 24 post scald hour (PSH), and on 3, 7 and 14 post scald days (PSD). The SP content in the wound was detected with radioimmunoassay method. (2) The murine granulation tissue fibroblasts (GTF) were cultured with different culture media, and divided into control, SP and Spantide (SP receptor antagonism) groups. The effects of SP and Spantide on the cellular activity and apoptotic rate of murine GTF were assessed in vitro., Results: There was significant difference of the SP content among the superficial (145 +/- 78) ng/g, partial (94 +/- 48 ng/g) and full thickness (53 +/- 27 ng/g) scald wounds at 24 PSH (P < 0.01), while the SP content in partial thickness burn wound on 3 and 7 PSD obviously increased; and that in deep partial thickness burn wound obviously increased on 7 and 14 PSD. But the SP content remained unchanged in full thickness scald wound. (2) SP could promote the activity of GTF and inhibit its apoptosis (The GTF activity in control, SP groups were 0.21 +/- 0.05, 0.36 +/- 0.07, respectively, P < 0.01). Spantide could inhibit the interaction between SP and GTF., Conclusion: SP can promote GTF proliferation, and the SP content in wound is closely associated with the depth of the injury and wound healing capacity.

Objective: To evaluate the development of the chest wall after costal cartilage harvesting in children., Methods: Thirty-nine patients, who underwent microtia reconstruction with costal cartilage grafts, were examined in the donor-site with physical examination and radiography. Forty normal children were selected as control., Results: There were no significant differences in size between the bilateral chests, and compared to the control. The rib deformity in each donor site was not observed on the radiography., Conclusions: The costal cartilage harvesting in children has no significant evidence to influence the development of the chest wall.

Objective: To evaluate a new reliable surgical technique for correction the congenital cupped ear., Methods: With 96 patients, a stainless steel wire was introduced to suspend auricular cartilage on the pericranium after the cupped ear was corrected. The follow-ups were carried out after the operation., Results: Up to 3 years follow-ups with 52 cases, the results were satisfactory and durable., Conclusions: The above mentioned technique could be a reliable way to correct mild and moderate cupped ear abnormalities.

Objective: A simple and effective therapy for single side constricted ear., Methods: Transplanting normal side free composite auricular grafts to constricted ear (15 patients and 15 sides), then lengthening the helix, exposing the scapha, correcting deformity., Results: The 15 patients composite grafts all survived. The helix has been lengthened, the scapha exposed, the normal ear reduced, the constricted ear augmented and two sides ear have become symmetry., Conclusion: This method is simple and results are satisfied.

Objective: To introduce a new technique for the treatment of helical keloid., Methods: The procedure consisted of two steps. In the first step, a kidney-shaped expander of 50 ml was placed subcutaneously in the retroauricular area. Routine inflation with normal saline followed. In the second step, about two months afterwards, the expander was taken out and the helical keloid was excised. The expanded flap was advanced to cover the wound., Results: The operation has been performed on 12 patients of 16 sites of helical keloid since 2000. Postoperative follow-up from 3 months to 2 years revealed satisfactory results. The reconstructed ear maintained a good contour., Conclusion: The technique creates a retroauricular flap rich in blood supply, which can be used to close the defect left by helical keloid excision. It provides a good treatment for the helical keloid replaced with normal skin from the mastoid region.

Objective: To investigate the inhibiting action of transforming growth factor-beta type R II receptor(TGF-beta R II) antibody to fibroblasts., Methods: Four groups of cultured skin fibroblasts were treated with different dosages of TGF-beta R II antibody. Examinations were performed with HYP, MTT, microscope, and flow cytometry techniques., Results: TGF-beta R II antibody resulted in significant inhibition of fibroblasts(P < 0.01)., Conclusion: TGF-beta R II antibody has inhibiting effects on the proliferation of skin fibroblasts and with a dose-dependent manner.

Insulin-like growth factors (IGFs) increase the rate of motor axon elongation, prevent motoneuron death, and may support the reestablishment of synapses following nerve injury. In situ hybridization was used in the present study to examine the temporal and spatial distribution of IGF gene expression in soleus muscle following sciatic nerve crush in rats. In intact muscle, IGF-II gene expression was generally low, and localized to interstitial cells, possibly fibroblast and Schwann cells. These cells were found in the middle of muscle which is enriched in neuromuscular junctions. IGF-II gene expression, 4-6 days postcrush, was increased in interstitial cells. Thereafter, IGF-II gene expression was also increased in muscle cells or cells closely associated with muscle fibers, such as satellite cells. IGF-II gene expression was increased to a much greater extent in the midregion of muscle enriched in end-plates than in the two ends of muscle, but returned towards normal following the reestablishment of functional synapses. On the other hand, IGF-I gene expression was only slightly increased following nerve crush, and this increase was associated with interstitial, but not muscle cells. These results show that the IGF-I and IGF-II genes are regulated by independent signals and may play separate roles during nerve regeneration. For example, a regional increase in IGF-II gene expression may support preferential nerve terminal sprouting in the middle of muscle enriched in neuromuscular junctions, thereby increasing the probability for the reestablishment of synapses., (Copyright 1999 Elsevier Science B.V.)

The prolonged disconnection of nerve from muscle results in the death of motoneurons and permanent paralysis. Because clinical nerve injuries generally involve postbirth motoneurons, there is interest in uncovering factors that may support their survival. A rich history of research dating back to the time of Santiago Ramon y Cajal and Viktor Hamburger supports the inference that there are soluble neurotrophic factors associated with nerve and muscle. However, the endogenous factors normally required for motoneuron survival following nerve injury have eluded identification. Two interrelated hypotheses were tested: (1) administration of insulin-like growth factor-II (IGF-II) can support the survival of postbirth motoneurons, and (2) endogenous IGFs are essential for motoneuron survival following nerve injury. We report that IGF-II locally administered close to the proximal nerve stump prevented the death of motoneurons (estimated by relative numbers of neuronal profiles) which ordinarily follows sciatic nerve transection in neonatal rats. By contrast, anti-IGF antiserum, as well as IGF binding proteins-4 and -6, significantly increased (P < 0.01) motoneuron death. This report shows that IGF-II can support survival, and contains the novel observation that endogenous IGF activity in or near nerves is required for motoneuron survival. Other studies have determined that IGF gene and protein expression are increased in nerve and muscle following sciatic nerve crush, and that IGFs are required for nerve regeneration. Taken together, these data show that IGFs are nerve- and muscle-derived soluble factors that support motoneuron survival as well as nerve regeneration.

Neural disturbances are observed in the peripheral and central nervous systems of patients with insulin-dependent diabetes mellitus (IDDM) and non-IDDM (NIDDM). Insulin-like growth factors (IGFs) are neurotrophic growth factors that can support nerve regeneration and neuronal survival in the types of neurons known to be afflicted in diabetes. We tested the hypotheses that IGF gene expression is reduced in neural tissues and liver of spontaneously diabetic obese Zucker (fa/fa) rats and that IGF treatment can prevent neuropathy. There was a significant early reduction in IGF-II mRNA content as measured per mg of wet tissue or per poly(A)+ RNA in sciatic nerves, spinal cord and brain from spontaneously diabetic obese (fa/fa) vs. nondiabetic lean (+/+) adult rats. In addition, IGF-I mRNA content was reduced in liver but not nerve or spinal cord of NIDDM rats. Pain/pressure thresholds were abnormal (hyperalgesia) in diabetic (fa/fa) vs. nondiabetic (+/+) rats, and subcutaneous infusion of IGF-II restored thresholds toward normal. The low dose of IGF-II that prevented hyperalgesia in contrast had no effect on hyperglycemia or obesity. These data suggest that IGF treatment may provide rational therapy for diabetic neuropathy and that therapy may be effective even in patients unable to adequately control their hyperglycemia.

Diabetic neuropathy is a debilitating disorder whose causation is poorly understood. A new theory proposes that neuropathy may arise as a consequence of loss of neurotrophic insulin-like growth factor (IGF) activity due to diabetes, superimposed on a slow continual loss due to aging. The prediction that IGF-I and IGF-II gene expression are reduced in diabetic nerves was recently tested and validated. Here we tested the prediction that IGF administration can prevent or reverse diabetic sensory neuropathy. Subcutaneous infusion of IGF-I or IGF-II, but not vehicle, halted (P < 0.01) the progression of hyperalgesia in streptozotocin-diabetic rats. Moreover, impaired sensory nerve regeneration was partially reversed within 2 weeks after treatment of diabetic rats with IGFs (P < 0.01). Impaired regeneration could also be prevented by daily subcutaneous IGF injections. The low replacement doses of IGFs were effective despite unabated hyperglycemia and weight loss. These results show that IGF replacement therapy can reverse or prevent diabetic sensory neuropathy independently of hyperglycemia or weight loss.

Previous studies have demonstrated that the regeneration of mammalian peripheral nerves is dependent on endogenous insulin-like growth factors (IGFs). In the present study, in situ hybridization was used to examine the temporal and spatial expression of the IGF-I and IGF-II genes in rat sciatic nerve after crush. Such expression was characterized in relation to Schwann cell proliferation and the presence of neurofilaments in returning axons during regeneration. The results show that both IGF-I and IGF-II mRNAs were increased in the sciatic nerve distal to the crush site. However, each transcript had a distinctly different temporal and spatial distribution during regeneration. IGF-I gene expression was intensely increased at the crush site within 4 days after nerve crush. Along the portion of the nerve distal to the crush site, a moderate increase was observed to reach maximal levels 10 days postcrush, and was decreased thereafter back towards baseline at 20 days postcrush. Furthermore, this increase was associated with the proliferation of Schwann cells, and the return toward baseline with the regeneration of axons containing neurofilaments. By contrast, IGF-II gene expression was unchanged at or near the site of injury, but unexpectedly was increased in more distal, intramuscular reaches of the nerves. This had a slower time course beginning 10 days postcrush, and was further increased at 20 days postcrush. These results show that the IGF-I and IGF-II genes are regulated by independent signals and probably play different roles during nerve regeneration. They support the hypotheses that IGF-I contributes to the initial sprouting and subsequent elongation of axons in nerves, whereas IGF-II enhances the regeneration of certain axons into neuromuscular branches of nerves, and/or the re-establishment of neuromuscular synapses.