Naphthylisoquinoline alkaloids, a new structural template inhibitor of Nav1.7 sodium channel.

Voltage-gated sodium channel 1.7 (Nav1.7) remains one of the most promising drug targets for pain relief. In the current study, we conducted a high-throughput screening of natural products in our in-house compound library to discover novel Nav1.7 inhibitors, then characterized their pharmacological properties. We identified 25 naphthylisoquinoline alkaloids (NIQs) from Ancistrocladus tectorius to be a novel type of Nav1.7 channel inhibitors. Their stereostructures including the linkage modes of the naphthalene group at the isoquinoline core were revealed by a comprehensive analysis of HRESIMS, 1D, and 2D NMR spectra as well as ECD spectra and single-crystal X-ray diffraction analysis with Cu Kα radiation. All the NIQs showed inhibitory activities against the Nav1.7 channel stably expressed in HEK293 cells, and the naphthalene ring in the C-7 position displayed a more important role in the inhibitory activity than that in the C-5 site. Among the NIQs tested, compound 2 was the most potent with an IC50 of 0.73 ± 0.03 µM. We demonstrated that compound 2 (3 µM) caused dramatical shift of steady-state slow inactivation toward the hyperpolarizing direction (V1/2 values were changed from -39.54 ± 2.77 mV to -65.53 ± 4.39 mV, which might contribute to the inhibition of compound 2 against the Nav1.7 channel. In acutely isolated dorsal root ganglion (DRG) neurons, compound 2 (10 µM) dramatically suppressed native sodium currents and action potential firing. In the formalin-induced mouse inflammatory pain model, local intraplantar administration of compound 2 (2, 20, 200 nmol) dose-dependently attenuated the nociceptive behaviors. In summary, NIQs represent a new type of Nav1.7 channel inhibitors and may act as structural templates for the following analgesic drug development.

Symmetrical Midfacial Growth After Pediatric Mandibular Reconstruction With Free Fibula Flap.

BACKGROUND: Free fibula is the workhorse flap for mandibular reconstruction and is increasingly being used in pediatric patients. However, craniomaxillofacial growth and development involve interdependent processes, and it remains unknown whether mandibular reconstruction with free fibula allows symmetric growth of the midface. PURPOSE: The study evaluated midfacial symmetry after pediatric mandibular defect reconstruction. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study included pediatric patients aged ≤14 years who underwent mandibular reconstruction with free fibula flap. Postoperative computed tomography data were obtained at predefined follow-up time points. Midfacial symmetry was evaluated based on 3-dimensional (3D) cephalometry. PREDICTOR VARIABLE: The predictor variable was the side of the midface (affected or healthy side relative to the mandibular defect). MAIN OUTCOME VARIABLES: The primary outcome variable was postoperative midfacial symmetry (at 1 week, 6 months, 1 year, 2 years, and >3 years, or after the age of 18 years), assessed in horizontal, vertical, and anteroposterior dimensions using 3D cephalometry. Another outcome variable was patient satisfaction based on a self-evaluation using visual analog scoring. COVARIATES: Sex, age, diagnosis, and type of denture restoration. ANALYSES: Paired t tests were performed to assess the relationship between the predictor and outcome variables, with the significance level of P < .05. RESULTS: A total of 13 patients were included in this study (9 males and 4 females; mean age: 12.23 ± 2.39 years). The average distance from upper first molar point (U6) to the horizontal plane on the affected side became greater than on the healthy side (difference: 0.7 ± 0.5 mm to 1.6 ± 1.4 mm, P < .05), while the average distance from pterygomaxillary fissure to coronal plane on affected side became shorter than that on the healthy side (difference: 0.6 ± 0.6 mm to 1.2 ± 1.1 mm, P < .05) from 1 year after the surgery. There were no statistically significant differences in the remaining measurements between the 2 sides (P > .05). All the patients were satisfied with their postoperative facial symmetry. CONCLUSIONS AND RELEVANCE: There were no severe midface deformities after pediatric mandibular reconstruction with free fibula flap. Meanwhile, pediatric mandibular reconstruction and proper occlusion could promote midfacial growth and symmetry.

[Construction of a predictive model for performing bronchoalveolar lavage in children with Mycoplasma pneumoniae pneumonia and pulmonary consolidation]. / 存在肺实变的肺炎支原体肺炎患儿行支气管肺泡灌洗术的预测模型构建.

OBJECTIVES: To investigate the risk factors for performing bronchoalveolar lavage (BAL) in children with Mycoplasma pneumoniae pneumonia (MPP) and pulmonary consolidation, and to construct a predictive model for performing BAL in these children. METHODS: A retrospective analysis was performed for the clinical data of 202 children with MPP who were hospitalized in the Department of Pediatrics, Changzhou No. 2 People's Hospital Affiliated to Nanjing Medical University, from August 2019 to September 2022. According to whether BAL was performed, they were divided into BAL group with 100 children and non-BAL group with 102 children. A multivariate logistic regression analysis was used to identify the risk factors for performing BAL in MPP children with pulmonary consolidation. Rstudio software (R4.2.3) was used to establish a predictive model for performing BAL, and the receiver operator characteristic (ROC) curve, C-index, and calibration curve were used to assess the predictive performance of the model. RESULTS: The multivariate logistic regression analysis demonstrated that the fever duration, C-reactive protein levels, D-dimer levels, and presence of pleural effusion were risk factors for performing BAL in MPP children with pulmonary consolidation (P<0.05). A nomogram predictive model was established based on the results of the multivariate logistic regression analysis. In the training set, this model had an area under the ROC curve of 0.915 (95%CI: 0.827-0.938), with a sensitivity of 0.826 and a specificity of 0.875, while in the validation set, it had an area under the ROC curve of 0.983 (95%CI: 0.912-0.996), with a sensitivity of 0.879 and a specificity of 1.000. The Bootstrap-corrected C-index was 0.952 (95%CI: 0.901-0.986), and the calibration curve demonstrated good consistency between the predicted probability of the model and the actual probability of occurrence. CONCLUSIONS: The predictive model established in this study can be used to assess the likelihood of performing BAL in MPP children with pulmonary consolidation, based on factors such as fever duration, C-reactive protein levels, D-dimer levels, and the presence of pleural effusion. Additionally, the model demonstrates good predictive performance.

Reconstruction of Complete Bilateral Maxillary Defects With Free Flaps.

ABSTRACT: Reconstruction of complete bilateral maxillary defects (CBMDs) can be challenging due to the extensive loss of bone and soft tissues. This is a retrospective case series of 46 consecutive patients with CBMDs that were reconstructed with different micro-vascular free flaps. The authors aimed to evaluate the surgical outcomes and discuss the different reconstruction options in this case series. Thirty-six patients underwent reconstruction following ablation surgery for malignant tumors, 6 for benign tumors, 3 patients were treated for osteomyelitis, and 1 patient underwent free flap reconstruction for posttraumatic defects. Free fibula flap (n = 26) is the most commonly used reconstruction method in this case series, which was used in all defect types. This is followed by anterolateral thigh flap (n = 10), 5 rectus abdominis myocutaneous free flap, 3 radial forearm free flaps, and 2 composite free flaps. In this series, 44 free flaps survived, whereas only 2 flaps were lost. All patients could resume a soft diet postoperatively. Reconstruction of CBMDs with vascularized free flaps is a safe and reliable procedure.

Factors influencing the accuracy of multimodal image fusion for oral and maxillofacial tumors: a retrospective study.

BACKGROUND: Ensuring high accuracy in multimodal image fusion for oral and maxillofacial tumors is crucial before further application. The aim of this study was to explore the factors influencing the accuracy of multimodal image fusion for oral and maxillofacial tumors. METHODS: Pairs of single-modality images were obtained from oral and maxillofacial tumor patients, and were fused using a proprietary navigation system by using three algorithms (automatic fusion, manual fusion, and registration point-based fusion). Fusion accuracy was evaluated including two aspects-overall fusion accuracy and tumor volume fusion accuracy-and were indicated by mean deviation and fusion index, respectively. Image modality, fusion algorithm, and other characteristics of multimodal images that may have potential influence on fusion accuracy were recorded. Univariate and multivariate analysis were used to identify relevant affecting factors. RESULTS: Ninety-three multimodal images were generated by fusing 31 pairs of single-modality images. The interaction effect of image modality and fusion algorithm (P = 0.02, P = 0.003) and thinner slice thickness (P = 0.006) were shown to significantly influence the overall fusion accuracy. The tumor volume (P < 0.001), tumor location (P = 0.007), and image modality (P = 0.01) were significant influencing factors for tumor volume fusion accuracy. CONCLUSIONS: To ensure high overall fusion accuracy, manual fusion was not preferred in CT/MRI image fusion, and neither was automatic fusion in image fusion containing PET modality. Using image sets with thinner slice thickness could increase overall fusion accuracy. CT/MRI fusion yielded higher tumor volume fusion accuracy than fusion containing PET modality. The tumor volume fusion accuracy should be taken into consideration during image fusion when the tumor volume is small and the tumor is located in the mandible.

Cardiac parameters affect prognosis in patients with non-large atherosclerotic infarction.

BACKGROUND: Although large artery atherosclerosis (LAA) is the most common type of cerebral infarction, non-LAA is not uncommon. The purpose of this paper is to investigate the prognosis of patients with non-LAA and to establish a corresponding nomogram. PATIENTS AND METHODS: Between June 2016 and June 2017, we had 1101 admissions for acute ischemic stroke (AIS). Of these, 848 were LAA and 253 were non-LAA. Patients were followed up every 3 months with a minimum of 1 year of follow-up. After excluding patients who were lost follow-up and patients who did not meet the inclusion criteria, a total of 152 non-LAA patients were included in this cohort study. After single-factor analysis and multifactor logistic regression analysis, the risk factors associated with prognosis were derived and different nomograms were developed based on these risk factors. After comparison, the best model is derived. RESULTS: Logistics regression found that the patient's National Institutes of Health Stroke Scale (NIHSS) score, ejection fraction (EF), creatine kinase-MB (CK-MB), age, neutrophil-to-lymphocyte ratio (NLR), aspartate aminotransferase (AST), and serum albumin were independently related to the patient's prognosis. We thus developed three models: model 1: single NIHSS score, AUC = 0.8534; model 2, NIHSS + cardiac parameters (CK-MB, EF), AUC = 0.9325; model 3, NIHSS + CK-MB + EF + age + AST + NLR + albumin, AUC = 0.9598. We compare the three models: model 1 vs model 2, z = - 2.85, p = 0.004; model 2 vs model 3, z = - 1.58, p = 0.122. Therefore, model 2 is considered to be the accurate and convenient model. CONCLUSIONS: Predicting the prognosis of patients with non-LAA is important, and our nomogram, built on the NIHSS and cardiac parameters, can predict the prognosis accurately and provide a powerful reference for clinical decision making.

Prognostic nomogram for microvascular decompression-treated trigeminal neuralgia.

This study aimed to establish an effective prognostic nomogram for microvascular decompression (MVD)-treated trigeminal neuralgia (TN). The nomogram was based on a retrospective cohort study of 1054 patients with TN. During the period 2005-2014, 845 patients at our department treated TN with MVD and served as a development cohort. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The model was externally validated by 209 TN patients during 2014-2016. Multivariate cox analysis suggested that the patient's age, atypical pain, vascular type, number of offending vessels, and second MVD were significant factors influencing the prognosis of MVD-treated TN. The C index of nomogram in the development cohort was 0.767 (95% CI, 0.739-0.794), and 0.749 (95% CI, 0.688-0.810) in the validation cohort. We developed and validated a nomogram to predict 3-year overall remission rate after MVD treatment of TN. The nomogram can be used in clinical trials to determine the likelihood of pain recurrence in TN patients treated with MVD for 3 years to aid in the comprehensive treatment of TN.

Hypermethylated PAX1 and ZNF582 genes in the tissue sample are associated with aggressive progression of oral squamous cell carcinoma.

BACKGROUND: DNA methylation of paired box gene 1 (PAX1) and zinc finger 582 (ZNF582) is promising cancer biomarkers for oral squamous cell carcinoma detection. This study aims to investigate the correlation between PAX1 or ZNF582 methylation and the progression of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: A total of 135 OSCC cases from Peking University School and Hospital of Stomatology were enrolled in this study. Tissue specimens were collected from the lesion site and corresponding adjacent normal site. The methylation level of these two genes was evaluated in primary and recurrent OSCC group. RESULTS: Hypermethylation of PAX1 or ZNF582 was observed in lesion sites among primary and recurrent OSCC cases. In the lesion site of primary cases, promoter methylation was observed in T3/T4 (PAX1: P = .02; ZNF582: P = .01), stage III/IV (PAX1: P = .03; ZNF582: P = .01), and bone invasion cases (PAX1: P = .02; ZNF582: P = .047). In the subgroup analysis, the correlation between hypermethylation and OSCC severity remains significant with exposure to smoking/alcohol consumption. CONCLUSIONS: Hypermethylated PAX1 and ZNF582 can sufficiently act as biomarkers to reflect the severity or progression of OSCC.

Three-Dimensional Accuracy of Bone Contouring Surgery for Zygomaticomaxillary Fibrous Dysplasia Using Virtual Planning and Surgical Navigation.

PURPOSE: Fibrous dysplasia (FD) is a benign condition in which normal cancellous bone is replaced by immature woven bone and fibrous tissue. The present study aimed to estimate and compare the 3-dimensional (3D) accuracy of bone contouring surgery for zygomaticomaxillary FD performed using virtual planning and surgical navigation versus surgeon's intraoperative assessment. PATIENTS AND METHODS: This is a retrospective cross-sectional study. Patients with zygomaticomaxillary FD who underwent bone contouring surgery between 2012 and 2019 were reviewed. They were divided into 2 groups: group A underwent bone contouring surgery using virtual planning and surgical navigation, and group B underwent bone contouring surgery by surgeon's intraoperative assessment. The predictor variable was surgical technique. The other variables were gender, age, and operative region. The primary outcome variable was 3D accuracy, which was indicated by root mean square, calculated as a measure of the deviation of the postoperative computed tomography from the preoperative virtual plan. The other outcome variables were patient satisfaction with the outcome by self-evaluation score and operative times. Correlation analysis between the predictor variables and outcome variables was performed. RESULTS: The sample comprised 24 patients (17 males and 7 females, mean age, 25.7 ± 10.45 years), 13 patients in group A and 11 patients in group B. The mean root mean square was significantly lower in group A than in group B (P = .007). Patient satisfaction with facial symmetry was significantly better in group A (P = .015). Mean operative time was comparable between the 2 groups (P = .918). Surgical technique (P = .011) and operative region (P = .01) were significant influence factors in 3D accuracy of surgery. CONCLUSIONS: Virtual planning and surgical navigation can significantly improve the 3D accuracy and patient satisfaction of bone contouring surgery for zygomaticomaxillary FD, without prolonging operative time.

Double-Barrel Fibula Flap Versus Vascularized Iliac Crest Flap for Mandibular Reconstruction.

PURPOSE: The double-barrel fibula flap and vascularized iliac crest flap are both commonly used for mandibular reconstruction. The present study compared the usage and reconstruction outcomes of transplanted bone with these 2 methods. PATIENTS AND METHODS: The data from 30 patients who had undergone mandibular osteotomy and reconstruction were retrospectively reviewed. Of the 30 patients, 20 received a vascularized iliac crest flap (group A) and 10 received a double-barrel fibula flap (group B). The following variables were compared between the 2 groups: volume of bone flap (VBF), volume of effective bone flap (VEBF; ie, overlap between the volume of the ideal mandible [VIM] and the VBF), usage of the bone flap (VEBF divided by the VBF), mandibular reconstruction rate (VEBF divided by the VIM), volume of needless bone flap (VNBF; ie, VBF minus VEBF; the VNBF included the volume of needless buccal bone flap [VNBBF] and the volume of needless lingual bone flap [VNLBF]), percentage of alveolar crest restoration (PACR; ie, effective bone flap width divided by ideal alveolar crest width), and height of the bone flap (HBF). The independent-samples t test and the χ2 test were used to compare the variables between the 2 groups. Statistical significance was at P ≤ .05. RESULTS: Usage of the bone flap and the length of the mandibular defect were significantly greater in group B than in group A (P = .039 and P < .001, respectively). The VBF, VNBF, and VNLBF were significantly greater in group A than in group B (P < .001 for both). The mandibular reconstruction rate, VNBBF, PACR, HBF, and tooth implantation rate were comparable between the 2 groups. CONCLUSIONS: The double-barrel fibula flap can effectively restore the height of the alveolar crest, reconstruct longer mandibular defects, and provide a better buccal and lingual appearance compared with the vascularized iliac crest flap. Although the vascularized iliac crest flap can provide sufficient bone quantity, it must be contoured to the mandible.

Factors Affecting Volume Change of Anterolateral Thigh Flap in Head and Neck Defect Reconstruction.

PURPOSE: The anterolateral thigh flap (ALTF) volume will decrease over time after surgery. We measured and identified the risk factors for postoperative volume changes in the ALTF. MATERIALS AND METHODS: We designed and performed a retrospective cohort study of patients who had undergone reconstruction of oral and maxillofacial defects using ALTFs at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from June 2012 to December 2018. We measured the volume of the ALTFs at 1, 3, 6, 12, and 24 months postoperatively; the flap volume at 1 month postoperatively was taken as the baseline. The primary outcome variables were the residual ALTF rates at 3, 6, 12, and 24 months postoperatively, defined as the ratio between the present volume at each month and at baseline. The primary predictor variables were the clinical variables that might be associated with ALTF volume loss. Descriptive and bivariate statistics were computed, and the P value for statistical significance was set at ≤ .05. RESULTS: The sample included 70 subjects with a mean age of 53.8 years (46 men and 24 women). The postoperative residual rates at 3, 6, 12, and 24 months were 72.3, 69.0, 67.9, and 68.7%, respectively, of the baseline volume. The use of postoperative radiotherapy (P < .01) and low body mass index (BMI; P = .006) were significantly associated with postoperative ALTF volume loss. CONCLUSIONS: The results of the present study suggest that ALTF volume shrinkage mainly occurs within 6 months postoperatively and that postoperative radiotherapy and a low BMI are risk factors for volume loss. Overcorrection should be performed to account for the shrinkage of ALTFs, and postoperative nutrition management is important to avoid ALTF volume loss.

Regeneration of the Neocondyle After Free Fibular Flap Reconstruction of the Mandibular Condyle.

PURPOSE: Shifting of the flap position after condylar reconstruction with free fibular flaps is known to occur, but its long-term effects on postoperative esthetic outcomes have not been sufficiently reported. Therefore, in this study, we evaluated the long-term morphologic stability of the free fibular flap neocondyle. PATIENTS AND METHODS: This was a retrospective cohort study. The primary outcome variables were neocondyle regeneration and neocondyle position including the distance between the glenoid fossa and the initial neocondyle (Fo-Co), the distance between the glenoid fossa and the stable neocondyle (Fo-Co'), and shifting of the neocondyle (defined as the distance between the stable neocondyle and the initial neocondyle). The primary predictor variable was time. The other variables were age, gender, diagnosis, and number of fibular segments. Correlation analysis between the predictor variables and outcome variables was performed. RESULTS: The sample was composed of 26 patients (11 male and 15 female patients) with a mean age of 31 years. Diagnosis and number of fibular segments were significantly associated with Fo-Co and Fo-Co' (P < .05). Among the 26 patients, only 11 showed neocondyle regeneration at follow-up (group A) whereas 15 did not (group B). Neocondyle regeneration was significantly associated with patient age (P < .01). Stable Fo-Co and stable time were significantly associated with neocondyle regeneration (P < .05). The mean stable time was significantly shorter in group A (3.64 ± 1.12 months) than in group B (6.67 ± 3.85 months) (P < .05), and the mean Fo-Co' was significantly shorter in group A (13.65 ± 3.94 mm) than in group B (20.68 ± 8.87 mm) (P < .05). CONCLUSIONS: The possibility of neocondyle regeneration is higher in pediatric patients than in adults. Neocondyle regeneration could result in the movement of the neocondyle toward the glenoid fossa with a shorter stable time, which could improve neocondyle repositioning. Repositioning of the neocondyle with free fibular flaps for mandibular condyle defects is a self-adaption process for temporomandibular joint function.

Selection of Guiding Plate Combined With Surgical Navigation for Microsurgical Mandibular Reconstruction.

PURPOSE: The present study summarized selection of guiding plate combined with surgical navigation for microsurgical mandibular reconstruction. METHODS: Data from preoperative maxillofacial enhanced computed tomography (CT) scans were imported to ProPlan CMF. The authors performed virtual mandibulectomy and superimposed 3-dimensional (3D) iliac images on mandibular defects. Guiding plates including mandibular fixation device, reconstruction plate, guiding model, and occlusal splint for various mandibular hemimandibular central lateral (HCL) defects were fabricated to fix bilateral residual mandible. The model was scanned, and data were imported into ProPlan CMF and the intraoperative navigation system. Through landmark points upon the guiding plate, position of the residual mandible was determined during surgical navigation. Intraoperative navigation was used to implement the virtual plan. Sagittal, coronal, axial, and 3D reconstruction images displayed by the navigation system were used to accurately determine osteotomy sites and osteotomy trajectory during surgery. Surgical probe guidance was used to mark the osteotomy line and transfer the virtual procedure to real-time surgery. Accuracy was evaluated using chromatographic analysis. RESULTS: Different guiding plates combined with surgical navigation could be used for various mandibular defects, including mandibular fixation devices for LCL defects, reconstruction plates for LC/L/C defects, and guiding models and occlusal splints for H/L/LC defects (including mandibular ramus). In our study, average and largest shift of the mandible and osteotomy site was <5 mm. CONCLUSION: The authors summarized different ways of combining guiding plates with surgical navigation for reconstruction of various mandibular defects, which could improve clinical outcomes of this procedure with high accuracy.

Hsa_circ_101882 promotes migration and invasion of gastric cancer cells by regulating EMT.

BACKGROUND: At present, gastric cancer (GC) is a serious threat to human life and health. Non-coding circular RNAs (circRNAs) have been found abnormal expression in multiple tumors. However, circRNAs remain largely unknown in tumor progression. In the present study, we mainly examined the expression, function, and molecular mechanisms of a new circRNAs (hsa_circ_101882) in GC. MATERIALS AND METHODS: The expression of hsa_circ_101882 in GC tissue, corresponding adjacent normal tissues, and GC cell lines was examined by RT-PCR. The function of hsa_circ_101882 in GC was evaluated by MTT assay, cell migration, and invasion assay, colony formation assay, and flow cytometric assay. The effect of hsa_circ_101882 on epithelial-to-mesenchymal transition (EMT)-related gene expression was detected by RT-PCR and Western blot. RESULTS: Hsa_circ_101882 expression levels were significantly increased in GC tissue and GC cell lines. Functionally, low expression of hsa_circ_101882 revealed anti-tumor effects via inhibiting cell growth, migration, and invasion and promoting cell apoptosis. Mechanically, the dysregulated expression of hsa_circ_101882 affects EMT signaling pathway, which was examined by detecting E-cadherin, N-cadherin, vimentin, and Snail expression levels. CONCLUSIONS: Therefore, our research reveals that hsa_circ_101882 is considered a metastasis promoter by activating EMT and may serve as a critical oncogene and potential new biomarker in GC.

Outcomes of Zygomatic Complex Reconstruction With Patient-Specific Titanium Mesh Using Computer-Assisted Techniques.

PURPOSE: Zygomatic complex defects after extensive maxillectomy can cause severe esthetic and functional deformities. Patient-specific titanium mesh fabricated using a computer-assisted technique is a promising method for such midface reconstruction. The aim of this study was to evaluate the application and clinical outcomes of this technique. PATIENTS AND METHODS: This was a retrospective study that included 9 patients with zygomatic complex defects after extensive maxillectomy from 2015 through 2017 at the authors' institution. A 3-dimensional stereo model was obtained based on mirror images of the unaffected side to fabricate a patient-specific titanium mesh using computer-assisted design and manufacturing. Titanium mesh was used to restore the contour of the zygomatic complex with free flap reconstruction after tumor resection. Anterolateral thigh flaps were used in 8 cases and a myocutaneous fibula flap was used in 1 case. Symmetry of the zygomatic complex was evaluated by measuring the zygomatic eminence on the postoperative computed tomogram, and complications were recorded during follow-up visits. Facial symmetry was self-evaluated and scored. RESULTS: Mean duration for follow-up was 27.3 months (range, 15 to 39 months). Mean deviation of the zygomatic eminence between the reconstructed and unaffected sides was 1.4 ± 0.5 mm. No significant difference was noted in the zygomatic eminence between the reconstructed and unaffected sides (P = .591). Titanium mesh exposure occurred in only 1 patient after radiotherapy. There were no other remarkable complications. All patients were satisfied with their postoperative facial symmetry. CONCLUSION: Patient-specific titanium mesh fabricated using a computer-assisted technique was an alternative option for extensive zygomatic complex reconstruction, resulting in acceptable clinical outcomes. A study with a larger sample and long-term follow-up is needed for the observation of long-term outcomes and risk of titanium mesh-related complications.

Calmodulin in complex with the first IQ motif of myosin-5a functions as an intact calcium sensor.

The motor function of vertebrate myosin-5a is inhibited by its tail in a Ca2+-dependent manner. We previously demonstrated that the calmodulin (CaM) bound to the first isoleucine-glutamine (IQ) motif (IQ1) of myosin-5a is responsible for the Ca2+-dependent regulation of myosin-5a. We have solved the crystal structure of a truncated myosin-5a containing the motor domain and IQ1 (MD-IQ1) complexed with Ca2+-bound CaM (Ca2+-CaM) at 2.5-Å resolution. Compared with the structure of the MD-IQ1 complexed with essential light chain (an equivalent of apo-CaM), MD-IQ1/Ca2+-CaM displays large conformational differences in IQ1/CaM and little difference in the motor domain. In the MD-IQ1/Ca2+-CaM structure, the N-lobe and the C-lobe of Ca2+-CaM adopt an open conformation and grip the C-terminal and the N-terminal portions of the IQ1, respectively. Remarkably, the interlobe linker of CaM in IQ1/Ca2+-CaM is in a position opposite that in IQ1/apo-CaM, suggesting that CaM flip-flops relative to the IQ1 during the Ca2+ transition. We demonstrated that CaM continuously associates with the IQ1 during the Ca2+ transition and that the binding of CaM to IQ1 increases Ca2+ affinity and substantially changes the kinetics of the Ca2+ transition, suggesting that the IQ1/CaM complex functions as an intact Ca2+ sensor responding to distinct calcium signals.

The Risk Factors for Facial Numbness After Microvascular Decompression in Patients With Trigeminal Neuralgia.

OBJECT: Microvascular decompression (MVD) is the most popular surgical procedure for treating Trigeminal neuralgia (TN). In this article, the authors conducted a large case series in which patients underwent MVD for TN, and focus on surgical outcomes, intraoperative findings, complications and risk factors. METHODS: From January 2017 to June 2017, a total of 84 patients with TN were treated with MVD in our department. The authors retrospectively analyzed the surgical outcomes and postoperative complications of these patients. Risk factors were analyzed by binary logistic regression analysis. RESULTS: Of the 84 patients, 69 had complete postoperative symptom relief (BNI I-II). A total of 28 patients developed postoperative facial numbness (BNI III-IV) and 1 patient died intraoperatively. With binary logistic regression analysis, significant risk factors for postoperative Facial numbness (FN) were longer operation time (odds ratio [OR] 1.153, P <0.05) and longer hospital stay (OR 1.371, P <0.05). The patients' age, the length of the disease, the gender, and the side of the disease did not affect the occurrence of postoperative FN. CONCLUSIONS: The study found that patients with TN treated with MVD had a good response rate after surgery. The incidence of FN after surgery is not low, and longer duration of surgery and longer hospital stay are risk factors for FN. In the case of ensuring the success rate of surgery, reducing unnecessary operations, reducing the operation time, will help to reduce the occurrence of FN.

The role of ß-adrenergic receptors and p38MAPK signaling pathways in physiological processes of cardiosphere-derived cells.

The effects of ß adrenergic receptors (ß-ARs) and p38 mitogen-activated protein kinases (MAPK) pathways on cardiosphere-derived cells (CDCs) are largely unknown. This study aimed to investigate the roles of ß-ARs and p38MAPK pathways on the proliferation, apoptosis, and differentiation capacity of CDCs. The CDCs were treated with ß1-AR blocker (Met group), ß2-AR antagonist (ICI group), and p38MAPK inhibitor (SB group), non-selective ß-AR blocker (PRO group), and ß-AR agonist (ISO group). The viability, apoptotic rate and differentiation status of CDCs were determined by MST-1 assay, flow cytometery, and Western blot, respectively. The CDCs viability significantly reduced in ICI group (all P < 0.05), and SB group had a significant high viability after 48 h treatment (P < 0.05). Compared with control group, all treated groups had a low apoptotic rate. After treatment for 72 h, ISO treatment elevated the expression of Nkx2.5, and could partially or fully attenuate the inhibitory effects of ß-AR antagonists and/or p38MAPK inhibitor. A similar overall trend of protein expression levels among all groups could be observed between protein pairs of cTnT and ß1-AR as well as c-Kit and ß2-AR, respectively. These results suggested that ß-ARs and p38MAPK signaling pathways play crucial roles in the proliferation and differentiation of CDCs. Our findings should be helpful for better understanding the molecular mechanism underlying the physiological processes of CDCs.

The Globular Tail Domain of Myosin-5a Functions as a Dimer in Regulating the Motor Activity.

Myosin-5a contains two heavy chains, which are dimerized via the coiled-coil regions. Thus, myosin-5a comprises two heads and two globular tail domains (GTDs). The GTD is the inhibitory domain that binds to the head and inhibits its motor function. Although the two-headed structure is essential for the processive movement of myosin-5a along actin filaments, little is known about the role of GTD dimerization. Here, we investigated the effect of GTD dimerization on its inhibitory activity. We found that the potent inhibitory activity of the GTD is dependent on its dimerization by the preceding coiled-coil regions, indicating synergistic interactions between the two GTDs and the two heads of myosin-5a. Moreover, we found that alanine mutations of the two conserved basic residues at N-terminal extension of the GTD not only weaken the inhibitory activity of the GTD but also enhance the activation of myosin-5a by its cargo-binding protein melanophilin (Mlph). These results are consistent with the GTD forming a head to head dimer, in which the N-terminal extension of the GTD interacts with the Mlph-binding site in the counterpart GTD. The Mlph-binding site at the GTD-GTD interface must be exposed prior to the binding of Mlph. We therefore propose that the inhibited Myo5a is equilibrated between the folded state, in which the Mlph-binding site is buried, and the preactivated state, in which the Mlph-binding site is exposed, and that Mlph is able to bind to the Myo5a in preactivated state and activates its motor function.

Infected Abdominal Aortic Aneurysms Treated with Extra-anatomic Prosthesis Bypass in the Retroperitoneum.

BACKGROUND: Infected abdominal aortic aneurysms (iAAAs) are rare but life-threatening diseases. The purpose of the present study was to report our experience of extra-anatomic prosthesis bypass in the retroperitoneum as a treatment for iAAAs. METHODS: Data of 8 consecutive patients diagnosed with iAAAs and treated by an extra-anatomic prosthesis bypass in the retroperitoneum were retrospectively collected. Operative details were as follows: one side of the retroperitoneal space was selected to build a track, and a bifurcated expanded polytetrafluoroethylene prosthesis was placed through the track. The proximal end of the prosthesis was sutured with the normal segment of abdominal aorta proximal to the infected aneurysm by end-to-end anostomosis. The 2 distal ends of the prosthesis were, respectively, sutured with the external iliac artery distal to the aneurysm. The anastomoses were then consolidated with the nearby connective tissue. After the closure of the retroperitoneum, the infected aneurysm was incised, and the infected tissue was debrided. Drainage tubes were placed in the aneurysm sac, which was packed with an omentum flap. All patients received perioperative antibiotic therapy for a period of time. All 8 patients were regularly followed up by outpatient observation. RESULTS: Eight patients with iAAAs underwent an extra-anatomic prosthesis bypass in the retroperitoneum and debridement of the infected aneurysm. An emergency operation was performed for 1 patient who underwent concomitant gastrointestinal procedures for aortoduodenal fistula. All 8 patients were definitively diagnosed by one or more sequential computed tomography scans combined with other methods. The blood or tissue cultures of all cases were positive in the perioperative period, with Salmonella (5 cases) being the most common pathogens. Other pathogens included Burkholderia pseudomallei (2 cases) and Escherichia coli (1 case). All patients survived and were discharged in 4-5 weeks after their operations. All patients were free from graft infection during the follow-up period. CONCLUSIONS: The extra-anatomic prosthesis bypass in the retroperitoneum for treating iAAAs was safe and effective. Our experience with the procedure may provide a new approach for the treatment of this disease.