Orthognathic surgery improves compromised natural head position and pharyngeal airway in patients with Skeletal Class II or III malocclusion.

BACKGROUND: Natural head position (NHP), pharyngeal airway and maxillofacial growth pattern are correlated. The author's previous studies proved that following surgical correction of Skeletal Class II malocclusion, the over-extended NHP returned upright, and the pharyngeal airway space (PAS) dimension expanded. OBJECTIVE: The present study compares the post-operative change in NHP and PAS after orthognathic surgery in Skeletal Class II and III malocclusion patients. METHODS: Patients receiving orthognathic procedures to correct Skeletal Class II or III malocclusions were reviewed in this retrospective study. Pre-operative and 6-week post-operative cone-beam computed tomography datasets were collected. Variables representing the craniofacial pattern, the NHP and the PAS were measured three-dimensionally. Post-operative variables were compared with their pre-operative counterparts using either repeat-measure 2-way analysis of variance or Wilcoxon matched-pairs signed rank test. RESULTS: Thirty cases of Skeletal Class II malocclusion and 13 cases of Skeletal Class III malocclusion were collected. Preoperatively, the inter-group differences were significant in craniofacial pattern (68.14 ± 3.552 degree vs. 79.63 ± 2.497 degree, p < .0001) and the NHP (68.77 ± 11.02 degree vs. 82.83 ± 7.738 degree, p = .0002) while not significant in PAS; after surgery, the intergroup differences in craniofacial pattern and the NHP between groups decreased, and the PAS increased in both groups. CONCLUSION: Orthognathic surgery may improve compromised NHP and increase PAS in Skeletal Class II and III malocclusion patients.

Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients.

Tibial cortex transverse distraction is a surgical method for treating severe diabetic foot ulcers (DFUs), but the underlying mechanism is unclear. We show that antioxidant proteins and small extracellular vesicles (sEVs) with multiple-tissue regenerative potential are released during bone transport (BT) in humans and rats. These vesicles accumulate in diabetic wounds and are enriched with microRNAs (miRNAs) (e.g., miR-494-3p) that have high regenerative activities that improve the circulation of ischemic lower limbs while also promoting neovascularization, fibroblast migration, and nerve fiber regeneration. Deletion of miR-494-3p in rats reduces the beneficial effects of BT on diabetic wounds, while hydrogels containing miR-494-3p and reduced glutathione (GSH) effectively repair them. Importantly, the ginsenoside Rg1 can upregulate miR-494-3p, and a randomized controlled trial verifies that the regimen of oral Rg1 and GSH accelerates wound healing in refractory DFU patients. These findings identify potential functional factors for tissue regeneration and suggest a potential therapy for DFUs.

Fluorofenidone attenuates renal fibrosis by inhibiting lysosomal cathepsin­mediated NLRP3 inflammasome activation.

Currently, no antifibrotic drug in clinical use can effectively treat renal fibrosis. Fluorofenidone (AKFPD), a novel pyridone agent, significantly reduces renal fibrosis by inhibiting the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome; however, the underlying mechanism of this inhibition is not fully understood. The present study aimed to reveal the molecular mechanism underlying the suppression of NLRP3 inflammasome activation by AKFPD. It investigated the effect of AKFPD on NLRP3 activation and lysosomal cathepsins in a unilateral ureteral obstruction (UUO) rat model, and hypoxia/reoxygenation (H/R)-treated HK-2 cells and murine peritoneal-derived macrophages (PDMs) stimulated with lipopolysaccharide (LPS) and ATP. The results confirmed that AKFPD suppressed renal interstitial fibrosis and inflammation by inhibiting NLRP3 inflammasome activation in UUO rat kidney tissues. In addition, AKFPD reduced the production of activated caspase-1 and maturation of IL-1ß by suppressing NLRP3 inflammasome activation in H/R-treated HK-2 cells and murine PDMs stimulated with LPS and ATP. AKFPD also decreased the activities of cathepsins B, L and S both in vivo and in vitro. Notably, AKFPD downregulated cathepsin B expression and NLRP3 colocalization in the cytoplasm after lysosomal disruptions. Overall, the results suggested that AKFPD attenuates renal fibrosis by inhibiting lysosomal cathepsin-mediated activation of the NLRP3 inflammasome.

SIRT1 and miR-34a-5p Expression in PBMCs as Potential Biomarkers for Patients With Type 2 Diabetes With Cognitive Impairments.

CONTEXT: Patients with type 2 diabetes mellitus (T2DM) are at significantly increased risk of Alzheimer disease (AD). However, no biomarkers are available for early identification of patients with T2DM with cognitive impairment (T2DM-CI). Mitochondrial dysfunction is linked to AD. Silent Information Regulator 1 (SIRT1), which is responsible for regulating mitochondrial biogenesis, and its related miRNAs were also altered in AD. OBJECTIVE: This study aimed to determine whether mitochondrial function in peripheral blood mononuclear cells (PBMCs) of patients with T2DM-CI was altered and if these alterations could be used as biomarkers. METHODS: A total of 374 subjects were enrolled, including AD, T2DM-CI, T2DM-nCI (T2DM without cognitive impairment), and healthy controls. The mitochondrial function was determined using a commercial assay kit. The mitochondrial DNA (mtDNA) content, the expression of SIRT1, and selected miRNAs in PBMCs were measured by quantitative polymerase chain reaction. The correlations and diagnostic accuracy were assessed using the Spearman correlation coefficient or receiver operating characteristics analysis, respectively. RESULTS: We found significant changes in mitochondrial function in PBMCs of patients with AD compared with controls (all P < .05), which were not found in T2DM-CI. However, mtDNA content and SIRT1 mRNA expression were lower in PBMCs of patients with T2DM-CI, while miR-34a-5p expression was higher than in patients with T2DM-nCI (all P < .05). A combination of SIRT1 and miR-34a-5p demonstrated excellent discrimination between T2DM-CI and T2DM-nCI (area under the curve = 0.793; sensitivity: 80.01%; specificity: 78.46%). Furthermore, correlation analysis revealed a link between miR-34a-5p expression and hyperglycemia in T2DM-CI. CONCLUSION: Our findings revealed that there was an alteration of mitochondria at the peripheral level in patients with T2DM-CI. SIRT1 combined with miR-34a-5p in PBMCs performed well in identifying patients with T2DM-CI and may be a promising biomarker.

Comprehensive transcriptomics and metabolomics analyses reveal that hyperhomocysteinemia is a high risk factor for coronary artery disease in a chinese obese population aged 40-65: a prospective cross-sectional study.

BACKGROUND: Clinical observations suggest a complex relationship between obesity and coronary artery disease (CAD). This study aimed to characterize the intermediate metabolism phenotypes among obese patients with CAD and without CAD. METHODS: Sixty-two participants who consecutively underwent coronary angiography were enrolled in the discovery cohort. Transcriptional and untargeted metabolomics analyses were carried out to screen for key molecular changes between obese patients with CAD (CAD obese), without CAD (Non-CAD obese), and Non-CAD leans. A targeted GC-MS metabolomics approach was used to further identify differentially expressed metabolites in the validation cohorts. Regression and receiver operator curve analysis were performed to validate the risk model. RESULTS: We found common aberrantly expressed pathways both at the transcriptional and metabolomics levels. These pathways included cysteine and methionine metabolism and arginine and proline metabolism. Untargeted metabolomics revealed that S-adenosylhomocysteine (SAH), 3-hydroxybenzoic acid, 2-hydroxyhippuric acid, nicotinuric acid, and 2-arachidonoyl glycerol were significantly elevated in the CAD obese group compared to the other two groups. In the validation study, targeted cysteine and methionine metabolomics analyses showed that homocysteine (Hcy), SAH, and choline were significantly increased in the CAD obese group compared with the Non-CAD obese group, while betaine, 5-methylpropanedioic acid, S-adenosylmethionine, 4-PA, and vitamin B2 (VB2) showed no significant differences. Multivariate analyses showed that Hcy was an independent predictor of obesity with CAD (hazard ratio 1.7; 95%CI 1.2-2.6). The area under the curve based on the Hcy metabolomic (HCY-Mtb) index was 0.819, and up to 0.877 for the HCY-Mtb.index plus clinical variables. CONCLUSION: This is the first study to propose that obesity with hyperhomocysteinemia is a useful intermediate metabolism phenotype that could be used to identify obese patients at high risk for developing CAD.

Cardiovascular mortality by cancer risk stratification in patients with localized prostate cancer: a SEER-based study.

Purpose: The risk of cardiovascular disease (CVD) mortality in patients with localized prostate cancer (PCa) by risk stratification remains unclear. The aim of this study was to determine the risk of CVD death in patients with localized PCa by risk stratification. Patients and methods: Population-based study of 340,806 cases in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with localized PCa between 2004 and 2016. The proportion of deaths identifies the primary cause of death, the competing risk model identifies the interaction between CVD and PCa, and the standardized mortality rate (SMR) quantifies the risk of CVD death in patients with PCa. Results: CVD-related death was the leading cause of death in patients with localized PCa, and cumulative CVD-related death also surpassed PCa almost as soon as PCa was diagnosed in the low- and intermediate-risk groups. However, in the high-risk group, CVD surpassed PCa approximately 90 months later. Patients with localized PCa have a higher risk of CVD-related death compared to the general population and the risk increases steadily with survival (SMR = 4.8, 95% CI 4.6-5.1 to SMR = 13.6, 95% CI 12.8-14.5). Conclusions: CVD-related death is a major competing risk in patients with localized PCa, and cumulative CVD mortality increases steadily with survival time and exceeds PCa in all three stratifications (low, intermediate, and high risk). Patients with localized PCa have a higher CVD-related death than the general population. Management of patients with localized PCa requires attention to both the primary cancer and CVD.

Paramedian Lateral-angled Mandibulotomy for Resection of Squamous Cell Carcinoma in the Oral Cavity.

Mandibulotomy provides good access for monobloc compartmental resection of squamous cell carcinoma in the proper oral cavity. Various designs of osteotomy have been reported, but few of them have considered the local anatomical conditions, and thus related complications occasionally happen. We devised a paramedian lateral-angled mandibulotomy to reduce the side injuries.

Three-Dimensional Printed Titanium Prosthesis for Mandibular Condyle Reconstruction After Extensive Resection of Chondrosarcoma: A 6-year Follow-Up.

Chondrosarcomas (CHS) are malignant mesenchymal tumors arising from cartilage. Chondrosarcomas arising in the temporomandibular joint are especially rare. Herein, the authors report an unusual case of a 50-year-old female who presented with a progressive swelling in the left preauricular region. Computed tomography and magnetic resonance imaging revealed an osteolytic and expansive lesion in the left condyle. The diagnosis tended to be a malignant tumor. A resection guide and 3-dimensional printed titanium prosthesis for condyle reconstruction were designed. Extended resection of the left condyle and reconstruction were performed. The pathologic diagnosis was consistent with CHS (grade II). There was no tumor recurrence or distant metastasis at the 6-year follow-up, and good occlusion and satisfactory function of the temporomandibular joint were regained.

Squamous Cell Carcinoma Arising From Odontogenic Cyst Epithelium or Oral Mucosa Epithelium After Marsupialization of Odontogenic Radicular Cyst in Posterior Mandible?

Squamous cell carcinomas (SCCs) are common malignant tumors in the oral and maxillofacial region. However, SCCs secondary to marsupialization of odontogenic radicular cysts are extremely rare. The authors report an unusual case of a 43-year-old male presented with dull pain in the right molar region of the mandible without numbness of lower lips, who had a long history of smoking, alcohol consumption, and betel nut chewing. Computerized tomography revealed a round well-defined unilocular radiolucent at the apex of lower right premolars, 2 nonvital teeth. The clinical diagnosis was the radicular cyst of the right mandible. The patient was initially treated with root canal therapy of the teeth followed by marsupialization with a mandibular vestibular groove incision. While the patient did not follow the instruction of irrigation of the cyst and had no regular follow-up. The reexamination of computerized tomography indicated a round well-defined unilocular radiolucent at the apex of lower right premolars and filled with a soft tissue without clear boundary with buccal muscles at 31 months follow-up. There were no masses or ulcer around the mandibular vestibular groove incision and the patient had no sign of numbness of lower lips. The clinical diagnosis was the radicular cyst of right mandible with infection. A curettage was performed. However, the pathologic diagnosis was well-differentiated SCC. An extended radical surgical resection including segmental resection of the right mandible was performed. The histopathology was well-differentiated SCC without the cyst epithelium and invasion of bone, which can be distinguished from primary intraosseous SCC. The case indicates that marsupialization performed in patients with a history of smoking, alcohol consumption, and betel nut chewing, has a risk of suffering from oral SCC.

Non-cancer-specific survival in patients with primary central nervous system lymphoma: A multi-center cohort study.

Objective: The study aimed to evaluate the non-cancer-specific death risk and identify the risk factors affecting the non-cancer-specific survival (NCSS) in patients with primary central nervous system lymphoma (PCNSL). Methods: This multi-center cohort study included 2497 patients with PCNSL in the Surveillance, Epidemiology and End Results (SEER) database from 2007 to 2016, with a mean follow-up of 4.54 years. The non-cancer-specific death risk in patients with PCNSL and primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) was evaluated using the proportion of deaths, standardized mortality ratio (SMR), and absolute excess risk (AER). Univariate and multivariate competing risk regression models were utilized to identify the risk factors of NCSS. Results: PCNSL was the most frequent cause of death in PCNSL patients (75.03%). Non-cancer-specific causes constituted a non-negligible portion of death (20.61%). Compared with the general population, PCNSL patients had higher risks of death from cardiovascular disease (CVD) (SMR, 2.55; AER, 77.29), Alzheimer's disease (SMR, 2.71; AER, 8.79), respiratory disease (SMR, 2.12; AER, 15.63), and other non-cancer-specific diseases (SMR, 4.12; AER, 83.12). Male sex, Black race, earlier year of diagnosis (2007-2011), being unmarried, and a lack of chemotherapy were risk factors for NCSS in patients with PCNSL and PCNS-DLBCL (all P < 0.05). Conclusion: Non-cancer-specific causes were important competing causes of death in PCNSL patients. More attention is recommended to non-cancer-specific causes of death in the management of PCNSL patients.

Vision-based estimation of MDS-UPDRS scores for quantifying Parkinson's disease tremor severity.

Parkinson's disease (PD) is a common neurodegenerative movement disorder among older individuals. As one of the typical symptoms of PD, tremor is a critical reference in the PD assessment. A widely accepted clinical approach to assessing tremors in PD is based on part III of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). However, expert assessment of tremor is a time-consuming and laborious process that poses considerable challenges to the medical evaluation of PD. In this paper, we proposed a novel model, Global Temporal-difference Shift Network (GTSN), to estimate the MDS-UPDRS score of PD tremors based on video. The PD tremor videos were scored according to the majority vote of multiple raters. We used Eulerian Video Magnification (EVM) pre-processing to enhance the representations of subtle PD tremors in the videos. To make the model better focus on the tremors in the video, we proposed a special temporal difference module, which stacks the current optical flow to the result of inter-frame difference. The prediction scores were obtained from the Residual Networks (ResNet) embedded with a novel module, the Global Shift Module (GSM), which allowed the features of the current segment to include the global segment features. We carried out independent experiments using PD tremor videos of different body parts based on the scoring content of the MDS-UPDRS. On a fairly large dataset, our method achieved an accuracy of 90.6% for hands with rest tremors, 85.9% for tremors in the leg, and 89.0% for the jaw. An accuracy of 84.9% was obtained for postural tremors. Our study demonstrated the effectiveness of computer-assisted assessment for PD tremors based on video analysis. The latest version of the code is available at https://github.com/199507284711/PD-GTSN.

Effect of sex on the association between arterial partial pressure of oxygen and in-hospital mortality in ICU patients with cardiogenic shock: a retrospective cohort study.

Background: Maintaining tissue perfusion and oxygen supply are essential for cardiogenic shock (CS) treatment. Sex has been reported to be associated with mortality and oxygen use in patients with CS. Males and females respond differently to hypoxia. We designed this cohort study to evaluate the effects of sex on the association between the arterial partial pressure of oxygen (PaO2) and in-hospital mortality. Methods: We used the Medical Information Mart for Intensive Care (MIMIC) IV database for this cohort study. The outcome was in-hospital mortality. The relationship between the PaO2 and in-hospital mortality was compared with sex (via an interaction test) using multivariable Cox regression models. Presence of interaction between PaO2 and sex was tested by using inter interaction terms. Results: A total of 1,772 patients with CS were enrolled in this study. The association between PaO2 and in-hospital mortality appeared to differ between males and females [hazard ratio (HR): 0.997, 95% confidence interval (CI): 0.995-0.999 vs. HR: 1.002, 95% CI: 0.999-1.003, P for interaction =0.002]. We repeated the analyses, based on different PaO2 category (PaO2 <60 mmHg; PaO2 60-100 mmHg; PaO2 >100 mmHg) and the results remained stable, P for interaction =0.008. Conclusions: Sex affects the relationship between PaO2 and in-hospital mortality in CS patients. Our findings may lead to the development of individualized therapies that focus on the use of different target oxygen partial pressures in different sexes to treat patients with CS.

[Correlation of betel nut chewing and clinicopathologic factors of oral squamous cell carcinoma].

PURPOSE: To investigate the correlation of clinicopathologic factors and immunophenotypic features with betel nut chewing in oral squamous cell carcinoma(OSCC). METHODS: The data of 88 patients with OSCC were collected. According to the habit of betel nut chewing, the clinicopathologic factors and immunohistochemical parameters were analyzed. The relationship between clinicopathologic factors of OSCC and betel nut chewing was analyzed with univariate analysis and multivariate analysis using SPSS 17.0 software package. RESULTS: 46.6% of patients had the habit of betel nut chewing and 67.0% of patients had tongue cancer and buccal cancer. The pathological stages were mainly T2 (40.9%). From univariate analysis of the results, differentiation degree, ki-67, p53 was significantly correlated with the habit of betel nut chewing(P<0.05); while gender, age, location, pathological T stage and cervical lymph node metastasis were not significantly correlated with habit of betel nut chewing (P>0.05). From multivariate analysis of the results, location and differentiation degree were significantly correlated with the habit of betel nut chewing (P<0.05). CONCLUSIONS: ki-67 and p53 protein are lowly expressed in OSCC patients with the habit of betel nut chewing, suggesting that clinicopathologic factors such as the proliferation activity, malignancy, differentiation and prognosis of tumor are much better. Differentiation degree are relatively good in OSCC patients with the habit of betel nut chewing. Cheek and tongue are the most common site of OSCC.

Anti-hepatitis B virus activity and hepatoprotective effect of des(rhamnosyl) verbascoside from Lindernia ruellioides in vitro.

Although clinically approved hepatitis B virus (HBV) polymerase inhibitors (lamivudine-3TC, entecavir, etc.) serve as effective therapeutics, the virus can easily generate resistance to them. Therefore, the treatment of HBV infection remains a public health problem. Numerous studies have shown that natural products have prospective anti-HBV activity. The purpose of this study was to isolate and extract des(rhamnosyl) verbascoside from Lindernia ruellioides (Colsm.) Pennell and explore its anti-HBV and hepatoprotective effects. Anti-HBV activity was evaluated in HepG2.2.15 cells, a human hepatocellular carcinoma cell line with HBV-stable infection, and its protective effect was evaluated in HL-7702 cells, a normal human liver cell line. HepG2.2.15 cells maintained normal growth morphology within the selected concentration range of des(rhamnosyl) verbascoside. It also inhibited the expression of HBV antigens and HBV DNA in a dose- and time-dependent manner in vitro. Further, western blot experiments showed that it could downregulate HBV X protein (HBx) expression in a dose-dependent manner. In the H2 O2 -induced hepatocyte injury model, the cell-survival rate of the HL-7702 cells with the highest drug dose reached 85.25%, which was significantly improved compared with that of the model group. Most of the cells returned to normal morphology, showing polygonal or fusiform structures. Thus, it may be stated that des(rhamnosyl) verbascoside exhibits anti-HBV activity and hepatoprotective effects in vitro and may exert an anti-HBV effect via antigen inhibition, HBV DNA secretion, and HBx protein expression.

Intraosseous Lipoma in the Mandibular Condyle.

Intraosseous lipomas are rare benign tumors of the bone, especially for the mandible. The etiology remains unclear, although several hypotheses have been proposed, such as trauma, blood vessel infarction, aging and inflammation. Clinically, the symptoms mainly depend on the location and size of the tumors. Radiographically, the lesions are usually radiolucent occasionally accompanied by radiopacity. The diagnosis is challenging, and histopathologic examination is necessary for definite diagnosis. Herein, the authors report an unusual patient with intraosseous lipoma in the mandibular condyle.

Six Visual Rating Scales as A Biomarker for Monitoring Atrophied Brain Volume in Parkinson's Disease.

The focus of our investigation was to determine the feasibility of using six visual rating scales as whole-brain imaging markers for monitoring atrophied brain volume in Parkinson's disease (PD). This was a prospective cross-sectional single-center observational study. A total of 98 PD patients were enrolled and underwent an MRI scan and a battery of neuropsychological evaluations. The brain volume was calculated using the online resource MRICloud. Brain atrophy was rated based on six visual rating scales. Correlation analysis was performed between visual rating scores and brain volume and clinical features. We found a significant negative correlation between the total scores of visual rating scores and quantitative brain volume, indicating that six visual rating scales reliably reflect whole brain atrophy in PD. Multiple linear regression-based analyses indicated severer non-motor symptoms were significantly associated with higher scores on the visual rating scales. Furthermore, we performed sample size calculations to evaluate the superiority of visual rating scales; the result show that using total scores of visual rating scales as an outcome measure, sample sizes for differentiating cognition injury require significantly fewer subjects (n = 177) compared with using total brain volume (n = 2524). Our data support the use of the total visual rating scores rather than quantitative brain volume as a biomarker for monitoring cerebral atrophy.

Pseudovascular adenoid squamous cell carcinoma of the tongue: a case report and literature review.

Pseudovascular adenoid squamous cell carcinoma (PASCC) is an uncommon histologic variant of squamous cell carcinoma, characterized by acantholysis in the cancer nests resulting in a pseudovascular appearance, and a subtype of acantholytic squamous cell carcinoma. It is relatively common in sun-exposed skin, but is extremely rare in oral cavity. A 56-year-old woman was referred to our department presented with a fast-growing mass in the front of the tongue for more than two months. Physical examination revealed a exophytic lesion with a pedicle in the anterior tongue. An incisional biopsy was performed. On microscopic examination, the tumor was composed of vessel-like anastomosing channels and dilated vessel-like spaces, similar to hemangioma, and the anastomosing channels contained free tumor cells. The nests of tumor cells with significant acantholysis were observed in some regions. Immunohistochemical examination revealed cells positive for pan-CK, CK5/6, p63, and negative for CD31 and CD34. The pathological diagnosis was confirmed as pseudovascular adenoid squamous cell carcinoma. The extended resection of the tumor and neck dissection was performed. There was no tumor recurrence or distant metastasis after 15 months of follow-up.

Open Surgery Versus Closed Treatment of Unilateral Mandibular Condyle Fractures.

PURPOSE: The aim of this meta-analysis was to evaluate the efficacy of open surgery and closed treatment for unilateral moderately displaced mandibular condyle fractures. METHODS: PubMed, Embase, and Cochrane Library databases were searched according to PRISMA guidelines from inception to October, 2018. Inclusion criteria were based on humans randomized controlled trials in the English literature. Pertinent data were collected and the incidence of the complications was calculated. RESULTS: A total of 6 studies with 227 patients were included in the meta-analysis. The results showed that there were no significant differences in incidence of malocclusion (odds ratio [OR], 0.33; 95% confidence interval [CI]: 0.07-1.46; P = 0.14). However, open surgery group had a better maximal mouth opening (WMD = 3.82, 95% CI: 1.93-5.71, P < 0.01), protrusion (WMD = 1.16, 95% CI: 0.42-1.89, P < 0.01) and sum of both laterotrusions (WMD: 2.50, 95% CI: 1.77-3.22, P < 0.01). And the incidence of temporomandibular joint pain was lower than closed treatment group (OR: 0.15, 95% CI: 0.06-0.37, P < 0.01). CONCLUSIONS: Compared with closed treatment, open surgery has significant advantages in improving mouth opening and mandibular movement, and reducing the incidence of temporomandibular joint pain, provided that open surgery was a promising application in treatment of unilateral moderately displaced mandibular condyle fractures.

Analysis of Exon Dosage Using Multiplex Ligation-Dependent Probe Amplification in Chinese Patients with Early-Onset Parkinson's Disease.

INTRODUCTION: Several studies have identified a number of genes associated with Parkinson's disease (PD). Genomic rearrangements (exon dosage variations) in these genes have emerged as significant, causing mutations. However, exon dosage variations in several PD genes were rarely investigated in Chinese patients. OBJECTIVE: This study was aimed at determining the prevalence of PD-causing genes' exon rearrangements in Chinese sporadic early-onset PD (EOPD) patients. METHODS: A total of 150 Chinese sporadic EOPD patients and 100 healthy controls were enrolled. Multiplex ligation-dependent probe amplification (MLPA) was used to detect exon dosage in PD genes, including SNCA, PARKIN, UCHL1, PINK1, DJ1, LRRK2, and ATP13A2. Positive results were verified by real-time quantitative polymerase chain reaction. And exon sequencing was employed to screen for subtle mutations. Novel exon dosage variations were screened in families and controls. RESULTS: PARKIN exon rearrangements were detected in 10 (6.7%) patients, including a novel heterozygous duplication of PARKIN exons 1-4. Clinical investigation showed that the percentage of individuals with PARKIN exon rearrangements was higher in the younger patients. Notably, the MLPA screening detected a heterozygous deletion of UCHL1 exon 1 in a patient. MLPA analysis in the family detected the deletion in an asymptomatic sister, indicating incomplete penetrance. CONCLUSION: Exon copy number variations (CNVs) in the PARKIN gene are relatively common among Chinese sporadic EOPD patients, whereas exon CNVs in other known PD genes can also be detected. Our findings demonstrate that it is important to perform exon dosage analysis for several known PD genes to obtain a better mechanistic insight into PD pathogenesis.

Correlation study of increase of pharyngeal airway space after mandibular advancement, taking natural head position into consideration.

The increase in the pharyngeal airway space after mandibular advancement has not been well explained, and in this study we aimed to show whether there is a correlation in the increase of pharyngeal airway space as a consequence of the mandibular advancement or of the relative change between the mandibular position and the natural head position (NHP). Fifteen patients who had bilateral sagittal split osteotomy for mandibular advancement with or without genioplasty were studied retrospectively. The primary variables of mandibular position, NHP, and pharyngeal airway space were measured in three dimensions using preoperative and postoperative cone-beam computed tomographic datasets and were compared using the paired t test. The secondary variable of pharyngeal airway space was defined as the square root of the mean cross-sectional area (CSA1/2) of the pharyngeal airway space. Pearson's correlation coefficient was used to find out whether there was a correlation between the change in CSA1/2 and the change in mandibular position, or the relative change between the mandibular position and the NHP. Volumes and minimal cross-sectional areas were increased in the pharyngeal airway space, and lengths of airways decreased. Correlation existed only between the increase in CSA1/2 and the relative change between the mandibular position and NHP. The increase in pharyngeal airway space after mandibular advancement correlated with the relative changes between the mandibular position and the NHP.