Dysphagia Pattern in Early to Moderate Parkinson's Disease Caused by Abnormal Pharyngeal Kinematic Function.

Airway invasion is common in patients with Parkinson's disease (PD) and can cause serious complications. However, a PD-related dysphagic pattern has not been clearly elucidated. In this study, 53 patients with early to moderate PD were enrolled to undergo a videofluoroscopic study of swallowing evaluation (VFSS) and a battery of neuropsychological assessments. A set of VFSS variables (three visuoperceptual, nine temporal, and six spatial) were measured. The main effects of bolus viscosity and volume on airway invasion were calculated. Statistical analyses were performed to determine key kinematic factors of airway invasion for swallowing each bolus type. Airway invasion frequency was significantly higher for liquid boluses (liquid vs. pudding P < 0.001; liquid vs. honey P = 0.006). Laryngeal vestibule closure reaction time (LVCrt) was the key kinematic factor of airway invasion for 3 ml liquid swallow (P = 0.040), anterior displacement of hyoid bone was the key kinematic factor for both 5 ml and 10 ml liquid swallows (P = 0.010, 0.034, respectively). Male sex and advanced Hoehn and Yahr stage were significantly related to reduced anterior displacement of hyoid bone. These results reveal the dysphagic pattern related to PD, demonstrating that prolonged LVCrt and reduced anterior displacement of hyoid bone are two crucial kinematic factors contributing to airway invasion during the liquid swallow. In addition, hyoid bone dysfunction was correlated with disease severity and male sex. Our findings warrant further investigation of the pathophysiological mechanism of dysphagia in PD and would guide clinical intervention.

Postural deformities in Parkinson's disease: A bibliometric analysis based on web of science.

Objective: Postural deformities are common debilitating conditions during the progression of Parkinson's disease (PD). However, the underlying pathophysiology and optimal treatment strategy are unclear. In this study, we aimed to identify primary research fields, important achievements and emerging trends in postural deformities in PD. Methods: Web of Science Core Collection database was searched to retrieve all literature related to postural deformities in PD over the past 20 years. Data such as annual numbers of publications, countries of origin, publication journals, cooperation between countries, citation index and keywords were retrieved from the selected publications. Bibliometrix Package in R software were used for bibliometric analysis and visualization. Results: In total, 211 publications that met the criteria were collected. Analyses had shown that the annual numbers of publications increased gradually with fluctuations. Japan was the most prolific country (n = 59). Italy participated in international cooperation the most frequently. Parkinsonism & related disorders (n = 25) took a prominent lead among all journals, and the most productive institution in this area was University of Verona (n = 27). The most local cited author was Tinazzi Michele. According to the thematic map, "scoliosis", "fusion", and "balance" have rapidly become research hot spots in related fields. Conclusions: Articles pertaining to postural deformities in PD are still being published, in which the etiology is a combination of peripheral plus central involvement. Treatment approaches include rehabilitative exercises, oral medication, botulinum toxin injection, deep brain stimulation and spine surgery, which is getting current attention and would be a hot topic of future research.

MiR-5195-3p functions as a tumor suppressor in prostate cancer via targeting CCNL1.

BACKGROUND: Accumulating evidence indicates that miR-5195-3p exerts tumor-suppressive roles in several tumors. However, the clinical significance and biological function of miR-5195-3p in prostate cancer (PCa) have not been reported yet. METHODS: The expression levels of miR-5195-3p and Cyclin L1 (CCNL1) were determined using quantitative real-time PCR in clinical specimens and cell lines. The clinical significance of miR-5195-3p in patients with PCa was evaluated using Kaplan-Meier survival analysis and Cox regression models. Cell proliferation and cell cycle distribution were measured by CCK-8 assay and flow cytometry, respectively. The association between miR-5195-3p and CCNL1 was analyzed by luciferase reporter assay. RESULTS: MiR-5195-3p expression levels were significantly downregulated in 69 paired PCa tissues compared with matched adjacent normal tissues. The decreased miR-5195-3p expression was associated with Gleason score and TNM stage, as well as worse survival prognosis. The in vitro experiments showed that miR-5195-3p overexpression suppressed the proliferation and cell cycle G1/S transition in PC-3 and DU145 cells. Elevated miR-5195-3p abundance obviously impaired tumor formation in vivo using PC-3 xenografts. Mechanistically, CCNL1 was a direct target of miR-5195-3p in PCa cells, which was inversely correlated with miR-5195-3p in PCa tissues. Importantly, CCNL1 knockdown imitated, while overexpression reversed, the effects of miR-5195-3p overexpression on PCa cell proliferation and cell cycle G1/S transition. CONCLUSIONS: Our data suggest that miR-5195-3p functions as a tumor suppressor by targeting CCNL1 in PCa.

Anterior Selective Lumbar Fusion Saving More Distal Fusion Segments Compared with Posterior Approach in the Treatment of Adolescent Idiopathic Scoliosis with Lenke Type 5: A Cohort Study with More Than 8-Year Follow-up.

OBJECTIVE: To investigate whether anterior selective fusion (ASF) could save more distal fusion segments compared with posterior approach in the treatment of Lenke type 5 adolescent idiopathic scoliosis with long term follow-up. METHODS: A retrospective cohort study. From 2008 to 2011, 22 AIS girls with Lenke type 5 who underwent ASF or posterior selective fusion (PSF) with more than 8-year follow-up, were extracted from the database. 13 girls in the ASF group had an average age of 14.3 ± 1.3 years and Risser sign of 3.3 ± 1.1; 9 PSF girls had an average age of 16.2 ± 3.6 years and Risser sign of 3.8 ± 1.5. The radiographic outcome was compared between groups preoperatively, 6-month postoperatively, 8-year postoperatively and at last follow-up (>8 years). RESULTS: The average follow-up duration was 8.7 ± 0.4 (ASF) and 8.8 ± 0.5 (PSF) years, respectively. There was no significant difference at baseline in age, Risser sign and preoperative curve pattern in the coronal and sagittal plane between the groups (P > 0.05). The ASF group had significantly shorter fusion segments (5.1 ± 0.6 vs. 7.0 ± 1.3) and decreased upper instrumented vertebra (UIV) (T11 ± 0.8 vs. T10 ± 0.8) than the PSF (P < 0.05); while no significant difference was found in the lower instrumented vertebra (LIV) and distal reserved segments (P > 0.05), which suggested that ASF could shorten the fusion segments by lowering UIV. The distal compensatory curve in the ASF group (9.0° ± 3.9°) was significantly larger than in the PSF group (3.3° ± 2.4°, P = 0.003), despite of no significant difference in the incidence of coronal imbalance (P > 0.05), indicating that both two approaches could obtain satisfactory correction in the coronal plane. In the sagittal plane, PSF patients had significantly larger lumbar lordosis (LL, 59.1° ± 10.5°), thoracic kyphosis (TK, 37.2° ± 13.3°) and proximal junctional angle (PJA, 13.3° ± 6.1°) at the last follow-up than the ASF (LL: 43.4° ± 9.4°; TK: 20.7° ± 8.4°; PJA: 4.7° ± 3.4°; P < 0.05), but without significant difference in proximal junctional kyphosis (PJK) and sagittal vertical axis (SVA) (P > 0.05). After controlling for age, Risser sign, and radiographic parameters related to the primary curve pattern, shorter fusion segments and more distal reserved segments still remained significant in the ASF group with greater Risser sign (P < 0.05). No major intra- or post-operative complications occurred. CONCLUSIONS: Both ASF and PSF could obtain satisfactory coronal and sagittal correction for Lenke 5 AIS; compared with PSF, ASF could shorten the fusion segments by lowering UIV, and save more distal fusion segments only in patients with greater skeletal maturity.

Renal metastases from esophageal cancer and retroperitoneal lymphoma detected via chromosome duplications identified by fluorescence in situ hybridization in urine exfoliated cells: First 2 case reports.

RATIONALE: Renal-occupying lesions positive for urine fluorescence in situ hybridization (FISH) are usually considered urothelial carcinomas. Here, we describe 2 cases of renal metastases with chromosome duplications in urine exfoliated cells. PATIENT SYMPTOMS: Patient 1, a 56-year-old male with a history of esophageal cancer, was admitted to our hospital on May 2017 after presenting with right back pain with microscopic hematuria for 1 month. Magnetic resonance imaging (MRI) showed right renal space-occupying lesions (5.4 cm × 4.6 cm) and multiple enlarged lymph nodes in the right renal hilum and retroperitoneum. The cystoscopy results were negative, and FISH analysis of urine exfoliated cells was positive, indicative of chromosome 3, 7, and 17 amplifications. Patient 2 was a 50-year-old male who was admitted to our hospital on May 2019 with no obvious cause of abdominal pain and abdominal distension (lasting for 7 days), with a serum creatinine level of 844 µmol/L. Patient 2 had no hematuria or fever, and MRI showed left renal inferior and medial space-occupying lesions, and multiple mesenteric nodules at the junction of the left adrenal gland, retroperitoneum, abdomen, and pelvis, which were partially fused. The tumor lesions were approximately 3.1 cm × 2.3 cm in size. The urine FISH results were positive, indicating chromosome 3, 7, and 17 amplifications. DIAGNOSES: Both patients were diagnosed with renal tumors with unknown pathology. INTERVENTIONS: Patient 1 underwent laparoscopic resection of the kidney and ureter, and sleeve cystectomy. The postoperative pathological diagnosis was metastatic keratinized squamous cell carcinoma, with squamous cell carcinoma in the right hilar lymph node. Histological FISH of the primary esophageal cancer and renal metastases were consistent with the urine FISH test results. Patient 2 underwent a biopsy of the left renal inferior and retroperitoneal areas, and was diagnosed with diffuse large B-cell lymphoma. OUTCOMES: Patient 1 survived 6 months after urological surgery. After treating patient 2 with the R-CHOP regimen and kinase inhibitors, his renal function recovered significantly and the mass become undetectable. LESSONS: Our results imply that FISH-positive renal occupying lesions should be considered as potential renal metastases with chromosome aberrations when making a differential diagnosis.

NT5E inhibition suppresses the growth of sunitinib-resistant cells and EMT course and AKT/GSK-3ß signaling pathway in renal cell cancer.

We aimed to explore the mechanisms of sunitinib-resistance in renal cell cancer (RCC) and provide new therapeutic evidence and biomarkers for RCC treatment using human clear-cell renal cell carcinoma (ccRCC) cell line, 786-O. Microarray analysis, quantitative real time PCR (qRT-PCR), Western blot, and immunohistochemistry were used to detect Ecto-5'-nucleotidase (NT5E) expressions in sunitinib-resistant tissues in RCC. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT), cell-count kit 8 (CCK-8), wound healing, and Transwell assays were used to investigate the influences of sunitinib and NT5E on 786-O cell line and sunitinib-resistant 786-O cell line (S786-O). Protein expressions related to epithelial-mesenchymal transition (EMT) and AKT/GSK-3ß signaling pathway in 786-O cells and S786-O cells were determined by Western blot. In vivo experiment was performed using NCr-nu/nu mice to explore the effects of NT5E on cell growth and EMT signal in sunitinib environment. NT5E expression was upregulated in sunitinib-resistant RCC tissues and cells. NT5E downregulation repressed RCC cell proliferation, migration as well as invasion. EMT course and AKT/GSK-3ß signal pathway both in vitro and in vivo in sunitinib environment was suppressed to varying degrees via NT5E inhibition. NT5E inhibition could suppress the growth of sunitinib-resistant RCC cells and restrain EMT course and AKT/GSK-3ß signal pathway in sunitinib environment in RCC. © 2018 IUBMB Life, 71(1):113-124, 2019.

Robotic-assisted Laparoscopic Nephrectomy with Vein Thrombectomy: Initial Experience and Outcomes from a Single Surgeon.

This study was designed to explore the safety and feasibility of robotic-assisted laparoscopic nephrectomy with vein thrombectomy (RAL-NVT) for the treatment of renal cell carcinoma (RCC) with venous tumor thrombus (VTT). Clinical data of 6 patients treated with RAL-NVT between July 2016 and November 2017 in our hospital were retrospectively collected and analyzed. There were 5 males and 1 female with their age ranging from 48 years to 68 years. Five renal tumors were right-sided and one left-sided. Three cases fell in level 0 VTT, one in level I and two in level II. Preoperative imaging revealed lymph node involvement in 1 case and distant metastasis in 2 cases. For RCC with level 0 VTT, the renal vein of the affected side was adequately and carefully dissected around the thrombus to the proximity of inferior vena cava (IVC) and was ligated with Hem-o-loks without cross-clamping the IVC. For level I and II VTT, the IVC was crossclamped cephalically and caudally around the tumor thrombus and all tributaries were sequentially blocked to ensure the safe retrieval of VTT. All operations were successfully completed without conversion to open operation. The mean operative time was 150 (115-230) min. Cross-clamping of the IVC happened in 3 cases, and the blocking time was 14, 19 and 20 min, respectively. The mean estimated blood loss during the operation was 400 (200-580) mL. The peritoneal drainage tube was removed 5 to 9 days after the operation, and all patients were postoperatively discharged at 6 to 11 days. Postoperative pathological analysis confirmed that the RCCs were comprised of 4 clear cell RCCs, 1 papillary cell RCC, and 1 medullary cell RCC; 2 cases were Fuhrman grade II, 3 cases grade III, and 1 case undefined grade. No recurrence or progression was observed during the follow-up of 4.2 (3-6) months. We concluded that RAL-NVT is highly challenging but safe and feasible for the treatment of RCC with VTT.

MiR-514a-3p inhibits cell proliferation and epithelial-mesenchymal transition by targeting EGFR in clear cell renal cell carcinoma.

PURPOSE: Dysregulation of miR-514a-3p has been reported in multiple human malignancies. However, its biological function and molecular mechanisms in renal cell cancer (RCC) remain unclear. The aims of this study were to explore the role of miR-514a-3p and its potential mechanism in human RCC. METHODS: The expression level of miR-514a-3p was quantified by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 20 cases of paired ccRCC and adjacent normal tissues and RCC cell lines. The role of miR-514a-3p in RCC cells was further evaluated by functional analyses. Western blot was applied to probe into the biological mechanism of miR-514a-3p in RCC cells. RESULTS: The qRT-PCR results confirmed that miR-514a-3p was dramatically down-regulated in ccRCC specimens. Restoration of miR-514a-3p expression might distinctively suppress cell proliferation, viability, migration and invasion in comparison with negative control in RCC cells and negatively regulate the proteins related to epithelial-mesenchymal transition (EMT), such as E-Cadherin, N-Cadherin and Vimentin. Results of luciferase reporter assay and Western blot analysis identified that miR-514a-3p might inversely regulate the expression of epidermal growth factor receptor (EGFR) directly by binding to its 3'-untranslated region (3'-UTR) at the translational level. Further studies showed that the phenotypic changes of RCC cells caused by miR-514a-3p occurred through EGFR/MAPK/ERK pathway rather than PI3K/AKT signaling. Moreover, the inhibitory effect of miR-514a-3p was also confirmed in vivo study. CONCLUSIONS: MiR-514a-3p is a novel tumor suppressor in ccRCC and potentially functions through EGFR/MAPK/ERK pathway.