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Introduction: Early diagnosis of Parkinson's disease (PD) remains challenging. It has been suggested that abnormal brain iron metabolism leads to excessive iron accumulation in PD, although the mechanism of iron deposition is not yet fully understood. Ferritin and transferrin receptor (TfR) are involved in iron metabolism, and the exosome pathway is one mechanism by which ferritin is transported and regulated. While the blood of healthy animals contains a plentiful supply of TfR positive exosomes, rare study has examined ferritin and TfR in plasma neural-derived exosomes in PD. Methods: Plasma exosomes were obtained from 43 patients with PD and 34 healthy controls. Neural-derived exosomes were isolated with anti-human L1CAM antibody immunoabsorption. Transmission electron microscopy and western blotting were used to identify the exosomes. ELISAs were used to quantify ferritin and TfR levels in plasma neural-derived exosomes of patients with PD and controls. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of ferritin and TfR. Independent predictors of the disease were identified using logistic regression models. Results: Neural-derived exosomes exhibited the typical exosomal morphology and expressed the specific exosome marker CD63. Ferritin and TfR levels in plasma neural-derived exosomes were significantly higher in patients with PD than controls (406.46 ± 241.86 vs. 245.62 ± 165.47 ng/mg, P = 0.001 and 1728.94 ± 766.71 vs. 1153.92 ± 539.30 ng/mg, P < 0.001, respectively). There were significant positive correlations between ferritin and TfR levels in plasma neural-derived exosomes in control group, PD group and all the individuals (rs = 0.744, 0.700, and 0.752, respectively). The level of TfR was independently associated with the disease (adjusted odds ratio 1.002; 95% CI 1.000-1.003). ROC performances of ferritin, TfR, and their combination were moderate (0.730, 0.812, and 0.808, respectively). However, no relationship was found between the biomarkers and disease progression. Conclusion: It is hypothesized that ferritin and TfR in plasma neural-derived exosomes may be potential biomarkers for PD, and that they may participate in the mechanism of excessive iron deposition in PD. [ABSTRACT FROM AUTHOR]

Background: Early detection, diagnosis, and treatment of children with CHD has been the focus of research attention. Hainan is the southernmost underdeveloped province in China, where the technology of screening, diagnosis, and treatment for children with CHD has not been fully developed. Objectives: This study aimed to introduce and promote an appropriate technology system for screening, diagnosis, and evaluation of neonatal CHD. Methods: Two indicators, namely cardiac auscultation plus pulse oximetry (POX), were used by screening staff to screen live newborns within six to 72 hours afterbirth at all screening institutions in Hainan province from January 1, 2019, to December 31,2021. Diagnosis procedure for the screened-positive newborns was performed in 31 certified medical institutions, and evaluation procedure for the newborns confirmed with CHD was performed in six certified medical institutions. Data about screening, diagnosis, evaluation, and treatment were obtained, uploaded, and managed online through a neonatal CHD screening information management net. Results: A total of 321447 live births were included in the CHD screening project, and an overall screening rate of 97.59% (321447/329387) was determined. According to our results, 8032 cases were screened-positive. A total of 1099 cases of CHD were confirmed, suggesting a CHD prevalence of 3.419 per 1000 live births. Atrial septal defect (ASD) was the most common CHD lesion, with a prevalence of 1.313 per 1000 live births. The sensitivity of cardiac auscultation, POX, and two indicators' combination (i.e., cardiac auscultation plus POX) for CHD detection were 69.15%, 33.49%, and 91.90%, respectively; and the specificity of them were 98.36%, 99.43%, and 97.81%, respectively. The ratio of both positive in two indicators among the children with major (serious and critical) CHD at the initial screening was significantly higher than that of single positive in any indicator (χ² = 59.455, P < 0.001). All children with CHD were evaluated, out of who 154 children with major CHD were treated promptly. Only 15 cases of children with major CHD died, and the standardized mortality of children aged 0-1 years with CHD was 4.67/100,000. Conclusions: It was concluded that the combination of two indicators (i.e., cardiac auscultation plus POX) for CHD screening was reliable as well as non-invasive, simple, and easy to operate so that it was conducive for promotion. It was also found that introducing and promoting an appropriate technology for screening, diagnosis, and evaluation of neonatal CHD were extremely significant since they may have contributed to the timely diagnosing and treating children with CHD, especially those with major CHD. [ABSTRACT FROM AUTHOR]

Background: Dexamethasone is widely used in the prevention of postoperative complications in oral surgery and strengthening the analgesic effect after anesthesia, but the efficacy is controversial, and the relationship between postoperative complications and pain is still unclear. The purpose of this study was to evaluate the analgesic effect of dexamethasone in the treatment of jaw cyst and to explore the relationship between postoperative complications and pain. Methods: We conducted a prospective, randomized, double-blind clinical trial. 120 patients were divided into two groups, dexamethasone group (group D) and control group (Group C). All patients were given 0.02 mg·kg−1 of hydromorphone to relieve pain in advance at 10 min before the beginning of operation. Meanwhile, dexamethasone was injected 0.2 mg·kg−1 intravenously in group D and normal saline was injected in group C. The primary endpoint was pain intensity at 2 h, 6 h, 12 h, 24 h and 48 h after surgery. The secondary endpoints were the incidence and extent of complications after surgery, including facial swelling and trismus. Results: Compared with group C, the visual analogue scale (VAS) scores and occurrence of painful event postoperatively in group D were significantly lower both at rest (P < 0.0001 and P = 0.0014) and during mobilization (P < 0.0001 both). The degree of facial swelling and trismus in group D were significantly lower than that in group C at 24 h (P < 0.0001 and P = 0.00022) and 48 h (P < 0.0001 and P = 0.00015) after surgery, but there was no difference at 6 h and 12 h (P = 0.137 and P = 0.083) after surgery. The C-reactive protein (CRP) level at 24 h after operation in group D was lower than group C (P = 0.012), but there was no significant difference in blood glucose concentration between the two groups (P = 0.608). Conclusion: Dexamethasone can reduce the degree of facial swelling and trismus after jaw cyst surgery by inhibiting the production of inflammation, which alleviated the postoperative pain of patients significantly. In addition, it did not increase the risk of hyperglycemia. Trial registration: This study was registered with the Chinese Clinical Trial Registry on May 07, 2020 (URL: http://www.chictr.org.cn/showproj.aspx?proj=53344. Registry number: ChiCTR2000032693). Registered on 07/05/2020. [ABSTRACT FROM AUTHOR]

Microbial communities analysis is drawing growing attention due to the rapid development fire of high-throughput sequencing techniques nowadays. The observed data has the following typical characteristics: it is high-dimensional, compositional (lying in a simplex) and even would be leptokurtic and highly skewed due to the existence of overly abundant taxa, which makes the conventional correlation analysis infeasible to study the co-occurrence and co-exclusion relationship between microbial taxa. In this article, we address the challenges of covariance estimation for this kind of data. Assuming the basis covariance matrix lying in a well-recognized class of sparse covariance matrices, we adopt a proxy matrix known as centered log-ratio covariance matrix in the literature. We construct a Median-of-Means estimator for the centered log-ratio covariance matrix and propose a thresholding procedure that is adaptive to the variability of individual entries. By imposing a much weaker finite fourth moment condition compared with the sub-Gaussianity condition in the literature, we derive the optimal rate of convergence under the spectral norm. In addition, we also provide theoretical guarantee on support recovery. The adaptive thresholding procedure of the MOM estimator is easy to implement and gains robustness when outliers or heavy-tailedness exist. Thorough simulation studies are conducted to show the advantages of the proposed procedure over some state-of-the-arts methods. At last, we apply the proposed method to analyze a microbiome dataset in human gut. [ABSTRACT FROM AUTHOR]

Purpose: Spinal solitary fibrous tumor/hemangiopericytoma (SFT/HPC), a rare mesenchymal tumor that arises from pericytes of Zimmerman, comprises only 0.08% of all primary bone tumors and 0.1% of primary malignant bone tumor and rarely occurs in the spine. We attempt to correlate the clinical factors and different treatment options with the recurrence rate and overall survival of SFT/HPC over time.Methods: A retrospective study of 20 patients with spinal osseous SFT/HPCs who were surgically treated in our center between 2003 and 2015 was performed. Kaplan-Meier curves and log-rank tests were used to compare the survival probability or recurrence-free probability between groups, and P values < 0.05 were considered statistically significant.Results: Three surgical management strategies, including subtotal resection, piecemeal total resection, and total en bloc spondylectomy (TES) were applied. Postoperative radiotherapy was carried out in 14 cases. The mean follow-up period was 38.3 (median 35, range 7-93) months, and 6 patients passed away with the mean follow-up time of 47.7 (median 41, range 24-77) months. Relapse was detected in 9 patients (45%) with the mean time from surgery to recurrence being 36.6 (median 28, range 12-73) months. Our results indicate that grade III is an adverse prognostic factor for both recurrence and over survival (OS) for spinal osseous SFT/HPC, while total resection, especially TES, is a positive prognostic factor.Conclusions: Spinal osseous SFT/HPC is a challenging clinical entity given its high local recurrence rate. Surgical management plays a crucial role in the whole treatment of spinal SFT/HPCs and total excision, especially TES, should be strived for whenever possible. Postoperative radiotherapy is recommended to lower the recurrent rate. This study also confirms that pathology grade III is an adverse prognostic factor for spinal osseous SFT/HPCs. [ABSTRACT FROM AUTHOR]

Background: Spinal metastatic paraganglioma (MPG) is rare and only reported in individual case reports. The low incidence makes it difficult to define appropriate therapy and prognosis. Our study illustrated the largest series to discuss the possible treatment and outcomes of patients with spinal MPG.Methods: A retrospective study of 15 patients with spinal MPG who were surgically treated between 2005 and 2014 was performed. Three surgical modalities were applied, and radiotherapy and chemotherapy were utilized as adjuvant therapy.Results: The mean patients age was 40.9 (range 23-58) years. The period between primary surgery and spinal metastasis averaged 8.2 (0.5-15) years. Lesions were mainly located in cervical spine (2), thoracic spine (8), lumbar spine (3), and sacrum (2). The mean follow-up period was 35.0 months. Lesion progression was detected in nine patients, whereas five patients (33.3%) passed away. For solitary spine, multiple bone and both bone and nonosseous metastasis cases, the mean progression-free survival was 41 (range 9-56), 22.5 (range 12-38) and 8.3 (range 3-18) months, respectively.Conclusions: The cases presented in the current study highlight the crucial role of surgery. Total en bloc for solitary spinal MPG could result in a satisfying prognosis and piecemeal total resection with postoperative radiotherapy could be an alternative therapy. Radiotherapy and chemotherapy were advocated, especially for the multiple metastasis. [ABSTRACT FROM AUTHOR]

Background: The Musculoskeletal Tumor Society (MSTS) scoring system is a disease-specific instrument to determine the physical and mental health for patients with extremity sarcoma. This study aims to investigate the reliability and validity of the Chinese version of the MSTS, and to evaluate functional outcomes of the surgical treatment of lower extremity sarcoma using the Chinese MSTS.Methods: A cohort of 98 patients who had undergone surgery for lower extremity sarcoma were included. All the patients completed the clinical assessment with the Chinese MSTS and the Chinese Toronto Extremity Salvage Score (TESS). Assessment of psychometric properties was carried out through reliability and validity test. The reliability of Chinese MSTS was evaluated through test-retest analysis, inter-observer analysis and internal consistency. The inter-observer and test-retest reliability was analyzed with intra-class correlation coefficient (ICC). The internal consistency was evaluated by Cronbach's α, with a value >0.70 considered acceptable. The discriminant validity was evaluated through comparison of the MSTS score between patients undergoing amputation surgeries and those undergoing limb-salvage surgeries. The construct validity was evaluated with the factor analysis.Results: The mean MSTS score was 21.5 ± 7.1. The ICC was 0.91 (95% confidence interval (CI) = 0.85-0.96) for the test-retest reliability and 0.90 (95% CI = 0.86-0.93) for the inter-observer analysis. The test for internal consistency showed a Cronbach's α of 0.86 for the MSTS. Patients undergoing amputation surgery had remarkably lower MSTS score than patients undergoing limb-salvage surgeries (18.8 ± 5.4 vs. 23.5 ± 6.3, p = 0.005), which indicated a good discrinimant validity of the Chinese MSTS. The factor analysis indicated a 1-factor model with acceptable goodness of fit.Conclusions: The Chinese MSTS scoring system is a reliable and valid instrument with well-accepted psychometric properties. Through application of the Chinese MSTS, we demonstrated that patients receiving limb-salvage surgeries may have better functional outcome and QoL than those undergoing amputation surgeries. [ABSTRACT FROM AUTHOR]

Background: Ku80 is a DNA repair protein which involves in cell apoptosis and chemoresistance. However, it is unclear whether Ku80 correlates with the efficiency of neoadjuvant chemotherapy in human lung adenocarcinoma, and modulates cisplatin/pemetrexed-induced lung cancer cell apoptosis in vitro.Methods: We recruited 110 patients with stage IIIA lung adenocarcinoma, who received 2 cycles of neoadjuvant chemotherapy, and their lungs were reevaluated by CT scan. Immunohistochemistry and qRT-PCR was performed to detect the expression level of Ku80. A549 cells were transfected by lentiviral vector containing shRNA and full length cDNA to knockdown or upregulate Ku80 gene expression. CCK8 assay, flow cytometry and Western blot were employed to determine the viability and apoptosis of A549 cells treated with cisplatin combined with pemetrexed.Results: Ku80 expression was detected in 76 patients (69%). There were 38 patients who responded to chemotherapy, where Ku80 was positively expressed in 7 cases (18.4%). Immunohistochemical score of Ku80 protein in the response group (2.079 ± 1.617) to chemotherapy was lower than that in the nonresponse group (5.597 ± 2.114, P < 0.05). Tissue samples from the nonresponse group exhibited higher Ku80 mRNA levels compared to the response group. Ku80 knockdown by shRNA augmented cisplatin/pemetrexed-induced decline in viability, whereas Ku80 overexpression attenuated viability reduction induced by these drugs compared to control A549 cells. Both flow cytometry and Western blot analysis displayed that the apoptotic rate of Ku80 shRNA-transfected A549 cells was significantly increased compared to control cells treated with cisplatin/pemetrexed, which was lowered by Ku80 overexpression.Conclusion: Ku80 could predict the probability of resistance to neoadjuvant chemotherapy in lung adenocarcinoma, and reduced cisplatin and pemetrexed-induced apoptosis in A549 cells. [ABSTRACT FROM AUTHOR]

Background: The possible advantages of laparoscopic radical hysterectomy (LRH) versus open radical hysterectomy (RH) have not been well reviewed systematically. The aim of this study was to systematically review the comparative effectiveness between LRH and RH in the treatment of cervical cancer based on the evaluation of the Perioperative outcomes, oncological clearance, complications and long-term outcomes.Methods: The systematic review was conducted by searching PubMed, MEDLINE, EMBASE, the Cochrane Library and BIOSIS databases. All original studies that compared LRH with RH were included for critical appraisal. Data were pooled and analyzed.Results: A total of twelve original studies that compared LRH (n = 754) with RH (n = 785) in patients with cervical cancer fulfilled quality criteria were selected for review and meta-analysis. LRH compared with RH was associated with a significant reduction of intraoperative blood loss (weighted mean difference = -268.4 mL (95 % CI -361.6, -175.1; p < 0.01), a reduced risk of postoperative complications (OR = 0.46; 95 % CI 0.34-0.63) and shorter hospital stay (weighted mean difference = -3.22 days; 95 % CI-4.21, -2.23 days; p < 0.01). These benefits were at the cost of longer operative time (weighted mean difference = 26.9 min (95 % CI 8.08-45.82). The rate of intraoperative complications was similar in the two groups. Lymph nodes yield and positive resection margins were similar between the two groups. There were no significant differences in 5-year overall survival (HR 0.91, 95 % CI 0.48-1.71; p = 0.76) and 5-year disease-free survival (hazard ratio [HR] 0.97, 95 % CI 0.56-1.68; p = 0.91).Conclusions: LRH shows better short term outcomes compared with RH in patients with cervical cancer. The oncologic outcome and 5-year survival were similar between the two groups. [ABSTRACT FROM AUTHOR]

Background: Brain-specific metastasis occurs frequently in lung cancer, and the mechanism is still unclear. The present study was designed to investigate the correlation between CXCR4 expression and brain-specific metastasis of non-small cell lung cancer. Methods: The brain metastatic tumors and lung cancer tissues from 32 patients with solitary brain metastasis of non-small cell lung cancer (M1 group), who underwent combined surgical treatment from January 1998 to June 2008, and 32 paired patients without distant metastasis (M0 group) and 30 patients with primary brain tumor, were examined by immunohistochemistry to detect the expression of CXCR4 protein. The difference of CXCR4 expression was compared by the McNemar χ test or Fisher's exact test. Estimation of survival was calculated with the Kaplan-Meier method, and the statistical differences were analyzed with the log-rank test. Results: Overexpression of CXCR4 protein was observed in 29 (90.6%) M1 non-small cell lung cancers and in all (100%) brain metastatic tumors, which was significantly higher than that in the paired M0 non-small cell lung cancer and the primary brain tumors, respectively ( p = 0.000). The 3- and 5-year cumulative survival rates of patients with solitary brain metastasis of lung cancer were 21.9 and 12.5%, significantly lower than the corresponding survival rates of M0 group patients ( p = 0.005). Conclusions: CXCR4 protein was highly overexpressed in M1 non-small cell lung cancer and brain metastatic tumors, which indicated that high-level CXCR4 expression correlates with brain-specific metastasis of non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

The article discusses a case of a 45-year-old woman, who was diagnosed with inflammatory pseudomotor (IPT) of the esophagus. It states the postoperative recovery of the patient, but a slight hoarseness in her voice was still observed following the resection of the mass in her esophagus. It is said that the most common anatomic site where inflammatory myofibroblastic tumor (IMT) develops are in lungs and mesentery or omentum. Also noted are potential treatments for IMT if a resection is not possible because of anatomic site or comorbidities.

Nuclear localization of the androgen receptor (AR) is necessary for its activation as a transcription factor. Defining the mechanisms regulating AR nuclear localization in androgen-sensitive cells and how these mechanisms are dysregulated in castration-resistant prostate cancer (CRPC) cells is fundamentally important and clinically relevant. According to the classical model of AR intracellular trafficking, androgens induce AR nuclear import and androgen withdrawal causes AR nuclear export. The present study has led to an updated model that AR could be imported in the absence of androgens, ubiquitinated, and degraded in the nucleus. Androgen withdrawal caused nuclear AR degradation, but not export. In comparison with their parental androgen-sensitive LNCaP prostate cancer cells, castration-resistant C4-2 cells exhibited reduced nuclear AR polyubiquitination and increased nuclear AR level. We previously identified 3-(4-chlorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (CPPI) in a high-throughput screen for its inhibition of androgen-independent AR nuclear localization in CRPC cells. The current study shows that CPPI is a competitive AR antagonist capable of enhancing AR interaction with its E3 ligase MDM2 and degradation of AR in the nuclei of CRPC cells. Also, CPPI blocked androgen-independent AR nuclear import. Overall, these findings suggest the feasibility of targeting androgen-independent AR nuclear import and stabilization, two necessary steps leading to AR nuclear localization and activation in CRPC cells, with small molecule inhibitors. [ABSTRACT FROM AUTHOR]

Background: Methadone maintenance treatment (MMT) reduces the harms of opioid use disorder and is being rapidly scaled-up in China. This study evaluated the real-world implementation of MMT system in Wuhan, China.Methods: Data extracted from electronic medical records collected in 2010 on 8811 patients were used to compute for each patient indices of the prescribed and consumed daily methadone doses, an adherence index, dose adjustments following missed doses, the rates of opiate positive urine tests, self-reported drug use, injection drug use (IDU), and the duration of MMT exposure.Findings: The modal daily doses prescribed were 60 mg and above for 68.5% of patients. Adherence was variable: 51% of patients attended less than 60% and 26% attended 80-100% of their treatment days; and patients with long MMT exposure had significantly higher adherence rates than patients with short MMT exposure. The differences between doses dispensed immediately before and after the interruption in dosing days ranged from 0 to 7 mg, independently of the length of the interruption or the prescribed dosing level. The overall rate of opiate positive tests was 20%; 45% of patients had at least one opiate positive test; 29% reported past month drug use and 53% of them reported past month IDU. Adherence and MMT exposure duration correlated significantly with the proportion of opiate negative urine tests (r=0.355, p<0.001; r=0.351, p<0.001, respectively). Treatment for males and females was comparable.Conclusions: Provision of safe methadone dosing after absences and improving daily attendance are identified as priority improvement areas. [ABSTRACT FROM AUTHOR]