Abstract Background The development of cognitive impairment may be delayed if its risk factors are identified and detected, if its developmental trend can be predicted, and if early intervention can be performed. This study primarily aimed to investigate the association between global cognitive function and hearing loss, educational level, and occupation type and to determine any differences in such associations according to sex among older Chinese adults. Methods In this cross-sectional study, we prospectively recruited 219 individuals above 55 years old in an otolaryngology outpatient clinic who could write independently and had no severe vision impairment. Audiometric examinations included otoscopy, acoustic immittance, pure-tone audiometry, and speech audiometry for each ear. Cognitive function was evaluated by using the Chinese version of the Mini-Mental State Examination (MMSE). Multivariable linear regression analyses were performed to evaluate the relationship between variables and MMSE scores after adjusting for independent variables that were statistically significant in the univariable analyses. Results We enrolled 219 individuals: 98 men (mean ± standard deviation age, 63.08 ± 6.64 years) and 121 women (62.64 ± 7.17 years). The overall MMSE scores of the normal hearing group and the mild, moderate, and severe-to-profound hearing loss groups were 24.00 (5.00), 24.00 (5.00), 23.00 (5.00), and 23.00 (13.00), respectively. MMSE scores were higher among participants with higher educational levels ( p < 0.001) and were significantly correlated with occupation type ( p < 0.001). MMSE scores were significantly higher in men than in women ( p < 0.001). However, after the analysis of the five subdomains, significant differences were only observed for attention and calculation ( p < 0.001) and language ( p = 0.011). We further compared the distribution of educational levels between men and women by using the chi-square test; there was no significant difference in educational level between the sexes ( p = 0.070). Conclusions We reported statistically significant relationships between global cognitive function and sex, educational level, and occupation type. Sex-specific strategies may be required to improve healthcare policies.
Epileptic seizure is associated with significant morbidity diseases and mortality. An early identification of seizure activity can help prevent patients from adverse outcomes. Electroencephalography (EEG) raw data is a good source to recognize epileptic seizure from other brain activities. Numerous previous studied have applied feature engineering techniques to extract clinical meaningful features in order to indentify Seizure from EEG raw data. However, these techniques required intensive clinical, radiology and engineering expertise. In this study, we applied 6 machine learning algorithms (including naïve bayes, logistic regression, support vector machine, random forest and K-nearest neighbours and gradient boosting decision trees) and 3 deep learning architecture (including convolutional neural network (CNN), long-short term network (LSTM) and Gated Recurrent Unit (GRU)) to conduct binary and multi-label brain activities classification. Our best results of binary classification yielded that ensemble classifiers can classify seizure from other activities with a high accuracy and AUC over 0.96. In multi-label classification, both GRU and RNN yielded an averaged accuracy over 0.7. A compared study was also presented to analyze the performance of each configuration. In conclusion, machine learning and deep learning demonstrated their potential usage in epileptic seizure identification using EEG raw data. Future work may be experimented in a larger dataset to enable the seizure identification at a timely manner.
Primary congenital glaucoma (PCG) is one of the major diseases causing blindness in children, but its pathogenesis has remained unclear. Genetic factors play an important role in the pathogenesis of PCG. Molecular genetics of candidate genes such as CYP1B1, MYOC, LTBP2 and FOXC1 has so far been explored, but no disease-causing gene has been identified. Molecular genetic research on PCG including candidate gene screening and research strategies are reviewed here.
Aging is a major risk factor for cerebrovascular disease; however, the molecular mechanisms of cerebrovascular aging remain to be clarified. The aim of this study was to reveal the molecular signaling pathways involved in cerebrovascular aging. This study used high-resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in combination with quantitative 6-plex tandem mass tag labeling, to profile protein changes in brain vessels from three groups of healthy rhesus macaques (3-years, 6-years, and 20-years). Western blot analyses were used to validate the proteomic data. A total of 2,934 proteins were identified and analyzed. Twenty-two proteins were continuously downregulated with increasing age, while three proteins were continuously upregulated. When comparing Group C vs. Group B, 270 proteins were downregulated, while 73 proteins were upregulated. All these 368 significantly changed proteins were used for further analysis. Bioinformatic analysis showed that the changed proteins were involved in several signaling pathways during cerebrovascular aging. Proteins in the NRF2 pathway, such as Glutathione S-transferase Mu (GSTM), were consistently downregulated especially after 6-years old, whereas proteins related to miRNA targets in the extracellular matrix (ECM) and membrane receptors were upregulated. Protein-protein interaction networks demonstrated that disorders of energy pathways and serine/threonine kinases were critical during cerebrovascular aging. Data are available via ProteomeXchange under the identifier PXD012306. Our results indicated that during aging, the disorders of energy metabolism and dysfunction of antioxidant activity caused over-production of reactive oxygen species (ROS) may exacerbate cerebrovascular aging. In addition, accumulation of ECM proteins during aging might be closely associated with age-related arterial stiffening and decreased compliance.
Abstract Unilateral aural stimulation has been shown to cause massive cortical reorganization in brain with congenital deafness, particularly during the sensitive period of brain development. However, it is unclear which side of stimulation provides most advantages for auditory development. The left hemisphere dominance of speech and linguistic processing in normal hearing adult brain has led to the assumption of functional and developmental advantages of right over left implantation, but existing evidence is controversial. To test this assumption and provide evidence for clinical choice, we examined 34 prelingually deaf children with unilateral cochlear implants using near-infrared spectroscopy. While controlling for age of implantation, residual hearing, and dominant hand, cortical processing of speech showed neither developmental progress nor influence of implantation side weeks to months after implant activation. In sharp contrast, for nonspeech (music signal vs. noise) processing, left implantation showed functional advantages over right implantation that were not yet discernable using clinical, questionnaire-based outcome measures. These findings support the notion that the right hemisphere develops earlier and is better preserved from adverse environmental influences than its left counterpart. This study thus provides, to our knowledge, the first evidence for differential influences of left and right auditory peripheral stimulation on early cortical development of the human brain.
COVID-19 survivors complained of the experience of cognitive impairments, which also called "brain fog" even recovered. The study aimed to describe long-term cognitive change and determine psychosocial factors in COVID-19 survivors. A cross-sectional study was recruited 285 participants from February 2020 to April 2020 in 17 hospitals in Sichuan Province. Cognitive function, variables indicative of the virus infection itself, and psychosocial variables were collected by telephone interview. Univariate logistic regression and Lasso logistic regression models were used for variable selection which plugged into a multiple logistics model. Overall prevalence of moderate or severe cognitive impairment was 6.3%. Logistic regression showed that sex, religion, smoking status, occupation, self-perceived severity of illness, sleep quality, perceived mental distress after COVID-19, perceived discrimination from relatives and friends, and suffered abuse were associated with cognitive impairment. The long-term consequences of cognitive function are related to multiple domains, in which psychosocial factors should be taken into consideration.
Background Sarcoma is a highly heterogeneous malignancy with a poor prognosis. Although chemotherapy and targeted therapy have improved the prognosis to some extent, the efficacy remains unsatisfactory in some patients. The efficacy and safety of immunotherapy in sarcoma need further evaluation. Methods We conducted a two-center study of sarcoma patients receiving PD-1 immunotherapy at Tianjin Medical University Cancer Institute and Hospital and Henan Provincial Cancer Hospital. The treatment regimens included PD-1 inhibitor monotherapy and combination therapy based on PD-1 inhibitors. The observed primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). Survival curves were compared using the Kaplan−Meier method. Results A total of 43 patients were included from the two centers. The median follow-up time for all patients was 13 months (range, 1-48 months). In the group of 37 patients with advanced or unresectable sarcoma, the mPFS was 6 months (95%CI: 5-12 months), and the mOS was 16 months (95%CI: 10-28 months). The ORR was 10.8% (4/37), and the DCR was 18.9% (7/37). Subgroup analysis showed no significant differences in mPFS (p=0.11) and mOS (p=0.88) between patients with PD-L1 negative/positive expression. There were also no significant differences in mPFS (p=0.13) or mOS (p=0.72) between PD-1 inhibitor monotherapy and combination therapy. Additionally, there were no significant differences in mPFS (p=0.52) or mOS (p=0.49) between osteogenic sarcoma and soft tissue sarcoma. Furthermore, the results showed no significant differences in mPFS (p=0.66) or mOS (p=0.96) between PD-1 inhibitors combined with targeted therapy and PD-1 inhibitors combined with AI chemotherapy. Among the 6 patients receiving adjuvant therapy after surgery, the mPFS was 15 months (95%CI: 6-NA months), and the mOS was not reached. In terms of safety, most adverse events were mild (grade 1-2) and manageable. The most severe grade 4 adverse events were bone marrow suppression, which occurred in 4 patients but resolved after treatment. There was also one case of a grade 4 adverse event related to hypertension. Conclusion Immunotherapy is an effective treatment modality for sarcoma with manageable safety. Further inclusion of more patients or prospective clinical trials is needed to validate these findings.
As the third cancer worldwide, the incidence and the cancer-related mortality is both high in colorectal cancer (CRC) patients. The treatment of CRC has standard methods, including radiotherapy, chemotherapy and other general therapy. However, these systemic therapies are not specific, which are also toxic for normal cells and show many side effects in patients. New immunotherapeutic strategies have changed the landscape of treatment of metastatic CRC (mCRC), especially immune checkpoint inhibitors (ICIs). After research, the condition of microsatellite instability (MSI) has proven to be one of the main influencing factors of ICIs' efficacy. This review comprehensively analyses the possible mechanisms underlying the varying efficacy of ICIs in the treatment of different MSI tumors and evaluates potential therapeutic strategies that offer possible ways to overcome resistance mechanisms.
Abstract The pineal gland, an endocrine organ located at the brain's geometric center, primarily secretes melatonin to regulate circadian rhythms. Pineal gland calcification (PGC) is the formation of pineal stones, composed of mainly hydroxyapatite. In vivo study using computed tomography showed patients with Alzheimer’s disease (AD) have significantly higher the degree of PGC than controls. However, the biological function of PGC and its alterations in AD remain unknown. Here we show that PGC is part of a brain filtration system that adsorbs metal ions and has a neuroprotective function. This function is diminished due to decreased carbonate substitution in pineal stones of individuals with AD. We identified four main types of pineal stone by surface micromorpho-elemental analysis, indicating a greater surface morphological diversity in AD. Furthermore, AD pineal stone nanocrystals exhibit neuronotoxicity and promote the formation of soluble amyloid-beta (Aβ)42 oligomers. We propose pineal gland radiomics and serum metallomics as tools for auxiliary diagnosis of AD. We anticipate our assay as an initial step towards advancing basic biological research on PGC and understanding its clinical significance in AD.
Objective To investigate the safety and efficacy of re-hepatic resection (rHR) versus radiofrequency ablation (RFA) in the treatment of recurrent hepatocellular carcinoma (RHCC) in Asia through a meta-analysis. Methods PubMed, CNKI, and Wanfang Data were searched for related studies published up to June 15, 2020. Two reviewers independently searched for the articles and extracted related data, and RevMan 5.4.1 was used to perform the meta-analysis. Results A total of 2 randomized controlled trials and 18 retrospective cohort studies met the inclusion criteria and involved 2903 patients with RHCC from Asian countries. The mortality rate in the perioperative period was 2% in the rHR group and 0 in the RFA group, and the incidence rate of perioperative complications was 22.4% in the rHR group and 3.3% in the RFA group. The 1-, 3-, and 5-year overall survival rates were 92.3%, 66.3%, and 51.1%, respectively, in the rHR group and 91.4%, 69.2%, and 39.9%, respectively, in the RFA group. The 1-, 3-, and 5-year disease-free survival rates were 67.9%, 48.3%, and 34.4%, respectively, in the rHR group and 57.5%, 27.9%, and 14.0%, respectively, in the RFA group. The Meta-analysis showed that there was no significant difference in overall survival rate between the two groups (hazard ratio [HR]=0.89, 95% confidence interval [CI]: 0.77-1.02, P=0.10), while the rHR group had a significantly higher disease-free survival rate than the RFA group (HR=0.79, 95% CI: 0.72-0.87, P Conclusion Current evidence shows that rHR may help to achieve a higher disease-free survival rate than RFA in the treatment of RHCC, while rHR and RFA have a similar overall survival rate.
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