Mass Spectrometric Analysis of Urinary N-Glycosylation Changes in Patients with Parkinson's Disease.

Urine is thought to provide earlier and more sensitive molecular changes for biomarker discovery than blood. Numerous glycoproteins, peptides, and free glycans are present in urine through glomerular filtration of plasma, cell shedding, apoptosis, proteolytic cleavage, and exosome secretion. Urine biomarkers have enormous diagnostic potential, and the use of these biomarkers is a long-standing practice. The discovery of non-urological disease biomarkers from urine is also gaining attention due to its non-invasive sample collection and ease of analysis. Abnormal protein glycosylation in plasma or cerebrospinal fluid has been associated with Parkinson's disease, however, whether urine with Parkinson's disease has characteristic glycosylation remains to be explored. Here, we use mass spectrometry-based glycomics and glycoproteomics approaches to analyze urine samples for glycans, glycosites, and intact glycopeptides of urine samples. Reduced abundance of N-glycans was detected at the level of total glycans as well as specific glycosites of glycopeptides. The most abundant N-glycan in urine is S(6)1H5N4F1; S(6)2H5N4 and N4H4F1 are highly present in serum and urine, and 10 biantennary galactosylated N-glycans in the urine of PD patients were significantly decreased. The downregulation of sialylation may be due to the reduction of ST3GAL2. Site-specific N-glycosylation analysis revealed that AMBP, UMOD, and RNase1 have PD-specific N-glycosylation sites. GO and KEGG analysis revealed that N-glycosylation changes may provide clues to identify disease-specific glycosylation biomarkers in Parkinson's disease.

High-resolution mass spectrometry for glycoproteomics.

Tweetable abstract Bottom-up glycoproteomics combined with top-down strategy allows direct analysis of glycoform-mapped glycosylation and its glycans by high-resolution mass spectrometry.

Development of a Psychometric Test: A Care Risk Scale for Homebound Older People With Dementia.

Background: Homebound older people with dementia (OPWD) face a series of care risks due to disease characteristics, care issues, and the family environment. However, China lacks a quantitative assessment tool for care risk. Thus, we attempted to develop a care risk scale for homebound OPWD. Methods: A care risk scale, with initially 18 items, was designed based on a systematic literature review, expert consultation, and a pilot study with 20 OPWD. The initial scale was validated among 1,045 homebound OPWD in Ningbo, China from November 1, 2020 to July 30, 2021. After removing three items that lacked discrimination power, the reliability and validity of the remaining 15 items was evaluated. Factor extraction was performed via principal axis factoring and Cattell's scree plot analysis, with the resulting factors then being subjected to a varimax rotation. Results: The final scale consisted of 15 items assessed on a 5-point Likert scale that loaded on to three different factors, including dementia symptoms (four items), family support (four items), and home environment (seven items). These three factors were found to explain 72.9% of the cumulative variance. The overall Cronbach's alpha for the final scale was 0.907. The correlation coefficients in the item-to-total analysis ranged from 0.511 to 0.662. Conclusion: The validation analysis indicated satisfactory reliability and validity of the 15-item scale for assessing care risk of homebound OPWD. This scale can help long-term care professionals and family caregivers identify care risks and help them take targeted measures to enhance safety of care for OPWD.

How Do Chinese People View Cyberbullying? A Text Analysis Based on Social Media.

The rise of cyberbullying has been of great concern for the general public. This study aims to explore public attitudes towards cyberbullying on Chinese social media. Cognition and emotion are important components of attitude, and this study innovatively used text analysis to extract the cognition and emotion of the posts. We used a web crawler to collect 53,526 posts related to cyberbullying in Chinese on Sina Weibo in a month, where emotions were detected using the software "Text Mind", a Chinese linguistic psychological text analysis system, and the content analysis was performed using the Latent Dirichlet Allocation topic model. Sentiment analysis showed the frequency of negative emotion words was the highest in the posts; the frequency of anger, anxiety, and sadness words decreased in turn. The topic model analysis identified three common topics about cyberbullying: critiques on cyberbullying and support for its victims, rational expressions of anger and celebrity worship, and calls for further control. In summary, this study quantitatively reveals the negative attitudes of the Chinese public toward cyberbullying and conveys specific public concerns via three common topics. This will help us to better understand the demands of the Chinese public so that targeted support can be proposed to curb cyberbullying.

Network Anonymity and Cyberbullying among Chinese Adolescents: A Moderated Mediation Model.

Cyberbullying is an important issue which prevails among children and adolescents. The present study aimed to investigate the association between network anonymity and cyberbullying behavior and examine the mediating role of network morality and the moderating role of self-control in the linkage of network anonymity and cyberbullying behavior. A total of 620 participants were recruited from three high schools in southeast China and were required to complete a questionnaire measuring network anonymity, cyberbullying behavior, network morality, and self-control. A moderated mediation model was conducted by using PROCESS Macro for SPSS 3.5. The results showed that network anonymity was negatively associated with cyberbullying behavior among Chinese adolescents. Network morality mediated the association and self-control moderated the indirect association between network anonymity and cyberbullying behavior via network morality. These findings indicate that improving the network morality and self-control of adolescents with the joint efforts of individuals, families, government, and society as a whole may be an effective intervention strategy for cyberbullying behavior under the framework of digital citizens.

Prevalence of Depressive Symptoms and Associated Factors among Internal Migrants with Tuberculosis: A Cross-Sectional Study in China.

There are hundreds of millions of internal migrants in China, and tuberculosis (TB) is an important health threat to them. However, the mental health problems of internal migrants with TB in China have been ignored. The present study aimed to determine the prevalence of depressive symptoms and its associated risk factors among internal migrants with TB in China. A cross-sectional survey was conducted between June 2018 and March 2019 in Shenzhen, southern China. Data were collected from 1,057 internal migrants with TB using a structured questionnaire. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Multinomial logistic regression analysis was used to identify risk factors for depressive symptoms. Of the 1,057 participants included in this study, 53.8% had depressive symptoms. Of these, 38.9% had mild, whereas 14.9% had moderate-to-severe depressive symptoms. Multinomial logistic regression analysis suggested that higher likelihoods of depressive symptoms were associated with female gender, lower education, family dysfunction, poor doctor-patient communication, and TB-related stigma. This study shows that the prevalence of depressive symptoms among internal migrants with TB is high in China. Targeting interventions and treatment of depressive symptoms among internal migrants with TB are needed.

Facile assembly of bifunctional, magnetically retrievable mesoporous silica for enantioselective cascade reactions.

An integrated immobilization to encapsulate the Pd/C-coated magnetic nanoparticles within the chiral Ru/diamine-functionalized silica shell for the construction of a bifunctional magnetic catalyst is developed. This catalyst realizes a synergistic Suzuki cross-coupling/asymmetric transfer hydrogenation and a successive reduction/asymmetric transfer hydrogenation for the preparation of chiral aromatic alcohols.

Cigarette Smoking Preferentially Affects Intracranial Vessels in Young Males: A Propensity-Score Matching Analysis.

PURPOSE: Cigarette smoking (CS) is one of the major risk factors of cerebral atherosclerotic disease, however, its level of contribution to extracranial and intracranial atherosclerotic stenosis (ECAS and ICAS) was not fully revealed yet. The purpose of our study was to assess the association of CS to cerebral atherosclerosis along with other risk factors. MATERIALS AND METHODS: All consecutive patients who were angiographically confirmed with severe symptomatic cerebral atherosclerotic disease between January 2002 and December 2012 were included in this study. Multivariate logistic regression analyses were performed to identify risk factors for ECAS and ICAS. Thereafter, CS group were compared to non-CS group in the entire study population and in a propensity-score matched population with two different age-subgroups. RESULTS: Of 1709 enrolled patients, 794 (46.5%) had extracranial (EC) lesions and the other 915 (53.5%) had intracranial (IC) lesions. CS group had more EC lesions (55.8% vs. 35.3%, P<0.001) whereas young age group (<50 years) had more IC lesion (84.5% vs. 47.6%, P<0.001). In multivariate analysis, seven variables including CS, male, old age, coronary heart disease, higher erythrocyte sedimentation rate, multiple lesions, and anterior lesion were independently associated with ECAS. In the propensity-score matched CS group had significant more EC lesion compared to non-CS group (65.7% vs. 47.9%) only in the old age subgroup. CONCLUSION: In contrast to a significant association between CS and severe symptomatic ECAS shown in old population, young patients did not show this association and showed relatively higher preference of ICAS.

Overuse of antibiotics for the common cold - attitudes and behaviors among doctors in rural areas of Shandong Province, China.

BACKGROUND: Irrational antibiotic use is common in rural areas of China, despite the growing recognition of the importance of appropriate prescribing to contain antibiotic resistance. The aim of this study was to analyze doctors' attitudes and prescribing practices related to antibiotics in rural areas of Shandong province, focusing on patients with the common cold. METHODS: A survey was conducted with doctors working at thirty health facilities (village clinics, township health centers and county general hospitals) in three counties within Shandong province. Questions were included on knowledge and attitudes towards antibiotic prescribing. Separately, a random selection of prescriptions for patients with the common cold was collected from the healthcare institutions at which the doctors worked, to investigate actual prescribing behaviors. RESULTS: A total of 188 doctors completed the survey. Most doctors (83%, 149/180) had attended training on antibiotic use since the beginning of their medical practice as a doctor, irrespective of the academic level of their undergraduate training. Of those that had training, most had attended it within the past three years (97%, 112/116). Very few doctors (2%, 3/187) said they would give antibiotics to a patient with symptoms of a common cold, and the majority (87%, 156/179) would refuse to prescribe an antibiotic even if patients were insistent on getting them. Doctors who had attended training were less likely to give antibiotics in this circumstance (29% vs. 14%, p < 0.001). A diagnosis of common cold was the only diagnosis reported on 1590 out of 8400 prescriptions. Over half (55%, 869/1590) of them included an antibiotic. Prescriptions from village clinics were more likely to contain an antibiotic than those from other healthcare institutions (71% vs. 44% [township] vs. 47% [county], p < 0.001). CONCLUSIONS: Most doctors have recently attended training on antibiotic use and report they would not prescribe antibiotics for patients with a common cold, even when placed under pressure by patients. However, more than half of the prescriptions from these healthcare institutions for patients with the common cold included an antibiotic. Exploring and addressing gaps between knowledge and practice is critical to improving antibiotic use in rural China.

Differential expression of immune-related genes between healthy volunteers and type 2 diabetic patients with spleen-deficiency pattern.

OBJECTIVE: To investigate the clinical differentia tion of spleen-deficiency pattern (SDP), a group of symptoms and signs defined in terms of Traditional Chinese Medicine for its clinical practice. METHODS: Peripheral venous blood (> 3 mL) was collected from each of six type 2 diabetes mellitus (T2DM)-SDP patients and six healthy volunteers. After the isolation of peripheral white blood cells (PWBCs), total RNA was extracted, and quality control was performed on all RNA samples. Microarray experiments were conducted using the Agilent human whole genome gene chip, and genes demonstrating differential expression were screened. Bioinformatics analysis was conducted on these genes using several online databases. RESULTS: We screened a total of 175 differentially expressed genes (DEGs), of which 111 (63%) were down-regulated and 64 (37%) were up-regulated in T2DM-SDP patients compared with healthy controls. Among the 175 genes, 158 had biological function annotations: 46 (29%) were directly related to an individual's immune regulation or response, 25 (16%) were associated with substance and energy metabolism of PWBCs which could also indirectly influence immunity, and the remaining 87 (55%) were involved in a variety of PWBC biological processes that might eventually influence the immune function. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the DEGs were predominantly enriched in seven immune-related pathways. Hierarchical cluster analysis identified gene expression patterns that were distinguishable between the two study groups. CONCLUSION: Our results suggest that T2DM-SDP patients experience significant hypoimmunity and/or immune dysfunctions, and possess a specific gene expression profile. These findings offer new insights into SDP and the clinical pattern differentiation of T2DM-SDP.

Varying high levels of faecal carriage of extended-spectrum beta-lactamase producing Enterobacteriaceae in rural villages in Shandong, China: implications for global health.

Antibiotic resistance is considered a major threat to global health and is affected by many factors, of which antibiotic use is probably one of the more important. Other factors include hygiene, crowding and travel. The rapid resistance spread in Gram-negative bacteria, in particular extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae (ESBL-E), is a global challenge, leading to increased mortality, morbidity and health systems costs worldwide. Knowledge about resistance in commensal flora is limited, including in China. Our aim was to establish the faecal carriage rates of ESBL-E and find its association with known and suspected risk factors in rural residents of all ages in three socio-economically different counties in the Shandong Province, China. Faecal samples and risk-factor information (questionnaire) were collected in 2012. ESBL-E carriage was screened using ChromID ESBL agar. Risk factors were analysed using standard statistical methods. Data from 1000 individuals from three counties and in total 18 villages showed a high and varying level of ESBL-E carriage. Overall, 42% were ESBL-E carriers. At county level the carriage rates were 49%, 45% and 31%, respectively, and when comparing individual villages (n = 18) the rate varied from 22% to 64%. The high level of ESBL-E carriage among rural residents in China is an indication of an exploding global challenge in the years to come as resistance spreads among bacteria and travels around the world with the movement of people and freight. A high carriage rate of ESBL-E increases the risk of infection with multi-resistant bacteria, and thus the need for usage of last resort antibiotics, such as carbapenems and colistin, in the treatment of common infections.

Expression of AEG-1 and microvessel density correlates with metastasis and prognosis of oral squamous cell carcinoma.

Astrocyte elevated gene 1 (AEG-1) expression is up-regulated in various human cancers and plays an important role in tumorigenesis and progression. The aim of this study was to explore AEG-1 expression in oral squamous cell carcinoma (OSCC) and to assess whether it is associated with microvessel density (MVD), metastasis, and survival. Specimens from 87 patients with OSCC were investigated by immunohistochemistry staining for AEG-1 and MVD. By statistical analysis, we studied the correlations between the expression of AEG-1 and MVD and various clinicopathological factors, including overall survival (OS). We found that AEG-1 was highly expressed in 51.72% of OSCC. Expression was closely correlated with differentiation, clinical stage, T classification, and lymph node metastasis. The MVD had similar results. Expression of AEG-1 correlated positively with MVD. The lymph node metastatic rate in patients with high AEG-1/high MVD was significantly higher than in patients with high AEG-1/low MVD, low AEG-1/high MVD, or low AEG-1/low MVD. Patients with high AEG-1 expression showed far lower OS rates than those with low expression. For MVD, there were similar results. Only AEG-1 and MVD expression were independent prognostic factors for OS by multivariate analysis. Expression of AEG-1 may be correlated with tumor angiogenesis and metastasis and is a valuable prognostic factor in patients with OSCC.

Role of EZH2 in oral squamous cell carcinoma carcinogenesis.

Oral squamous cell carcinoma (OSCC) is a common human malignancy with high incidence rate and poor prognosis. Although the polycomb group protein enhancer of zeste homolog 2 (EZH2) plays a crucial role in cell proliferation and differentiation during the occurrence and development progress of several kinds of malignant tumors, the impact of EZH2 on the development and progression of OSCC is unclear. In this study, we demonstrate that EZH2 is overexpressed in OSCC cells and clinical tissue. With in vitro RNAi analysis, we generated stable EZH2 knocking down cell lines from two OSCC cell lines, with two sh-RNAs targeting to EZH2, respectively. We found that knocking down of EZH2 could decrease the proliferation ability and induce apoptosis of OSCC cells. Moreover, we demonstrated that of EZH2 inhibition decreased the migration and metastasis of OSCC cells. In conclusion, the results of the current study demonstrated an association between EZH2 expression and OSCC cell development. We recommend that EZH2 acts as an oncogene and plays an important role in OSCC carcinogenesis.