Ameliorating parkinsonian motor dysfunction by targeting histamine receptors in entopeduncular nucleus-thalamus circuitry.

In Parkinson's disease (PD), reduced dopamine levels in the basal ganglia have been associated with altered neuronal firing and motor dysfunction. It remains unclear whether the altered firing rate or pattern of basal ganglia neurons leads to parkinsonism-associated motor dysfunction. In the present study, we show that increased histaminergic innervation of the entopeduncular nucleus (EPN) in the mouse model of PD leads to activation of EPN parvalbumin (PV) neurons projecting to the thalamic motor nucleus via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to postsynaptic H2R. Simultaneously, this effect is negatively regulated by presynaptic H3R activation in subthalamic nucleus (STN) glutamatergic neurons projecting to the EPN. Notably, the activation of both types of receptors ameliorates parkinsonism-associated motor dysfunction. Pharmacological activation of H2R or genetic upregulation of HCN2 in EPNPV neurons, which reduce neuronal burst firing, ameliorates parkinsonism-associated motor dysfunction independent of changes in the neuronal firing rate. In addition, optogenetic inhibition of EPNPV neurons and pharmacological activation or genetic upregulation of H3R in EPN-projecting STNGlu neurons ameliorate parkinsonism-associated motor dysfunction by reducing the firing rate rather than altering the firing pattern of EPNPV neurons. Thus, although a reduced firing rate and more regular firing pattern of EPNPV neurons correlate with amelioration in parkinsonism-associated motor dysfunction, the firing pattern appears to be more critical in this context. These results also confirm that targeting H2R and its downstream HCN2 channel in EPNPV neurons and H3R in EPN-projecting STNGlu neurons may represent potential therapeutic strategies for the clinical treatment of parkinsonism-associated motor dysfunction.

A Social Media-Based Mindfulness Psycho-Behavioral Intervention (MCARE) for Patients With Acute Coronary Syndrome: Randomized Controlled Trial.

BACKGROUND: Psychological distress is common among patients with acute coronary syndrome (ACS) and has considerable adverse impacts on disease progression and health outcomes. Mindfulness-based intervention is a promising complementary approach to address patients' psychological needs and promote holistic well-being. OBJECTIVE: This study aims to examine the effects of a social media-based mindfulness psycho-behavioral intervention (MCARE) on psychological distress, psychological stress, health-related quality of life (HRQoL), and cardiovascular risk factors among patients with ACS. METHODS: This study was a 2-arm, parallel-group randomized controlled trial. We recruited 178 patients (mean age 58.7, SD 8.9 years; 122/178, 68.5% male) with ACS at 2 tertiary hospitals in Jinan, China. Participants were randomly assigned to the MCARE group (n=89) or control group (n=89). The 6-week intervention consisted of 1 face-to-face session (phase I) and 5 weekly WeChat (Tencent Holdings Ltd)-delivered sessions (phase II) on mindfulness training and health education and lifestyle modification. The primary outcomes were depression and anxiety. Secondary outcomes included psychological stress, HRQoL, and cardiovascular risk factors (ie, smoking status, physical activity, dietary behavior, BMI, blood pressure, blood lipids, and blood glucose). Outcomes were measured at baseline (T0), immediately after the intervention (T1), and 12 weeks after the commencement of the intervention (T2). RESULTS: The MCARE group showed significantly greater reductions in depression (T1: ß=-2.016, 95% CI -2.584 to -1.449, Cohen d=-1.28, P<.001; T2: ß=-2.089, 95% CI -2.777 to -1.402, Cohen d=-1.12, P<.001) and anxiety (T1: ß=-1.024, 95% CI -1.551 to -0.497, Cohen d=-0.83, P<.001; T2: ß=-0.932, 95% CI -1.519 to -0.346, Cohen d=-0.70, P=.002). Significantly greater improvements were also observed in psychological stress (ß=-1.186, 95% CI -1.678 to -0.694, Cohen d=-1.41, P<.001), physical HRQoL (ß=0.088, 95% CI 0.008-0.167, Cohen d=0.72, P=.03), emotional HRQoL (ß=0.294, 95% CI 0.169-0.419, Cohen d=0.81, P<.001), and general HRQoL (ß=0.147, 95% CI 0.070-0.224, Cohen d=1.07) at T1, as well as dietary behavior (ß=0.069, 95% CI 0.003-0.136, Cohen d=0.75, P=.04), physical activity level (ß=177.542, 95% CI -39.073 to 316.011, Cohen d=0.51, P=.01), and systolic blood pressure (ß=-3.326, 95% CI -5.928 to -0.725, Cohen d=-1.32, P=.01) at T2. The overall completion rate of the intervention (completing ≥5 sessions) was 76% (68/89). Positive responses to the questions of the acceptability questionnaire ranged from 93% (76/82) to 100% (82/82). CONCLUSIONS: The MCARE program generated favorable effects on psychological distress, psychological stress, HRQoL, and several aspects of cardiovascular risk factors in patients with ACS. This study provides clues for guiding clinical practice in the recognition and management of psychological distress and integrating the intervention into routine rehabilitation practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033526; https://www.chictr.org.cn/showprojEN.html?proj=54693.

Design, synthesis, and evaluation of 2,2'-bipyridyl derivatives as bifunctional agents against Alzheimer's disease.

Alzheimer's disease (AD) is a complex multifactorial neurodegenerative disease. Metal ion dyshomeostasis and Aß aggregation have been proposed to contribute to AD progression. Metal ions can bind to Aß and promote Aß aggregation, and ultimately lead to neuronal death. Bifunctional (metal chelation and Aß interaction) compounds are showing promise against AD. In this work, eleven new 3,3'-diamino-2,2'-bipyridine derivatives 4a-4k were synthesized, and evaluated as bifunctional agents for AD treatment. In vitro Aß aggregation inhibition assay confirmed that most of the synthesized compounds exhibited significant self-induced Aß1-42 aggregation inhibition. Among them, compound 4d displayed the best inhibitory potency of self-induced Aß1-42 aggregation with IC50 value of 9.4 µM, and it could selectively chelate with Cu2+ and exhibited 66.2% inhibition of Cu2+-induced Aß1-42 aggregation. Meanwhile, compound 4d showed strong neuroprotective activity against Aß1-42 and Cu2+-treated Aß1-42 induced cell damage. Moreover, compound 4d in high dose significantly reversed Aß-induced memory impairment in mice.

Semaphorin 3A inhibits tumor progression via the downregulation of Lin28B in ovarian cancer.

Semaphorin 3A (Sema3A) has recently been proven to play an essential role in tumorigenesis. Here, the role of Sema3A in ovarian cancer is explored. The prognostic value of Sema3A was evaluated using the Kaplan-Meier plotter database, and stable expression cells were established by the delivery of lentivirus harboring SEMA3A cDNA or shRNA into OVCA433 and SKOV3 cells, respectively. Then CCK-8 assay, colony-formation assay, wound-healing assay, and Transwell assay were utilized to verify the effect of Sema3A on tumorigenesis. Co-cultures of ovarian cancer cells (OVCA433 and SKOV3) with a conditional medium collected from the established cells were further utilized to confirm the function of Sema3A. Then, the RNA-seq assay was adopted to explore the underlying mechanism. The results demonstrated that low expression of Sema3A was predictive of poor overall survival in patients with ovarian cancer. Functional experiments revealed that Sema3A inhibited proliferation, migration, and invasion in ovarian cancer cells. Secreted Sema3A in a conditioned culture medium also exhibited an anti-tumor effect in ovarian cancer cells. RNA-seq assay suggested that focal adhesion and Lin28B were involved in regulating Sema3A. Rescue assays further verified that Lin28B/ROCK1 axis was vital in the regulation of Sema3A and Lin28B significantly upregulated ROCK1 through let-7g microRNA. The presented data indicate that Sema3A inhibits proliferation and metastasis via the downregulation of Lin28B/ROCK1 in ovarian cancer.

eHealth Literacy of Chinese Residents During the Coronavirus Disease 2019 Pandemic: A Cross-sectional Survey.

The Coronavirus Disease 2019 (COVID-19) pandemic has become a leading societal concern. eHealth literacy is important in the prevention and control of this pandemic. The purpose of this study is to identify eHealth literacy of Chinese residents about the COVID-19 pandemic and factors influencing eHealth literacy. A total of 15 694 individuals clicked on the link to the questionnaire, and 15 000 agreed to participate and completed the questionnaire for a response rate of 95.58%. Descriptive statistics, χ 2 test, and logistic regression analysis were conducted to analyze participants' level of eHealth literacy about COVID-19 and its influencing factors. The results showed 52.2% of participants had relatively lower eHealth literacy regarding COVID-19 (eHealth literacy score ≤ 48). The scores of the information judgment dimension (3.09 ± 0.71) and information utilization dimension (3.18 ± 0.67) of the eHealth literacy scale were relatively lower. The logistics regression showed that sex, age, education level, level of uncertainty, having people around the respondent diagnosed with COVID-19, relationship with family, and relationship with others were associated to eHealth literacy (χ 2 = 969.135, P < .001). The public's eHealth literacy about COVID-19 needs to be improved, especially the ability to judge and utilize online information. Close collaboration among global health agencies, governments, healthcare institutions, and media is needed to provide reliable online information to the public. Interventions to improve eHealth literacy should take into account and accentuate the importance of sex, age, educational background, level of uncertainty, exposure to disease, and social support.

Help-Seeking Intentions for Depression from Mental Health Professionals Among Community-Dwelling Persons in Central China.

Understanding the intention of community residents to seek help from mental health professionals (MHPs) is essential in targeting interventions that promote the prevention and treatment of depression. This study aimed to investigate the current status of Chinese community populations' depression help-seeking intentions from MHPs and explore factors influencing the intentions. Data were used from a survey conducted in a city in central China (n = 919 aged 38.68 ± 17.34, 72.1% female). Help-seeking intentions, help-seeking attitude, depression stigma, family function and depressive symptoms were measured. The total mean score on the intent to seek help from MHPs was 11.01 ± 7.78 and most of respondents were unwilling to seek professional help. Multiple linear regression showed that participants who were students, held a positive help-seeking attitude and had low personal stigma were more likely to have the intention to seek help from MHPs. It is necessary to utilize effective interventions to improve community residents' intention to seek professional help. These include promoting the importance of seeking professional assistance, optimizing the quality of mental health services and altering residents' prejudice to seeking professional help.

[Melanogenesis of quality markers in Vernonia anthelmintica Injection based on UPLC-Q-TOF-MS combined network pharmacology].

This study aimed to evaluate the biological effect and mechanism of Vernonia anthelmintica Injection(VAI) on melanin accumulation. The in vivo depigmentation model was induced by propylthiouracil(PTU) in zebrafish, and the effect of VAI on melanin accumulation was evaluated based on the in vitro B16F10 cell model. The chemical composition of VAI was identified according to the high-performance liquid chromatography quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Network pharmaco-logy was applied to predict potential targets and pathways of VAI. A "VAI component-target-pathway" network was established, and the pharmacodynamic molecules were screened out based on the topological characteristics of the network. The binding of active molecules to key targets was verified by molecular docking. The results showed that VAI promoted tyrosinase activity and melanin production in B16F10 cells in a dose-and time-dependent manner and could restore the melanin in the body of the zebrafish model. Fifty-six compounds were identified from VAI, including flavonoids(15/56), terpenoids(10/56), phenolic acids(9/56), fatty acids(9/56), steroids(6/56), and others(7/56). Network pharmacological analysis screened four potential quality markers, including apigenin, chrysoeriol, syringaresinol, and butein, involving 61 targets and 65 pathways, and molecular docking verified their binding to TYR, NFE2L2, CASP3, MAPK1, MAPK8, and MAPK14. It was found that the mRNA expression of MITF, TYR, TYRP1, and DCT in B16F10 cells was promoted. By UPLC-Q-TOF-MS and network pharmacology, this study determined the material basis of VAI against vitiligo, screened apigenin, chrysoeriol, syringaresinol, and butein as the quality markers of VAI, and verified the efficacy and internal mechanism of melanogenesis, providing a basis for quality control and further clinical research.

Experiences and challenges faced by community mental health workers when providing care to people with mental illness: a qualitative study.

BACKGROUND: Mental illness is a major burden of disease worldwide. Community Mental Health Services (CMHS) are key to achieving community-based recovery for people with mental illness. In China, even though the community management of patients with mental illness is improving, the barriers faced by Community Mental Health Workers (CMHWs) are unclear. This study explores the difficulties and challenges in CMHS from the perspective of CMHWs. The results of this study may provide a practical basis for the training of CMHWs. METHODS: We carried out a qualitative study using an empirical phenomenological approach. Nine CMHWs were recruited from nine communities in Wuhan, Hubei Province, using purposive and snowball sampling. Face to face semi-structured in-depth interviews were conducted with them from December 27 to 28, 2019. Interview recordings were converted to text content by Nvivo 11.0 software and analyzed using Colaizzi's phenomenological method. RESULTS: Three main themes were identified in this study: 1) Lack of role orientation leads to role ambiguity, 2) Failure to establish a therapeutic trust relationship with patients, and 3) Lack of communication and collaboration with various departments and peers. Seven sub themes were also identified. In these themes, CMHWs emphasized the importance of role clarity, therapeutic trusting relationships, and effective communication and coordination mechanisms. CONCLUSION: Although China has made great efforts on the road to improving the quality of CMHS, several salient issues regarding CMHWs must be addressed to optimize the quality of services provided by CMHWs. Community mental health institutions should help CMHWs overcome these difficulties, by maximizing its value and promoting the development of CMHS.

Laparoscopic single-layer running "trapezoid-shaped" suture versus mechanical stapling for esophagojejunostomy after total gastrectomy for gastric cancer: cost-effect analysis of propensity score-matched study cohorts.

OBJECTIVES: Totally laparoscopic total gastrectomy has been developed with difficulty in intracorporeal esophagojejunostomy. Although mechanical stapling has been widely used for intracorporeal esophagojejunostomy, manual suture holds great promise with the emergence of high-resolution 3D vision and robotic surgery. After exploration of how to improve the safety and efficiency of intracorporeal suture for esophagojejunostomy, we recommended the technique of single-layer running "trapezoid-shaped" suture. The cost-effectiveness was analyzed by comparing with conventional mechanical stapling. METHODS: The study retrospectively reviewed the patients undergoing laparoscopic gastrectomy for gastric cancer from January 2010 to December 2021. The patients were divided into two cohorts based on the methods of intracorporeal esophagojejunostomy: manual suture versus stapling suture. Propensity score matching was performed to match patients from the two cohorts at a ratio of 1:1. Then group comparison was made to determine whether manual suture was non-inferior to stapling suture in terms of operation time, anastomotic complications, postoperative hospital stay, and surgical cost. RESULTS: The study included 582 patients with laparoscopic total gastrectomy. The manual and stapling suture for esophagojejunostomy were performed in 50 and 532 patients, respectively. In manual suture cohort, the median time for the whole operation and digestive tract reconstruction were 300 min and 110 min. There was no anastomotic bleeding and stenosis but two cases of anastomotic leak which occurred at 3 days after surgery. The median length of postoperative hospital stay was 11 days. After propensity score matching, group comparison yielded two variables with statistical significance: time for digestive tract reconstruction and surgery cost. The manual suture cohort spent less money but more time for esophagojejunostomy. Intriguingly, the learning curve of manual suture revealed that the time for digestive tract reconstruction was declined with accumulated number of operations. CONCLUSIONS: Laparoscopic single-layer running "trapezoid-shaped" suture appears safe and cost-effective for intracorporeal esophagojejunostomy after total gastrectomy. Although the concern remains about prolonged operation time for beginners of performing the suture method, adequate practice is expected to shorten the operation time based on our learning curve analysis.

Investigation of retinal microvasculature and choriocapillaris in adolescent myopic patients with astigmatism undergoing orthokeratology.

BACKGROUND: To observe alterations of fundus microcirculation and retinal thickness in adolescent myopic patients with astigmatism after toric and spherical orthokeratology using optical coherence tomography angiography (OCTA), to explore the effects of orthokeratology on the retinal thickness and choroidal blood flow. METHODS: A total of 48 patients were enrolled and divided into two group (toric orthokeratology (T) group and spherical orthokeratology (S) group) according to the type of lens design. OCTA was used to measure the superficial and deep retinal vessel densities at the macular region, radial peripapillary capillary (RPC) density, foveal avascular zone (FAZ) area, and choriocapillaris (ChC) perfusion area before and after orthokeratology for 3 months. The data were statistically analyzed by SPSS 19.0 software. RESULTS: Compared with before orthokeratology, the superficial vessel density in the fovea and parafovea in the T group significantly increased, and the deep vessel density in the whole area and fovea were significantly elevated after 3 months (P < 0.05). The superficial vessel density was significantly higher only in the parafovea in the S group after 3 months than that before orthokeratology (P < 0.05), deep vessel density in the whole area and parafovea after 3 months was significantly higher than that before orthokeratology (P < 0.05). RPC density in the two groups increased after 3 months of orthokeratology in the whole area and inside the disc area (P < 0.05). Three months after toric orthokeratology, FAZ area in the T group was significantly reduced by 0.05 (- 0.41 to + 0.08) mm2, while ChC perfusion area was enlarged by 0.06 ± 0.12 mm2. FAZ area in the S group significantly decreased by 0.01 (- 0.19 to + 0.01) mm2, whereas ChC perfusion area increased by 0.06 (- 0.07 to + 0.50) mm2. Retinal thickness in the two groups increased after 3 months of orthokeratology in the whole area and parafoveal area (P < 0.05). CONCLUSION: Orthokeratology improved retinal blood flow in macular area and RPC while controlling myopia. The changes in FAZ and ChC perfusion areas did not significantly differ between toric and spherical orthokeratology.

Gender differences in the relationships between housework and metabolic markers: a longitudinal cohort study in China.

BACKGROUND: Metabolic syndrome has become a major health threat throughout the world, but there are few studies that focus on the effects of housework on human metabolism. This study explores the association between housework and metabolic markers and examines whether there are gender differences in the relationship of housework intensity on these markers. METHODS: We obtained data for 2,624 participants from the China Health and Nutrition Survey and used binary logistic regression to analyze the association between housework and metabolic markers (triglycerides, high- and low-density lipoprotein cholesterol, hemoglobin, blood glucose, cholesterol, and blood pressure). RESULTS: We observed no association between housework and metabolic markers for men. However, we find that women who engaged in housework had a higher risk of triglycerides than those who did not (OR=1.16, 95% CI: 1.16, 4.25). Compared with low-intensity, we also find that women who performed moderate- and high-housework intensity had a higher risk of triglycerides (moderate-intensity: OR=1.78, 95% CI: 1.14, 2.78; high-intensity: OR=1.91, 95% CI: 1.22, 2.98), MetS (OR=1.54, 95% CI: 0.98, 2.43; OR=1.68, 95% CI: 1.07, 2.66), pre-hypertension (OR=1.68, 95% CI: 1.08, 2.62; OR=1.63, 95% CI: 1.04, 2.55), and obesity (OR=1.65, 95% CI: 1.01, 2.70; OR=1.66, 95% CI: 1.01, 2.72). CONCLUSION: In women, we find that housework is positively associated with the metabolic markers, triglycerides, MetS, and pre-hypertension. However, we did not find evidence that this relationship exists in men, f or any biomarkers we considered. One possible explanation is that people who engage in high-intensity housework are more stressed and sleep less, which could be a mechanism by which housework becomes associated with metabolic disease.

When health care workers became patients with COVID-19: A qualitative study.

AIMS: This study aimed to describe the experiences of nurses and other health care workers who were infected with coronavirus disease 2019. METHODS: An empirical phenomenological approach was used. Sixteen participants were recruited in Wuhan using purposive and snowball sampling. Semistructured, in-depth interviews were conducted by telephone in February 2020. Interviews were transcribed verbatim and analysed following Colaizzi's method. RESULTS: Two themes emerged: (1) Intense emotional distress since becoming infected. Participants were fearful of spreading the virus to family and overwhelmed by a lack of information, experienced uncertainty and worried about treatment, felt lonely during isolation and reported moral distress about inadequate health care staffing. (2) Coping strategies were needed. They tried their best to address negative psychological reactions using their professional knowledge and gaining support from others and community resources. CONCLUSIONS: Preparedness for catastrophic events and providing timely and accurate information are major considerations in government policy development, related to pandemics and adequacy of health care personnel. Mental health resources and support, both short- and long-term should be anticipated for health care providers to alleviate their fear and anxiety.

Electronic health literacy among older adults in the context of the COVID-19 pandemic: A mixed-methods study.

AIM: This study aimed to investigate eHealth literacy about coronavirus disease 2019 (COVID-19) among older adults during the pandemic. BACKGROUND: The COVID-19 pandemic promoted the development of online health care. Higher demand for accessing information from the Internet was seen. METHODS: This was a sequential explanatory mixed-method study, involving a survey of older adults to explore the status and influencing factors of eHealth literacy regarding COVID-19. Semi-structured interviews were used to understand experiences and challenges regarding information retrieval, judgment and utilization. RESULTS: A total of 337 older adults participated in the online questionnaire survey. Overall, older adults had slightly higher scores on eHealth literacy during the COVID-19 pandemic. Participants' location in the past month and current health issues were associated with eHealth literacy. Qualitative data were collected from nine older adults and included that some older adults retrieved health-related information during the pandemic. However, those who used non-smartphones described difficulties in information retrieval. A glut of misinformation has resulted in an 'infodemic', which has not only increased the difficulty of judging information but also posed challenges in information utilization for older adults. CONCLUSION: Improving older adults' eHealth literacy is essential in promoting an improved response to major public health events and in providing better health care for this group in the future. It is essential that government health agencies and health care providers provide evidence-based health information via social media platforms. Further efforts are needed to combine aspects of traditional and online health care services and provide reliable and updated online information and resources for older adults. IMPLICATIONS FOR NURSING MANAGEMENT: Providing evidence to eHealth literacy improvement and health management of older adults in the context of public health events.

Identification of circular RNAs as novel biomarkers and potentially functional competing endogenous RNA network for myelodysplastic syndrome patients.

Circular RNAs (circRNAs) have been identified to exert vital biological functions and can be used as new biomarkers in a number of tumors. However, little is known about the functions of circRNAs in myelodysplastic syndrome (MDS). Here, we aimed to investigate circRNA expression profiles and to investigate the functional and clinical value of circRNAs in MDS. Differential expression of circRNAs between MDS and control subjects was analyzed using circRNA arrays, in which we identified 145 upregulated circRNAs and 224 downregulated circRNAs. Validated by real-time quantitative PCR between 100 MDS patients and 20 controls, three upregulated (hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_104634) and three downregulated (hsa_circRNA_103846, hsa_circRNA_102817, and hsa_circRNA_102526) circRNAs matched the arrays. The receiver operating characteristic curve analysis of these circRNAs showed that the area under the curve was 0.7266, 0.8676, 0.7349, 0.7091, 0.8806, and 0.7472, respectively. Kaplan-Meier survival analysis showed that only hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817 were significantly associated with overall survival. Furthermore, we generated a competing endogenous RNA network focused on hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed that the three circRNAs were linked with some important cancer-related functions and pathways.

Intervention of Tyrosine Hydroxylase Expression Alters Joint Inflammation and Th17/Treg Imbalance in Collagen-Induced Arthritis.

BACKGROUND/AIMS: Neuroendocrine dysregulation has been associated with rheumatoid arthritis (RA). Tyrosine hydroxylase (TH), a rate-limiting enzyme for synthesis of neuroendocrine hormones such as epinephrine, is also expressed in T lymphocytes and regulates balance between helper T (Th) 17 cells and regulatory T (Treg) cells. Herein, we aimed to show that TH expression in joints alleviates joint inflammation and Th17/Treg imbalance in collagen-induced arthritis (CIA), an animal model of RA, and these effects may be implemented by the mechanism of epinephrine action on α1-adrenoreceptor (α1-AR) in T cells. METHODS: CIA was prepared by intradermal injection of collagen type II in tail base of DBA1/J mice. On the 33rd day post-immunization, lentiviral vectors encoding TH or TH shRNA were injected into ankle joints of CIA mice. Limb inflammation of the mice was assessed beginning from day 21 until day 69 post-immunization by measurement of limb swelling, erythema and rigidity. Th17 and Treg differentiation and function in ankle joints were assessed on day 69 post-immunization by test of the expression of Th17 transcriptional factor ROR-γt and the levels of proinflammatory cytokines interleukin (IL)-17 and IL-22 as well as the expression of Treg transcriptional factor Foxp3 and the levels of antiinflammatory cytokines transforming growth factor (TGF)-ß1 and IL-10. T cells were obtained from the spleen of mice that had been immunized with collagen type II 41 day earlier and treated with epinephrine or α1-AR agonist phenylephrine in vitro. Flow cytometry was used to analyze the percentages of CD25-IL-17+ cells and CD25+Foxp3+ cells in CD4+ T cells. RESULTS: TH gene overexpression in ankle joints of CIA mice reduced limb inflammation and Th17-related transcription factor expression and inflammatory cytokine production but increased Treg-related antiinflammatory cytokine production in the joints. In contrast, TH gene silence in ankle joints of CIA mice enhanced limb inflammation and Th17 cell activity but decreased Treg cell function in the joints. Epinephrine upregulated α1-AR expression in T cells derived from CIA mice. Both epinephrine and phenylephrine reduced CIA-induced Th17 transcription factor expression and inflammatory cytokine production but enhanced Treg antiinflammatory cytokine production in vitro. CONCLUSION: Upregulating TH expression in joints alleviates joint inflammation and Th17/Treg imbalance in CIA at least partially by enhancing epinephrine action on α1-AR in T cells.

Dopamine receptor D2 on CD4+ T cells is protective against neuroinflammation and neurodegeneration in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disease. Recently, neuroinflammation driven by CD4+ T cells has been involved in PD pathophysiology. Human and murine lymphocytes express all the five subtypes of dopamine receptors (DRs), DRD1 to DRD5. However, roles of DRs particularly DRD2 expressed on CD4+ T cells in PD remain elucidated. Global Drd1- or Drd2-knockout (Drd1-/- or Drd2-/-) mice or CD4+ T cell-specific Drd2-knockout (Drd2fl/fl/CD4Cre) mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD with the different mutants. On the 7th day following MPTP injection, mice were assessed for dopaminergic neurodegeneration, locomotor impairments, microglial activation, as well as CD4+ T-cell differentiation and function. Furthermore, in vitro CD4+ T cells were exposed to DRD2 agonist and antagonist and then differentiation and function of the cells were determined. MPTP induced dopaminergic neuronal loss in the nigrostriatal system, motor coordinative and behavioral impairments, microglial activation, and CD4+ T-cell polarization to pro-inflammatory T-helper (Th)1 and Th17 phenotypes. Importantly, either Drd2-/- or Drd2fl/fl/CD4Cre mice manifested more severe dopaminergic neurodegeneration, motor deficits, microglial activation, and CD4+ T-cell bias towards Th1 and Th17 phenotypes in response to MPTP, but Drd1-/- did not further alter MPTP intoxication. DRD2 agonist sumanirole inhibited shift of CD4+ T cells obtained from MPTP-intoxicated mice to Th1 and Th17 phenotypes and DRD2 antagonist L-741,626 reversed sumanirole effects. These findings suggest that DRD2 expressed on CD4+ T cells is protective against neuroinflammation and neurodegeneration in PD. Thus, developing a therapeutic strategy of stimulating DRD2 may be promising for mitigation of PD.

A Meta-Analysis of Alterations in the Retina and Choroid in High Myopia Assessed by Optical Coherence Tomography Angiography.

BACKGROUND: High myopia (HM) is a risk factor for several pathological structural changes in retinal and choroidal thickness or vessel. To date, changes in retinal and choroidal microvasculature circulations in HM have yielded inconsistent results. OBJECTIVES: The objective of this article was to evaluate alterations in retinal and choroidal thickness, and capillary microvasculature using optical coherence tomography angiography (OCTA) in HM. METHODS: PubMed, Embase, and the Cochrane Library databases were searched for relevant published studies. Primary outcomes were foveal avascular zone, vessel density, retinal nerve fiber layer (RNFL) thickness, foveal thickness, sub-foveal choroidal thickness, and chorio-capillary density. Alterations in outcomes were evaluated by standardized mean difference with a 95% confidence interval. RESULTS: Eleven eligible articles were included for the meta-analysis. The whole superficial and deep vessel densities of macular and parapapillary superficial vessel density were lower in HM than in control eyes. The thickness of parafoveal RNFL, parapapillary RNFL, and sub-foveal choroid was significantly lower in HM eyes. Also, chorio-capillary density was shown to be lower in HM eyes. CONCLUSIONS: The retinal and choroidal vessel network change may be related to the axial elongation in the progression of myopia. Furthermore, OCTA is an effective and noninvasive technology for monitoring the progress of myopia eyes.

Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease.

Fifteen chalcone derivatives 3a-3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self-induced Aß1-42 aggregation effectively ranged from 45.9-94.5 % at 20 µM, and acted as potential antioxidants. Their structure-activity relationships were summarized. In particular, (2E)-3-[4-(dimethylamino)phenyl]-1-(pyridin-2-yl)prop-2-en-1-one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 µM, and it could disassemble the self-induced Aß1-42 aggregation fibrils with ratio of 57.1 % at 20 µM concentration. In addition, compound 3g displayed good chelating ability for Cu2+ , and could effectively inhibit and disaggregate Cu2+ -induced Aß aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aß1-42 -induced SH-SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine-induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy.

Relationship between eHealth literacy and psychological status during COVID-19 pandemic: A survey of Chinese residents.

AIMS: To investigate the eHealth literacy and the psychological status of Chinese residents during the COVID-19 pandemic and explore their interrelationship. BACKGROUND: The COVID-19 outbreak has placed intense psychological pressure on community residents. Their psychological status may be affected by eHealth literacy due to home isolation during this rampant pandemic. METHODS: This is a Web-based cross-sectional survey conducted on the JD Health platform, which resulted in 15,000 respondents having participated in this survey. The eHealth Literacy Questionnaire (EHLQ), Patient Health Questionnaire-9 (PHQ-9), Insomnia Severity Index (ISI) and Impact of Event Scale-Revised (IES-R) were used. The Pearson correlation was used to analyse the relationship between eHealth literacy and depression, insomnia and post-traumatic stress disorder. RESULTS: The score of eHealth literacy was 48.88 ± 8.46, and 11.4%, 6.8% and 20.1% of respondents experienced moderate to severe depression, insomnia and post-traumatic stress disorder. eHealth literacy negatively correlated with depression (r = -0.331), insomnia (r = -0.366) and post-traumatic stress disorder (r = -0.320). CONCLUSION: eHealth literacy is closely related to psychological status. Improving eHealth literacy may contribute to maintaining good psychological well-being. IMPLICATIONS FOR NURSING MANAGEMENT: It is necessary to strengthen the education of primary health care providers to enhance their ability to help community residents effectively use eHealth information.

Stigma towards depression in a community-based sample in China.

OBJECTIVE: Understanding the general public's beliefs about depression is essential if public education and anti-stigma interventions are to be effective. This study aimed to examine Chinese respondents' personal attitudes towards depression and their perceptions about the attitudes of others regarding depression and to identify the correlates of personal stigma and perceived stigma towards depression. METHODS: A community survey was conducted among 1697 residents aged between 16 and 89 years of a large city in central China using the Depression Stigma Scale. Participants completed questionnaires assessing experiences of depression and family functioning. RESULTS: Participants reported high levels of stigma towards depression, with greater perceived stigma than personal stigma. Increasing age was correlated with greater personal stigma and perceived stigma. Higher personal stigma was also significantly correlated with being male, unemployed and good family function. CONCLUSION: Concerningly high levels of stigmatizing beliefs towards depression were prevalent among the public. This may be a reason why people with mental disorders do not seek assistance. This highlights the importance of the need for health education and promotion activities. Findings from this study suggest that targeted, culturally appropriate education programs are needed to improve knowledge about depression in the broader community.