Publications by authors named "Xin-Min Li"

183 Publications

Effects of adenoidectomy or adenotonsillectomy on the cardiovascular system in children: a meta-analysis.

Eur Arch Otorhinolaryngol 2021 Jul 16. Epub 2021 Jul 16.

Basic Medicine College, Henan University of Chinese Medicine, Zhengzhou, 450000, China.

Objective: Adenoid or adenotonsillar hypertrophy (AATH) causes upper airway obstruction, leading to cardiovascular complications. This meta-analysis was conducted to evaluate the efficacy of adenoidectomy or adenotonsillectomy (AATE) on the cardiovascular system.

Methods: Using the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE databases, we identified studies involving a comparison of preoperative and postoperative cardiovascular function in children with AATH. The Cochrane Collaboration's Review Manager 5.3 software was used for meta-analysis.

Results: A total of 13 studies with 706 participants were included. The meta-analysis demonstrated a significant reduction in mean pulmonary artery pressure (mPAP) of patients after AATE compared with preoperative values. The left ventricular myocardial function index (LVMPI) and the right ventricular myocardial function index (RVMPI) showed a significant decrease after the operation. Moreover, AATE prominently increased left ventricular ejection time (LVET) and right ventricular ejection time (RVET) and reduced the left ventricular interventricular septum diameter (LVIVSD) and the right ventricular end-diastolic diameter (RVedD). There was no significant difference in mPAP, LVMPI, RVMPI, LVET, RVET, LVIVSD, and RVedD between postoperative patients and healthy children (P  > 0.05).

Conclusion: AATE can improve cardiovascular function in pediatric patients with AATH. Specifically, it reduces mPAP and LVMPI/RVMPI in pediatric patients. Furthermore, AATE increases LVET and RVET and reduces LVIVSD and RVedD.
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http://dx.doi.org/10.1007/s00405-021-06986-0DOI Listing
July 2021

Behavioral and neurobiological changes in a novel mouse model of schizophrenia induced by the combination of cuprizone and MK-801.

Brain Res Bull 2021 Jun 11;174:141-152. Epub 2021 Jun 11.

Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Beijing Engineering Research Center for Nerve System Drugs, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China. Electronic address:

Schizophrenia is a mental illness characterized by episodes of psychosis, apathy, social withdrawal, and cognitive impairment. White matter lesions and glutamatergic hypofunction are reported to be the key pathogeneses underlying the multiple clinical symptoms of schizophrenia. Cuprizone (CPZ) is a copper chelator that selectively injures oligodendrocytes, and MK-801 is an antagonist of the N-methyl d-aspartate (NMDA) receptor. To better mimic the psychosis and complicated pathogenesis of schizophrenia, a novel possible mouse model was established by the combination of CPZ and MK-801. After exposure to CPZ for 5 weeks, the mice received a daily intraperitoneal injection of MK-801 for 2-weeks. Behavioral changes in the mouse model were evaluated using Y-maze, object recognition, and open field tests. Pathological changes were observed by transmission electron microscopy, oil red O staining, immunohistochemistry, and western blotting. The results showed that the novel mouse model induced by CPZ plus MK-801 exhibited severe spatial and recognition memory deficits, hyperactivity, and anxiety disorder. Moreover, the mice showed obvious demyelination and white matter damage and decreased expression levels of myelin basic protein (MBP) and 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in the corpus callosum. Furthermore, the phosphorylation levels of Fyn and NMDA receptor 2B in the corpus callosum and NMDA receptor 1 in the cerebral cortex were noticeably decreased. Taken together, the novel mouse model induced by the combination of cuprizone and MK-801 showed comprehensive behavioral and neurobiological changes, which might make it a suitable animal model for schizophrenia.
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http://dx.doi.org/10.1016/j.brainresbull.2021.06.007DOI Listing
June 2021

Exploratory study on neurochemical effects of low-intensity pulsed ultrasound in brains of mice.

Med Biol Eng Comput 2021 May 21;59(5):1099-1110. Epub 2021 Apr 21.

Department of Electrical and Computer Engineering, Faculty of Engineering, University of Alberta, Edmonton, Canada.

There is now a relatively large body of evidence suggesting a relationship between dysfunction of myelin and oligodendrocytes and the etiology of several neuropsychiatric disorders, including depression and schizophrenia, and also suggesting that ultrasound methods may alleviate some of the symptoms of depression. We have applied low-intensity pulsed ultrasound (LIPUS) to the brains of mice treated with the demyelinating drug cuprizone, a drug that has been used as the basis for a rodent model relevant to a number of psychiatric and neurologic disorders including depression, schizophrenia, and multiple sclerosis. Prior to conducting the studies in mice, preliminary studies were carried out on the effects of LIPUS in vitro in neuron-like SH-SY5Y cells and primary glial cells. In subsequent studies in mice, female C57BL/6 mice were restrained in plastic tubes for 20 min daily with the ultrasound transducer near the end of the tube directly above the mouse's head. LIPUS was used at an intensity of 25 mW/cm once daily for 22 days in control mice and in mice undergoing daily repetitive restraint stress (RRS). Behavioral or neurochemical studies were done on the mice or the brain tissue obtained from them. The studies in vitro indicated that LIPUS stimulation at an intensity of 15 mW/cm delivered for 5 min daily for 3 days in an enclosed sterile cell culture plate in an incubator increased the viability of SH-SY5Y and primary glial cells. In the studies in mice, LIPUS elevated levels of doublecortin, a marker for neurogenesis, in the cortex compared to levels in the RRS mice and caused a trend in elevation of brain levels of brain-derived neurotrophic factor in the hippocampus relative to control levels. LIPUS also increased sucrose preference (a measure of the attenuation of anhedonia, a common symptom of several psychiatric disorders) in the RRS model in mice. The ability of LIPUS administered daily to rescue damaged myelin and oligodendrocytes was studied in mice treated chronically with cuprizone for 35 days. LIPUS increased cortex and corpus callosum levels of myelin basic protein, a protein marker for mature oligodendrocytes, and neural/glial antigen 2, a protein marker for oligodendrocyte precursor cells, relative to levels in the cuprizone + sham animals. These results of this exploratory study suggest that future comprehensive time-related studies with LIPUS on brain chemistry and behavior related to neuropsychiatric disorders are warranted. Exploratory Study on Neurochemical Effects of Low Intensity Pulsed Ultrasound in Brains of Mice. Upper part of figure: LIPUS device and in-vitro cell experimental set-up. The center image is the LIPUS generating box; the image in the upper left shows the cell experiment set-up; the image in the upper right shows a zoomed-in sketch for the cell experiment; the image in the lower left shows the set-up of repetitive restraint stress (RRS) with a mouse; the image in the lower middle shows the set-up of LIPUS treatment of a mouse; the image in the lower right shows a zoomed-in sketch for the LIPUS treatment of a mouse.
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http://dx.doi.org/10.1007/s11517-021-02351-9DOI Listing
May 2021

Gender Differences in Satisfaction With a Text Messaging Program (Text4Hope) and Anticipated Receptivity to Technology-Based Health Support During the COVID-19 Pandemic: Cross-sectional Survey Study.

JMIR Mhealth Uhealth 2021 04 15;9(4):e24184. Epub 2021 Apr 15.

Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Background: In March 2020, Text4Hope-a community health service-was provided to Alberta residents. This free service aims to promote psychological resilience and alleviate pandemic-associated stress, anxiety, and depression symptoms during the COVID-19 pandemic.

Objective: This study aimed to evaluate the feedback, satisfaction, experience, and perceptions of Text4Hope subscribers and to examine any differences based on gender after subscribers received 6 weeks of daily supportive text messages. Additionally, this study examined subscribers' anticipated receptivity to technology-based medical services that could be offered during major crises, emergencies, or pandemics.

Methods: Individuals self-subscribed to Text4Hope to receive daily supportive text messages for 3 months. Subscribers were invited to complete a web-based survey at 6 weeks postintervention to provide service satisfaction-related information. Overall satisfaction was assessed on a scale of 0-10, and satisfaction scores were analyzed using a related-measures t test. Likert scale satisfaction responses were used to assess various aspects of the Text4Hope program. Gender differences were analyzed using one-way analysis of variance (ANOVA) and Chi-square analyses.

Results: A total of 2032 subscribers completed the baseline and 6-week surveys; 1788 (88%) were female, 219 (10.8%) were male, and 25 (1.2%) were other gender. The mean age of study participants was 44.58 years (SD 13.45 years). The mean overall satisfaction score was 8.55 (SD 1.78), suggesting high overall satisfaction with Text4Hope. The ANOVA analysis, which was conducted using the Welch test (n=1716), demonstrated that females had significantly higher mean satisfaction scores than males (8.65 vs 8.11, respectively; mean difference=0.546; 95% CI 0.19 to 0.91; P<.001) and nonsignificantly lower satisfaction scores than other gender respondents (mean difference=-0.938; 95% CI -0.37 to 2.25; P=.15). More than 70% of subscribers agreed that Text4Hope helped them cope with stress (1334/1731, 77.1%) and anxiety (1309/1728, 75.8%), feel connected to a support system (1400/1729, 81%), manage COVID-19-related issues (1279/1728, 74%), and improve mental well-being (1308/1731, 75.6%). Similarly, subscribers agreed that messages were positive, affirmative, and succinct. Messages were always or often read by 97.9% (1681/1716) of respondents, and more than 20% (401/1716, 23.4%) always or often returned to messages. The majority of subscribers (1471/1666, 88.3%) read the messages and either reflected upon them or took a positive action. Subscribers welcomed almost all technology-based services as part of their health care during crisis or emergency situations. Text4Hope was perceived to be effective by many female subscribers, who reported higher satisfaction and improved coping after receiving text messages for 6 weeks.

Conclusions: Respondents affirmed the high quality of the text messages with their positive feedback. Technology-based services can provide remotely accessible and population-level interventions that align with the recommended physical distancing practices for pandemics. Text4Hope subscriber feedback revealed high satisfaction and acceptance at 6 weeks postintervention.

International Registered Report Identifier (irrid): RR2-10.2196/19292.
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http://dx.doi.org/10.2196/24184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051435PMC
April 2021

Gender Differences in Satisfaction With a Text Messaging Program (Text4Hope) and Anticipated Receptivity to Technology-Based Health Support During the COVID-19 Pandemic: Cross-sectional Survey Study.

JMIR Mhealth Uhealth 2021 04 15;9(4):e24184. Epub 2021 Apr 15.

Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Background: In March 2020, Text4Hope-a community health service-was provided to Alberta residents. This free service aims to promote psychological resilience and alleviate pandemic-associated stress, anxiety, and depression symptoms during the COVID-19 pandemic.

Objective: This study aimed to evaluate the feedback, satisfaction, experience, and perceptions of Text4Hope subscribers and to examine any differences based on gender after subscribers received 6 weeks of daily supportive text messages. Additionally, this study examined subscribers' anticipated receptivity to technology-based medical services that could be offered during major crises, emergencies, or pandemics.

Methods: Individuals self-subscribed to Text4Hope to receive daily supportive text messages for 3 months. Subscribers were invited to complete a web-based survey at 6 weeks postintervention to provide service satisfaction-related information. Overall satisfaction was assessed on a scale of 0-10, and satisfaction scores were analyzed using a related-measures t test. Likert scale satisfaction responses were used to assess various aspects of the Text4Hope program. Gender differences were analyzed using one-way analysis of variance (ANOVA) and Chi-square analyses.

Results: A total of 2032 subscribers completed the baseline and 6-week surveys; 1788 (88%) were female, 219 (10.8%) were male, and 25 (1.2%) were other gender. The mean age of study participants was 44.58 years (SD 13.45 years). The mean overall satisfaction score was 8.55 (SD 1.78), suggesting high overall satisfaction with Text4Hope. The ANOVA analysis, which was conducted using the Welch test (n=1716), demonstrated that females had significantly higher mean satisfaction scores than males (8.65 vs 8.11, respectively; mean difference=0.546; 95% CI 0.19 to 0.91; P<.001) and nonsignificantly lower satisfaction scores than other gender respondents (mean difference=-0.938; 95% CI -0.37 to 2.25; P=.15). More than 70% of subscribers agreed that Text4Hope helped them cope with stress (1334/1731, 77.1%) and anxiety (1309/1728, 75.8%), feel connected to a support system (1400/1729, 81%), manage COVID-19-related issues (1279/1728, 74%), and improve mental well-being (1308/1731, 75.6%). Similarly, subscribers agreed that messages were positive, affirmative, and succinct. Messages were always or often read by 97.9% (1681/1716) of respondents, and more than 20% (401/1716, 23.4%) always or often returned to messages. The majority of subscribers (1471/1666, 88.3%) read the messages and either reflected upon them or took a positive action. Subscribers welcomed almost all technology-based services as part of their health care during crisis or emergency situations. Text4Hope was perceived to be effective by many female subscribers, who reported higher satisfaction and improved coping after receiving text messages for 6 weeks.

Conclusions: Respondents affirmed the high quality of the text messages with their positive feedback. Technology-based services can provide remotely accessible and population-level interventions that align with the recommended physical distancing practices for pandemics. Text4Hope subscriber feedback revealed high satisfaction and acceptance at 6 weeks postintervention.

International Registered Report Identifier (irrid): RR2-10.2196/19292.
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http://dx.doi.org/10.2196/24184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051435PMC
April 2021

Low field magnetic stimulation promotes myelin repair and cognitive recovery in chronic cuprizone mouse model.

Clin Exp Pharmacol Physiol 2021 Aug 7;48(8):1090-1102. Epub 2021 Apr 7.

Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.

Background: Multiple sclerosis (MS) is an inflammatory demyelinating disease featured with neuroinflammation, demyelination, and the loss of oligodendrocytes. Cognitive impairment and depression are common neuropsychiatric symptoms in MS that are poorly managed with the present interventions.

Objective: This study aimed to investigate the effects of low field magnetic stimulation (LFMS), a novel non-invasive neuromodulation technology, on cognitive impairment and depressive symptoms associated with MS using a mouse model of demyelination.

Methods: C57BL female mice were fed with a 0.2% cuprizone diet for 12 weeks to induce a chronic demyelinating model followed by 4 weeks of cuprizone withdrawal with either sham or LFMS treatment.

Results: Improved cognition and depression-like behaviour and restored weight gain were observed in mice with LFMS treatment. Immunohistochemical and immunoblotting data showed enhanced myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein expressions (MOG) in the prefrontal cortex of mice with LFMS treatment, supporting that myelin repair was promoted. LFMS also increased the protein expression of mature oligodendrocyte biomarker glutathione-S-transferase (GST-π). In addition, expression of TGF-β and associated receptors were elevated with LFMS treatment, implicating this pathway in the response.

Conclusion: Results from the present study revealed LFMS to have neuroprotective effects, suggesting that LFMS has potential therapeutic value for treating cognitive impairment and depression related to demyelination disorders.
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http://dx.doi.org/10.1111/1440-1681.13490DOI Listing
August 2021

Text4Hope: Receiving Daily Supportive Text Messages for 3 Months During the COVID-19 Pandemic Reduces Stress, Anxiety, and Depression.

Disaster Med Public Health Prep 2021 Feb 8:1-5. Epub 2021 Feb 8.

Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.

Background: This study reports on the changes in stress, anxiety, and depressive symptoms of subscribers after 3 months using Text4Hope, a supportive text messaging program designed to provide support during the pandemic.

Methods: Standardized self-report measures were used to evaluate perceived stress (measured with the Perceived Stress Scale-10 [PSS-10]), anxiety (measured with the General Anxiety Disorder Scale 7 [GAD-7]), and depressive symptoms (measured with the Patient Health Questionnaire [PHQ-9]), at baseline and 3rd month (n = 373).

Results: After 3 months of using Text4Hope, subscribers' self-reports revealed significant (p< 0.001) mean score reductions compared with baseline on: the GAD-7 by 22.7%, PHQ-9 by 10.3%, and PSS-10 scores by 5.7%. Reductions in inferred prevalence rates for moderate to high symptoms were also observed, with anxiety demonstrating the largest reduction (15.7%).

Conclusions: Observed Text4Hope-related reductions in psychological distress during COVID-19 indicate that Text4Hope is an effective, convenient, and accessible means of implementing a population-level psychological intervention.
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http://dx.doi.org/10.1017/dmp.2021.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985636PMC
February 2021

Individualized identification of first-episode bipolar disorder using machine learning and cognitive tests.

J Affect Disord 2021 03 18;282:662-668. Epub 2020 Dec 18.

Department of Psychiatry, University of Alberta, Alberta, Canada.

Identifying cognitive dysfunction in the early stages of Bipolar Disorder (BD) can allow for early intervention. Previous studies have shown a strong correlation between cognitive dysfunction and number of manic episodes. The objective of this study was to apply machine learning (ML) techniques on a battery of cognitive tests to identify first-episode BD patients (FE-BD). Two cohorts of participants were used for this study. Cohort #1 included 74 chronic BD patients (CHR-BD) and 53 healthy controls (HC), while the Cohort #2 included 37 FE-BD and 18 age- and sex-matched HC. Cognitive functioning was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The tests examined domains of visual processing, spatial memory, attention and executive function. We trained an ML model to distinguish between chronic BD patients (CHR-BD) and HC at the individual level. We used linear Support Vector Machines (SVM) and were able to identify individual CHR-BD patients at 77% accuracy. We then applied the model to Cohort #2 (FE-BD patients) and achieved an accuracy of 76% (AUC = 0.77). These results reveal that cognitive impairments may appear in early stages of BD and persist into later stages. This suggests that the same deficits may exist for both CHR-BD and FE-BD. These cognitive deficits may serve as markers for early BD. Our study provides a tool that these early markers can be used for detection of BD.
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http://dx.doi.org/10.1016/j.jad.2020.12.046DOI Listing
March 2021

Changes in Stress, Anxiety, and Depression Levels of Subscribers to a Daily Supportive Text Message Program (Text4Hope) During the COVID-19 Pandemic: Cross-Sectional Survey Study.

JMIR Ment Health 2020 Dec 18;7(12):e22423. Epub 2020 Dec 18.

Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Background: In addition to the obvious physical medical impact of COVID-19, the disease poses evident threats to people's mental health, psychological safety, and well-being. Provision of support for these challenges is complicated by the high number of people requiring support and the need to maintain physical distancing. Text4Hope, a daily supportive SMS text messaging program, was launched in Canada to mitigate the negative mental health impacts of the pandemic among Canadians.

Objective: This paper describes the changes in the stress, anxiety, and depression levels of subscribers to the Text4Hope program after 6 weeks of exposure to daily supportive SMS text messages.

Methods: We used self-administered, empirically supported web-based questionnaires to assess the demographic and clinical characteristics of Text4Hope subscribers. Perceived stress, anxiety, and depression were measured with the 10-Item Perceived Stress Scale (PSS-10), the Generalized Anxiety Disorder-7 (GAD-7) scale, and the Patient Health Questionnaire-9 (PHQ-9) scale at baseline and sixth week time points. Moderate or high perceived stress, likely generalized anxiety disorder, and likely major depressive disorder were assessed using cutoff scores of ≥14 for the PSS-10, ≥10 for the GAD-7, and ≥10 for the PHQ-9, respectively. At 6 weeks into the program, 766 participants had completed the questionnaires at both time points.

Results: At the 6-week time point, there were statistically significant reductions in mean scores on the PSS-10 and GAD-7 scales but not on the PHQ-9 scale. Effect sizes were small overall. There were statistically significant reductions in the prevalence rates of moderate or high stress and likely generalized anxiety disorder but not likely major depressive disorder for the group that completed both the baseline and 6-week assessments. The largest reductions in mean scores and prevalence rates were for anxiety (18.7% and 13.5%, respectively).

Conclusions: Text4Hope is a convenient, cost-effective, and accessible means of implementing a population-level psychological intervention. This service demonstrated significant reductions in anxiety and stress levels during the COVID-19 pandemic and could be used as a population-level mental health intervention during natural disasters and other emergencies.

International Registered Report Identifier (irrid): RR2-10.2196/19292.
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http://dx.doi.org/10.2196/22423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752184PMC
December 2020

Application of ozonated water for treatment of gastro-thoracic fistula after comprehensive esophageal squamous cell carcinoma therapy: A case report.

World J Clin Cases 2020 Oct;8(19):4550-4557

Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.

Background: Gastro-thoracic fistula is a serious complication after radical surgery for esophageal cancer, and a conservative approach or endoscopic intervention is commonly applied to treat most cases.

Case Summary: Here we describe the case of a patient with a gastro-thoracic fistula which could not be closed during gastroscopy after receiving postoperative radiotherapy, together with severe multiple drug-resistant bacterial infection and chest wall fistula. The abscess was drained and local irrigation applied with ozonated water, together with oral ozonated water, which achieved a good effect and highlighted a new way to cure fistula in such patients.

Conclusion: Patients with gastro-thoracic fistula that cannot be closed and severe infection can be treated by drainage and flushing with ozonated water.
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http://dx.doi.org/10.12998/wjcc.v8.i19.4550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559680PMC
October 2020

The role of Chinese medicine in COVID-19 pneumonia: A systematic review and meta-analysis.

Am J Emerg Med 2020 10 8;38(10):2153-2159. Epub 2020 Jul 8.

School of Basic Medicine, Henan University of Chinese Medicine, Zhengzhou 450000, China.

Introduction: Chinese medicine (CM) has been used to treat Novel Coronavirus 2019 (COVID-19) pneumonia in China. This meta-analysis was conducted to evaluate the clinical efficacy and safety of CM in the treatment of COVID-19 pneumonia.

Methods: Randomized controlled trials (RCTs) involving CM in the treatment of COVID-19 pneumonia were identified from Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Wanfang Database and VIP Information Database. The methodological quality of trials was evaluated with Cochrane Hanadbook criteria, and the Cochrane Collaboration's Review Manager 5.3 software was used for meta-analysis.

Results: A total of 7 valid studies involving 681 patients were included. The meta-analysis exhibited in comparison to conventional treatment, CM combined with conventional treatment significantly improved clinical efficacy (RR = 1.21, 95% CI [1.08,1.36]), and significantly increased viral nucleic acid negative conversion rate (RR = 1.49, 95% CI [1.13,1.97]). CM also prominently reduced pulmonary inflammation (RR = 1.27, 95% CI [1.12,1.44]), and improved host immune function (WBC, MD = 0.92, 95% CI [0.07,1.76]; LYM, MD = 0.33, 95% CI [0.08,0.57]; LYM%, MD = 2.90, 95% CI [2.09,3.71]; CRP, MD = -12.66, 95% CI [-24.40, -0.92]). Meanwhile, CM did not increase the incidence of adverse reactions (RR = 1.17, 95% CI [0.39,3.52]).

Conclusion: According to the allocated data, CM has demonstrated clinical efficacy and safety on COVID-19 pneumonia, which need to be confirmed by high quality, multiple-center, large sample randomized controlled trials.
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http://dx.doi.org/10.1016/j.ajem.2020.06.069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342052PMC
October 2020

The piRNA CHAPIR regulates cardiac hypertrophy by controlling METTL3-dependent N-methyladenosine methylation of Parp10 mRNA.

Nat Cell Biol 2020 11 5;22(11):1319-1331. Epub 2020 Oct 5.

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China.

PIWI-interacting RNAs (piRNAs) are abundantly expressed during cardiac hypertrophy. However, their functions and molecular mechanisms remain unknown. Here, we identified a cardiac-hypertrophy-associated piRNA (CHAPIR) that promotes pathological hypertrophy and cardiac remodelling by targeting METTL3-mediated N-methyladenosine (mA) methylation of Parp10 mRNA transcripts. CHAPIR deletion markedly attenuates cardiac hypertrophy and restores heart function, while administration of a CHAPIR mimic enhances the pathological hypertrophic response in pressure-overloaded mice. Mechanistically, CHAPIR-PIWIL4 complexes directly interact with METTL3 and block the mA methylation of Parp10 mRNA transcripts, which upregulates PARP10 expression. The CHAPIR-dependent increase in PARP10 promotes the mono-ADP-ribosylation of GSK3β and inhibits its kinase activity, which results in the accumulation of nuclear NFATC4 and the progression of pathological hypertrophy. Hence, our findings reveal that a piRNA-mediated RNA epigenetic mechanism is involved in the regulation of cardiac hypertrophy and that the CHAPIR-METTL3-PARP10-NFATC4 signalling axis could be therapeutically targeted for treating pathological hypertrophy and maladaptive cardiac remodelling.
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http://dx.doi.org/10.1038/s41556-020-0576-yDOI Listing
November 2020

Prenatal Stress Impairs Postnatal Learning and Memory Development via Disturbance of the cGMP-PKG Pathway and Oxidative Phosphorylation in the Hippocampus of Rats.

Front Mol Neurosci 2020 4;13:158. Epub 2020 Sep 4.

Department of Integrated Traditional Chinese and Western Medicine, School of Basic Medical Medicine, Henan University of Chinese Medicine, Zhengzhou, China.

Clinical and animal studies have found that prenatal stress can lead to pathological changes in embryos and fetuses. However, the mechanisms through which this occurs have not been made clear. In the present study, pregnant rats were subjected to chronic psychological stress during gestational days using an improved communication box system, and the changes in behavioral performance and proteins in the hippocampus of offspring were analyzed. It was found that prenatal stress caused postnatal growth retardation and impairment in spatial learning and memory. Furthermore, in isobaric tags for relative and absolute quantitation-based proteomics analyses, 158 significantly differentially expressed proteins (DEPs) were found between the two groups. Further analyses showed that these DEPs are involved in different molecular function categories and participate in several biological processes, such as energy metabolism, learning or memory, and synaptic plasticity. Moreover, the enrichment of pathways showed that the learning and memory impairment was primarily connected with the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) pathway and oxidative phosphorylation. At the same time, the cGMP level and the expression of PKG protein were significantly decreased, and the neuronal mitochondria appeared to have a swollen and irregular shape in the hippocampus of offspring of stressed rats. These results suggest that the chronic psychological stress that pregnant rats were subjected to during gestational days may have impaired the spatial learning and memory of offspring. This affected the hippocampal oxidative phosphorylation and inhibited the cGMP-PKG pathway.
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http://dx.doi.org/10.3389/fnmol.2020.00158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509422PMC
September 2020

COVID-19 Pandemic and Mental Health: Prevalence and Correlates of New-Onset Obsessive-Compulsive Symptoms in a Canadian Province.

Int J Environ Res Public Health 2020 09 24;17(19). Epub 2020 Sep 24.

Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2B7, Canada.

: This cross-sectional online survey investigates the prevalence of obsessive-compulsive disorder (OCD) symptoms at an early stage of the COVID-19 pandemic in Canada. : OCD symptoms, moderate/high stress, likely generalized anxiety disorder (GAD) and likely major depressive disorder (MDD) were assessed with the Brief Obsessive-Compulsive Scale (BOCS), Perceived Stress Scale (PSS), Generalized Anxiety Disorder 7-item (GAD-7) scale, and Patient Health Questionnaire-9 (PHQ-9) scale, respectively. : Out of 32,805 individuals subscribed to Text4Hope, 6041 completed an online survey; the response rate was 18.4%. Overall, 60.3% of respondents reported onset of OCD symptoms and 53.8% had compulsions to wash hands during the COVID-19 pandemic. Respondents who showed OCD symptoms only since the start of COVID-19 were significantly more likely to have moderate/high stress (z = 6.4, < 0.001), likely GAD (z = 6.0, < 0.001), and likely MDD (z = 2.7, < 0.01). Similarly, respondents who engaged in compulsive hand washing were significantly more likely to have moderate/high stress (z = 4.6, < 0.001) and likely GAD (z = 4.6 < 0.001), but not likely MDD (z = 1.4, = 0.16). : The prevalence of OCD symptoms increased during the COVID-19 pandemic, at a rate significantly higher than pre-pandemic rates reported for the sample population. Presenting with OCD symptoms increased the likelihood of presenting with elevated stress, likely GAD, and likely MDD.
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http://dx.doi.org/10.3390/ijerph17196986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579625PMC
September 2020

Prevalence of Perceived Stress, Anxiety, Depression, and Obsessive-Compulsive Symptoms in Health Care Workers and Other Workers in Alberta During the COVID-19 Pandemic: Cross-Sectional Survey.

JMIR Ment Health 2020 Sep 25;7(9):e22408. Epub 2020 Sep 25.

Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Background: During pandemics, effective containment and mitigation measures may also negatively influence psychological stability. As knowledge about COVID-19 rapidly evolves, global implementation of containment and mitigation measures has varied greatly, with impacts to mental wellness. Assessing the impact of COVID-19 on the mental health needs of health care workers and other workers may help mitigate mental health impacts and secure sustained delivery of health care and other essential goods and services.

Objective: This study assessed the self-reported prevalence of stress, anxiety, depression, and obsessive-compulsive symptoms in health care workers and other workers seeking support through Text4Hope, an evidence-based SMS text messaging service supporting the mental health of residents of Alberta, Canada, during the COVID-19 pandemic.

Methods: An online cross-sectional survey gathered demographic (age, gender, ethnicity, education, relationship, housing and employment status, employment type, and isolation status) and clinical characteristics using validated tools (self-reported stress, anxiety, depression, and contamination/hand hygiene obsessive-compulsive symptoms). Descriptive statistics and chi-square analysis were used to compare the clinical characteristics of health care workers and other workers. Post hoc analysis was conducted on variables with >3 response categories using adjusted residuals. Logistic regression determined associations between worker type and likelihood of self-reported symptoms of moderate or high stress, generalized anxiety disorder, and major depressive disorder, while controlling for other variables.

Results: Overall, 8267 surveys were submitted by 44,992 Text4Hope subscribers (19.39%). Of these, 5990 respondents were employed (72.5%), 958 (11.6%) were unemployed, 454 (5.5%) were students, 559 (6.8%) were retired, 234 (2.8%) selected "other," and 72 (0.9%) did not indicate their employment status. Most employed survey respondents were female (n=4621, 86.2%). In the general sample, the 6-week prevalence rates for moderate or high stress, anxiety, and depression symptoms were 85.6%, 47.0%, and 44.0%, respectively. Self-reported symptoms of moderate or high stress, anxiety, and depression were all statistically significantly higher in other workers than in health care workers (P<.001). Other workers reported higher obsessive-compulsive symptoms (worry about contamination and compulsive handwashing behavior) after the onset of the pandemic (P<.001), while health care worker symptoms were statistically significantly higher before and during the COVID-19 pandemic (P<.001). This finding should be interpreted with caution, as it is unclear the extent to which the adaptive behavior of health care workers or the other workers might be misclassified by validated tools during a pandemic.

Conclusions: Assessing symptoms of prevalent stress, anxiety, depression, and obsessive-compulsive behavior in health care workers and other workers may enhance our understanding of COVID-19 mental health needs. Research is needed to understand more fully the relationship between worker type, outbreak phase, and mental health changes over time, as well as the utility of validated tools in health care workers and other workers during pandemics. Our findings underscore the importance of anticipating and mitigating the mental health effects of pandemics using integrated implementation strategies. Finally, we demonstrate the ease of safely and rapidly assessing mental health needs using an SMS text messaging platform during a pandemic.

International Registered Report Identifier (irrid): RR2-10.2196/19292.
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http://dx.doi.org/10.2196/22408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527165PMC
September 2020

Synthesis of a New Phenyl Chlormethine-Quinazoline Derivative, a Potential Anti-Cancer Agent, Induced Apoptosis in Hepatocellular Carcinoma Through Mediating Sirt1/Caspase 3 Signaling Pathway.

Front Pharmacol 2020 26;11:911. Epub 2020 Jun 26.

Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China.

Quinazoline derivatives display multiple pharmacological activities and target various biological receptors. Based on the skeleton of quinazoline core, we designed and synthesized three new quinazoline-phenyl chlormethine conjugates (I-III) bearing a Schiff base (C = N) linker, and investigated their anti-tumor effects on HepG2-xenografted tumor and human cancer cell line HepG2. Among these compounds, compound II showed better inhibitory effect against HepG2 cells. In the present study, TUNEL staining, western blot, molecular docking, and siRNA were used to investigate the inhibitory mechanism of compound II towards hepatoma. Compound II inhibited HepG2-xenografted tumor growth in nude mice. Moreover, Compound II not only up-regulated Bax/Bcl-2 ratio and active-caspase 3 level, but also down-regulated Sirt1 expression and its activity, as well as PGC-1α expression. Furthermore, compound II also significantly suppressed the promotion of HepG2 cell proliferation, as evidenced by MTT assay and lactate dehydrogenase (LDH) release assay. Of note, the cytotoxicity of Compound II on HepG2 cells mainly regulating Sirt1/caspase 3 signaling pathway, consisting with the results . Intriguingly, z-DEVD-FMK, a caspase 3 inhibitor, almost abolished the inhibitory effects of compound II. Of note, knockdown of caspase 3 by siRNA significantly reversed the inhibitory effect of compound II on HepG2. Interestingly, compound II directly bonded to Sirt1, indicating that Sirt1 might be a promising therapeutic target of compound II. In summary, our findings reveal that compound II, a new synthetical phenyl chlormethine-quinazoline derivative, contributes to the apoptosis of HepG2 cells both and through mediating Sirt1/caspase 3 singling pathway. These findings demonstrate that compound II may be a new potent agent against hepatocellular carcinoma.
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http://dx.doi.org/10.3389/fphar.2020.00911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332554PMC
June 2020

Long-Term Mental Health Effects of a Devastating Wildfire Are Amplified by Sociodemographic and Clinical Antecedents in College Students.

Disaster Med Public Health Prep 2020 Jun 15:1-11. Epub 2020 Jun 15.

Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Objectives: The aim of this study is to assess prevalence of major depressive disorder (MDD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD) in students of Keyano College 18 months after a wildfire and to determine the predictors of likely MDD, GAD, and PTSD in the respondents.

Methods: A quantitative cross-sectional survey was used to collect data through self-administered, paper-based questionnaires to determine likely MDD, GAD, and PTSD using the PHQ 9, GAD-7, and the PTSD Checklist for DSM 5, Part 3, respectively. Data were analyzed with SPSS version 20 (IBM Corp, Armonk, NY) using univariate analysis with chi-square tests.

Results: Eighteen months after the wildfire, the 1-month prevalence rates for MDD, GAD, and PTSD among the college students were 23.4%, 18.7%, and 11.0%, respectively. There were statistically significant associations between multiple sociodemographic variables and the likelihood respondents presented with MDD, GAD, and PTSD 18 months after the wildfire. There were also associations between the likely MDD, GAD, and PTSD and abuse/dependence on alcohol and substances in respondents at 18 months.

Conclusion: Our study has established prevalence rates for MDD, GAD, and PTDS among college students 18 months after the Fort McMurray wildfires. Further studies are needed to explore the impact of college-based mental health interventions on the long-term mental health effects of the wildfires.
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http://dx.doi.org/10.1017/dmp.2020.87DOI Listing
June 2020

Long-Term Mental Health Effects of a Devastating Wildfire Are Amplified by Socio-Demographic and Clinical Antecedents in Elementary and High School Staff.

Front Psychiatry 2020 26;11:448. Epub 2020 May 26.

Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Objectives: To assess the likely prevalence rates of Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD) and Post-Traumatic Stress Disorder (PTSD) in staff of Fort McMurray School Districts eighteen months after a May 2016 wildfire, and to determine possible predictors.

Methods: A quantitative cross-sectional survey was used to collect data through self-administered online questionnaires to determine likely MDD, GAD and PTSD using well validated self-report questionnaires.

Results: Of 1,446 staff who were sent the online survey link in an e-mail, 197 completed the survey, of which there were 168 females (85%) and 29 males (15%). The one-month prevalence rates for likely MDD, GAD and PTSD among the school staff were 18.3, 15.7 and 10.2% respectively. There were statistically significant associations between multiple socio-demographic and clinical variables likely MDD, GAD and PTSD among respondents.

Conclusion: Knowledge of key factors for MDD, GAD and PTSD may be helpful for policy makers when formulating population level social and clinical programs, to mitigate the mental health effects of future natural disasters.
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http://dx.doi.org/10.3389/fpsyt.2020.00448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265240PMC
May 2020

Closing the Psychological Treatment Gap During the COVID-19 Pandemic With a Supportive Text Messaging Program: Protocol for Implementation and Evaluation.

JMIR Res Protoc 2020 Jun 22;9(6):e19292. Epub 2020 Jun 22.

Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Background: Coronavirus disease (COVID-19) has spread globally with far-reaching, significant, and unprecedented impacts on health and everyday life. Threats to mental health, psychological safety, and well-being are now emerging, increasing the impact of this virus on world health. Providing support for these challenges is difficult because of the high number of people requiring support in the context of a need to maintain physical distancing. This protocol describes the use of SMS text messaging (Text4Hope) as a convenient, cost-effective, and accessible population-level mental health intervention. This program is evidence-based, with prior research supporting good outcomes and high user satisfaction.

Objective: The project goal is to implement a program of daily supportive SMS text messaging (Text4Hope) to reduce distress related to the COVID-19 crisis, initially among Canadians. The prevalence of stress, anxiety, and depressive symptoms; the demographic correlates of the same; and the outcomes of the Text4Hope intervention in mitigating distress will be evaluated.

Methods: Self-administered anonymous online questionnaires will be used to assess stress (Perceived Stress Scale), anxiety (Generalized Anxiety Disorder-7 scale [GAD-7]), and depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]). Data will be collected at baseline (onset of SMS text messaging), the program midpoint (6 weeks), and the program endpoint (12 weeks).

Results: Data analysis will include parametric and nonparametric techniques, focusing on primary outcomes (ie, stress, anxiety, and depressive symptoms) and metrics of use, including the number of subscribers and user satisfaction. Given the large size of the data set, machine learning and data mining methods will also be used.

Conclusions: This COVID-19 project will provide key information regarding prevalence rates of stress, anxiety, and depressive symptoms during the pandemic; demographic correlates of distress; and outcome data related to this scalable population-level intervention. Information from this study will be valuable for practitioners and useful for informing policy and decision making regarding psychological interventions during the pandemic.

International Registered Report Identifier (irrid): DERR1-10.2196/19292.
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http://dx.doi.org/10.2196/19292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309448PMC
June 2020

Selective Targeting of Guanine-Vacancy-Bearing G-Quadruplexes by G-Quartet Complementation and Stabilization with a Guanine-Peptide Conjugate.

J Am Chem Soc 2020 07 18;142(26):11394-11403. Epub 2020 Jun 18.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P. R. China.

Stabilization of G-quadruplexes (G4s) formed in guanine-rich (G-rich) nucleic acids by small-molecule ligands has been extensively explored as a therapeutic approach for diseases such as cancer. Finding ligands with sufficient affinity and specificity toward G4s remains a challenge, and many ligands reported seemed to compromise between the two features. To cope with this challenge, we focused on targeting a particular type of G4s, i.e., the G-vacancy-bearing G-quadruplexes (GVBQs), by taking a structure complementation strategy to enhance both affinity and selectivity. In this approach, a G-quadruplex-binding peptide RHAU23 is guided toward a GVBQ by a guanine moiety covalently linked to the peptide. The filling-in of the vacancy in a GVBQ by the guanine ensures an exclusive recognition of GVBQ. Moreover, the synergy between the RHAU23 and the guanine dramatically improves both the affinity toward and stabilization of the GVBQ. Targeting a GVBQ in DNA by this bifunctional peptide strongly suppresses replication. This study demonstrates a novel and promising alternative targeting strategy to a distinctive panel of G4s that are as abundant as the canonical ones in the human genome.
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http://dx.doi.org/10.1021/jacs.0c00774DOI Listing
July 2020

Aberrant posterior cingulate connectivity classify first-episode schizophrenia from controls: A machine learning study.

Schizophr Res 2020 06 24;220:187-193. Epub 2020 Mar 24.

Mental Health Center, Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address:

Background: Posterior cingulate cortex (PCC) is a key aspect of the default mode network (DMN). Aberrant PCC functional connectivity (FC) is implicated in schizophrenia, but the potential for PCC related changes as biological classifier of schizophrenia has not yet been evaluated.

Methods: We conducted a data-driven approach using resting-state functional MRI data to explore differences in PCC-based region- and voxel-wise FC patterns, to distinguish between patients with first-episode schizophrenia (FES) and demographically matched healthy controls (HC). Discriminative PCC FCs were selected via false discovery rate estimation. A gradient boosting classifier was trained and validated based on 100 FES vs. 93 HC. Subsequently, classification models were tested in an independent dataset of 87 FES patients and 80 HC using resting-state data acquired on a different MRI scanner.

Results: Patients with FES had reduced connectivity between PCC and frontal areas, left parahippocampal regions, left anterior cingulate cortex, and right inferior parietal lobule, but hyperconnectivity with left lateral temporal regions. Predictive voxel-wise clusters were similar to region-wise selected brain areas functionally connected with PCC in relation to discriminating FES from HC subject categories. Region-wise analysis of FCs yielded a relatively high predictive level for schizophrenia, with an average accuracy of 72.28% in the independent samples, while selected voxel-wise connectivity yielded an accuracy of 68.72%.

Conclusion: FES exhibited a pattern of both increased and decreased PCC-based connectivity, but was related to predominant hypoconnectivity between PCC and brain areas associated with DMN, that may be a useful differential feature revealing underpinnings of neuropathophysiology for schizophrenia.
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http://dx.doi.org/10.1016/j.schres.2020.03.022DOI Listing
June 2020

Interaction of 22 risk SNPs with infection and risk of gastric cardia adenocarcinoma.

Future Oncol 2019 Nov 25;15(31):3579-3585. Epub 2019 Oct 25.

Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, PR China.

To determine the prevalence of infection and correlation between infection and single nucleotide polymorphism (SNPs) identified in gastric cardia adenocarcinoma (GCA) patients. A case control study was performed. 22 risks of GCA-related SNPs were identified by genotyping assay and the relationship between susceptibility loci for GCA and infection was further analyzed. infection was associated with GCA significantly (odds ratio: 1.40; 95% CI: 1.29-1.53 p < 0.01). Five GCA risk SNPs had their genotypes significantly different between positive patients and negative patients. The interaction between SNPs susceptibility loci and infection is associated with an increased risk of GCA.
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http://dx.doi.org/10.2217/fon-2019-0319DOI Listing
November 2019

Mental Health Effects in Primary Care Patients 18 Months After a Major Wildfire in Fort McMurray: Risk Increased by Social Demographic Issues, Clinical Antecedents, and Degree of Fire Exposure.

Front Psychiatry 2019 18;10:683. Epub 2019 Sep 18.

Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

To assess prevalence of posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD) in patients attending the only out-of-hours primary care clinic in Fort McMurray some 18 months following a major fire. A quantitative cross-sectional survey was used to collect data through self-administered paper-based questionnaires to determine PTSD, MDD, and GAD using the PTSD Checklists for Diagnostic and Statistical Manual (DSM) 5, Patient Health Questionnaire (PHQ) 9, and GAD-7, respectively, from residents of Fort McMurray who were impacted by the wildfires. This was carried out eighteen (18) months after a major wildfire, which required the rapid evacuation of the entire city population (approximately 90,000 individuals). We achieved a response rate of 48% and results from the 290 respondents showed the 1 month prevalence rate for likely PTSD was 13.6%, likely MDD was 24.8%, and likely GAD was 18.0%. Compared to self-reported prevalence rates before the wildfire (0%, 15.2%, and 14.5% respectively), these were increased for all diagnoses. After controlling for other factors in a logistic regression model, there were statistically significant associations between individuals who had likely PTSD, MDD, and GAD diagnoses and multiple socio-demographic, clinical, and exposure-related variables as follows: PTSD: History of anxiety disorder and received counselling had odds ratios (ORs) of 5.80 and 7.14, respectively. MDD: Age, witnessed the burning of homes, history of depressive disorder, and receiving low level support from friends and family had ORs of 2.08, 2.29, 4.63, and 2.5, respectively. GAD: Fearful for their lives or the lives of friends/family, history of depressive disorder, and history of anxiety disorder had ORs of 3.52, 3.04, and 2.68, respectively. There were also associations between individuals with a likely psychiatric diagnosis and those who also had likely alcohol or drug abuse/dependence. Our study suggests there are high prevalence rates for mental health and addiction conditions in patients attending the out-of-hours clinic 18 months after the wildfires, with significant associations between multiple variables and likely PTSD, MDD, and GAD. Further studies are needed to explore the impact of population-based mental health interventions on the long-term mental health effects of the wildfires.
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http://dx.doi.org/10.3389/fpsyt.2019.00683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760025PMC
September 2019

NAL8 encodes a prohibitin that contributes to leaf and spikelet development by regulating mitochondria and chloroplasts stability in rice.

BMC Plant Biol 2019 Sep 11;19(1):395. Epub 2019 Sep 11.

National Key Laboratory of Plant Molecular Genetics, CAS Centre for Excellence in Molecular Plant Sciences and Collaborative Innovation Center of Genetics & Development, Shanghai Institute of Plant Physiology & Ecology, Shanghai Institute for Biological Sciences, Chinese Academic of Sciences, Shanghai, 200032, China.

Background: Leaf morphology and spikelet number are two important traits associated with grain yield. To understand how genes coordinating with sink and sources of cereal crops is important for grain yield improvement guidance. Although many researches focus on leaf morphology or grain number in rice, the regulating molecular mechanisms are still unclear.

Results: In this study, we identified a prohibitin complex 2α subunit, NAL8, that contributes to multiple developmental process and is required for normal leaf width and spikelet number at the reproductive stage in rice. These results were consistent with the ubiquitous expression pattern of NAL8 gene. We used genetic complementation, CRISPR/Cas9 gene editing system, RNAi gene silenced system and overexpressing system to generate transgenic plants for confirming the fuctions of NAL8. Mutation of NAL8 causes a reduction in the number of plastoglobules and shrunken thylakoids in chloroplasts, resulting in reduced cell division. In addition, the auxin levels in nal8 mutants are higher than in TQ, while the cytokinin levels are lower than in TQ. Moreover, RNA-sequencing and proteomics analysis shows that NAL8 is involved in multiple hormone signaling pathways as well as photosynthesis in chloroplasts and respiration in mitochondria.

Conclusions: Our findings provide new insights into the way that NAL8 functions as a molecular chaperone in regulating plant leaf morphology and spikelet number through its effects on mitochondria and chloroplasts associated with cell division.
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http://dx.doi.org/10.1186/s12870-019-2007-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737680PMC
September 2019

Translational Regulation of Plant Response to High Temperature by a Dual-Function tRNA Guanylyltransferase in Rice.

Mol Plant 2019 08 7;12(8):1123-1142. Epub 2019 May 7.

National Key Laboratory of Plant Molecular Genetics, CAS Centre for Excellence in Molecular Plant Sciences and Collaborative Innovation Center of Genetics & Development, Shanghai Institute of Plant Physiology & Ecology, Shanghai Institute for Biological Sciences, Chinese Academic of Sciences, Shanghai 200032, China; University of the Chinese Academy of Sciences, Beijing 100049, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. Electronic address:

As sessile organisms, plants have evolved numerous strategies to acclimate to changes in environmental temperature. However, the molecular basis of this acclimation remains largely unclear. In this study we identified a tRNA guanylyltransferase, AET1, which contributes to the modification of pre-tRNA and is required for normal growth under high-temperature conditions in rice. Interestingly, AET1 possibly interacts with both RACK1A and eIF3h in the endoplasmic reticulum. Notably, AET1 can directly bind to OsARF mRNAs including the uORFs of OsARF19 and OsARF23, indicating that AET1 is associated with translation regulation. Furthermore, polysome profiling assays suggest that the translational status remains unaffected in the aet1 mutant, but that the translational efficiency of OsARF19 and OsARF23 is reduced; moreover, OsARF23 protein levels are obviously decreased in the aet1 mutant under high temperature, implying that AET1 regulates auxin signaling in response to high temperature. Our findings provide new insights into the molecular mechanisms whereby AET1 regulates the environmental temperature response in rice by playing a dual role in tRNA modification and translational control.
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http://dx.doi.org/10.1016/j.molp.2019.04.012DOI Listing
August 2019

White Matter Abnormalities in Major Depression Biotypes Identified by Diffusion Tensor Imaging.

Neurosci Bull 2019 Oct 6;35(5):867-876. Epub 2019 May 6.

Mental Health Centre, West China Hospital, Sichuan University, Chengdu, 610041, China.

Identifying data-driven biotypes of major depressive disorder (MDD) has promise for the clarification of diagnostic heterogeneity. However, few studies have focused on white-matter abnormalities for MDD subtyping. This study included 116 patients with MDD and 118 demographically-matched healthy controls assessed by diffusion tensor imaging and neurocognitive evaluation. Hierarchical clustering was applied to the major fiber tracts, in conjunction with tract-based spatial statistics, to reveal white-matter alterations associated with MDD. Clinical and neurocognitive differences were compared between identified subgroups and healthy controls. With fractional anisotropy extracted from 20 fiber tracts, cluster analysis revealed 3 subgroups based on the patterns of abnormalities. Patients in each subgroup versus healthy controls showed a stepwise pattern of white-matter alterations as follows: subgroup 1 (25.9% of patient sample), widespread white-matter disruption; subgroup 2 (43.1% of patient sample), intermediate and more localized abnormalities in aspects of the corpus callosum and left cingulate; and subgroup 3 (31.0% of patient sample), possible mild alterations, but no statistically significant tract disruption after controlling for family-wise error. The neurocognitive impairment in each subgroup accompanied the white-matter alterations: subgroup 1, deficits in sustained attention and delayed memory; subgroup 2, dysfunction in delayed memory; and subgroup 3, no significant deficits. Three subtypes of white-matter abnormality exist in individuals with major depression, those having widespread abnormalities suffering more neurocognitive impairments, which may provide evidence for parsing the heterogeneity of the disorder and help optimize type-specific treatment approaches.
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http://dx.doi.org/10.1007/s12264-019-00381-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754492PMC
October 2019

Crop Improvement Through Temperature Resilience.

Annu Rev Plant Biol 2019 04;70:753-780

Key Laboratory of Plant Molecular Physiology, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China; email:

Abnormal environmental temperature affects plant growth and threatens crop production. Understanding temperature signal sensing and the balance between defense and development in plants lays the foundation for improvement of temperature resilience. Here, we summarize the current understanding of cold signal perception/transduction as well as heat stress response. Dissection of plant responses to different levels of cold stresses (chilling and freezing) illustrates their common and distinct signaling pathways. Axillary bud differentiation in response to chilling is presented as an example of the trade-off between defense and development. Vernalization is a cold-dependent development adjustment mediated by -GlcNAcylation and phosphorylation to sense long-term cold. Recent progress on major quantitative trait loci genes for heat tolerance has been summarized. Molecular mechanisms in utilizing temperature-sensitive sterility in super hybrid breeding in China are revealed. The way to improve crop temperature resilience using integrative knowledge of omics as well as systemic and synthetic biology, especially the molecular module program, is summarized.
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http://dx.doi.org/10.1146/annurev-arplant-050718-100016DOI Listing
April 2019

Venlafaxine Improves the Cognitive Impairment and Depression-Like Behaviors in a Cuprizone Mouse Model by Alleviating Demyelination and Neuroinflammation in the Brain.

Front Pharmacol 2019 5;10:332. Epub 2019 Apr 5.

Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Growing evidence has implicated that myelin deficits and neuroinflammation are the coexisted pathological features that contribute to the mood swing and cognitive decline in major depressive disorder (MDD) and multiple sclerosis (MS). Therefore, attenuation of neuroinflammation and reduction of demyelination became newly emerging treatment strategies for the mood and cognitive symptoms. Antidepressant venlafaxine has been used in depression and anxiety through its multiple neuroprotective effects. However, it is unclear whether venlafaxine can improve myelin integrity and alter inflammation status in the brain. By using a well-established cuprizone-induced acute mouse model of demyelination, we investigated the protective effects of venlafaxine on these facets. The cuprizone-fed animals exhibited cognitive impairment and mood disturbances together with myelin loss and prominent neuroinflammation in the brain. Our present study showed that a high dose of venlafaxine alleviated the loss of myelin and oligodendrocytes (OLs), mitigated depression-like behaviors, and improved cognitive function in cuprizone-fed animals. Data from the present study also showed that venlafaxine reduced microglia-mediated inflammation in the brains of cuprizone-fed animals. These findings suggest that venlafaxine may exert its therapeutic effects facilitating myelin integrity and controlling neuroinflammation, which may provide extra benefits to MS patients with depression and anxiety beyond the symptom management.
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http://dx.doi.org/10.3389/fphar.2019.00332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460225PMC
April 2019

Effectiveness and safety of Chinese herbal medicine for pediatric adenoid hypertrophy: A meta-analysis.

Int J Pediatr Otorhinolaryngol 2019 Apr 19;119:79-85. Epub 2019 Jan 19.

Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Pediatrics, Nanjing, China. Electronic address:

Objective: Chinese herbal medicine has been gradually used to treat pediatric adenoid hypertrophy. This meta-analysis were conducted to evaluate the clinical efficacy and safety of Chinese herbal medicine in the treatment of pediatric adenoid hypertrophy.

Methods: Randomized controlled trials involving Chinese herbal medicine in the treatment of pediatric adenoid hypertrophy were identified from Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Wanfang Database and VIP Information Database. The methodological quality of trials was evaluated with Cochrane Handbook criteria, and the Cochrane Collaboration's Review Manager 5.3 software was used for Meta-analysis.

Results: A total of 13 valid articles involving 1038 patients were included. The meta-analysis showed that: Compared with western medicine treatment, Chinese herbal medicine significantly improved clinical efficacy (RR = 1.33, 95% CI [1.24,1.43]), and significantly decreased A/N ratio (MD = -0.04,95%CI [-0.05,-0.03]). Chinese herbal medicine also prominently improved the quality of life (MD = -4.77,95%CI [-8.35,-1.20]). Meanwhile, it dramatically improved snoring (MD = -0.46,95%CI [-0.62,-0.30]); mouth breathing (MD = -0.52,95%CI [-0.66,-0.39]); nasal obstruction (MD = -0.56,95%CI [-0.68,-0.45]).

Conclusion: Chinese herbal medicine has good clinical efficacy and safety on pediatric adenoid hypertrophy, which need to be confirmed by high quality, multiple-centre, large sample randomized controlled trials.
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http://dx.doi.org/10.1016/j.ijporl.2019.01.022DOI Listing
April 2019
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