Small Molecules Promote the Rapid Generation of Dental Epithelial Cells from Human-Induced Pluripotent Stem Cells.

Human-induced pluripotent stem cells (hiPSCs) offer a promising source for generating dental epithelial (DE) cells. Whereas the existing differentiation protocols were time-consuming and relied heavily on growth factors, herein, we developed a three-step protocol to convert hiPSCs into DE cells in 8 days. In the first phase, hiPSCs were differentiated into non-neural ectoderm using SU5402 (an FGF signaling inhibitor). The second phase involved differentiating non-neural ectoderm into pan-placodal ectoderm and simultaneously inducing the formation of oral ectoderm (OE) using LDN193189 (a BMP signaling inhibitor) and purmorphamine (a SHH signaling activator). In the final phase, OE cells were differentiated into DE through the application of Purmorphamine, XAV939 (a WNT signaling inhibitor), and BMP4. qRT-PCR and immunostaining were performed to examine the expression of lineage-specific markers. ARS staining was performed to evaluate the formation of the mineralization nodule. The expression of PITX2, SP6, and AMBN, the emergence of mineralization nodules, and the enhanced expression of AMBN and AMELX in spheroid culture implied the generation of DE cells. This study delineates the developmental signaling pathways and uses small molecules to streamline the induction of hiPSCs into DE cells. Our findings present a simplified and quicker method for generating DE cells, contributing valuable insights for dental regeneration and dental disease research.

Effect of Dimethyloxalylglycine on Stem Cells Osteogenic Differentiation and Bone Tissue Regeneration-A Systematic Review.

Dimethyloxalylglycine (DMOG) has been found to stimulate osteogenesis and angiogenesis of stem cells, promoting neo-angiogenesis in bone tissue regeneration. In this review, we conducted a comprehensive search of the literature to investigate the effects of DMOG on osteogenesis and bone regeneration. We screened the studies based on specific inclusion criteria and extracted relevant information from both in vitro and in vivo experiments. The risk of bias in animal studies was evaluated using the SYRCLE tool. Out of the 174 studies retrieved, 34 studies met the inclusion criteria (34 studies were analyzed in vitro and 20 studies were analyzed in vivo). The findings of the included studies revealed that DMOG stimulated stem cells' differentiation toward osteogenic, angiogenic, and chondrogenic lineages, leading to vascularized bone and cartilage regeneration. Addtionally, DMOG demonstrated therapeutic effects on bone loss caused by bone-related diseases. However, the culture environment in vitro is notably distinct from that in vivo, and the animal models used in vivo experiments differ significantly from humans. In summary, DMOG has the ability to enhance the osteogenic and angiogenic differentiation potential of stem cells, thereby improving bone regeneration in cases of bone defects. This highlights DMOG as a potential focus for research in the field of bone tissue regeneration engineering.

Causal associations of sleep traits with cancer incidence and mortality.

To explore the correlation and causality between multidimensional sleep traits and pan-cancer incidence and mortality among patients with cancer. The multivariable Cox regression, linear and nonlinear Mendelian randomization (MR), and survival curve analyses were conducted to assess the impacts of chronotype, sleep duration, and insomnia symptoms on pan-cancer risk (N = 326,417 from United Kingdom Biobank) and mortality (N = 23,956 from United Kingdom Biobank). In the Cox regression, we observed a linear and J-shaped association of sleep duration with pan-cancer incidence and mortality among cancer patients respectively. In addition, there was a positive association of insomnia with pan-cancer incidence (HR, 1.03, 95% CI: 1.00-1.06, p = 0.035), all-cause mortality (HR, 1.17, 95% CI: 1.06-1.30, p = 0.002) and cancer mortality among cancer patients (HR, 1.25, 95% CI: 1.11-1.41, p < 0.001). In the linear MR, there was supporting evidence of positive associations between long sleep duration and pan-cancer incidence (OR, 1.41, 95% CI: 1.08-1.84, p = 0.012), and there was a positive association between long sleep duration and all-cause mortality in cancer patients (OR, 5.56, 95% CI: 3.15-9.82, p = 3.42E-09). Meanwhile, a strong association between insomnia and all-cause mortality in cancer patients (OR, 1.41, 95% CI: 1.27-1.56, p = 4.96E-11) was observed in the linear MR. These results suggest that long sleep duration and insomnia play important roles in pan-cancer risk and mortality among cancer patients. In addition to short sleep duration and insomnia, our findings highlight the effect of long sleep duration in cancer prevention and prognosis.

Association of Caffeine Consumption and Brain Amyloid Positivity in Cognitively Normal Older Adults.

BACKGROUND: Several epidemiological studies have reported the protective role of caffeine on health outcomes; however, it remained debatable on caffeine consumption and brain amyloid positivity. OBJECTIVE: We aimed to determine the relationship between caffeine consumption and brain amyloid pathology in cognitively normal older adults. METHODS: The dataset used for analysis in this cross-sectional study was selected from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study. Multivariable logistic regression analyses were performed to explore the association between caffeine consumption and amyloid positivity using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In total, 4,394 participants were included in the final analysis. No significant association between caffeine consumption and amyloid positivity was observed in the whole participants (OR, 0.95; 95% CI, 0.78-1.14; p = 0.558). Subgroup analysis showed that caffeine intake was significantly associated with decreased amyloid positivity in males (OR, 0.72; 95% CI, 0.54-0.97; p = 0.032) but not in females (OR, 1.14; 95% CI, 0.90-1.46; p = 0.280), and the association between caffeine and amyloid positivity was not affected by age or APOE genotypes. In addition, different levels of caffeine were not associated with amyloid positivity. CONCLUSION: The findings suggest that caffeine consumption was not significantly associated with amyloid positivity in the whole sample. However, caffeine consumption may be inversely associated with amyloid positivity among males but not females. More studies are needed to explore the mechanisms underlying caffeine consumption and brain amyloid positivity.

Somatic symptoms mediate the association between subclinical anxiety and depressive symptoms and its neuroimaging mechanisms.

BACKGROUND: Subclinical anxiety, depressive and somatic symptoms appear closely related. However, it remains unclear whether somatic symptoms mediate the association between subclinical anxiety and depressive symptoms and what the underlying neuroimaging mechanisms are for the mediating effect. METHODS: Data of healthy participants (n = 466) and participants in remission of major depressive disorder (n = 53) were obtained from the Human Connectome Project. The Achenbach Adult Self-Report was adopted to assess anxiety, depressive and somatic symptoms. All participants completed four runs of resting-state functional magnetic resonance imaging. Mediation analyses were utilized to explore the interactions among these symptoms and their neuroimaging mechanisms. RESULTS: Somatic symptoms partially mediated the association between subclinical anxiety and depressive symptoms in healthy participants (anxiety→somatic→depression: effect: 0.2785, Boot 95% CI: 0.0958-0.3729; depression→somatic→anxiety: effect: 0.0753, Boot 95% CI: 0.0232-0.1314) and participants in remission of MDD (anxiety→somatic→depression: effect: 0.2948, Boot 95% CI: 0.0357-0.7382; depression→somatic→anxiety: effect: 0.0984, Boot 95% CI: 0.0007-0.2438). Resting-state functional connectivity (FC) between the right medial superior frontal gyrus and the left thalamus and somatic symptoms as chain mediators partially mediated the effect of subclinical depressive symptoms on subclinical anxiety symptoms in healthy participants (effect: 0.0020, Boot 95% CI: 0.0003-0.0043). The mean strength of common FCs of subclinical depressive and somatic symptoms, somatic symptoms, and the mean strength of common FCs of subclinical anxiety and somatic symptoms as chain mediators partially mediated the effect of subclinical depressive symptoms on subclinical anxiety symptoms in remission of MDD (effect: 0.0437, Boot 95% CI: 0.0024-0.1190). These common FCs mainly involved the insula, precentral gyri, postcentral gyri and cingulate gyri. Furthermore, FC between the triangular part of the left inferior frontal gyrus and the left postcentral gyrus was positively associated with subclinical anxiety, depressive and somatic symptoms in remission of MDD (FDR-corrected p < 0.01). CONCLUSIONS: Somatic symptoms partially mediate the interaction between subclinical anxiety and depressive symptoms. FCs involving the right medial superior frontal gyrus, left thalamus, triangular part of left inferior frontal gyrus, bilateral insula, precentral gyri, postcentral gyri and cingulate gyri maybe underlie the mediating effect of somatic symptoms.

Blunted superior temporal gyrus activity to negative emotional expression after mindfulness-based cognitive therapy for late-life depression.

Facial emotion recognition plays an important role in social functioning. Patients with late-life depression (LLD) often have abnormal facial emotion recognition. Mindfulness-based cognitive therapy (MBCT) is beneficial in treating depression. This study examined whether MBCT can act as an effective augmentation of antidepressants and improve facial emotion recognition in patients with LLD and its underlying neural mechanism. Patients with LLD were randomized into two groups (n = 30 per group). The MBCT group received an eight-week MBCT in conjunction with stable medication treatment. The other group was treated as usual (TAU group) with stable medication treatment. The positive affect (PA) scale, negative affect (NA) scale, and facial emotion recognition task with an fMRI scan were performed before and after the trial. After eight weeks of treatment, the repeated ANOVA showed that the PA score in the MBCT group significantly increased [F (1,54) = 13.31, p = 0.001], but did not change significantly [F (1,54) = 0.58, p = 0.449] in the TAU group. The NA scores decreased significantly in both the MBCT group [F (1,54) = 19.01, p < 0.001] and the TAU group [F (1,54) = 16.16, p < 0.001]. Patients showed an increase in recognition accuracy and speed of angry and sad faces after 8 weeks of MBCT. No improvement was detected in the TAU group after treatment. A significant interaction effect was found in the change of activation of the left superior temporal gyrus (L-STG) to negative emotional expression between time and groups. Furthermore, a decrease in activation of L-STG to negative emotional expression was positively correlated with the increase in PA score. The MBCT is beneficial for improving affect status and facial emotion recognition in patients with LLD, and the L-STG is involved in this process.

Disrupted gut microbiota aggravates working memory dysfunction induced by high-altitude exposure in mice.

Background: The widely accepted microbiome-gut-brain axis (MGBA) hypothesis may be essential for explaining the impact of high-altitude exposure on the human body, especially brain function. However, studies on this topic are limited, and the underlying mechanism remains unclear. Therefore, this study aimed to determine whether high-altitude-induced working memory dysfunction could be exacerbated with gut microbiota disruption. Methods and results: C57BL/6 mice were randomly divided into three groups: control, high-altitude exposed (HAE), and high-altitude exposed with antibiotic treatment (HAE-A). The HAE and HAE-A groups were exposed to a low-pressure oxygen chamber (60-65 kPa) simulating the altitude of 3,500-4,000 m for 14 days, The air pressure level for the control group was maintained at 94.5 kPa. Antibiotic water (mixed with 0.2 g/L of ciprofloxacin and 1 g/L of metronidazole) was provided to the HAE-A group. Based on the results of the novel object test and P300 in the oddball behavioral paradigm training test, working memory dysfunction was aggravated by antibiotic treatment. We determined the antioxidant capacity in the prefrontal cortex and found a significant negative influence (p < 0.05) of disturbed gut microbiota on the total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content, as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The same trend was also observed in the apoptosis-related functional protein content and mRNA expression levels in the prefrontal cortex, especially the levels of bcl-2, Bax, and caspase-3. The high-altitude environment and antibiotic treatment substantially affected the richness and diversity of the colonic microbiota and reorganized the composition and structure of the microbial community. S24-7, Lachnospiraceae, and Lactobacillaceae were the three microbial taxa with the most pronounced differences under the stimulation by external factors in this study. In addition, correlation analysis between colonic microbiota and cognitive function in mice demonstrated that Helicobacteraceae may be closely related to behavioral results. Conclusion: Disrupted gut microbiota could aggravate working memory dysfunction induced by high-altitude exposure in mice, indicating the existence of a link between high-altitude exposure and MGBA.

Connectome-based predictive modelling of smoking severity in smokers.

The functional connectivity within and between networks could provide a framework to characterize the neurobiological mechanism of nicotine addiction. This study examined the brain regions that were functionally connected in response to smoking cues and established the brain-behaviour relationships in smokers. Sixty-seven male smokers were enrolled and scanned while performing the cue-reactivity and Stroop task. A whole-brain analysis approach, connectome-based predictive modelling (CPM), was conducted on the data from the cue-reactivity task to identify the networks that could predict the smoking severity with the Shen atlas as templates. Then, the brain-behaviour relationships were verified in a different brain state (Stroop task). CPM identified the smoking severity-related network, as indicated by a significant correlation between predicted and actual smoking severity scores (r = 0.31, p = 0.02). Identified networks mainly involved the canonical networks implicated in the reward process (motor/sensory network and salience network) and executive control (frontoparietal network). Network strength in the Stroop task marginally significantly predicted smoking severity scores (r = 0.23, p = 0.06), partially replicating the brain-behaviour relationship. The CPM results identified the whole-brain neural network related to smoking severity, which was cross-validated by the AAL and Shen atlas. These findings contribute to more profound insights into neural substrates underlying the smoking severity.

The effect of perceived stress on cognition is mediated by personality and the underlying neural mechanism.

Perceived stress impairs cognitive function across the adult lifespan, but the extent to which cognition decline is variable across individuals. Individual differences in the stress response are described as personality traits. Substantial individual differences in the magnitude of cognitive impairment that is induced by short-term perceived stress are poorly understood. The present study tested the hypothesis that the relationship between short-term perceived stress and different aspects of cognition is mediated by personality traits. The study included 1066 participants with behavior and neuroimaging data from the Human Connectome Project after excluding individuals with missing variables. In the result, the parallel multiple mediation model demonstrated that the influence of perceived stress on the total and crystalized cognition is mainly mediated by neuroticism (indirect effect = -0.04, p < 0.05) and conscientiousness (indirect effect = 0.05, p < 0.05) in adults. Cortical thickness value (n = 1066) of the right superior frontal gyrus (SFG) showed not only positive correlations with short-term perceived stress and neuroticism, but negative associations with cognition. The chain mediation model found that the right SFG and neuroticism play a small but significant chain mediating effect between stress and total cognition. The strength of the resting-state functional connectivity (n = 968) between the left orbitofrontal cortex versus the left superior medial frontal cortex was positively correlated with crystallized cognition and negatively associated with conscientiousness. These results extend previous findings by the impacts of short-term perceived stress on cognitive function is mediated by neuroticism and the right SFG was the underlying neural mechanism.

Patterns and influencing factors of COVID-19 vaccination willingness among college students in China.

BACKGROUND: Vaccination is an important preventive measure against the coronavirus disease 19 (COVID-19) pandemic. We aimed to examine the willingness to vaccination and influencing factors among college students in China. METHODS: From March 18 to April 26, 2021, we conducted a cross-sectional online survey among college students from 30 universities in Wuhan, Hubei Province, China. The survey was composed of the sociodemographic information, psychological status, experience during pandemic, the willingness of vaccination and related information. Students' attitudes towards vaccination were classified as 'vaccine acceptance', 'vaccine hesitancy', and 'vaccine resistance'. Multinomial logistic regression analyses were performed to identify the influencing factors associated with vaccine hesitancy and resistance. RESULTS: Among 23,143 students who completed the survey, a total of 22,660 participants were included in the final analysis with an effective rate of 97.9% after excluding invalid questionnaires. A total of 60.6% of participants would be willing to receive COVID-19 vaccine, 33.4% were hesitant to vaccination, and 6.0% were resistant to vaccination. Social media platforms and government agencies were the main sources of information vaccination. Worry about the efficacy and adverse effects of vaccine were the top two common reason of vaccine hesitancy and resistance. Multiple multinomial logistic regression analysis identified that participants who worried about the adverse effects of vaccination were more likely to be vaccine hesitancy (aOR = 2.44, 95% CI = 2.30, 2.58) and resistance (aOR = 2.71, 95% CI = 2.40, 3.05). CONCLUSION: More than half of college students are willing to receive the COVID-19 vaccine, whereas nearly one-third college students are still hesitant or resistant. It is crucial to provide sufficient and scientific information on the efficacy and safety of vaccine through social media and government agencies platforms to promote vaccine progress against COVID-19 and control the pandemic in China.

Mindfulness-Based Cognitive Therapy Regulates Brain Connectivity in Patients With Late-Life Depression.

Late-life depression (LLD) is an important public health problem among the aging population. Recent studies found that mindfulness-based cognitive therapy (MBCT) can effectively alleviate depressive symptoms in major depressive disorder. The present study explored the clinical effect and potential neuroimaging mechanism of MBCT in the treatment of LLD. We enrolled 60 participants with LLD in an 8-week, randomized, controlled trial (ChiCTR1800017725). Patients were randomized to the treatment-as-usual (TAU) group or a MBCT+TAU group. The Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to evaluate symptoms. Magnetic resonance imaging (MRI) was used to measure changes in resting-state functional connectivity and structural connectivity. We also measured the relationship between changes in brain connectivity and improvements in clinical symptoms. HAMD total scores in the MBCT+TAU group were significantly lower than in the TAU group after 8 weeks of treatment (p < 0.001) and at the end of the 3-month follow-up (p < 0.001). The increase in functional connections between the amygdala and middle frontal gyrus (MFG) correlated with decreases in HAMA and HAMD scores in the MBCT+TAU group. Diffusion tensor imaging analyses showed that fractional anisotropy of the MFG-amygdala significantly increased in the MBCT+TAU group after 8-week treatment compared with the TAU group. Our study suggested that MBCT improves depression and anxiety symptoms that are associated with LLD. MBCT strengthened functional and structural connections between the amygdala and MFG, and this increase in communication correlated with improvements in clinical symptoms. Randomized Controlled Trial; Follow-Up Study; fMRI; Brain Connectivity.

Exploration of the Mechanism of Lianhua Qingwen in Treating Influenza Virus Pneumonia and New Coronavirus Pneumonia with the Concept of "Different Diseases with the Same Treatment" Based on Network Pharmacology.

The 31 main components of Lianhua Qingwen (LHQW) were obtained through a literature and database search; the components included glycyrrhizic acid, emodin, chlorogenic acid, isophoroside A, forsythia, menthol, luteolin, quercetin, and rutin. Sixty-eight common targets for the treatment of novel coronavirus pneumonia (NCP) and influenza virus pneumonia (IVP) were also obtained. A "component-target-disease" network was constructed with Cytoscape 3.2.1 software, and 20 key targets, such as cyclooxygenase2 (COX2), interleukin-6 (IL-6), mitogen-activated protein kinase14 (Mapk14), and tumor necrosis factor (TNF), were screened from the network. The David database was used to perform a Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis and gene ontology (GO) biological process enrichment. Results showed that the key targets of LHQW in the treatment of NCP and IVP mainly involved biological processes, such as immune system process intervention, cell proliferation, apoptosis and invasion, toxic metabolism, cytokine activity, and regulation of the synthesis process. KEGG enrichment analysis revealed that 115 signalling pathways were related to the treatment of LHQW. Amongst them, IL-17, T cell receptor, Th17 cell differentiation, TNF, toll-like receptor, MAPK, apoptosis, and seven other signalling pathways were closely related to the occurrence and development of NCP and IVP. Molecular docking showed that each component had different degrees of binding with six targets, namely, 3C-like protease (3CL), angiotensin-converting enzyme 2 (ACE2), COX2, hemagglutinin (HA), IL-6, and neuraminidase (NA). Rutin, isoforsythiaside A, hesperidin and isochlorogenic acid B were the best components for docking with the six core targets. The first five components with the best docking results were isoforsythiaside, hesperidin, isochlorogenic acid B, forsythin E, and quercetin. In conclusion, LHQW has many components, targets, and pathways. The findings of this work can provide an important theoretical basis for determining the mechanism of LHQW in treating NCP and IVP.

The Impact of Quarantine on Pain Sensation among the General Population in China during the COVID-19 Pandemic.

During the pandemic era, quarantines might potentially have negative effects and disproportionately exacerbate health condition problems. We conducted this cross-sectional, national study to ascertain the prevalence of constant pain symptoms and how quarantines impacted the pain symptoms and identify the factors associated with constant pain to further guide reducing the prevalence of chronic pain for vulnerable people under the pandemic. The sociodemographic data, quarantine conditions, mental health situations and pain symptoms of the general population were collected. After adjusting for potential confounders, long-term quarantine (≥15 days) exposures were associated with an increased risk of constant pain complaints compared to those not under a quarantine (Odds Ratio (OR): 1.26; 95% Confidence Interval (CI): 1.03, 1.54; p = 0.026). Risk factors including unemployment (OR: 1.55), chronic disease history (OR: 2.38) and infection with COVID-19 (OR: 2.15), and any of mental health symptoms including depression, anxiety, insomnia and PTSD (OR: 5.44) were identified by a multivariable logistic regression. Additionally, mediation analysis revealed that the effects of the quarantine duration on pain symptoms were mediated by mental health symptoms (indirect effects: 0.075, p < 0.001). These results advocated that long-term quarantine measures were associated with an increased risk of experiencing pain, especially for vulnerable groups with COVID-19 infection and with mental health symptoms. The findings also suggest that reducing mental distress during the pandemic might contribute to reducing the burden of pain symptoms and prioritizing interventions for those experiencing a long-term quarantine.

The neural correlation of emotion recognition ability and depressive symptoms-evidence from the HCP database.

Introduction: Negative bias of emotional face is the core feature of depression, but its underlying neurobiological mechanism is still unclear. The neuroimaging findings of negative emotional recognition and depressive symptoms are inconsistent. Methods: The neural association between depressive symptoms and negative emotional bias were analyzed by measuring the associations between resting state functional connectivity (FC), brain structures, negative emotional bias, and depressive problems. Then, we performed a mediation analysis to assess the potential overlapping neuroimaging mechanisms. Results: We found a negative correlation between depressive symptoms and emotional recognition. Secondly, the structure and function of the inferior and lateral orbitofrontal gyrus are related to depressive symptoms and emotional recognition. Thirdly, the thickness of the inferior orbitofrontal cortex and the FC between the inferior orbitofrontal gyrus and fusiform gyrus, precuneate and cingulate gyrus mediated and even predicted the interaction between emotion recognition and depressive symptoms. Finally, in response to a negative stimulus, the activation of the frontal pole and precuneus lobe associated with the inferior orbitofrontal gyrus was higher in participants with depressive symptoms. Conclusion: The core brain regions centered on the inferior orbitofrontal cortex such as middle temporal gyrus, precuneus lobe, frontal pole, insula and cingulate gyrus are the potential neuroimaging basis for the interaction between depressive symptoms and emotional recognition.

COVID-19 Vaccine-Related Psychological Stress Among General Public in China.

Background: The COVID-19 pandemic is our generation's greatest global challenge to our public health system. Vaccines are considered one of the most effective tools available for preventing COVID-19 infection and its complications and sequelae. Understanding and addressing the psychological stress related to COVID-19 vaccination may promote acceptance of these vaccines. Methods: We conducted an online survey from January 29 to April 26, 2021 to explore stress levels related to COVID-19 vaccination among the general public in China. Participants were asked to evaluate their psychological stress of considering whether or not to get vaccinated at the beginning period of the COVID-19 mass vaccination, after getting access to the information about the vaccine, as well as after getting vaccinated, using visual analog stress scale. Multiple linear regression analysis was performed to explore factors potentially associated with COVID-19-related psychological stress levels before and after getting vaccinated. Results: A total of 34,041 participants were included in the final analysis. The mean stress score concerning COVID-19 vaccination was 3.90 ± 2.60 among all participants, and significantly decreased over time. In addition, the vaccine-related stress level significantly decreased after accessing information about the COVID-19 vaccine (N = 29,396), as well as after getting vaccinated (N = 5,103). Multivariable regression analysis showed higher stress levels related to COVID-19 vaccination in participants who were younger, having lower education level, having history of chronic diseases, mistrusting vaccine's efficacy, experience of vaccine allergy events, being affected by the COVID-19 epidemic, and having mental illness symptoms. Moreover, mistrust in vaccine efficacy and experience of vaccine allergy events had a long-term impact on psychological stress levels about COVID-19 vaccination even after getting vaccinated. Conclusions: The current findings profiled the COVID-19 vaccine-related psychological stress among the general public in China. Population-specific management and interventions targeting the stress related to COVID-19 vaccination are needed to help governments and policy makers promote individual's willingness to get vaccinations for public well-being during the COVID-19 pandemic.

Public Willingness and Determinants of COVID-19 Vaccination at the Initial Stage of Mass Vaccination in China.

The present study assessed the willingness of the general population to receive COVID-19 vaccines and identified factors that influence vaccine hesitancy and resistance. A national online survey was conducted from 29 January 2021 to 26 April 2021 in China. Multinomial logistic regression analyses were conducted to identify factors that influence vaccine hesitancy and resistance. Of the 34,041 participants surveyed, 18,810 (55.3%) were willing to get vaccinated, 13,736 (40.3%) were hesitant, and 1495 (4.4%) were resistant. Rates of vaccine acceptance increased over time, with geographical discrepancies in vaccine hesitancy and resistance between provinces in China. Vaccine safety was the greatest concern expressed by most participants (24,461 [71.9%]), and the major reason for participants' refusing vaccination (974 [65.2%]). Government agencies (23,131 [68.0%]) and social media (20,967 [61.6%]) were the main sources of COVID-19 vaccine information. Compared with vaccination acceptance, female, young and middle-aged, high income, and perceived low-risk of infection were associated with vaccine hesitancy. Histories of allergic reactions to other vaccines and depression symptoms were related to vaccine resistance. Common factors that influenced vaccine hesitancy and resistance were residing in cities and perceiving less protection with vaccines than with other protective measures. The results indicate that the rate of vaccine resistance is relatively low, but vaccine hesitancy is common. Individuals who are female, young and middle-aged, with a high income, and residing in cities are more likely to be hesitant for vaccination and should be the target populations for vaccination campaigns. Specific vaccine messaging from the government and social media could alleviate public concerns about vaccine safety and efficacy.

Anticholinergic drugs and the risk of dementia: A systematic review and meta-analysis.

Dementia is one of the greatest global challenges for public health; however, the relationship between anticholinergic drugs and dementia remains unclear. The aim of the present study was to perform a systematic review and meta-analysis of the predictive roles of anticholinergic drugs in dementia risk. After pooling fourteen longitudinal and case-control studies with a total of 1,564,181 subjects, anticholinergic drug use was associated with an increased risk of all-cause dementia and Alzheimer's disease. Both low and high anticholinergic drug burdens were associated with dementia. Moreover, there was a dose-dependent relationship between anticholinergic drugs and risk of dementia. With respect to the categories of anticholinergic drugs, antiparkinson, urological drugs, and antidepressants increased the risk for dementia; however, cardiovascular and gastrointestinal drugs played potentially protective roles. These findings underscore the importance of anticholinergic drugs as a potential modifiable risk factor for dementia and provide treatment priorities to optimize dementia prevention.

Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation.

Sleep deprivation (SD) is increasingly common in modern society, which can lead to the dysregulation of inflammatory responses and cognitive impairment, but the mechanisms remain unclear. Emerging evidence suggests that gut microbiota plays a critical role in the pathogenesis and development of inflammatory and psychiatric diseases, possibly via gut microbiota-brain interactions and neuroinflammation. The present study investigated the impact of SD on gut microbiota composition and explored whether alterations of the gut microbiota play a causal role in chronic inflammatory states and cognitive impairment that are induced by SD. We found that SD-induced gut dysbiosis, inflammatory responses, and cognitive impairment in humans. Moreover, the absence of the gut microbiota suppressed inflammatory response and cognitive impairment induced by SD in germ-free (GF) mice. Transplantation of the "SD microbiota" into GF mice activated the Toll-like receptor 4/nuclear factor-κB signaling pathway and impaired cognitive function in the recipient mice. Mice that harbored "SD microbiota" also exhibited increases in neuroinflammation and microglial activity in the hippocampus and medial prefrontal cortex. These findings indicate that gut dysbiosis contributes to both peripheral and central inflammatory processes and cognitive deficits that are induced by SD, which may open avenues for potential interventions that can relieve the detrimental consequences of sleep loss.

Sleep disturbances during pregnancy and adverse maternal and fetal outcomes: A systematic review and meta-analysis.

Sleep disturbances are highly prevalent in pregnancy and are frequently overlooked as a potential cause of significant morbidity. The association between sleep disturbances and pregnancy outcomes remains largely controversial and needs to be clarified to guide management. To evaluate the association between sleep disturbances and maternal complications and adverse fetal outcomes, we performed a systematic search of PubMed, Embase and Web of Science for English-language articles published from inception to March 6, 2020, including observational studies of pregnant women with and without sleep disturbances assessing the risk of obstetric complications in the antenatal, intrapartum or postnatal period, and neonatal complications. Data extraction was completed independently by two reviewers. We utilized the Newcastle-Ottawa Scales to assess the methodological quality of included studies and random-effect models to pool the associations. A total of 120 studies with 58,123,250 pregnant women were included. Sleep disturbances were assessed, including poor sleep quality, extreme sleep duration, insomnia symptoms, restless legs syndrome, subjective sleep-disordered breathing and diagnosed obstructive sleep apnea. Significant associations were found between sleep disturbances in pregnancy and a variety of maternal complications and adverse fetal outcomes. Overall sleep disturbances were significantly associated with pre-eclampsia (odds ratio = 2.80, 95% confidence interval: 2.38-3.30), gestational hypertension (1.74, 1.54-1.97), gestational diabetes mellitus (1.59, 1.45-1.76), cesarean section (1.47, 1.31-1.64), preterm birth (1.38, 1.26-1.51), large for gestational age (1.40, 1.11-1.77), and stillbirth (1.25, 1.08-1.45), but not small for gestational age (1.03, 0.92-1.16), or low birth weight (1.27, 0.98-1.64). Sleep disturbances were related to higher morbidities in pregnant women who are 30 y or older and overweight before pregnancy. The findings indicate that sleep disturbances, which are easily ignored and treatable for both pregnant women and clinical services, deserve more attention from health care providers during prenatal counseling and health care services.