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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.

Inconsistent results regarding the relationship between sleep traits and cancer incidence and mortality exist. Using data from UK Biobank participants, we conducted multivariable Cox regression, linear and non-linear Mendelian randomization (MR), and survival curve analyses to simultaneously assess the independent impact of chronotype, sleep duration, and insomnia symptoms on pan-cancer risk and mortality, including all-cause mortality, 5-year cancer mortality, and cancer mortality among cancer patients. A definite evening chronotype, long sleep duration, and frequent insomnia symptoms were associated with higher pan-cancer risk and mortality among cancer patients and potential causal risk factors of mortality in patients with cancer. Long sleep duration also had a causal relationship with pan-cancer incidence. In addition, the current study showed that the genetically predicted morning chronotype was associated with a reduction in pan-cancer risk and mortality among patients with cancer. These results suggest that some sleep traits, such as longer sleep duration, evening chronotype, and insomnia, play individual and joint roles in pan-cancer risk and mortality among cancer patients, which could be beneficial from the morning chronotype. Our findings highlight the importance of sleep management in cancer prevention and prognosis.

Background High-quality mental health services can improve outcomes for people with mental health problems and abate the burden of mental disorders. We sought to identify the challenges the country’s mental health system currently faces and the human resource situation related to psychological services and to provide recommendations on how the mental health workforce situation could be addressed in China. Methods This study used a cross-sectional survey design. A web-based questionnaire approach and a convenience sampling method were adopted. It was carried out from September 2020 to January 2021 in China, and we finally included 3824 participants in the analysis. Descriptive statistical analysis of the characteristics of the study sample was performed. The risk factors for competence in psychological counseling/psychotherapy were assessed using multiple linear regression analysis. Results Workforce related to psychotherapy is scarce in China, especially in Western China and community mental health sectors. Psychiatrists (39.1%) and nurses (38.9%) were the main service providers of psychotherapy in psychiatric hospitals, and clinical psychologists (6.9%) and counsellors (5.0%) were seriously scarce in mental health care sectors. A total of 74.2% of respondents had no systematic psychological training, and 68.4 and 69.2% of them had no self-experience and professional supervision, respectively. Compared with clinical psychologists and counselors, psychiatrists and nurses had less training. Systematic psychological training (β = − 0.88), self-experience (β = − 0.59) and professional supervision (β = − 1.26) significantly influenced psychotherapy capacity (P Conclusions Sustained effort will be required to provide a high-quality, equitably distributed psychotherapy workforce in China, despite challenges for community mental health sectors and western China being likely to continue for some time. Because mental illness is implicated in so many burgeoning social ills, addressing this shortfall could have wide-ranging benefits.

Objective: To clarify the effects of escitalopram on sleep EEG power in patients with Major depressive disorder (MDD).Method: Polysomnography (PSG) was detected overnight, and blood samples were collected at 4 h intervals over 24 h from 13 male healthy controls and 13 male MDD patients before and after treatment with escitalopram for 8 weeks. The outcome measures included plasma melatonin levels, sleep architecture, and the sleep EEG power ratio.Results: Compared with healthy controls, MDD patients presented abnormalities in the diurnal rhythm of melatonin secretion, including peak phase delayed 3 h and a decrease in plasma melatonin levels at night and an increase at daytime, accompanied by sleep disturbances, a decrease in low-frequency bands and an increase in high-frequency bands, and the dominant right-side brain activity. Several of these abnormalities (abnormalities in the diurnal rhythm of melatonin secretion, partial sleep architecture parameters) persisted for at least the 8-week testing period.Conclusions: Eight weeks of treatment with escitalopram significantly improved subjective sleep perception and depressive symptoms of patients with MDD, and partially improved objective sleep parameters, while the improvement of circadian rhythm of melatonin was limited.

ObjectivesSleep disturbances increase the risk of dementia; however, there is insufficient information regarding this. We aimed to investigate public knowledge on the relationship between sleep disturbances and dementia, as well as attitudes towards improving sleep quality and obtaining knowledge on dementia.Design and settingA cross-sectional web-based questionnaire was administered between May and October 2019.ParticipantsAll participants provided informed consent and were able to respond to the survey.Primary outcomesFactors associated with the knowledge that sleep disturbances are risk factors for dementia and proportions of individuals with this knowledge; attitudes towards improving sleep quality and obtaining knowledge about dementia.ResultsOf the 3329 eligible samples, 72.57% correctly recognised that sleep disturbances increased the risk of dementia. In total, 92.97% of participants were willing to take at least one measure to improve sleep quality, and the percentages of those adopting these measures are as follows: 78.73% would lead a regular life, 67.88% would engage in strengthening exercise, 28.84% would undergo psychotherapy and 19.41% would take medication. The awareness regarding sleep disturbances increasing the risk of dementia was the only factor associated with the willingness to improve sleep quality in all four categories of measures. Almost all participants (95.25%) were willing to take at least one measure to acquire knowledge about dementia, with the following participants displaying higher willingness to obtain knowledge about dementia: female, had contact with dementia and considered sleep disturbances to increase the risk of dementia.ConclusionsOur findings indicate an association between people’s knowledge and attitudes, suggesting the importance of disseminating knowledge about sleep disturbances and dementia to achieve dementia prevention in future.

IL-10 producing B (B10) cells, a subset of regulatory B (Breg) cells, produce IL-10 and play immunosuppressive roles in antitumor immunity. B10 cells are associated with enhanced tumor-aggressiveness and a poorer prognosis. To specifically inhibit the IL-10 secreted by B cells, we constructed the recombinant plasmid pcCD19scFv-IL10R, which contained the gene of anti-CD19 single-chain variable fragment (CD19scFv) and the extracellular domain of IL-10R1. Soluble CD19scFv-IL10R protein was identified in vitro and in vivo after the cells were transfected with pcCD19scFv-IL10R plasmid or the mice were injected with the plasmid. The fusion protein had the bispecific ability to target both IL-10 and CD19 molecules in vitro. Intramuscularly (i.m.) injecting mice with pcCD19scFv-IL-10R plasmid inhibited hepatocellular carcinoma growth in vivo. Mice treated with pcCD19scFv-IL-10R showed a significant reduction in B10 cells and regulatory T (Treg) cells, but an increase in the anti-tumor Th1 immune response and the cytotoxic CD8+ T cell response. Thus, targeting B10 cells by CD19scFv-IL10R molecule may offer a new avenue for tumor therapy.

The immune system is felt to play an essential role in pulmonary fibrosis (PF). CD4

Macrophages are the primary host target cells of Mycobacterium tuberculosis (M. tb). As a subunit of immunoregulatory cytokines IL-27 and IL-35, Epstein–Barr virus-induced gene 3 (EBI3) has typically been explored as the secreted form and assessed in terms of its effects triggered by extracellular EBI3. However, little is known about intracellular EBI3 function. In the current study, we report that EBI3 production by macrophages is elevated in TB patients. We further demonstrate that increased EBI3 accumulates in virulent M. tb-treated murine macrophages. Eukaryotic translation elongation factor 1-alpha 1 (eEF1A1) binds to intracellular EBI3 to reduce Lys48 (K48)-linked ubiquitination of EBI3, leading to EBI3 accumulation. Moreover, the intracellular EBI3 inhibits caspase-3-mediated apoptosis in M. tb-treated macrophages. Herein, we propose a novel mechanism for accumulating intracellular EBI3 and its regulation of macrophage apoptosis in response to virulent M. tb., Accumulation of EBI3 is induced by eEF1A1-medicated reduction of K48-linked ubiquitination and inhibits apoptosis in virulent M. tb-treated murine macrophages.

Aims Glutamatergic transmission may play a critical role in the pathogenesis of Parkinson's disease (PD). Electroacupuncture (EA) has been demonstrated to effectively alleviate PD symptoms. In this study, a potential glutamate-dependent mechanism underlying the therapeutic action of EA was investigated. Methods The effects of EA stimulation on motor behaviors, dopamine contents, glutamate release, and group II metabotropic glutamate receptor (mGluR2/3) expression in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats were examined. Results Unilateral 6-OHDA lesions of the nigrostriatal system caused a marked increase in glutamate content in the ipsilateral cortex and striatum. mGluR2/3 protein expression and mGluR3 mRNA expression were reduced in the striatum. Noticeably, prolonged EA stimulation at 100 Hz significantly reversed these changes in the striatal glutamate system. Behaviorally, EA improved the motor deficits induced by 6-OHDA lesions. Intrastriatal infusion of an mGluR2/3 antagonist APICA blocked the improving effect of EA. Conclusions These data collectively demonstrate that the group II mGluR-mediated glutamatergic transmission in the striatum is sensitive to dopamine depletion and may serve as a substrate of EA for mediating the therapeutic effect of EA in a rat model of PD.

Immune dysregulation, specifically of inflammatory processes, has been linked to behavioral symptoms of depression in both human and rodent studies. Here, we evaluated the antidepressant effects of immunization with altered peptide ligands of myelin basic protein (MBP)-MBP

The immune system is felt to play an essential role in pulmonary fibrosis (PF). CD4+CD25+ regulatory T cells (Tregs) are crucial in maintaining immune tolerance and immune homeostasis, but their role in the pathogenesis of PF is controversial and still unclear. We here explored the relationship between peripheral blood CD4+CD25+ Tregs and the course of bleomycin-induced PF in mice. Mouse PF models were established by intratracheal instillation of bleomycin. Lung histology, hydroxyproline, Th1/Th2 balanc, CD4+CD25+ Tregse were analyzed at the 3rd，7th，14th，21st and 28th days after instillation. CD4+CD25+ Tregs were also transferred into mice with or without PF by tail vein injection. The trend of CD4+CD25+ Tregs changes was increased firstly, decreased, increased again from 7th to 28th days after bleomycin instillation, which had great relevance with alveolitis and fibrosis scores. There also were high Th1 polarization index from 3rd to 14th days and high Th2 polarization index at 21st and 28th days after bleomycin treatment. CD4+CD25+ Tregs could promote the secretion of Th2 cytokines and inhibit the secretion of Th1 cytokines, allow the Th1/Th2 balance to Th2 direction in PF. Moreover, preventive adoptive transfer of CD4+CD25+ Tregs may ameliorate the process of PF, while acute adoptive transfer of CD4+CD25+ Tregs may aggravate the process of PF. These findings suggested that the dynamic changes of CD4+CD25+ Tregs as dependent factor might designate a different course of PF induced by bleomycin in mice, and might be a selected drug use indicator for therapy of PF.

Relevance Acupuncture is an intrinsic part of traditional Chinese medicine. The current understanding of the acupuncture meridian system, acupoints and the potential utilizing Omics technologies are summarized in this review. Material and methods A systematic search for acupuncture involving Omics technologies was carried out using multiple online literature databases. The records retrieved were from the full collections of each database dated to September 2011. Data produced from functional genomic technologies were extracted from the collected acupuncture/moxibustion studies and subjected to evaluation. Analyses and comments were summarized on the advances in experimental research in acupuncture/moxibustion-related studies, and the future for strategies and approaches in the era of functional genomics highlighted. Results An overview of articles indicated that several diseases or symptoms with evidence of effectiveness had been piloted for using functional genomic technologies, such as Parkinson's disease, allergic disorders, pain, and spinal cord injury, most of which are chronic “difficult diseases”. High-throughput genomic and proteomic profiling of gene expression in tissues has been able to identify potential candidates for the effects of acupuncture and provide valuable information toward understanding the possible mechanisms of the therapy. However, without further holistic and sophisticated analyses in the context of metabolomics and systems biology, the current attempts and the foreseeable developments appear to be insufficient to produce firm conclusions. Noticeably, the recent rapid advances in functional molecular imaging targeting specific metabolites have shown great promise and if combined with other post-genomic technologies, could be extremely helpful for the acupuncture studies in human subjects. Conclusion This review suggest that disease-oriented studies using the approach of multi-indexed high-throughput technologies and systems biology analyses will be a preferred strategy for future acupuncture/moxibustion research.

Clinical and research evidence has shown that electroacupuncture (EA) promotes recovery of motor function in patients with Parkinson’s disease (PD). However, the “efficacy span” of EA treatment, especially the long-term effect of EA that is thought to last after the cessation of EA treatment, has not been investigated. The present study thus investigated and compared the effect of EA during and after chronic EA application on motor activity and dopamine lesions in a 6-hydroxydopamine (6-OHDA)-lesioned mouse model of PD. Chronic EA treatment (30 min a day, 6 days a week for 2 or 4 weeks) significantly attenuated motor deficiency and reduced dopamine neuron degeneration. Remarkably, EA showed a long-lasting effect after the cessation of EA stimulation. At 2 and 4 weeks after the termination of EA, EA continued to improve motor function in 6-OHDA-lesioned mice. Consistent with sustained behavioral effects, EA induced an enduring increase in the dopamine turnover ratio in the striatum 2 weeks after the cessation of EA treatment. Here we demonstrated that the therapeutic effect of EA outlasted the duration of EA application. During a relatively long period of time after the completion of EA treatment, EA is able to continue to improve motor function and enhance dopamine availability in 6-OHDA-lesioned PD mice.

Background The acupuncture or electroacupuncture (EA) shows the therapeutic effect on various neurodegenerative diseases. This effect was thought to be partially achieved by its ability to alleviate existing neuroinflammation and glial dysfunction. In this study, we systematically investigated the effect of EA on abnormal neurochemical changes and motor symptoms in a mouse neurodegenerative disease model. Methods The transgenic mouse which expresses a mutant α-synuclein (α-syn) protein, A53T α-syn, in brain astrocytic cells was used. These mice exhibit extensive neuroinflammatory and motor phenotypes of neurodegenerative disorders. In this study, the effects of EA on these phenotypic changes were examined in these mice. Results EA improved the movement detected in multiple motor tests in A53T mutant mice. At the cellular level, EA significantly reduced the activation of microglia and prevented the loss of dopaminergic neurons in the midbrain and motor neurons in the spinal cord. At the molecular level, EA suppressed the abnormal elevation of proinflammatory factors (tumor necrosis factor-α and interleukin-1β) in the striatum and midbrain of A53T mice. In contrast, EA increased striatal and midbrain expression of a transcription factor, nuclear factor E2-related factor 2, and its downstream antioxidants (heme oxygenase-1 and glutamate-cysteine ligase modifier subunits). Conclusions These results suggest that EA possesses the ability to ameliorate mutant α-syn-induced motor abnormalities. This ability may be due to that EA enhances both anti-inflammatory and antioxidant activities and suppresses aberrant glial activation in the diseased sites of brains.

Individual response to opioid analgesics varies among patients.This study sought to clarify the impact of distinct genetic variations on pain, opioid consumption, and opioid side effects in patients with postoperative pain.A systematic review and meta-analysis of associations between genetic single-nucleotide polymorphisms (SNPs) and opioids used for acute postoperative pain.This meta-analysis examined all studies involving an association between genetic polymorphisms and the analgesic efficacy or clinical outcome of opioid analgesics for postoperative pain.A literature search was performed up to January 31, 2014, using the PubMed, EMBase, ISI Web of Science, and Cochrane Library databases.Fifty-nine studies were included in this systematic review, and 23 studies (a total of 5,902 patients) were included in the final meta-analysis. The results showed that human μ-opioid receptor gene (OPRM1) 118G allele variant carriers consumed more opioids for analgesia (SMD = -0.17, 95% CI = [-0.25, -0.10], P0.00001), but reported higher pain scores (MD = -0.11, 95% CI = [-0.17, -0.04], P = 0.002) and less nausea and vomiting (odds ratio = 1.30, 95% CI = [1.08, 1.55], P = 0.005) than the homozygous 118AA patients during the first 24 hour but not the 48 hour postoperative period. Moreover, CYP3A4*1G carriers consumed less opioids than homozygous CYP3A4*1/*1 patients during the first 24 hours postoperative period (MD = 45.12, 95% CI = [36.17, 54.06], P0.00001). No significant differences were found in CYP3A5*3, ABCB1 C3435T, and G2477T/A genetic polymorphisms.Some potential non-genetic factors can modify the effects of gene SNP on pain and opioid consumption during the postoperative period, such as age, gender, mood, anxiety, and drug-drug interactions. But further analyses could not be performed in the present meta-analysis due to limited information.The results indicate that among the genetic SNPs we studied which include those affecting analgesic drug metabolism, transport of analgesic agents across the blood-brain barrier, and their activity at target receptors and ion channels and in the modulation of neurotransmitter pathways, the A118G allele variant of OPRM1 has the most potent influence on pain management of postoperative patients. Opioid receptor gene information may provide valuable information for clinicians to properly manage the analgesic use of opioids individually for better pain management.

Fluorescence lifetime imaging microscopy (FLIM) can reveal important biological information and recently stimulated emission (SE) has been applied in FLIM to improve the spatial resolution of micrographs and detect fluorophore over a long working distance. An issue with SE is that the SE signal is much weaker than the probe laser beam that is used to generate the SE, therefore the signal to background ratio is low. Here we demonstrate using interferometric setup to decrease this background laser intensity, thus achieving higher S/N ratio and dye concentration detection sensitivity in SE microscopy.

Currently, antidepressants are the dominative treatment for depression, but they have limitations in efficacy and may even produce troublesome side effects. Electroacupuncture (EA) has been reported to have therapeutic benefits in the treatment of depressive disorders. The present study was conducted to determine whether EA could enhance the antidepressant efficacy of a low dose of citalopram (an SSRI antidepressant) in the chronic unpredictable stress-induced depression model rats. Here, we show that a combined treatment with 2 Hz EA and 5 mg/kg citalopram for three weeks induces a significant improvement in depressive-like symptoms as detected by sucrose preference test, open field test, and forced swimming test, whereas these effects were not observed with either of the treatments alone. Further investigations revealed that 2 Hz EA plus 5 mg/kg citalopram produced a remarkably increased expression of BDNF and its receptor TrkB in the hippocampus compared with those measured in the vehicle group. Our findings suggest that EA combined with a low dose of citalopram could produce greater therapeutic effects, thereby, predictive of a reduction in drug side effects.

Background: Morinda officinalis oligosaccharides (MOs) have been reported to exert neuroprotective and antidepressant-like effects in the forced swim test (FST) in mice. However, the mechanisms that underlie the antidepressant-like effects of MOs are unclear. Methods: Chronic unpredictable stress (CUS) and FST were used to explore the antidepressant-like effects of MOs and resilience to stress in rats. The PI3K inhibitor LY294002 was microinjected in the medial prefrontal cortex (mPFC) to explore the role of GSK-3β in the antidepressant-like effects of MOs. The expression of brain-derived neurotrophic factor (BDNF), phosphorylated-Ser9-glycogen synthase kinase 3β (GSK-3β), β-catenin, and synaptic proteins was determined in the mPFC and the orbitofrontal cortex (OFC) by Western blot. Results: We found that MOs effectively ameliorated CUS-induced depression-like behaviors in the sucrose preference test (SPT) and FST. The MOs also significantly rescued CUS-induced abnormalities in the BDNF-GSK-3β-β-catenin pathway and synaptic protein deficits in the mPFC but not OFC. The activation of GSK-3β by the PI3K inhibitor LY294002 abolished the antidepressant-like effects of MOs in the FST. Naive rats that were treated with MOs exhibited resilience to CUS, accompanied by increases in the expression of BDNF, phosphorylated-Ser9-GSK-3β, and β-catenin in the mPFC. Conclusion: Our findings indicate that the BDNF-GSK-3β-β-catenin pathway in the mPFC may underlie the antidepressant-like effect of MOs and resilience to stress.

To study the occurrence and characteristics of hypokalemia to the patients with acute and severe mental disorders, and analyze its influencing factors.There were 815 patients with actue and severe mental disorder admitted into our psychiatry department from June 2009 to May 2010, who all received the examination of potassium concentration routinely at the admission. The patients were divided into hypokalemia group and non-hypokalemia group, and the clinical information were surveyed and compared between the two groups to find out the influencing factors of hypokalemia.There were 177 patients with hypokalemia, and the proportion was 21.72%. Between the two groups, the difference of age, sex, admission season, whether with physical diseases and diagnosis were statistically significant (P0.05), while spiritual movement situation was not significant different (P0.05). Spearman rank correlation analysis showed that the incidence of hypokalemia was negatively correlated with age (r = -0.55, P = 0.00). Furthermore, multivariate analysis found that women, poor diet and physical disease were risk factors of hypolalemia (P0.05).There is relatively high probability of hypokalemia occurrence to the patients with acute and severe mental disorders, which should be distinguished and treated at the admission timely.

Prior evidence shows that acupuncture improves symptoms in both Parkinson's disease (PD) patients and animal models. We examined the effects of high-frequency (100 Hz) electroacupuncture (EA) on behavior in a rat PD model induced by medial forebrain bundle (MFB) transection. Neurotransmitters levels in the striatum were measured using in vivo microdialysis and high performance liquid chromatography (HPLC). High-frequency EA stimulation at Dazhui (GV14) and Baihui (GV20) acupoints decreased rotational behavior induced by apomorphine (APO) and improved motor coordination, protected axotomized dopaminergic neurons from degeneration in the substantia nigra (SN), it did not increase striatal dopamine (DA) levels. However, EA stimulation at acupoints significantly decreased the abnormally elevated glutamate (Glu) and acetylcholine (ACh) levels in the lesioned side of striatum. Moreover, the Glu levels correlated significantly with survival ratios of dopaminergic neurons in the SNc and rotational bahavior. These data suggested that behavioral alleviation with EA stimulation may be associated with modulation of neurotransmitters release, such as Glu and ACh in the striatum, rather than with DA restoration.