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OBJECTIVE: Qiliqiangxin (QLQX) capsule- a traditional Chinese medicine used for treating heart failure (HF), can modulate inflammatory cytokines in rats with myocardial infarction. However, its immune-regulating effect on dilated cardiomyopathy (DCM) remains unknown. The aim of this study was to investigate whether QLQX has a unique regulatory role in the imbalance of pro- and anti-inflammatory cytokines in patients with DCM. METHODS: The QLQX-DCM is a randomized- double-blind trial conducted at 24 tertiary hospitals in China. A total of 345 patients with newly diagnosed virus-induced DCM were randomly assigned to receive QLQX capsules or placebo while receiving optimal medical therapy for HF. The primary endpoints were changes in plasma inflammatory cytokines and improvements in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDd) over the 12-month treatment. RESULTS: At the 12-month follow-up, the levels of IFN-γ, IL-17, TNF-α, and IL-4 decreased significantly, while the level of IL-10 increased in both groups compared with baselines (all P<0.0001). Furthermore-these changes, coupled with improvements in LVEF, NT-proBNP and New York Heart Association (NYHA) functional classification, excluding the LVEDd in the QLQX group, were greater than those in the placebo group (all P<0.001). Additionally, compared with placebo, QLQX treatment also reduced all-cause mortality and rehospitalization rates by 2.17% and 2.28%, respectively, but the difference was not statistically significant. CONCLUSION: QLQX has the potential to alleviate the imbalance of inflammatory cytokines in patients with DCM, potentially leading to further improvements in cardiac function when combined with anti-HF standard medications.
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The disorder operator is often designed to reveal the conformal field theory (CFT) information in quantum many-body systems. By using large-scale quantum Monte Carlo simulation, we study the scaling behavior of disorder operators on the boundary in the two-dimensional Heisenberg model on the square-octagon lattice with gapless topological edge state. In the Affleck-Kennedy-Lieb-Tasaki phase, the disorder operator is shown to hold the perimeter scaling with a logarithmic term associated with the Luttinger liquid parameter K. This effective Luttinger liquid parameter K reflects the low-energy physics and CFT for (1+1)D boundary. At bulk critical point, the effective K is suppressed but it keeps finite value, indicating the coupling between the gapless edge state and bulk fluctuation. The logarithmic term numerically captures this coupling picture, which reveals the (1+1)D SU(2)_{1} CFT and (2+1)D O(3) CFT at boundary criticality. Our Letter paves a new way to study the exotic boundary state and boundary criticality.
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INTRODUCTION: A standardized measure for inflammaging is lacking. We introduced the inflammatory age (iAge) as a quantification method and explored its associations with age-related traits and diseases in an older Chinese cohort. METHODS: Inflammatory markers including white blood cell count (WBC), neutrophils, lymphocytes, monocytes, C-reactive protein, platelets and albumin were measured. Quantitative real-time polymerase chain reaction was used to measure telomere length. Traditional multivariable linear, partial least squares, and logistic regression were used. RESULTS: iAge was constructed based on WBC, neutrophils, monocytes and albumin, which were associated with telomere length independently. A higher iAge indicated a heavier aging-related inflammation burden. Per 1-year increase in iAge was associated with higher body mass index (ß 0.86 (95 % CI 0.67, 1.05) kg/m2), waist circumference (ß 2.37 (95 % CI 1.85, 2.90) cm), glycosylated hemoglobin A1c (ß 0.06 (95 % CI 0.02, 0.10) %), systolic blood pressure (ß 1.06 (95 % CI 0.10, 2.03) mmHg), triglycerides (ß 0.05 (95 % CI 0.01, 0.08) mmol/L), 10-year cardiovascular diseases risk (ß 0.05 (95 % CI 0.02, 0.08) %), diabetes (OR 1.22 (95 % CI 1.02, 1.46)), hypertension (OR 1.21 (95 % CI 1.04, 1.42)) and metabolic syndrome risks (OR 1.25 (95 % CI 1.04, 1.51)), and lower fasting plasma glucose (ß -0.016 (95 % CI -0.024, -0.007) mmol/L), total cholesterol (ß -0.06 (95 % CI -0.12, -0.01) mmol/L) and high-density lipoprotein cholesterol (ß -0.05 (95 % CI -0.07, -0.03) mmol/L). CONCLUSION: The newly introduced iAge, derived from inflammatory markers and telomere length, aligns with various metabolic dysfunctions and age-related disease risks, underscoring its potential ability in identifying aging-related phenotypes.
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Aging , Inflammation , Humans , Male , Female , Aged , China/epidemiology , Aging/physiology , Aging/blood , Inflammation/blood , Biomarkers/blood , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/blood , Middle Aged , Risk Factors , Leukocyte Count , Body Mass Index , C-Reactive Protein/analysis , East Asian PeopleABSTRACT
The use of finite entanglement scaling with matrix product states (MPS) has become a crucial tool for studying one-dimensional critical lattice theories, especially those with emergent conformal symmetry. We argue that finite entanglement introduces a relevant deformation in the critical theory. As a result, the bipartite entanglement Hamiltonian defined from the MPS can be understood as a boundary conformal field theory with a physical and an entanglement boundary. We are able to exploit the symmetry properties of the MPS to engineer the physical conformal boundary condition. The entanglement boundary, on the other hand, is related to the concrete lattice model and remains invariant under this relevant perturbation. Using critical lattice models described by the Ising, Potts, and free compact boson conformal field theories, we illustrate the influence of the symmetry and the relevant deformation on the conformal boundaries in the entanglement spectrum.
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Liver kinase B1 (LKB1), an evolutionarily conserved serine/threonine kinase, is a master regulator of the AMPK subfamily and controls cellular events such as polarity, proliferation, and energy homeostasis. Functions and mechanisms of the LKB1-AMPK axis at specific subcellular compartments, such as lysosome and mitochondria, have been established. AMPK is known to be activated at the Golgi; however, functions and regulatory mechanisms of the LKB1-AMPK axis at the Golgi apparatus remain elusive. Here, we show that TBC1D23, a Golgi-localized protein that is frequently mutated in the neurodevelopment disorder pontocerebellar hypoplasia (PCH), is specifically required for the LKB1 signaling at the Golgi. TBC1D23 directly interacts with LKB1 and recruits LKB1 to Golgi, promoting Golgi-specific activation of AMPK upon energy stress. Notably, Golgi-targeted expression of LKB1 rescues TBC1D23 deficiency in zebrafish models. Furthermore, the loss of LKB1 causes neurodevelopmental abnormalities in zebrafish, which partially recapitulates defects in TBC1D23-deficient zebrafish, and LKB1 sustains normal neuronal development via TBC1D23 interaction. Our study uncovers a regulatory mechanism of the LKB1 signaling, and reveals that a disrupted Golgi-LKB1 signaling underlies the pathogenesis of PCH.
Subject(s)
AMP-Activated Protein Kinases , Cerebellar Diseases , Zebrafish , Animals , Zebrafish/metabolism , AMP-Activated Protein Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Signal Transduction , Golgi Apparatus/metabolismABSTRACT
In cancer treatment, adaptive therapy holds promise for delaying the onset of recurrence through regulating the competition between drug-sensitive and drug-resistant cells. Adaptive therapy has been studied in well-mixed models assuming free mixing of all cells and spatial models considering the interactions of single cells with their immediate adjacent cells. Both models do not reflect the spatial structure in glandular tumours where intra-gland cellular interaction is high, while inter-gland interaction is limited. Here, we use mathematical modelling to study the effects of adaptive therapy on glandular tumours that expand using either glandular fission or invasive growth. A two-dimensional, lattice-based model of sites containing sensitive and resistant cells within individual glands is developed to study the evolution of glandular tumour cells under continuous and adaptive therapies. We found that although both growth models benefit from adaptive therapy's ability to prevent recurrence, invasive growth benefits more from it than fission growth. This difference is due to the migration of daughter cells into neighboring glands that is absent in fission but present in invasive growth. The migration resulted in greater mixing of cells, enhancing competition induced by adaptive therapy. By varying the initial spatial spread and location of the resistant cells within the tumour, we found that modifying the conditions within the resistant cells containing glands affect both fission and invasive growth. However, modifying the conditions surrounding these glands affect invasive growth only. Our work reveals the interplay between growth mechanism and tumour topology in modulating the effectiveness of cancer therapy.
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Neoplasms , Humans , Models, TheoreticalABSTRACT
Bone-turnover marker (BTM) measurements in the blood or urine reflect the bone-remodeling rate and may be useful for studying and clinically managing metabolic bone diseases.Substantial evidence supporting the diagnostic use of BTMs has accumulated in recent years, together with the publication of several guidelines. Most clinical trials and observational and reference-interval studies have been performed in the Northern Hemisphere and have mainly involved Caucasian populations. This review focuses on the available data for populations from the Asia-Pacific region and offers guidance for using BTMs as diagnostic biomarkers in these populations. The procollagen I N-terminal propeptide and β-isomerized C-terminal telopeptide of type-I collagen (measured in plasma) are reference BTMs used for investigating osteoporosis in clinical settings. Premenopausal reference intervals (established for use with Asia-Pacific populations) and reference change values and treatment targets (used to monitor osteoporosis treatment) help guide the management of osteoporosis. Measuring BTMs that are not affected by renal failure, such as the bone-specific isoenzyme alkaline phosphatase and tartrate-resistant acid phosphatase 5b, may be advantageous for patients with advanced chronic kidney disease. Further studies of the use of BTMs in individuals with metabolic bone disease, coupled with the harmonization of commercial assays to provide equivalent results, will further enhance their clinical applications.
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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Unhealthy dietary habit is one of major risk factors of NAFLD. However, the associations between specific types of fish and meat consumption and NAFLD remain inconclusive. We explored the associations of fish and meat consumption with NAFLD risk in middle-aged and older Chinese. METHODS: We collected information on 1,862 participants aged 50 years or older from Guangzhou Biobank Cohort Study in 2009 to 2010. Fish and meat consumption was assessed using a validated food-frequency questionnaire. NAFLD was diagnosed by ultrasound. Multivariable logistic regression was used to examine the associations of fish and meat consumption with the presence of NAFLD. RESULTS: The average age was 61.0 (standard deviation = 6.5) years for the participants, 50.2% were women, and 37.2% were diagnosed with NAFLD. After adjusting for age, sex, education, family income, occupation, smoking status, drinking status, physical activity and several metabolic traits, compared with 0 serving/week (one serving = 50 g), fatty fish consumption of ≥ 3 servings/week showed higher odds of NAFLD (odds ratio (OR) and 95% confidence interval (CI): 1.64 (1.12, 2.39)). The highest (≥ 11 servings/week of red meat and poultry; ≥ 3 servings/week of processed meat) versus the lowest (0-3 servings/week of red meat and poultry; 0 serving/week of processed meat) consumption of all other types of meats, including red meat, poultry and processed meat, showed no association with NAFLD (1.17 (0.75, 1.81), 1.02 (0.42, 2.50) and 0.85 (0.50, 1.45), respectively). Aquatic and sea food, and red meat had negative indirect effects on NAFLD via systolic blood pressure and/or high-density lipoprotein cholesterol. Processed meat had positive indirect effects on NAFLD via body mass index, waist circumference, fasting plasma glucose and triglycerides. CONCLUSION: High consumption of fatty fish was associated with higher NAFLD risk. Our results, if causal, provide evidence that limiting consumption of fatty fish can be considered as part of NAFLD lifestyle prevention and treatment.
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Non-alcoholic Fatty Liver Disease , Middle Aged , Animals , Humans , Female , Aged , Infant, Newborn , Male , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/etiology , Cohort Studies , Biological Specimen Banks , Meat , Risk FactorsABSTRACT
Objective: The objective of this study was to analyze the clinical characteristics of pregnant women infected with the COVID-19 omicron variant and their neonates during the outbreak in Guangdong province, China. Methods: The clinical data of pregnant women infected with the COVID-19 omicron variant and their neonates were retrospectively collected from two hospitals in Guangdong province. Information recorded included age of mother, date of birth, sex, weight at birth, mode of delivery, gestational age, feeding mode, Apgar score, signs, medical records, underlying comorbidities and laboratory results. The presence of SARS-CoV-2 viral RNA was tested using an real-time PCR assay. Results: Seventy-nine pregnant women infected with COVID-19 omicron variant and their 68 neonates were included in this study. The vast majority (86.1%) of pregnant women was in their third trimester of pregnancy, and only 11 cases (15%) were in the first or second trimester. Of 79 pregnant women, 39 cases were asymptomatic at the time of infection, and 40 mothers presented with mild manifestations of COVID-19. The most common symptoms were fever (92.5%, 37/40) and cough (57.5%, 21/40). All of pregnant women did not receive chest computed tomography (CT) scan or X-ray. No pregnant woman developed severe pneumonia. A total of 68 neonates (3 set of twins) from 65 mothers with COVID-19 were reviewed. Among women who delivered, 34 cases underwent cesarean section, 31 cases underwent vaginal delivery. According to the timing of birth, there were 10 (14.7%) preterm neonates. Two babies were born dead (intrauterine fetal death after 22 weeks of gestation). Of the live babies born (66 cases) from mothers with COVID-19, 9 newborns were lower weight, and one preterm case was born with respiratory distress and intubated, he recovered and developed normally. SARS-CoV-2 nucleic acid testing was conducted on 41 neonates daily after birth, with only one neonate testing positive for SARS-CoV-2 infection on the third day after birth. The infected neonate exhibited typical fever and acute respiratory tract syndrome but ultimately had a good prognosis, recovering after 5 days of treatment. Conclusion: Although preliminary data suggests the risk of severe maternal and fetal complications from Omicron variant infection during pregnancy is lower than previous variants and Delta variant. Our study, which was conducted on a limited population sample, indicates that there is a possibility of severe complications, such as stillbirth, occurring in some fetal cases. These findings emphasize the need for continued attention from obstetricians.
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Delta check is an electronic error detection tool. It compares the difference in sequential results within a patient against a predefined limit, and when exceeded, the delta check rule is considered triggered. The patient results should be withheld for review and troubleshooting before releasing to the clinical team for patient management. Delta check was initially developed as a tool to detect wrong-blood-in-tube (sample misidentification) errors. It is now applied to detect errors more broadly within the total testing process. Recent advancements in the theoretical understanding of delta check has allowed for more precise application of this tool to achieve the desired clinical performance and operational set up. In this Chapter, we review the different pre-implementation considerations, the foundation concepts of delta check, the process of setting up key delta check parameters, performance verification and troubleshooting of a delta check flag.
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Quality control practices in the modern laboratory are the result of significant advances over the many years of the profession. Major advance in conventional internal quality control has undergone a philosophical shift from a focus solely on the statistical assessment of the probability of error identification to more recent thinking on the capability of the measurement procedure (e.g. sigma metrics), and most recently, the risk of harm to the patient (the probability of patient results being affected by an error or the number of patient results with unacceptable analytical quality). Nonetheless, conventional internal quality control strategies still face significant limitations, such as the lack of (proven) commutability of the material with patient samples, the frequency of episodic testing, and the impact of operational and financial costs, that cannot be overcome by statistical advances. In contrast, patient-based quality control has seen significant developments including algorithms that improve the detection of specific errors, parameter optimization approaches, systematic validation protocols, and advanced algorithms that require very low numbers of patient results while retaining sensitive error detection. Patient-based quality control will continue to improve with the development of new algorithms that reduce biological noise and improve analytical error detection. Patient-based quality control provides continuous and commutable information about the measurement procedure that cannot be easily replicated by conventional internal quality control. Most importantly, the use of patient-based quality control helps laboratories to improve their appreciation of the clinical impact of the laboratory results produced, bringing them closer to the patients.Laboratories are encouraged to implement patient-based quality control processes to overcome the limitations of conventional internal quality control practices. Regulatory changes to recognize the capability of patient-based quality approaches, as well as laboratory informatics advances, are required for this tool to be adopted more widely.
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Functional reference limits describe key changes in the physiological relationship between a pair of physiologically related components. Statistically, this can be represented by a significant change in the curvature of a mathematical function or curve (e.g., an observed plateau). The point at which the statistical relationship changes significantly is the point of curvature inflection and can be mathematically modeled from the relationship between the interrelated biomarkers. Conceptually, they reside between reference intervals, which describe the statistical boundaries of a single biomarker within the reference population, and clinical decision limits that are often linked to the risk of morbidity or mortality and set as thresholds. Functional reference limits provide important physiological and pathophysiological insights that can aid laboratory result interpretation. Laboratory professionals are in a unique position to harness data from laboratory information systems to derive clinically relevant values. Increasing research on and reporting of functional reference limits in the literature will enhance their contribution to laboratory medicine and widen the evidence base used in clinical decision limits, which are currently almost exclusively contributed to by clinical trials. Their inclusion in laboratory reports will enhance the intellectual value of laboratory professionals in clinical care beyond the statistical boundaries of a healthy reference population and pave the way to them being considered in shaping clinical decision limits. This review provides an overview of the concepts related to functional reference limits, clinical examples of their use, and the impetus to include them in laboratory reports.
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Clinical Laboratory Techniques , Laboratories , Humans , Reference Values , BiomarkersABSTRACT
Phospholipase A and acyltransferase (PLAAT) 4 is a class II tumor suppressor with phospholipid metabolizing abilities. It was characterized in late 2000s, and has since been referred to as 'tazarotene-induced gene 3' (TIG3) or 'retinoic acid receptor responder 3' (RARRES3) as a key downstream effector of retinoic acid signaling. Two decades of research have revealed the complexity of its function and regulatory roles in suppressing tumorigenesis. However, more recent findings have also identified PLAAT4 as a key anti-microbial effector enzyme acting downstream of interferon regulatory factor 1 (IRF1) and interferons (IFNs), favoring protection from virus and parasite infections. Unveiling the molecular mechanisms underlying its action may thus open new therapeutic avenues for the treatment of both cancer and infectious diseases. Herein, we aim to summarize a brief history of PLAAT4 discovery, its transcriptional regulation, and the potential mechanisms in tumor prevention and anti-pathogen defense, and discuss potential future directions of PLAAT4 research toward the development of therapeutic approaches targeting this enzyme with pleiotropic functions.
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Genes, Tumor Suppressor , Receptors, Retinoic Acid , Receptors, Retinoic Acid/genetics , Tretinoin , Acyltransferases/genetics , Phospholipases/geneticsABSTRACT
Background: Calibration is a critical component for the reliability, accuracy, and precision of mass spectrometry measurements. Optimal practice in the construction, evaluation, and implementation of a new calibration curve is often underappreciated. This systematic review examined how calibration practices are applied to liquid chromatography-tandem mass spectrometry measurement procedures. Methods: The electronic database PubMed was searched from the date of database inception to April 1, 2022. The search terms used were "calibration," "mass spectrometry," and "regression." Twenty-one articles were identified and included in this review, following evaluation of the titles, abstracts, full text, and reference lists of the search results. Results: The use of matrix-matched calibrators and stable isotope-labeled internal standards helps to mitigate the impact of matrix effects. A higher number of calibration standards or replicate measurements improves the mapping of the detector response and hence the accuracy and precision of the regression model. Constructing a calibration curve with each analytical batch recharacterizes the instrument detector but does not reduce the actual variability. The analytical response and measurand concentrations should be considered when constructing a calibration curve, along with subsequent use of quality controls to confirm assay performance. It is important to assess the linearity of the calibration curve by using actual experimental data and appropriate statistics. The heteroscedasticity of the calibration data should be investigated, and appropriate weighting should be applied during regression modeling. Conclusions: This review provides an outline and guidance for optimal calibration practices in clinical mass spectrometry laboratories.
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Calibration , Chromatography, Liquid/methods , Humans , Mass Spectrometry , Reference Standards , Reproducibility of ResultsABSTRACT
Background@#Calibration is a critical component for the reliability, accuracy, and precision of mass spectrometry measurements. Optimal practice in the construction, evaluation, and implementation of a new calibration curve is often underappreciated. This systematic review examined how calibration practices are applied to liquid chromatography-tandem mass spectrometry measurement procedures. @*Methods@#The electronic database PubMed was searched from the date of database inception to April 1, 2022. The search terms used were “calibration,” “mass spectrometry,” and “regression.” Twenty-one articles were identified and included in this review, following evaluation of the titles, abstracts, full text, and reference lists of the search results. @*Results@#The use of matrix-matched calibrators and stable isotope-labeled internal standards helps to mitigate the impact of matrix effects. A higher number of calibration standards or replicate measurements improves the mapping of the detector response and hence the accuracy and precision of the regression model. Constructing a calibration curve with each analytical batch recharacterizes the instrument detector but does not reduce the actual variability. The analytical response and measurand concentrations should be considered when constructing a calibration curve, along with subsequent use of quality controls to confirm assay performance. It is important to assess the linearity of the calibration curve by using actual experimental data and appropriate statistics. The heteroscedasticity of the calibration data should be investigated, and appropriate weighting should be applied during regression modeling. @*Conclusions@#This review provides an outline and guidance for optimal calibration practices in clinical mass spectrometry laboratories.
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Functional reference limits describe key changes in the physiological relationship between a pair of physiologically related components. Statistically, this can be represented by a significant change in the curvature of a mathematical function or curve (e.g., an observed plateau). The point at which the statistical relationship changes significantly is the point of curvature inflection and can be mathematically modeled from the relationship between the interrelated biomarkers. Conceptually, they reside between reference intervals, which describe the statistical boundaries of a single biomarker within the reference population, and clinical decision limits that are often linked to the risk of morbidity or mortality and set as thresholds. Functional reference limits provide important physiological and pathophysiological insights that can aid laboratory result interpretation. Laboratory professionals are in a unique position to harness data from laboratory information systems to derive clinically relevant values. Increasing research on and reporting of functional reference limits in the literature will enhance their contribution to laboratory medicine and widen the evidence base used in clinical decision limits, which are currently almost exclusively contributed to by clinical trials. Their inclusion in laboratory reports will enhance the intellectual value of laboratory professionals in clinical care beyond the statistical boundaries of a healthy reference population and pave the way to them being considered in shaping clinical decision limits. This review provides an overview of the concepts related to functional reference limits, clinical examples of their use, and the impetus to include them in laboratory reports.
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BackgroundDue to the COVID-19 pandemic, both teenagers' studies and personal life are critically affected, which has resulted in a variety of mental health problems. In this regard, scholars at home and abroad have carried out a large number of research concerning adolescent mental health, of which there still exists a lack of systematic combing and review. ObjectiveTo understand the status and development trend of research on adolescent mental health during the COVID-19 pandemic at home and abroad, and to grasp the current research hotspots and trends in this field, so as to provide references for relevant research and practice in the post-epidemic era. MethodsOn October 30, 2022, we searched through China Knowledge Network Infrastructure (CNKI) and Web of Science database, and the publishing time of articles to be retrieved was limited between December 1, 2019 and October 30, 2022. Excel and CiteSpace were used to perform visual analysis on these articles in terms of number, author, institution, country and keywords of the articles. ResultsA total of 7 608 articles were included. At home and abroad, the number of papers related to adolescent mental health generally increased at first and then decreased under the pandemic situation. Compared with foreign countries, the connection and cooperation among domestic scholars and institutions was not close enough. The top three countries in the number of English literature published were the United States, Britain and China, and those in intermediary center were Tunis, Cameroon and Anguilla. The parent-child relationship and mental health of teenagers during were much concerned by scholars both at home and abroad. With the passage of time, researchers at home and abroad had shifted their focus from only negative factors to positive factors. ConclusionChinese scholars or institutions need to strengthen more domestic and international exchanges and cooperation. Scholars from different countries can carry out cross-cultural study on research topics of common concern, and continue to explore the positive psychological changes of teenagers in the post-epidemic era.[Funded by National Social Science Foundation 2020 Education Youth Project of 13th Five-Year Plan (number, CHA200259)]
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Some quantum critical states cannot be smoothly deformed into each other without either crossing some multicritical points or explicitly breaking certain symmetries even if they belong to the same universality class. This brings up the notion of "symmetry-enriched" quantum criticality. While recent works in the literature focused on critical states with robust degenerate edge modes, we propose that the conformal boundary condition (B.C.) is a more generic characteristic of such quantum critical states. We show that in two families of quantum spin chains, which generalize the Ising and the three-state Potts models, the quantum critical point between a symmetry-protected topological phase and a symmetry-breaking order realizes a conformal B.C. distinct from the simple Ising and Potts chains. Furthermore, we argue that the conformal B.C. can be derived from the bulk effective field theory, which realizes a novel bulk-boundary correspondence in symmetry-enriched quantum critical states.
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OBJECTIVE: To observe the clinical effect of moxibustion with deqi on Alzheimer's disease (AD) rats, and evaluate its effect on ß-amyloid (Aß) transport and enzymatic degradation proteins, to explore its molecular mechanism for improving cognitive function. METHODS: Sixty SPF-grade male SD rats were randomly divided into a blank group (8 rats), a sham-operation group (8 rats) and a model establishment group (44 rats). The rats in the model establishment group were injected with Aß1-42 at bilateral ventricles to establish AD model. Among the 38 rats with successful model establishment, 8 rats were randomly selected as the model group, and the remaining rats were treated with mild moxibustion at "Dazhui" (GV 14), once a day, 40 min each time, for 28 days. According to whether deqi appeared and the occurrence time of deqi, the rats were divided into a deqi group (12 rats), a delayed deqi group (10 rats) and a non-deqi group (8 rats). After the intervention, the Morris water maze test was applied to evaluate the cognitive function; the HE staining was applied to observe the brain morphology; the Western blot method was applied to measure the protein expression of Aß and its receptor mediated transport [low-density lipoprotein receptor-related protein (LRP) 1, receptor for advanced glycation end products (RAGE), apolipoprotein E (ApoE)] and enzymatic degradation [neprilysin (NEP), insulin degrading enzyme (IDE), endothelin converting enzyme (ECE)-1 and angiotensin converting enzyme (ACE) 2]. RESULTS: Compared with the sham-operation group, in the model group, the escape latency was prolonged (P<0.01), and the times of platform crossing and the ratio of platform quadrant to total time were reduced (P<0.01); the brain tissue was seriously damaged; the expression of hippocampal Aß and RAGE was increased (P<0.01), and the expression of hippocampal LRP1, ApoE, NEP, IDE, ECE-1 and ACE2 was decreased (P<0.01). Compared with the model group, the escape latency was shortened in the deqi group (P<0.05, P<0.01), and the escape latency in the delayed deqi group and the non-deqi group was shortened from Day 2 to Day 5 (P<0.05, P<0.01), and the times of platform crossing and the ratio of platform quadrant to total time were increased in the deqi group and the delayed deqi group (P<0.01, P<0.05); the brain damage in each moxibustion group was reduced, which was smallest in the deqi group, followed by the delayed deqi group and the non-deqi group; the expression of Aß and RAGE was decreased (P<0.01, P<0.05) and the expression of LRP1 and IDE was increased in each moxibustion group (P<0.01, P<0.05); the expression of ApoE was increased in the deqi group and the delayed deqi group (P<0.01, P<0.05); the expression of NEP was increased in deqi group (P<0.05), and the expression of ECE-1 and ACE2 was increased in the deqi group and the delayed deqi group (P<0.05). Compared with the delayed deqi group and the non-deqi group, the escape latency in the deqi group was shortened from Day 3 to Day 5 (P<0.05), and the times of platform crossing and the ratio of platform quadrant to total time were increased (P<0.05, P<0.01). Compared with the non-deqi group, the expression of Aß was reduced (P<0.05), the expression of LRP1 and ApoE was increased in the deqi group (P<0.05). The expression of NEP in the deqi group was higher than that in the delayed deqi group and the non-deqi group (P<0.05). CONCLUSION: Compared with non-deqi, moxibustion with deqi could promote Aß transport and degradation, thereby reducing Aß level in the brain and improving cognitive function for AD rats.
Subject(s)
Alzheimer Disease , Moxibustion , Alzheimer Disease/genetics , Alzheimer Disease/therapy , Amyloid beta-Peptides/genetics , Angiotensin-Converting Enzyme 2 , Animals , Apolipoproteins E/metabolism , Hippocampus/metabolism , Male , Rats , Rats, Sprague-DawleyABSTRACT
The enrichment and translocation characteristics of Cd, Pb, Zn, and As by various parts of maize plants were investigated using field experiments in 22 maize varieties simultaneously under uncontaminated, low, middle, and serious heavy metal Cd, Pb, Zn, and As complex-contaminated farmland soil conditions. The relationship between the uptake of Cd, Pb, Zn, and As by maize plants and the morphological content of heavy metals in the soil was also discussed through principal component analysis and correlation analysis of the concentrations of eight heavy metals, including Cd, Hg, As, Pb, Cr, Cu, Ni, and Zn. The results showed that:â the distribution pattern of Cd and Zn contents in different parts of the maize plant was as follows:upper stalk>lower stalk>root>seed, the distribution pattern of Pb was As follows:root>lower stalk>upper stalk>seed, and the As distribution pattern was:root>upper stalk>lower stalk>seed. The different distribution patterns were closely related to the accumulation characteristics of the crop itself and the environmental activity of Cd, Pb, Zn, and As in the soil of the study area. â¡ There were significant differences in Cd and Pb accumulation among 22 maize cultivars due to their genetic background (P<0.05), which showed four trends:Cd and Pb compound high-accumulation varieties, single Cd or Pb low-accumulation varieties (low Cd and high Pb, low Pb and high Cd), and Cd and Pb compound low-accumulation varieties. Among them, the content of Cd in the grain of the three varieties exceeded the national food safety standard, and the content of Cd in the stem and leaf of 14 varieties exceeded the national food health standard. The Pb content in stems, leaves, and grains of all cultivars did not exceed the standard, but the Pb content in grains of some cultivars was close to the limit and had the risk of exceeding the standard. The content of As in the stem, leaf, and grain of different maize varieties was much lower than the standard limit value, showing a stable low-accumulation characteristic. The content of Zn in the stem and leaf of different maize varieties increased with the increase in the content of Zn in soil, but the content of Zn in grain remained within the threshold of normal plant growth. ⢠Cd, Pb, Zn, and As in maize plants in the study area had a certain homology and were mainly affected by the excessive levels of Cd, Pb, Zn, and As pollutants in the soil. This showed that anthropogenic sources were brought about by mine extraction and tailings stockpiles, whereas Cu elements in maize plants were affected by certain anthropogenic pollution sources, though to a limited extent. Hg, Ni, and Cr in maize plants had a certain homology; this showed the natural source of soil parent material and weathering product accumulation. ⣠The contents of Cd, Pb, Zn, and As elements in various parts of the corn plant, as well as the contents of Cr and Ni elements all had a very significant positive correlation (P<0.01). The transport mechanisms of Cd, Pb, Zn, and As elements in the plant may have a common. However, there was a synergistic effect in the migration from the root of the corn to the upper part of the ground, and the same was true for the elements of Cr and Ni. The elements of Hg and Cd, Pb, Zn, and As in the corn stems and leaves and Hg and Cd, Hg, As, Pb, Cr, Ni, and Zn in grains all showed certain antagonistic effects. ⤠The comparison method simultaneously satisfied the following requirements:the contents of Cd, Pb, and As in stems and leaves did not exceed the national food hygiene standards, and the contents of Cd, Pb, and As in the grains did not exceed the national food safety standards. The cluster analysis of Cd, Pb, and As in grains was a low-accumulation group, and the enrichment and transport coefficients of Cd, Pb, and As in the stems and leaves and grains were low as the optimal conditions. C18 (Xianyu 335) could be selected as the optimal maize variety with low accumulation of Cd, Pb, and As and normal Zn content in grain, which is suitable for promoting and applying in the heavy metal complex-polluted farmland around industrial and mining enterprises in north China.