Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier function.However, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could provide valuable insights into potential therapeutic strategies for Alzheimer's disease and related conditions.

Blood-brain barrier pathology in cerebral small vessel disease

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

The Effect of Blood Lipid Profiles on Chronic Kidney Disease in a Prospective Cohort:Based on a Regression Discontinuity Design

Objective Previous studies on the association between lipid profiles and chronic kidney disease(CKD)have yielded inconsistent results and no defined thresholds for blood lipids.Methods A prospective cohort study including 32,351 subjects who completed baseline and follow-up surveys over 5 years was conducted.Restricted cubic splines and Cox models were used to examine the association between the lipid profiles and CKD.A regression discontinuity design was used to determine the cutoff value of lipid profiles that was significantly associated with increased the risk of CKD.Results Over a median follow-up time of 2.2(0.5,4.2)years,648(2.00%)subjects developed CKD.The lipid profiles that were significantly and linearly related to CKD included total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),TC/HDL-C,and TG/HDL-C,whereas lowdensity lipoprotein cholesterol(LDL-C)and LDL-C/HDL-C were nonlinearly correlated with CKD.TC,TG,TC/HDL-C,and TG/HDL-C showed an upward jump at the cutoff value,increasing the risk of CKD by 0.90%,1.50%,2.30%,and 1.60%,respectively,whereas HDL-C showed a downward jump at the cutoff value,reducing this risk by 1.0%.Female and participants with dyslipidemia had a higher risk of CKD,while the cutoff values for the different characteristics of the population were different.Conclusion There was a significant association between lipid profiles and CKD in a prospective cohort from Northwest China,while TG,TC/HDL-C,and TG/HDL-C showed a stronger risk association.The specific cutoff values of lipid profiles may provide a clinical reference for screening or diagnosing CKD risk.

Blood cell counts and nonalcoholic fatty liver disease: Evidence from Mendelian randomization analysis

BACKGROUND Previous research has highlighted correlations between blood cell counts and chronic liver disease.Nonetheless,the causal relationships remain unknown.AIM To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease(NAFLD)risk.METHODS Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study(GWAS)conducted by the Blood Cell Consortium.Summary-level data for liver enzymes were obtained from the United Kingdom Biobank.NAFLD data were obtained from a GWAS meta-analysis(8434 cases and 770180 controls,discovery dataset)and the Fingen GWAS(2275 cases and 372727 controls,replication dataset).This analysis was conducted using the inverse-variance weighted method,followed by various sensitivity analyses.RESULTS One SD increase in the genetically predicted haemoglobin concentration(HGB)was associated with aβof 0.0078(95%CI:0.0059-0.0096),0.0108(95%CI:0.0080-0.0136),0.0361(95%CI:0.0156-0.0567),and 0.0083(95%CI:00046-0.0121)for alkaline phosphatase(ALP),alanine aminotransferase(ALT),aspartate aminotransferase,and gammaglutamyl transferase,respectively.Genetically predicted haematocrit was associated with ALP(β=0.0078,95%CI:0.0052-0.0104)and ALT(β=0.0057,95%CI:0.0039-0.0075).Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD[odds ratio(OR)=1.199,95%CI:1.087-1.322]and(OR=1.157,95%CI:1.071-1.250).The results of the sensitivity analyses remained significant.CONCLUSION Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis,which may facilitate the diagnosis and prevention of NAFLD.

Mediating function of heart failure in the causal relationship between diastolic blood pressure and hypertensive renal disease with renal failure:a mediated Mendelian randomization study

Objective:To study the causality relationship between diastolic blood pressure(DBP)and hypertensive renal disease with renal failure(HRDRF)and the mediating role of hear t failure(HF)in the causality relationship by network Mendelian randomization(MR).Methods:Genome-wide analysis of DBP,HRDRF,and HF was downloaded from the public database(Genome-Wide Analysis Study[GWAS])and was used to analyze the results and to conduct mediated MR analysis.Results:Analysis showed that DBP was positively correlated with HRDRF(OR=1.0002,95%CI:1.0001–1.0003,P=1.8076e-05)and DBP was positively correlated with HF(OR=1.0295,95%CI:1.0221–1.0370,P=2.5292e-15).HF and HRDRF had a positive causal effect(OR=1.0001,95%CI:1.0000–1.0001,P=0.0152).Mediation analysis showed that the contribution ratio of HF to the combined effect of DBP and HRDRF was 24.69%.Conclusions:DBP can increase the risk of renal disease with renal failure,and HF may play an impor tant role in mediating this causal relationship.

Comparative Analysis of Budesonide Treatments on Blood Gas and Inflammation in Chronic Obstructive Pulmonary Disease Remission

Objective:To investigate the effects of budesonide on blood gas and inflammation indexes in patients with chronic obstructive pulmonary disease(COPD)during remission.Methods:Fifty-one patients with COPD in remission,admitted to Zhongshan Hospital of Dalian University from July 2021 to December 2022,were selected and divided into two groups based on a randomized numerical table method.The control group(25 cases)received budesonide formoterol treatment,while the observation group(26 cases)received budesonide geforce treatment.Various indexes,including clinical efficacy,blood gas indexes,inflammation indexes,St.George’s Respiratory Questionnaire(SGRQ)scores,Chronic Obstructive Pulmonary Disease Assessment Test(CAT)scores,and 6-minute Walking Distance Test(6MWD)results,were compared between the two groups.Results:After 21 days of treatment,the total clinical effectiveness rate of the observation group was higher than that of the control group,with a statistically significant difference(P<0.05).Post-treatment,the PaO2 level and pH value in both groups were higher,and the PaCO_(2) level was lower compared to pre-treatment levels.The observation group showed better improvements in these indicators than the control group,with statistically significant differences(P<0.05).SGRQ and CAT scores for both groups were lower post-treatment,with the observation group scoring lower than the control group.Additionally,the 6MWD results were farther for both groups post-treatment,with the observation group achieving greater distances than the control group,with statistically significant differences(P<0.05).Conclusion:Budesonide can effectively improve blood gas indexes in patients with COPD in remission,alleviate related clinical symptoms,reduce inflammatory responses,and promote patient recovery.The treatment efficacy is significant.

MicroRNAs in blood and cerebrospinal fluid as diagnostic biomarkers of multiple sclerosis and to monitor disease progression

Multiple sclerosis is a chronic autoimmune disease of the central nervous system.It is the main cause of non-traumatic neurological disability in young adults.Multiple sclerosis mostly affects people aged 20–50 years;however,it can occur in young children and much older adults.Factors identified in the distribution of MS include age,gender,genetics,environment,and ethnic background.Multiple sclerosis is usually associated with progressive degrees of disability.The disease involves demyelination of axons of the central nervous system and causes brain and spinal cord neuronal loss and atrophy.Diagnosing multiple sclerosis is based on a patient’s medical history including symptoms,physical examination,and various tests such as magnetic resonance imaging,cerebrospinal fluid and blood tests,and electrophysiology.The disease course of multiple sclerosis is not well correlated with the biomarkers presently used in clinical practice.Blood-derived biomarkers that can detect and distinguish the different phenotypes in multiple sclerosis may be advantageous in personalized treatment with disease-modifying drugs and to predict response to treatment.The studies reviewed have shown that the expression levels of a large number of miRNAs in peripheral blood,serum,exosomes isolated from serum,and cerebrospinal fluid are altered in multiple sclerosis and can distinguish the disease phenotypes from each other.Further studies are warranted to independently validate these findings so that individual or pairs of miRNAs in serum or cerebrospinal fluid can be used as potential diagnostic markers for adult and pediatric multiple sclerosis and for monitoring disease progression and response to therapy.

Gastric emptying, postprandial blood pressure, glycaemia and splanchnic flow in Parkinson's disease

AIM: To determine gastric emptying, blood pressure, mesenteric artery blood flow, and blood glucose responses to oral glucose in Parkinson’s disease.METHODS: Twenty-one subjects (13 M, 8 F; age 64.2 ± 1.6 years) with mild to moderate Parkinson’s disease (Hoehn and Yahr score 1.4 ± 0.1, duration of known disease 6.3 ± 0.9 years) consumed a 75 g glucose drink, labelled with 20 MBq 99mTc-calcium phytate. Gastric emptying was quantified with scintigraphy, blood pressure and heart rate with an automated device, superior mesenteric artery blood flow by Doppler ultrasonography and blood glucose by glucometer for 180 min. Autonomic nerve function was evaluated with cardiovascular reflex tests and upper gastrointestinal symptoms by questionnaire.RESULTS: The mean gastric half-emptying time was 106 ± 9.1 min, gastric emptying was abnormally delayed in 3 subjects (14%). Systolic and diastolic blood pressure fell (P < 0.001) and mesenteric blood flow and blood glucose (P < 0.001 for both) increased, following the drink. Three subjects (14%) had definite autonomic neuropathy and 8 (38%) had postprandial hypotension. There were no significant relationships between changes in blood pressure, heart rate or mesenteric artery blood flow with gastric emptying. Gastric emptying was related to the score for autonomic nerve function (R = 0.55, P < 0.01). There was an inverse relationship between the blood glucose at t = 30 min (R = -0.52, P < 0.05), while the blood glucose at t = 180 min was related directly (R = 0.49, P < 0.05), with gastric emptying.CONCLUSION: In mild to moderate Parkinson’s disease, gastric emptying is related to autonomic dysfunction and a determinant of the glycaemic response to oral glucose.

Emotion processing in Parkinson's disease: a blood oxygenation level-dependent functional magnetic resonance imaging study

Parkinson's disease is a neurodegenerative disorder caused by loss of dopamine neurons in the substantia nigra pars compacta. Tremor, rigidity, and bradykinesia are the major symptoms of the disease. These motor impairments are often accompanied by affective and emotional dysfunctions which have been largely studied over the last decade. The aim of this study was to investigate emotional processing organization in the brain of patients with Parkinson's disease and to explore whether there are differences between recognition of different types of emotions in Parkinson's disease. We examined 18 patients with Parkinson's disease(8 men, 10 women) with no history of neurological or psychiatric comorbidities. All these patients underwent identical brain blood oxygenation level-dependent functional magnetic resonance imaging for emotion evaluation. Blood oxygenation level-dependent functional magnetic resonance imaging results revealed that the occipito-temporal cortices, insula, orbitofrontal cortex, basal ganglia, and parietal cortex which are involved in emotion processing, were activated during the functional control. Additionally, positive emotions activate larger volumes of the same anatomical entities than neutral and negative emotions. Results also revealed that Parkinson's disease associated with emotional disorders are increasingly recognized as disabling as classic motor symptoms. These findings help clinical physicians to recognize the emotional dysfunction of patients with Parkinson's disease.

Association of ABO blood groups with the severity of coronary artery disease: a cross-sectional study

Objective To investigate whether ABO blood groups is associated with the severity of coronary artery disease(CAD). Methods Between January 2015 and December 2017, 1425 first diagnosed CAD patients confirmed by selective coronary angiography were recruited into this cross-sectional study, and their baseline characteristics, ABO blood groups, Gensini score were collected. Multiple linear regression analysis was performed to test the association between the severity of CAD and ABO blood groups. Results The Gensini score was significantly higher in the blood group A than in the non-A groups(41.2 ± 32 vs. 38 ± 27;P = 0.026). After adjusting for age, male, smoking, family history of CAD, hypertension, diabetes mellitus and hypercholesterolemia, multivariate linear regression indicated that blood group A was associated with the severity of CAD(β= 3.298, 95% CI: 0.91–6.505, P = 0.044). In diabetes group, A blood type was also associated with increased Gensini score(P = 0.02) after adjusting for age, male, family history of CAD, hypercholesterolemia, smoking and hypertension. Conclusion In this cross-sectional study, the data indicated that blood group A was an independent risk factor of severity of CAD in Chinese population and Chinese patients with type 2 diabetes.

Case report of Graves' disease manifesting with odynophagia and heartburn

Graves' disease is an autoimmune disease, which can manifest with a variety of extrathyroidal clinical syndromes like ophthalmopathy, pretibial myxedema(dermopathy), acropathy, cardiomyopathy, and encephalopathy. Though quite rare, this disease can also manifest with gastrointestinal symptoms such as dysphagia, heartburn, nausea, vomiting and diarrhea. We report a clinical case of Graves' disease manifesting with dysfunction of the esophagus and heartburn in a 61-year-old man. In the muscular layer of the esophagus we found dystrophic changes led to its atony, which was documented by endoscopy and high-resolution manometry. The pathology features of esophageal symptoms were: focal proliferation of the basal cells, vascular distension, and dystrophy of the epithelial cells. Antithyroid treatment led to decrease of all clinical symptoms after 5 d of Thiamazole administration. Complete restoration of peristalsis in the esophagus, according to manometry, was observed in 1 mo after initiation of treatment.

Red blood cell distribution width in elderly hospitalized patients with cardiovascular disease

BACKGROUND Red blood cell distribution width(RDW)is elevated in patients with cardiovascular disease(CVD).AIM To determine RDW values and impact of CV and non-CV coexisting morbidities in elderly patients hospitalized with chronic CVD.METHODS This prospective study included 204 consecutive elderly patients(age 77.5[7.41]years,female 94[46%],left ventricular ejection fraction 53.00%[37.50,55.00])hospitalized with chronic CVD at the Cardiology Department of Larissa University General Hospital(Larissa,Greece)from January 2019 to April 2019.Elderly patients were selected due to the high prevalence of coexisting morbidities in this patient population.Hospitalized patients with acute CVD(acute coronary syndromes,new-onset heart failure[HF],and acute pericarditis/myocarditis),primary isolated valvular heart disease,sepsis,and those with a history of blood transfusions or cancer were excluded.The evaluation of the patients within 24 h from admission included clinical examination,laboratory blood tests,and echocardiography.RESULTS The most common cardiac morbidities were hypertension and coronary artery disease,with acutely decompensated chronic heart failure(ADCHF)and atrial fibrillation(AF)also frequently being present.The most common non-cardiac morbidities were anemia and chronic kidney disease followed by diabetes mellitus,chronic obstructive pulmonary disease,and sleep apnea.RDW was significantly elevated 15.48(2.15);121(59.3%)of patients had RDW>14.5%which represents the upper limit of normal in our institution.Factors associated with RDW in stepwise regression analysis were ADCHF(coefficient:1.406;95%confidence interval[CI]:0.830-1.981;P<0.001),AF(1.192;0.673 to 1.711;P<0.001),and anemia(0.806;0.256 to 1.355;P=0.004).ADCHF was the most significant factor associated with RDW.RDW was on average 1.41 higher for patients with than without ADCHF,1.19 higher for patients with than without AF,and 0.81 higher for patients with than without anemia.When patients were grouped based on the presence or absence of anemia,ADCHF and AF,heart rate was not increased in those with anemia but was significantly increased in those with ADCHF or AF.CONCLUSION RDW was elevated in elderly hospitalized patients with chronic CVD.Factors associated with RDW were anemia and CV factors associated with elevated heart rate(ADCHF,AF),suggesting sympathetic overactivity.

Red blood cell distribution width derivatives in alcohol-related liver cirrhosis and metabolic-associated fatty liver disease

BACKGROUND Looking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring.There are still plenty of unresolved issues related to the actual role of hematological indices as potential markers of liver function.AIM To study red blood cell distribution width(RDW),RDW-to-platelet ratio(RPR)and RDW-to-lymphocyte ratio(RLR) in alcohol-related liver cirrhosis(ALC) and metabolic-associated fatty liver disease(MAFLD).METHODS The study group was composed of 302 people:142 patients with ALC and 92 with MAFLD;68 persons were included as controls.RDW,RPR and RLR were measured in each person.Indirect and direct parameters of liver fibrosis were also assessed [aspartate transaminase to alkaline transaminase ratio,aspartate transaminase to platelet ratio index(APRI),fibrosis-4(FIB-4),gamma-glutamyl transpeptidase to platelet ratio(GPR),procollagen I carboxyterminal propeptide,procollagen Ⅲ aminoterminal propeptide,transforming growth factor-α,plateletderived growth factor AB,laminin].MELD score in ALC patients and nonalcoholic fatty liver disease(NAFLD) fibrosis score together with BARD score were obtained in the MAFLD group.The achieved results were compared to controls.Then a correlation between assessed markers was done.Diagnostic value of each investigated parameter and its suggested cut-off in the research group RESULTS RDW,RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls(ALC:P<0.0001;NAFLD:P<0.05,P<0.0001 and P<0.0001,respectively).RPR correlated positively with MELD score(P<0.01) and indirect indices of liver fibrosis(FIB-4 and GPR;P<0.0001) in ALC patients;negative correlations were found between PDGF-AB and both:RDW and RPR(P<0.01 and P<0.0001,respectively).RPR correlated positively with NAFLD fibrosis score and APRI(P<0.0001) in the MAFLD group;a positive relationship was observed between RDW and FIB-4,too(P<0.05).AUC values and suggested cut-offs for RDW,RPR and RLR in ALC patients were:0.912(>14.2%),0.965(>0.075) and 0.914(>8.684),respectively.AUC values and suggested cut-offs for RDW,RPR and RLR in MAFLD patients were:0.606(>12.8%),0.724(>0.047) and 0.691(>6.25),respectively.CONCLUSION RDW with its derivatives appear to be valuable diagnostic markers in patients with ALC.They can also be associated with a deterioration of liver function in this group.

Effects of SNPs at Newly Identified Lipids Loci on Blood Lipid Levels and Risk of Coronary Heart Disease in Chinese Han Population:A Case Control Study

Associations between ＂lipid-related＂ candidate genes,blood lipid concentrations and coronary artery disease（CHD） risk are not clear.We aimed to investigate the effect of three newly identified lipids loci from genome-wide association studies on CHD and blood lipid levels in Chinese Han population.The genotypes of SNPs at three newly identified lipid loci and blood lipids concentrations were examined in 1360 CHD patients and 1360 age-and sex-frequency matched controls from an unrelated Chinese Han population.Allele T of rs16996148 occurred less frequently in CHD patients with the odds ratio（OR） being 0.64（95% CI 0.50 to 0.81）,after adjusting for conventional risk factors and was associated with a 33% decreased CHD risk（P0.01） comparing with the major allele G.Individuals with GT genotype had the lowest CHD risk.No associations were found between the polymorphisms of other two loci with CHD risk and all three SNPs had no effect on lipid profile in this population.SNP rs16996148 on chromosome 19p13 is significantly associated with lower risk for CHD in Chinese Han population.However,it remains unresolved why these lipid-related loci had significantly less effects than the correspondingly expected effects on blood lipids levels in this population.

Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases

Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBD), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a f ixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient' s tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a "one-by-one" administration schedule. Evidencebased clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABD) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABD in surgical IBD patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within wellconstructed protocols will offer better prospects for blood conservation in selected IBD patients undergoing elective surgery.

Emerging blood exosome-based biomarkers for preclinical and clinical Alzheimer's disease:a meta-analysis and systematic review

Blood exosomes,which are extracellular vesicles secreted by living cells into the circulating blood,are regarded as a relatively noninvasive novel tool for monitoring brain physiology and disease states.An increasing number of blood cargo-loaded exosomes are emerging as potential biomarkers for preclinical and clinical Alzheimer's disease.Therefo re,we conducted a meta-analysis and systematic review of molecular biomarkers derived from blood exosomes to comprehensively analyze their diagnostic performance in preclinical Alzheimer's disease,mild cognitive impairment,and Alzheimer's disease.We performed a literature search in PubMed,Web of Science,Embase,and Cochrane Library from their inception to August 15,2020.The research subjects mainly included Alzheimer's disease,mild cognitive impairment,and preclinical Alzheimer's disease.We identified 34 observational studies,of which 15 were included in the quantitative analysis(Newcastle-Ottawa Scale score 5.87 points)and 19 were used in the qualitative analysis.The meta-analysis results showed that core biomarkers including Aβ_(1-42),P-T181-tau,P-S396-tau,and T-tau were increased in blood neuro nderived exosomes of preclinical Alzheimer's disease,mild cognitive impairment,and Alzheimer's disease patients.M olecules related to additional risk facto rs that are involved in neuroinflammation(C1q),metabolism disorder(P-S312-IRS-1),neurotrophic deficiency(HGF),vascular injury(VEGF-D),and autophagy-lysosomal system dysfunction(cathepsin D)were also increased.At the gene level,the differential expression of transc ription-related factors(REST)and microRNAs(miR-132)also affects RNA splicing,transport,and translation.These pathological changes contribute to neural loss and synaptic dysfunction.The data confirm that the above-mentioned core molecules and additional ris k-related factors in blood exosomes can serve as candidate biomarkers for preclinical and clinical Alzheimer's disease.These findings support further development of exosome biomarkers for a clinical blood test for Alzheimer's disease.This meta-analysis was registered at the International Prospective Register of Systematic Reviews(Registration No.CRD4200173498,28/04/2020).

TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

AIM:To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea,to investigate the association of TTV and HGV infections with blood transfusion,and to assess the correlation between TTV and HGV viremia and hepatic damage. METHODS:A total of 391 serum samples were examined in this study.Samples were obtained from healthy blood donors(n=110),hepatitis B surface antigen(HBsAg)-positive donors(n=112),anti-hepatitis C virus(anti-HCV)-positive donors(n=69),patients with type B chronic liver disease (n=81),and patients with type C chronic liver disease(n=19). Trv DNA was detected using the hemi-nested PCR.HGV RNA was tested using RT-PCR.A history of blood transfusion and serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were also determined. RESULTS:TTV DNA was detected in 8.2%of healthy blood donors,16.1%of HBsAg-positive donors,20.3%of anti- HCV-positive donors,21.0%of patients with type B chronic liver disease,and 21.1%of patients with type C chronic liver disease.HGV RNA was detected in 1.8%of healthy blood donors,1.8%of HBsAg-positive donors,17.4%of anti-HCV-positive donors,13.6%of patients with type B chronic liver disease,and 10.5%of patients with type C chronic liver disease.The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors(P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors.There was a history of transfusion in 66.7%of TTV DNA-positive patients and 76.9%of HGV RNA-positive patients(P<0.05).No significant increase in serum ALT and AST was detected in the TTV or HGV-positive donors and patients. CONCLUSION:TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors.However,there is no significant association between TTV or HGV infections and liver injury.

Empirical Studies of Effects of High Blood Pressure on Medical Costs and Heart Disease: Is the 2017 ACC/AHA Guideline Supported by Enough Evidence?

Background: The American College of Cardiology (ACC), American Heart Association (AHA) and other organizations announced a new hypertension guideline in November 2017. However, previous studies have pointed out that this new guideline might lack sufficient evidence to justify its use. Data and Methods: The effects of blood pressure (BP) on medical costs and on the probability of having heart disease as anamnesis are analyzed. We used a dataset containing 175,123 medical checkups and 6,312,125 receipts from 88,211 individuals obtained from three health insurance societies from April 2013 to March 2016. The dataset was divided into subgroups based on whether the patients had diabetes and took hypertension medications. The power transformation and probit models were used in the study. Results: We observed negative effects of systolic BP (SBP) on medical costs in most subgroups. We could not find evidence that higher SBP made the medical costs and probability of having heart diseases higher. The results raise uncertainty about the reliability of the new guideline, at least for SBP. Conclusion: The results of this study did not support the new 2017 ACC/AHA guideline, at least for SBP. The new guideline must be more carefully reevaluated by additional studies. Limitations: The dataset was observatory, the sample period was only 3 years, and we could not complete a time-series analysis of individuals.

Cerebrospinal fluid and blood biomarkers in Alzheimer’s disease

Due to an ever aging society and growing prevalence of Alzheimer’s disease(AD),the challenge to meet social and health care system needs will become increasingly difficult.Unfortunately,a definite ante mortem diagnosis is not possible.Thus,an early diagnosis and identification of AD patients is critical for promising,early pharmacological interventions as well as addressing health care needs.The most advanced and most reliable markers areβ-amyloid,total tau and phosphorylated tau in cerebrospinal fluid(CSF).In blood,no single biomarker has been identified despite an intense search over the last decade.The most promising approaches consist of a combination of several bloodbased markers increasing the reliability,sensitivity and specificity of the AD diagnosis.However,contradictory data make standardized testing methods in longitudinal and multi-center studies extremely difficult.In this review,we summarize a range of the most promising CSF and blood biomarkers for diagnosing AD.

Young blood products:emerging treatment for Alzheimer's disease?

Alzheimer＇s disease is the most common neurodegenerative disorder and no disease-modifying treatment is currently available.Research has shown that while brain neurogenesis continues in adult life,it declines with age.Using parabiosis,plasma transfusions and direct administration of neural growth factors,animal studies have demonstrated the positive impact of exposure to young blood products on neurogenesis and synaptic plasticity in an aging brain.The hippocampus and the sub-ventricular zones were identified as the main regions affected.Promising findings have prompted researchers to experiment their effects in subjects with an established neurocognitive disorder,such as Alzheimer＇s disease.They argued that modification of brain vasculature,reactivation of adult neural stem cells,and remodeling of their synaptic activity/plasticity may lead to cognitive enhancement and increased neurogenesis.One pilot human study found that young donor plasma infusion protocols for adults with Alzheimer＇s disease were safe and feasible;however,no statistically significant improvements in cognition were detected.There is a need to conduct additional placebo-controlled human studies in larger samples.Future studies should focus on identifying an “optimal age” at which an intervention in humans may yield significant cognitive enhancement,as well as determining the types of transfusions with the best efficacy and tolerability profiles.