Intestinal glucagon-like peptide-1:A new regulator of impaired counterregulatory responses to hypoglycemia in type 1 diabetes mellitus

In this article,we review the study by Jin et al,which examined the role of intestinal glucagon-like peptide-1(GLP-1)in counterregulatory responses to hypoglycemia in patients with type 1 diabetes mellitus(T1DM).With the global rise of T1DM,there is an increased burden on society and healthcare systems.Due to insulin therapy and islet dysfunction,T1DM patients are highly vulnerable to severe hypoglycemia,a leading cause of mortality.In healthy individuals,counterregulatory mechanisms restore blood glucose during hypoglycemia,but repeated episodes impair these responses.Jin et al demonstrated that overexpression of GLP-1 attenuates the sympathetic-adrenal reflex and disrupts the secretion of counterregulatory hormones such as glucagon during hypoglycemia,leading to counterregulatory dysfunction.These findings highlight the critical role of GLP-1 in the impaired counterregulatory response to hypoglycemia in T1DM patients and provide new insights into the potential application of GLP-1-related therapies in T1DM patients.

Nitrate reduction capacity of the oral microbiota is impaired in periodontitis:potential implications for systemic nitric oxide availability

The reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with periodontal health, but the impact of periodontitis on nitrate-reducing capacity(NRC)and, therefore, nitric oxide availability has not been evaluated. The current study aimed to evaluate how periodontitis affects the NRC of the oral microbiota. First, 16S rRNA sequencing data from five different countries were analyzed, revealing that nitratereducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals(P < 0.05 in all five datasets with n = 20–82 samples per dataset). Secondly, subgingival plaque, saliva, and plasma samples were obtained from 42 periodontitis patients before and after periodontal treatment. The oral NRC was determined in vitro by incubating saliva with 8 mmol/L nitrate(a concentration found in saliva after nitrate-rich vegetable intake) and compared with the NRC of 15healthy individuals. Salivary NRC was found to be diminished in periodontal patients before treatment(P < 0.05) but recovered to healthy levels 90 days post-treatment. Additionally, the subgingival levels of nitrate-reducing bacteria increased after treatment and correlated negatively with periodontitis-associated bacteria(P < 0.01). No significant effect of periodontal treatment on the baseline saliva and plasma nitrate and nitrite levels was found, indicating that differences in the NRC may only be revealed after nitrate intake. Our results suggest that an impaired NRC in periodontitis could limit dietary nitrate-derived nitric oxide levels, and the effect on systemic health should be explored in future studies.

Intestinal glucagon-like peptide-1:A new player associated with impaired counterregulatory responses to hypoglycaemia in type 1 diabetic mice

BACKGROUND Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic reactions.However,the pathogenesis of hypoglycaemic counterregulation is still unclear.Glucagon-like peptide-1(GLP-1)and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus(T1DM).The role of GLP-1 in counterregulatory dysfunction during hypoglycaemia in patients with T1DM has not been reported.AIM To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic mice.METHODS T1DM was induced in C57BL/6J mice using streptozotocin,followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia(DH5).Immunofluorescence,Western blot,and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon(GCG)secretion.The GLP-1 receptor agonist GLP-1(7-36)or the antagonist exendin(9-39)were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model mice.RESULTS The expression levels of intestinal GLP-1 and its receptor(GLP-1R)were significantly increased in DH5 mice.Consecutive instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex,leading to dysfunction of adrenal counterregulation during hypoglycaemia.DH5 mice showed increased pancreaticδ-cell mass,cAMP levels inδcells,and plasma somatostatin concentrations,while cAMP levels in pancreaticαcells and plasma GCG levels decreased.Furthermore,GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 group.Further experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstrated that intestinal GLP-1 during recurrent hypoglycaemia hindered the secretion of the counterregulatory hormone GCG via the endocrine pathway.CONCLUSION Excessive intestinal GLP-1 is strongly associated with impaired counterregulatory responses to hypoglycaemia,leading to reduced appetite and compromised secretion of adrenaline,noradrenaline,and GCG during hypoglycaemia.

METTL7A-mediated m6A modification of corin reverses bisphosphonates-impaired osteogenic differentiation of orofacial BMSCs

Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders.However,the role of corin in BRONJ-related BMSCs dysfunction remains unclarified.A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation.Corin knockdown inhibits BMSCs osteogenic differentiation,whereas corin overexpression or soluble corin(sCorin)exerts a promotion effect.Furthermore,corin expression is negatively regulated by bisphosphonates(BPs).Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability.Mechanistically,we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation.PD98059(a selective ERK inhibitor)blocks the corin-mediated promotion effect.With regard to the high methylation level of corin during osteogenic differentiation,we apply a non-selective m6A methylase inhibitor,Cycloleucine,which also blocks the corin-mediated promotion effect.Furthermore,we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function,indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability.To conclude,our study reveals that corin reverses BPs-induced BMSCs dysfunction,and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway.We hope this brings new insights into future clinical treatments for BRONJ.

Ambulatory Radio Iodine Therapy in the Management of Hyperthyroidism in Africa: African Systematic Review and Perspectives in Burkina Faso

Introduction: In hyperthyroidism, selective irradiation of the thyroid gland with radioactive iodine is a radical treatment and an alternative to surgery. The aim of this review is to assess the medium-term efficacy of outpatient treatment of hyperthyroidism with iodine-131 in Africa. Methods: We identified the studies carried out in Africa on outpatient radiation therapy between 2016 and 2020. For each article included, we noted the country concerned and the year of publication, the numbers studied, the socio-demographic characteristics of the patients, the indications for radio iodine therapy, the dose administered, the results of the hormonal dosage 6 months after radiation. Results: 13 retrospective studies were included to constitute a total population of 925 patients. The average age was 40.77 years, the sex ratio of 1/5.4 with a clear female predominance. The 3 main etiologies of hyperthyroidism justifying outpatient radio iodine therapy were Graves’ disease (55.89%), toxic multinodular goiter (22.70%) and toxic adenoma (21.40%). The average dose of iodine 131 administered per course is 13.7 mCi. No short-and medium-term complications were reported. The radio iodine therapy was effective in 86.08% (n = 796) of the patients with extremes of 72% and 100%. Conclusion: Radio iodine therapy is effective in Africa. It is simple, inexpensive on an outpatient basis and well tolerated. The introduction of outpatient radio iodine therapy could improve the management of patients with hyperthyroidism in Burkina Faso.

Lithium carbonate-induced giant goiter and subclinical hyperthyroidism in a patient with schizophrenia:A case report and review of literature

BACKGROUND Lithium carbonate is used to manage various mood disorders,but it can cause thyroid abnormalities,including goiter,hypothyroidism,and hyperthyroidism.In rare cases,it can lead to giant goiter and subclinical hyperthyroidism,which may require surgical intervention in severe cases.CASE SUMMARY This case represents a rare development of giant goiter and subclinical hyperthyroidism in a schizophrenia patient who was subjected to prolonged lithium carbonate treatment.The enlarged thyroid gland caused pressure on the airway and recurrent laryngeal nerve,which led to respiratory distress,hoarseness,and dysphagia.The immediate danger of suffocation required urgent surgical intervention.In this report,we describe the case of a 41-year-old Chinese woman.This sheds light on the etiology and challenges associated with managing a giant goiter.The patient underwent a subtotal thyroidectomy to relieve airway compression and facilitate airway expansion.Prior to the procedure,the patient was given iodine to prepare.Concurrently,changes were made to the psychiatric medication regimen.Following surgery,the patient's respiratory function and vocal cord functionality improved significantly,and her mental state remained stable.CONCLUSION It is essential to monitor thyroid function,test thyroid antibody levels,and perform thyroid ultrasounds consistently in all patients undergoing long-term lithium carbonate treatment.This vigilance helps prevent severe and potentially life-threatening thyroid enlargement.

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

Impaired Cognition and Stroke Rehabilitation Outcomes: Are They Related?

Background: Stroke survivors who exhibit impaired cognition at admission to inpatient rehabilitation may experience participation challenges and poorer functional outcomes than those without impaired cognition. Differences in functional outcomes between stroke survivors with and without impaired cognition may be attributed to age, level of cognitive impairment, and severity of stroke. Materials and Methods: A retrospective secondary data analysis was conducted using health-related administrative data acquired from a Southwestern Ontario hospital’s stroke rehabilitation database. The aim was to explore potential linkages between post-stroke impaired cognition and functional gains, rehabilitation stays, and living settings after discharge from rehabilitation. Results: An aggregate sample of 393 males and 314 females subclassified as experiencing mild, moderate, and severe stroke was analyzed. At inpatient rehabilitation admission, 21.5% (n = 152) of these patients had no impaired cognition, 33.7% (n = 238) had mild impaired cognition, 22.2% (n = 157) had moderate impaired cognition, and 22.6% (n = 160) had severe impaired cognition. Cognitively impaired stroke patients were significantly (p 0.001) older, had (mostly) moderate to severe stroke with significantly (p = 0.012) more moderate cognitive impairment, had significantly (p 0.001) longer rehabilitation stays, and a high propensity for being discharged to longer-term care facilities compared to non-cognitively impaired patients. Conclusion: Presence of significant dissimilarity in rehabilitation stays and post-discharge destinations among stroke survivors with and without cognitive impairment is attributed to the age of the patient, level of cognitive impairment, and rigorous rehabilitation interventions.

Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment

Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive impairment.We found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic stroke.In addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic stroke.Serum phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic stroke.Furthermore,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein levels.Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein levels.Taken together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.

Near-infrared brain functional characteristics of mild cognitive impairment with sleep disorders

BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patients with MCI is unclear.AIM To explore the near-infrared brain function characteristics of MCI with sleep disorders.METHODS A total of 120 patients with MCI(MCI group)and 50 healthy subjects(control group)were selected.All subjects underwent the functional near-infrared spec-troscopy test.Collect baseline data,Mini-Mental State Examination,Montreal Cognitive Assessment scale,fatigue severity scale(FSS)score,sleep parameter,and oxyhemoglobin(Oxy-Hb)concentration and peak time of functional near-infrared spectroscopy test during the task period.The relationship between Oxy-RESULTS Compared with the control group,the FSS score of the MCI group was higher(t=11.310),and the scores of Pittsburgh sleep quality index,sleep time,sleep efficiency,nocturnal sleep disturbance,and daytime dysfunction were higher(Z=-10.518,-10.368,-9.035,-10.661,-10.088).Subjective sleep quality and total sleep time scores were lower(Z=-11.592,-9.924).The sleep efficiency of the MCI group was lower,and the awakening frequency,rem sleep latency period,total sleep time,and oxygen desaturation index were higher(t=5.969,5.829,2.887,3.003,5.937).The Oxy-Hb concentration at T0,T1,and T2 in the MCI group was lower(t=14.940,11.280,5.721),and the peak time was higher(t=18.800,13.350,9.827).In MCI patients,the concentration of Oxy-Hb during T0 was negatively correlated with the scores of Pittsburgh sleep quality index,sleep time,total sleep time,and sleep efficiency(r=-0.611,-0.388,-0.563,-0.356).It was positively correlated with sleep efficiency and total sleep time(r=0.754,0.650),and negatively correlated with oxygen desaturation index(r=-0.561)and FSS score(r=-0.526).All comparisons were P<0.05.CONCLUSION Patients with MCI and sleep disorders have lower near-infrared brain function than normal people,which is related to sleep quality.Clinically,a comprehensive assessment of the near-infrared brain function of patients should be carried out to guide targeted treatment and improve curative effect.

The compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease

Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.

Left Ventricular Systolic Intraventricular Flow Field Assessment in Hyperthyroidism Patients Using Vector Flow Mapping

Summary： Intraventricular hydrodynamics is considered an important component of cardiac function assessment. Vector flow mapping （VFM） is a novel flow visualization method to describe cardiac pathophysiological condition. This study examined use of new VFM and flow field for assessment of left ventricular （LV） systolic hemodynamics in patients with simple hyperthyroidism （HT）. Thirty-seven simple HT patients were enrolled as HT group, and 38 gender- and age-matched healthy volunteers as control group. VFM model was used to analyze LV flow field at LV apical long-axis view. The follow- ing flow parameters were measured, including peak systolic velocity （Vs）, peak systolic flow （Fs）, total systolic negative flow （SQ） in LV basal, middle and apical level, velocity gradient from the apex to the aortic valve （AV）, and velocity according to half distance （V1/2）. The velocity vector in the LV cavity, stream line and vortex distribution in the two groups were observed. The results showed that there were no significant differences in the conventional parameters such as left ventricular ejection fraction （LVEF）, left ventricular end-diastolic diameter （LVEDD） and left atrium diameter （LAD） between HT group and control group （P〉0.05）. Compared with the control group, a brighter flow and more vortexes were detected in HT group. Non-uniform distribution occurred in the LV flow field, and the stream lines were discontinuous in HT group. The values of Vs and Fs in three levels, SQ in middle and basal levels, AV and V1/2 were higher in HT group than in control group （P〈0.01）. AV was positively correlated with serum free thyroxin （FT4） （r=0.48, P〈0.01）. Stepwise multiple regression analysis showed that LVEDD, FT4, and body surface area （BSA） were the influence factors of △V. The unstable left ventricular sys- tolic hydrodynamics increased in a compensatory manner in simple PIT patients. The present study in- dicated that VFM may be used for early detection of abnormal ventricle contraction in clinical settings.

Therapeutic plasma exchange and continuous renal replacement therapy for severe hyperthyroidism and multi-organ failure:A case report

BACKGROUND Severe hyperthyroidism is a life-threatening exacerbation of thyrotoxicosis,characterized by high fever and multiorgan failure. The most common medical treatments are administration of antithyroid drugs and radioactive iodine, and thyroidectomy. In some patients, antithyroid therapy is limited due to serious adverse effects or failure to control disease progression. In some extreme cases,such as thyroid storm, conventional therapy alone does not yield effective and rapid improvement before the development of multiorgan failure.CASE SUMMARY This report describes a Chinese patient with severe hyperthyroidism accompanied by multiorgan failure, who was transferred to the medical intensive care unit of our hospital. The patient presented with palpitations, vomiting,diarrhea, and shortness of breath for a week. Laboratory tests showed elevation of thyroid hormones. Hepatic failure occurred with high aminotransferase levels and jaundice. Given her abnormal liver function and medication history, we could not exclude diagnosis of propylthiouracil-induced hepatic failure.Moreover, she also suffered from heart failure. Therapeutic plasma exchange(commonly known as TPE) and continuous renal replacement therapy(commonly known as CRRT) were used as life-saving therapy, which resulted in notable improvement of clinical symptoms and laboratory tests.CONCLUSION Combined TPE and CRRT are safe and effective for patients with hyperthyroidism and multiorgan failure.

Aberrant seed development in Litchi chinensis is associated with the impaired expression of cell wall invertase genes

Cell wall invertase(CWIN)are known to play important roles in seed development.However,most reports to date have focused on a single gene family member,and have mainly investigated CWIN functions during the filling stage of seed development.In this study,we found significant lower levels of CWIN protein and activity associated with seed abortion in the Litchi chinensis cultivar“Nuomici.”We identified five litchi CWIN genes and observed that the expression of LcCWIN5 was limited to the flower tissues and decreased sharply with fruit development.Silencing of LcCWIN5 expression before 28 DAA(cell division stage)resulted in perturbed liquid endosperm development,smaller seeds,and higher seed abortion rate,while silencing after 28 DAA(filling stage)had no effect on seed development.In contrast,LcCWIN2 was mostly expressed in the funicle and seed coat,and increased with fruit development.Decreased LcCWIN2 expression and CWIN activity during early seed filling coincided with smaller seeds in the cultivar“Feizixiao.”Silencing of LcCWIN2 caused a reduction in the seed size without inducing seed abortion.We propose that CWIN activity in seed maternal tissues during cell division stage is likely due to LcCWIN5 expression,which regulates early seed development.On the other hand,CWIN activity during the filling stage is due to the expression of LcCWIN2,which may promote carbon import by creating a sucrose gradient.Comparable LcCWIN5 expression,but much lower CWIN activity,detected in the funicle of“Nuomici”is consistent with post-translational regulation.

Effects of Impaired Glucose Metabolism on Heart Rate Variability and Blood Pessure Variability in Essential Hpertensive Patients

To investigate the effects of impaired glucose metabolism （IGM） on cardiovascular autonomic nervous systems in essential hypertensive （EH） patients by comparing heart rate variability （HRV） and blood pressure variability （BPV） in EH patients with or without type 2 diabetes mellitus （T2DM）. Simultaneous 24-h recordings of ambulatory ECG and blood pressure monitoring were performed in 36 male old patients with simple EH and 33 male old patients with EH combined with T2DM. HRV analysis included time domain parameters such as SDNN, SDANN, SDNNi, rMSSD and pNN50, and total spectral power （TP） of HRV, which mainly consists of VLF, LF and HF component along with LF/HF ratio, was also obtained. The value of ambulatory blood pressure was represented as the mean blood pressure （mean systolic/mSBP, diastolic/mDBP and pulse pressure/mPP） during different periods （24 h/24 h, day time/d and night time/n）. Standard deviation （SD） as well as coefficient of variance （CV） of blood pressure during each above-mentioned period were obtained to reflect the long-term BPV. Our result showed that SDNN, SDNNi, SDANN, rMSSD, PNN50, TP and HF of HRV in cases of EH with T2DM were all significantly lower than those in simple EH subjects （P〈0.05）. No significant differences in VLF or LF was found between the two groups （P〉0.05）, while LF/HF ratio was significantly higher in EH with T2DM patients than in simple EH subjects （P〈0.01）. Moreover, dmSBP, 24 h-mPP and dmPP were all significantly higher in EH with T2DM patients than in simple EH subjects （P〈0.05）, while nmSBP, 24 h-mSBP, 24 h-mDBP, dmDBP, nmDBP or nmPP showed no significant difference between this two groups of patients （P〉0.05）. And dSBPSD, dSBPCV and 24 h-SBPSD were all significantly higher in EH with T2DM patients than in simple EH subjects （P〈0.05）, while the other BPV indexes showed no significant difference between this two groups （P〉0.05）. It is concluded that the cardiovascular autonomic nervous systems in EH patients was further impaired by T2DM, displaying lowering of HRV and enlargement of BPV, which in turn induced abnormal structural and functional changes of cardiovascular systems. Therefore, improving cardiovascular autonomic nervous systems might reduce the occurrence of cardiovascular complications in the EH patients with IGM.

APOE4 expression is associated with impaired autophagy and mitophagy in astrocytes

Among the risk factors for late onset sporadic Alzheimer's disease(AD)is the expression ofε4 allele of apolipoprotein E(APOE4)gene(Mahley et al.,2006).Elevated amyloid processing and reduced degradation of Aβ,which lead to Ap plaque deposition,are evident in APOE4-positive AD patients and mice(Mahley et al.,2006).These features correlate with neuronal cell loss.Impaired mitochondrial activity and increased oxidative stress have long been recognized as additional hallmarks of AD pathology(Mahley et al.,2006).The effect of APOE4 expression on autophagy and mitochondrial dynamics and activity in astrocytes is discussed in this perspective and is summarized in Figure 1.

Serum uric acid as an index of impaired renal function in congestive heart failure

Background Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid （UA） metabolism. This study was to assess their potential relations to UA metabolism in heart failure. Methods We retrospectively assessed clinical charac- teristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure （n = 553）. By clustering of indices, those variables were explored using factor analysis. Results In factor analysis, serum uric acid （SUA） formed part of a principal cluster of renal functional variables which included serum creatinine （SCr） and blood urea nitrogen （BUN）. Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN （r = 0.48, P 〈 0.001） and SCr （r = 0.47, P 〈 0.001）. Conclusions There was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.

Development of Nursing Protocol for Preventing Interruptions during Clinical Examinations and Treatments in the Early Days of Hospitalization for Acute Exacerbation of Chronic Heart Failure in Patients with Impaired Cognitive Function

The purpose of this study is to prepare a nursing protocol for preventing interruptions during clinical examinations and treatments performed in the early days of hospitalization for acute exacerbation of chronic heart failure in patients with impaired cognitive function. For the first stage of the research, we prepared a draft of the nursing protocol based on a basic survey. For the second stage, semi-structured interviews were conducted with 5 nurses specialized in chronic heart failure and 11 nurses in dementia care to ensure content validity of the draft protocol. For the third stage, we examined the possibility of clinical application of the revised version of the protocol draft prepared in the second stage of the study. For assessment items, significant points of nursing care, and specific nursing care practice in this revised version, 73 subjects (84.9%) considered effective for patients, in terms of prevention of interruptions during clinical examinations and treatments in the early days of hospitalization. All items and contents were considered useful by more than 60% of the nurses. Considering that the nurses working in the clinical setting reported 84.9% of usefulness, we concluded that this nursing protocol remained valid at a certain level. We consider that this nursing protocol will be useful especially for newly graduated/employed nurses as a procedure manual which can reduce their anxiety or stress caused by lack of knowledge or experiences.

Development of Nursing Protocol for Preventing Discontinuation of Treatments by Methods Other than Physical Restraint during Acute Exacerbation of Chronic Heart Failure in Patients with Impaired Cognitive Function

The purpose of this study is to prepare a nursing protocol for preventing discontinuation of treatments using a method other than physical restraint during acute exacerbation of chronic heart failure in patients with impaired cognitive function. For the first stage of the study, we prepared a draft of the nursing protocol based on a basic survey. For the second stage, semi-structured interviews were conducted with 5 nurses specialized in chronic heart failure and 10 nurses in dementia case to ensure content validity of the draft protocol. For the third stage, we examined the possibility of clinical application of the revised version of the protocol draft prepared in the second stage of the study. For assessment items, significant points of nursing care, and specific nursing care practice in this revised version, 154 subjects (93.9%) considered effective for patients, in terms of prevention of treatment discontinuation using a method other than physical restraint. All items and contents were considered useful by more than 60% of the nurses. Considering that the nurses working in the clinical setting reported 93.9% of usefulness, we concluded that this nursing protocol remained valid at a certain level. We also received a comment from the certified nurses that we should include the basic contents for newly graduated nurses. We consider that this nursing protocol will be also useful for newly graduated nurses to acquire knowledge. It helped to standardize nursing care in order to predict potential risks for patients with impaired cognitive function.

PREVALENCE OF IMPAIRED GLUCOSE REGULATION IN THE POPULATION OF TIANJIN

Objective To investigate the prevalence of impaired glucose regulation （IGR） in the population of Tianjin. Methods A cross-sectional study was conducted in Tianjin from June to September in 2005. The multi-phasic stratified cluster sampling method was adopted. Totally, 21454 people were selected as survey sample. Information on risk factors was collected through face-to-face questionnaire interview. Fasting capillary whole blood glucose level and other clinical indexes were tested. Results The prevalence of impaired fasting glucose （IFG） in the population was 5.61% （5.32% in male, 5.89% in female）. The prevalence of impaired glucose tolerance （IGT） was 2.91% （2.59% in male, 3.20% in female） in whole population, and the prevalence of female was significantly higher than that of male （P = 0.04）. The prevalences of IFG and IGT increased with the increasing of age. And the prevalences were also influenced by the profession, educational level, and income level. Conclusion The prevalences oflGT and IFG in Tianjin are similar to those in the other big cities of China.