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.

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.

Targeting Epac2 and GluA3-containing AMPARs:a novel therapeutic strategy for Alzheimer's disease

Alzheimer's disease(AD)is a neurodegenerative disease that manifests progressive decline in memory and cognition.In the early stage of AD,memory retrieval is impaired preceding memory acquisition and consolidation(Roy et al.,2016).Prior to the onset of symptoms,pathological amyloid-β(Aβ)plagues and tau protein tangles accumulate in extracellular and intracellular spaces,respectively,leading to neurodegeneration.Among these hallmark pathologies,Aβ is proposed to be the primary etiology by triggering a cascade of pathogenic events,including neuroinflammation,oxidative stress,tau hyperphosphorylation,synaptic/neuronal dysfunction,and neuronal death(Zhang et al.,2023b).

Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological thresholds.Mild hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate intake.Severe hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left untreated.Individuals with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

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.

Small heat shock protein B8:from cell functions to its involvement in diseases and potential therapeutic applications

Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and migration.HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.In line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation.In cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation.Moreover,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar hemorrhage.Of note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases.This is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its modulation.Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.

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.

Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.

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.

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.

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.

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.

Anti-BCMA CAR-T Cell Therapy in Relapsed or Refractory Multiple Myeloma Patients with Impaired Renal Function

Anti-B cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T-cell therapyis effective and well-tolerated for refractory or relapsed multiple myeloma(RRMM).The purposcof the present study was to analyze efficacy in RRMM patients with renal impairment treated byanti-BCMA CAR-T cell therapy.A total of 59 RRMM patients were selected,and divided intoimpaired renal function(lRF)group[basclinc cstimated giomerular filtration rate(eSFR)<90 m/min/1.73 m^2(n=18)]and normal renal function(NRF)group(baseline eGFR≥90 mL/min/1.73 m,n=41).For patients with IRF,eGFR at the 6th month post-CAR-T cells infusion was significantlyhigher than the baseline(P<0.05).The multivariate analysis showed that light chain type and beta-2 micro-globulin(bcta-2M)were associated factors with the decrease of serum creatinine.Medianprogression-free survival(PFS)in the NRF group and IRF group was 266 days and 181 daysrespectively.Overall survival(OS)in the NRF group and lRF group was 877 days and 238 daysrespectively.There was no significant difference in the objective response rate(ORR)between thelRF group and the NRF group.It is suggested that CAR-T cells therapy could improve the renalfunction during the treatment of RRMM.The renal function could be more significantly improvedin RRMM patients with light chain type than with other types.

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.

Impaired consciousness caused by injury of the lower ascending reticular activating system: evaluation by diffusion tensor tractography

A 34-year-old male patient underwent conservative management for traumatic hemorrhage in the right frontal lobe（Figure 1A）.The patient lost consciousness for approximately 4 weeks and experienced post-traumatic amnesia continuously from the time of the accident.The patient’s Glasgow Coma Scale score（Teasdale et al.,1974）was 6

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.