Heparin-binding protein (HBP) is a kind of granule protein produced by neutrophils in response to external stimuli. It plays a crucial role in increasing vascular permeability, chemotaxis, and regulating inflammatory response In recent years, studies have found that HBP can be used as an early predictor of sepsis. In addition, it has been confirmed that HBP can be used to evaluate the disease severity and prognosis in sepsis patients. This review focuses on the clinical value of HBP in sepsis.

Objective:To evaluate the value of plasma heparin binding protein (HBP) in the early diagnosis of sepsis, and to explore the application value of HBP for the severity and prognosis assessment of sepsis.Methods:A prospective observational study was conducted in Department of Critical Care Medicine of Northern Jiangsu People's Hospital. One hundred and ninety-eight patients with confirmed infections from June 2019 to June 2021 were enrolled in this study. According to the illness severity of sepsis, patients were assigned as non-sepsis (n=48), sepsis (n=52) and septic shock (n=98). Forty patients in the same period without infection were selected as control group. The differences in HBP, procalcitonin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and lactate (Lac) levels were compared and analyzed. The prognostic values on sepsis diagnosis and 28-day mortality were evaluated through drawing receiver operating characteristic (ROC) curve. Logistic regression analysis was used to clarify the factors affecting the prognosis of sepsis.Results:The plasma level of HBP was obviously elevated in septic shock group than patients in other three groups (P＜0.05), while patients in sepsis group had higher HBP than patients in non-sepsis group (P＜0.05). Take an optimal cutoff value of 35.8 ng/ml, the area under the curve (AUC) for HBP to distinguish sepsis from from non-sepsis was 0.922. The levels of HBP and Lac were also significantly elevated in non-survivors compared to survival group (P＜0.05). Ho sever, no significant differences of PCT, CRP and WBC levels were found between the two groups. Plasma HBP＞97.6 ng/ml was associated with elevated mortality, AUC of HBP predicting 28-day mortality of sepsis patients was 0.750, with a sensitivity of 65.5% and a specificity of 77.7%. The plasma HBP levels in death group were higher than those in survival group at 0 h, 24 h, 48 h and 72 h after admission (P＜0.05). Meanwhile, in death group, the plasma HBP level showed no statistical differences in each time point compared with that in the previous time point (P＞0.05).Conclusion:HBP can be a better and more specific early predictor of sepsis compared with PCT, CRP, WBC and Lactate. Meanwhile, the level and tendency of HBP has valuable to evaluate the severity of sepsis and mortality.

英国剑桥大学制定的 Addenbrooke认知评估量表（ Addenbrooke cognitive ex?amination， ACE）［1］在认知功能领域的研究成果已在国外相关文献报道。 ACE量表吸纳了简易智能状态检查量表（ mini?mental state examination， MMSE）［2］的优点，而Mioshi等［3］在2006年将ACE量表修正为 Addenbrooke 改良认知评估量表（ Addenbrooke cognitive examination?revised， ACE?R），使其准确性以及心理学特性更高。目前ACE?R量表已被翻译成超过20余种语言版本［4］，我国也逐渐引进这一筛查工具。本文重点介绍了ACE?R量表的特点、内容以及国内外的使用情况和研究进展。

Objective To assess the validity and reliability of COG-12 in Alzheimer's disease (AD) patients .Methods One hundred and forty-eight AD patients served as an AD group and 365 vol-unteers served as a control group in this study .Patients in two groups were assessed according to the AD8 ,CDR ,MMSE ,CDT and COG-12 ,respectively .Of the 148 AD patients ,100 were reas-sessed according to the COG-12 .Results T he Cronbach alpha coefficient and retested intraclass correlation coefficient for COG-12 were 0 .883 and 0 .883 ,respectively (P<0 .01) .The correlation coefficient for each COG-12 item score and total COG-12 score was 0 .41 -0 .79 (P< 0.05 ,P<0.01) .The total COG-12 score was negatively correlated with the MMSE and CDT ,and positively correlated with the total CDR and AD8 score (r= -0 .67 ,r= -0 .27 ,P<0 .01 ;r=0 .80 ,r=0.81 , P<0 .01) .The area under the ROC curve was 0 .902 when those with normal recognition and mild AD patients were identified according to the COG-12 with a sensitivity of 90 .0% and a specificity of 82 .5% when its cutoff was ≥6 .The area under the ROC curve was 0 .898 when the mild and moderate AD patients were identified according to the COG-12 with a sensitivity of 90.5% and a specificity of 76 .7% .Conclusion COG-12 ,with a good validity and reliability ,is a sensitive and accurate tool for the rapid screen of dementia and assessment of its severity .

Objective To explore the clinical and neuroimaging features of behavioral variant of frontotemporal dementia (bvFFD).Methods Thirty-eight patients with bvFTD compared with 22Alzheimer's disease (AD) patients were retrospectively evaluated by clinical and neuroimaging features from January 2007 to September 2013.The Addenbrooke's Cognitive Examination-revised (ACE-R),Frontal Behavioral Inventory (FBI),and Frontal Assessment Battery (FAB)were applied for cognitive and behavioral performances together with MRI.Results (1) The most common symptoms of bvFTD were followed by executive deficits,behavioral disinhibition,apathy,loss of sympathy,memory decline,hyperorality and compulsive behaviour.The misdiagnosis rate was high (31/38).(2) The age of bvFTD group was younger than AD group,but there were no significant differences in education,sex ratio and the duration of symptoms between two groups.And there were significant differences in the scores of ACE-R(38.0 ± 19.8 vs 25.7 ±15.9,t=2.472,P ＜0.05),FBI (30.9 ± 10.0 vs 17.8 ±7.6,t =5.313,P ＜0.01),FAB(8.0 ±3.1 vs 9.7 ±2.6,t =-2.127,P ＜0.05) between two groups.The optimal FBI cut-off score of 24.5 gave 76.3％sensitivity and 95.5％ specificity in distinguishing bvFTD from AD patients.(3) MRI studies of bvFTD patients revealed symmetrical or asymmetrical atrophy of the frontal and/or temporal lobes.The pattern of atrophy varies significantly.The atrophy of hippocampus was showed in 8 cases of bvFTD patients.Conclusions The early symptoms of bvFTD patients are complex,and easily misdiagnosed.Onset symptoms are mostly behavioral disinhibition,executive deficits,combination of behavioral and cognitive scales promotes early diagnosis.MRI studies show that bvFTD presents with a combination of anterior frontal and temporal cortical atrophy.

Idiopathic Parkinson's disease (PD) and progressive supranuclear palsy (PSP) are neurological movement disorders with various patterns of cognitive impairment. Parkinson's disease, a progressive neurodegenerative disease, is typically characterized with defective motor features, such as bradykinesia, tremor, rigidity and postural instability. Among the clinical symptoms, cognitive impairment, which is ranging from mild cognitive impairment (PD-MCI)to PD dementia (PDD), is highly relevant in PD, and an early dementia is often poorly diagnosed and treated. A 5-year follow-up study shows that 20 patients with early assessment of PD-MCI at an earlier assessment had converted to PD dementia and 50% of the remaining patients without dementia developed MCI. It has been previously demonstrated that 24 to 31% of PD patients have dementia, and PDD results in 3 to 4% of the dementia in the population. Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder, which is associated with a higher degree of disability and shorter survival than PD. PSP patients typically have deficits in parkinsonism, exhibiting early postural instability, falls, supranuclear gaze palsy, pseudobulbar symptoms and personality alterations. For PSP, the median time from symptom onset to a correct diagnosis is 3 to 4 years, so PSP can be easily misdiagnosed of PD. Similar to PD, cognitive impairment is common in PSP.The main obstacle of differential diagnosis of PD and PSP is attributable to the indistinct symptom, especially in the early stages of disease. Some tests have been employed in differential diagnosis between PSP and PD. For example, b rain imaging have been proposed to identify biomarker, and s ome investigators have proposed clinical progression of PSP and PD, such as motor ability. However, although cognitive tests have been suggested to differentiate between these two disorders, very limited numbers of studies have been performed to investigate the longitudinal change in cognition with PD and PSP. Thus, there is a necessity to develop a more accurate and objective approach for this unmet diagnostic requirement. The Addenbrooke's Cognitive Examination-Revised (ACE-R) is a brief cognitive assessment that can be useful for detecting subtypes of dementia including Alzheimer's disease, subcortical ischemic vascular dementia, frontotemporal dementia and other parkinsonian symptom s. It incorporates the widely used Mini-Mental State Examination (MMSE), expanding on memory, language and visuospatial components, with addition of a verbal fluency section. As a screening tool for dementia, it has high reliability and validity. Of note, greater sensitivity for diagnosing dementia than MMSE makes it easy to operate.In this study, we exploited the ACE-R for evaluating the differential diagnosis of patients with PD and PSP. The aims of the current prospective study were as follows: 1) to investigate the influence of demographic data on total scores of ACE-R and MMSE; 2) to test whether the ACE-R total, the ACE-R subscores or MMSE is useful in distinguishing between PD and PSP; 3) to determine the most accurate ACE-R cutoff value in this study. By comparing the outcome of differentially diagnosing PD and PSP, we found that ACE-R represented an objective approach that reveals the distinction between these two symptoms with the highest sensitivity. ACE-R maximum score is 100 points, containing 5 sub-scores: attention/orientation (18 points), memory (26 points), fluency (14 points), language (26 points) and visuospatial (16 points). Each one represents one cognitive domain. The ACE-R may take between 12 and 20 minutes to score and administer in a clinical setting.All participants were examined in the Department of Neurology at Nanjing Brain Hospital, affiliated to Nanjing Medical University, China, during the study period from January 2013 to July 2013, consisting of three groups: a PD group (n=33), a PSP group (n=13) and a Control group (n=17). The patients in PD group ful fi lled Queen Square Brain Bank criteria and contemporary clinical diagnosis for PSP were made according to consensus criteria. All participant s who communicated verbally could speak with reasonable vision and hearing ability. In this study, patients who had a history of schizophrenia, major depression, significant head injury, substance abuse or alcoholism would be excluded. All participants gave informed consent for participation in the study. We used the Addenbrooke's Cognitive Examination-revised (ACE-R) for cognitive testing and motor function was assessed with section III of the Unified Parkinson's Disease Rating Scale (UPDRS).All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) 11 for Windows, and a P value of 0.05 was considered statistically significant. For comparisons of continuous variables (age, years of education, total and subscores of ACE-R and score of MMSE) among groups, one-way analysis of variance (ANOVA) was used depending on the homogeneity of variance. Receiver operating characteristic (ROC) analysis was performed for ACE-R, MMSE and subscores of ACE-R by comparing their AUCs. Specificity and sensitivity were calculated. We compared the demographic data, MMSE, UPDRS III, ACE-R total and subscores within the three groups, as shown in Table 1. There were no significant differences in age, the years of education and UPDRS III among groups. One-way analysis of variance showed that there were significant differences among the three groups (Control, PD and PSP) in ACE-R total, Verbal fluency subscore, Language subscore and Visuospatial subscore (P<0.001). However, there were no significant differences in Attention & Orientation subtest, Memory subtest and MMSE between PD and PSP groups. In order to compare the ROC curve for ACE-R total scores with MMSE scores, we calculated these parameters for PD and PSP groups. As demonstrated by Figure 1, the ROC curve demonstrated the superiority of the ACE-R (AUC=0.784, P=0.003) over the MMSE (AUC=0.456, P=0.643) in identifying patients with PD and PSP in our sample. There was a significant difference for ACE-R in differential diagnosis of these two parkinsonian disorders. By contrast, this difference was not statistically significant for MMSE. The optimal ACE-R cutoff score for diagnosing PD from PSP was ≤ 67.0, which yielded a sensitivity of 0.606 and specificity of 0.923 in Table 2. Since no significant differences were displayed in Attention & Orientation subscore and Memory subscore in Table 1, we performed ROC curve analysis (Figure 2) to distinguish PD from PSP using ACE-R subscores except these two subtests above. Best differentiation was seen in the other three subtests (p<0.005), which demonstrated that Verbal fluency subscore of ACE-R (AUC = 0.866) was higher than Language subscore (AUC=0.822) and Visuospatial subscore(AUC=0.836) for classifying patients with PD, and these three subscores were more effective than the ACE-R total score(AUC=0.784) shown in Figure 1. Sensitivity and specificity which changed with varying cutoff scores of the ACE-R total, Verbal fluency subscore, Language subscore and Visuospatial subscore were then compared (Table 2). The optimal cutoff was determined as the score where Youden's index was maximized. With regard to Verbal fluency subscore, the optimal cutoff score to distinguish PD and PSP was <5.5, giving a sensitivity of 0.727 and a specificity of 0.923. For Language cutoff score, optimal cutoff was at 18.5, with showing good sensitivity (0.667) and specificity (0.846). At the optimal cutoff score of 9.5, Visuospatial subscore had high sensitivity (0.636) and specificity (0.923) to differentiate PD from PSP. Therefore, we concluded that these three subscores (Verbal fluency, Language and Visuospatial) of ACE-R were more effective in the differential diagnosis of PD and PSP. This study demonstrates that ACE-R has a high diagnostic accuracy in the differential diagnosis of patients with progressive supranuclear palsy and Parkinson's disease. In Table 1, our study accords with the finding that age and the year of education are not significant factors among these three groups. Admittedly, compared with health, MMSE total yields equally sufficient assessment in measuring cognition for people with PD or PSP, as compared the ACE-R. Of importance, ACE-R was markedly superior to the MMSE in identifying PD from PSP (P=0.328). ROC curves also show that ACE-R had comparable performance (AUC = 0.784, P =0.003) to differentiate PD from PSP, in contrast to MMSE (AUC=0.456, P=0.643). Giving that ACE-R needs to be taken a longer time than MMSE to administer, MMSE can be favored as a brief diagnostic cognitive test in people with PD/PSP to health. Nevertheless, in need of greater precision, the ACE-R is likely to hold clinical value. As previously demonstrated by Law E et al, some patients with PD who are below the ACE-R cutoff score in our study still have MMSE scores within the normal range (Figure 3). The AUC of the ACE-R in this study is low, compared with the findings in the study by Rittman T et al. This may be due to the relatively narrow difference of data collection and confidence intervals estimation in the study. Compared with the other instruments which were screened for the differential diagnosis of PD and PSP, ACE-R do not require specialized equipment or personnel and the procedure is relatively brief. It provides comprehensive coverage of neuropsychological function and can be used in numerous neurological conditions. It can be useful in assessment with elusive diagnosis. For PD-MCI, PDD and cognitive impairment of PSP, the ACE-R may offer an effective tool that could assess cognitive function. In conclusion, the ACE-R and the three subscores of the ACE-R are useful methods in supporting the differential diagnosis of PD and PSP. Importantly, ACE-R deficits are significant in terms of their effect on assessing patients' behavior and quality of life. ROC curve for ACE-R and MMSE in distinguishing between PD and PSP. Comparison of the area under the ROC curves for Verbal fluency, Language and Visuospatial subscores. ACE-R and MMSE scores for three groups with PD, PSP and control.

目的 初步探讨认知障碍简明评价表(cognitive-12 scale,Cog-12)在筛查慢性肾衰竭(chronic renalfailure,CRF)患者认知功能障碍中的应用价值.方法 招募南京地区四所三甲医院肾内科门诊及住院治疗的临床确诊的CRF患者共171例,按认知障碍诊断标准分为认知功能正常组、轻度认知功能障碍组(MCI)及痴呆组.采用Cog-12量表通过询问照料者对患者进行测评,采用Addenbrooke改良认知评估量表(Addenbrookecognitive examination revised,ACE-R)对各组患者进行神经心理评估,分析Cog-12量表、简易智能筛查量表(mini-mental state of examination,MMSE)与ACE-R结果的相关性.结果 (1)CRF患者Cog-12量表评分与ACE-R评分呈显著负相关(r=-0.909),且相关程度显著优于MMSE(r=0.847).(2)Cog-12对于CRF患者MCI的识别能力明显优于AD8(AUCCog-12=0.834;AUCAD8=0.802),在界值设定为5/6时,Cog-12量表对MCI的筛查效果最佳(敏感度0.769、特异度0.650、约登指数0.419).结论 Cog-12量表可有效检测CRF患者的认知功能损伤,同时易于发现早期轻度的认知功能损伤,可用于临床CRF患者认知功能的筛查.

Objective:To investigate the application of the Addenbrooke's cognitive examination-revised(ACE-R) to the assessment of global cognition in Parkinson's disease(PD). Methods:Twenty-four PD patients were included. Their cognitive functions were assessed according to the ACE-R scales. Results:Compared with 11 cases of abnormal MMSE scores and 13 cases of normal MMSE scores in 24 cases of PD patients,the age was significantly different in 2 groups with MMSE(P < 0.05),but the duration of symptoms,Hoehn-Yahr stage and UPDRS-motor were not significantly different. Compared with 14 cases of abnormal ACE-R scores and 10 cases of normal ACE-R scores in 24 cases of PD patients,the duration of symptoms,Hoehn-Yahr stage and UPDRS-motor were significantly different in 2 groups with ACE-R(P < 0.05),but the age was not significantly different. The scores of five cognitive subdomains in ACE-R(attention and concentration,memory,verbal fluency,language and visuospatial) in 2 groups with ACE-R were significantly different(P < 0.005). Conclusion:The ACE-R has higher sensitivity than the MMSE for cognitive assessment in PD patients. The ACE-R is more suitable than the MMSE as a cognitive screening tool for PD patients.