OBJECTIVETo explore the prevalence and clinicopathological features of aortic aneurysm (AA) in elderly inpatients at autopsy.

METHODSAll the AA cases were retrospectively analyzed in 909 autopsy cases aged 60-100 years in our hospital. The pathological changes, comorbidities and death reasons were evaluated.

RESULTSAA was diagnosed pathologically in 59 patients (6.5%), clinical diagnosis was not made in 37(62.7%) cases. The AA prevalence in patients aged ≥ 80 years was significantly higher than patients <80 years (10.2% vs. 2.9%, χ(2)=19.97, P<0.01). Abdominal AA was more common (91.5%) and the prevalence of multiple AA was 20.3%. Coronary artery disease (CAD) was diagnosed in 44 AA patients (74.6%) including 21(35.6%) with severe coronary artery stenosis and 7(11.9%) with three-vessel disease, 31 patients (52.5%) died of cardiac-cerebral diseases, including 7(11.9%) with ruptured AA.

CONCLUSIONSThe prevalence of AA was high in elderly inpatients aged ≥80 years with a relatively high missed diagnosis rate. AA was often complicated with CAD. The main cause of death of AA patients was cardiac-cerebral diseases. The screening, evaluation and treatment of AA should be enhanced in elderly patients, especially in patients aged 80 years and over.

Aged ; Aged, 80 and over ; Aortic Aneurysm ; Aortic Rupture ; Autopsy ; Coronary Artery Disease ; Coronary Stenosis ; Humans ; Inpatients ; Middle Aged ; Prevalence ; Retrospective Studies

Objective: To analyze the pathological feathers of the heart in elderly (60-99 years old) heart failure patients with preserved ejection fraction (HFpEF) and coronary artery disease (CAD) and to explore the misdiagnosis and missed diagnosis rates. Method: This retrospective study included 154 HFpEF (left ventricular ejection fraction (LVEF)≥50%) cases and 49 heart failure with reduced ejection fraction (HFrEF) (LVEF≤40%) cases aged 60-99 years old out of 1 485 consecutive autopsy cases. Pathological changes of the heart and coronary artery were compared between patients with HFpEF and HFrEF. The misdiagnosis and missed diagnosis rates of HFpEF were analyzed based on pathological examination. Results: Patients with HFpEF were older than those with HFrEF ((85.7±7.4) vs. (82.9±7.8) years old, P=0.017). Among all the cases, CAD was diagnosed in 105 (68.2%) HFpEF patients and 38 (77.6%) HFrEF patients. Compared with patients with HFrEF, HFpEF patients displayed less acute myocardial infarction (12.3%(19/154) vs. 59.2%(29/49), P<0.01) and more chronic myocardial ischemia (18.2%(28/154) vs. 6.1%(3/49), P=0.041). 51.9% (80/154) HFpEF and 71.4% (35/49) HFrEF patients (P=0.017) displayed >50% left anterior descending artery stenosis. Prevalence of >75% coronary arterial stenosis (51% (25/49) vs. 20.1%(31/154), P<0.001) and more than one vessel lesions (55.1%(27/49) vs. 33.8%(52/154), P=0.008) were significantly higher in HFrEF patients than in HFpEF patients. The misdiagnosis rate of CAD in HFpEF was 63.3% (31/49). Among HFpEF, the missed diagnosis rate of acute myocardial infarction was 57.9% (11/19) and the missed diagnosis rate of old myocardial infarction was 57.7% (45/78). Conclusions CAD and chronic myocardial ischemia are common in elderly patients with HFpEF. Chronic myocardial ischemia may play an important role in the development of HFpEF of elderly CAD patients. Among HFpEF patients, the misdiagnosis rate of CAD and missed diagnosis rate of myocardial infarction are high, so the accurate evaluation of myocardial ischemia status is of great importance.

Objective: To determine the frequency and extent of left ventricular amyloid deposition in patients aged over 85 years with heart failure and preserved ejection fraction (HFpEF). Methods: A total of 43 patients aged 85 to 100 years old were enrolled in this study based on the autopsy database of Beijing Hospital from February 1, 2003 to October 31, 2016. The frequency and extent of left ventricular amyloid deposition and myocardial fibrosis were determined in left ventricular specimens from patients with antemortem diagnosis of HFpEF without clinically apparent amyloid (n=28) and from control subjects (n=15) post Congo red staining and Masson's trichrome staining. Kappa test was used to evaluate the consistency of the myocardial amyloidosis and fibrosis. Results: The heart weight of the patients in HFpEF group and in control group were similar((452.7±107.7)g vs. (415.0±70.8)g, t=-1.218, P=0.23)). Positive Congo-red staining was found in 24 examples (24/28) in HFpEF group and 5 examples (5/15) in the control group; severe amyloid deposition was found in 7 examples (7/28) in HFpEF group, but not in the control group. Amyloid deposition was more severe in HFpEF group than in control group (χ²=12.205, P<0.01). Masson's trichrome staining evidenced moderate to severe fibrosis in 19 cases (19/28) in HFpEF group and 8 cases (8/15) in control group (χ²=1.019, P=0.35). A consistent evaluation of the degree of myocardial fibrosis and the degree of myocardial amyloid deposition in all selected participants was performed and results showed that these two parameters were not consistent (Kappa value=0.2, P=0.820). Conclusion Amyloid deposition is common in the elderly patients with heart failure and preserved ejection fraction, suggesting that myocardial amyloidosis may be related to the development of HFpEF. There is no significant correlation between myocardial amyloidosis and myocardial fibrosis in this cohort.

Lissencephaly(LIS)is a group of abnormal cerebral cortical dysplasias caused by the defective migration of neurons and it is characterized by thickening of the cerebral cortex, widening of the gyri and disappearance or shallowness of the sulci.Clinically, the patients often have manifestations such as epilepsy, mental retardation, and developmental delay.At present, there is no specific treatment and most patients have poor prognosis.There is currently no specific treatment, and most patients have a poor prognosis.Recently, with the widespreading clinical application of genetic testing, many disease-causing genes related to the lissencephaly have been discovered, so it is important for us to study its pathogenesis and the mode of inheritance.In this study, we reviewed the recent literature on genes associated with lissencephaly.

Tic disorders(TD), a complex chronic neuropsychiatric disorder characterized by rapid, involuntary, non rhythmic, single or multiple muscle movements or vocal twitches, usually occurs in children aged from 2 to 15 years.TD has various clinical manifestations, which are usually related to various psychopathology or behavioral comorbidities, including attention deficit hyperactivity disorder, anxiety, depression and obsessive-compulsive disorder.The etiology and pathogenesis of TD are still not completely clear.Immune, genetic, neurobiochemical and environmental factors are generally recognized as factors related to the pathogenesis of TD.In recent years, the research on TD and genetic factors has gradually increased, but so far there is no clear conclusion on the pathogenic genes of TD.This paper only discusses the genes related to TD.

Objective: To analyze the cardiac pathological features of elderly coronary artery disease (CAD) patients (60 years and over) and evaluate the pathological features at autopsy and risk factors of patients with acute myocardial infarction (AMI). Methods: Data from 471 elderly patients (aged from 60 to 100 years old) with CAD confirmed by autopsy hospitalized in our hospital from April 1969 to October 2013 were retrospectively reviewed. Patients were divided into 2 groups: AMI group(n=128) with AMI as the primary cause of death and the rest served as control group(n=343). The pathological features of coronary lesion and related risk factors of AMI were analyzed. Results: In patients aged 60 and over with CAD, 48.8%(230/471) had severe coronary stenosis, 18.7%(88/471) had three-vessel disease, 71.8% cases (338/471) had left anterior descending artery(LAD)grade Ⅲ and over stenosis, 29.9% (141/471) had LAD grade Ⅳ stenosis, 25.9%(122/471) had left main coronary artery(LM) grade Ⅲ and over stenosis, 9.6%(45/471) had LM grade Ⅳ stenosis, 27.1%(128/471) had AMI. The first AMI accounts for 39.1%(50/128), and 60.9%(78/128) had both AMI and old MI. Compared with the control group, AMI group were younger ((77.1±11.6) years vs. (83.2±9.1) years, P<0.01), had more severe coronary artery stenosis lesion (77.3%(99/128) vs. 38.2%(131/343), P<0.01), higher coronary index which reflects the overall arteriosclerosis (9.9±2.8 vs. 8.0±2.5, P<0.01), more three-vessel disease (30.3%(43/128) vs. 13.7%(45/343), P<0.01), heavier heart weight ((447.8±90.6)g vs. (426.6±99.1)g, P<0.05), higher prevlence of pulmonary congestion or edema (57.8%(74/128) vs. 39.9%(137/343), P<0.01). Twenty-three cardiac ruptures (23/128, 18.0%) were observed in AMI group. Logistic regression analysis showed that grade Ⅳ LAD stenosis (OR=3.55, 95%CI 2.05-6.17, P<0.01), three-vessel disease(OR=2.47, 95%CI 1.30-4.67, P<0.01) were the independent risk factors of AMI in elderly patients with CAD. Conclusions Severe coronary stenosis is common in CAD patients aged 60 and over. Patients aged 60 and over with AMI have more severe coronary artery stenosis lesion and heavier heart weight. Cardiac rupture is not uncommon in elderly patients with AMI. Severe LAD stenosis and three-vessel disease are the independent risk factors of AMI in the elderly.

Objective To characterize autopsy pathological changes of the coronary artery and left ventricular myocardium in elderly patients with moderate to severe calcified aortic stenosis,and to analyze the causes of death.Methods Seventeen cases of moderate to severe calcified aortic stenosis were identified from an autopsy database of Beijing Hospital containing 909 elderly patients(aged from 60-100 years)collected from April 1,1969 to October 31,2013.All cases were confirmed by autopsy and were analyzed retrospectively.The characteristics of coronary artery lesions,myocardial pathological changes and causes of death were summarized.Results Aortic stenosis was detected in 1.1％(2/190),1.9％(5/266),3.7％(11/297)and 6.4％(10/156)of patients in the 60-69,70-79,80-89 and 90-100 age groups,increasingly prevalent with age(x2=10.08,P=0.018).In addition,seventeencases were confirmed to have moderate to severe calcified aortic stenosis.Of these cases,13 (76.5％) had coronary artery disease and 5 (29.4 ％)had severe coronary stenosis.The left anterior descending (LAD) artery was most commonly involved(47.0 ％).No thrombus was found in the coronary arteries,and only one had chronic total occlusion(5.9 ％).Myocardial infarction was confirmed in all 13 patients with coronary artery disease,including six cases(35.3％)of AMI,11 cases(64.7 ％)of OMI and four cases (23.5 ％)of AMI and OMI.Among AMI cases,transmural infarction was shown only in one case,with two cases of non-transmural infarction,two cases of subendocardial infarction and one case of focal myocardial infarction.Among OMI cases,transmural infarction was shown in one case,with two cases of non-transmural infarction,four cases of subendocardial infarction and four cases of focal myocardial infarction.The clinical misdiagnosis rate of OMI was as high as 81.8％.Patients died mainly from cardiovascular disease(70.6 ％),with six cases (35.3 ％) from myocardial infarction,three from heart failure(17.6％) and three from malignant arrhythmia (17.6 ％).Six of the cases suffered from sudden cardiac death(35.3％)with biopsy-confirmed myocardial infarction changes.Conclusions The incidence of CAD in elderly patients with calcific aortic stenosis is high.Pathological changes of myocardial infarction,especially of subendocardial and focal infarction,occur in patients with moderate to severe aortic stenosis and coronary heart disease with a high clinical misdiagnosis rate.Aortic stenosis implicates both the valve and myocardium.Assessment of myocardial lesions in patients with calcific aortic stenosis should be carefully conducted in clinical practice.

Objective: To analyze the clinical and pathological characteristics of heart failure with preserved ejection fraction(HFpEF)in advanced elderly patients. Methods: Systematic anatomical data from pathology database of Beijing Hospital from April 1969 to October 2013 were retrospectively analyzed.The 154 HFpEF patients aged(85.7±7.4)years with left ventricular ejection fractions(LVEF)≥50%, and 49 patients aged(82.8±7.8)years who had heart failure with reduced LVEF ≤40%(HFrEF)were included.Clinical feature and pathological changes of heart and other organs were compared between patients with HFpEF and HFrEF, and between groups aged less 80 years versus over 80 years in HFpEF patients. Results: The parameters were higher in HFpEF group versus in HFrEF group as follows: the average age of patients(85.7±7.4 vs.82.8±7.8 years, P=0.017), hypertension(80.5% or 124 cases vs.26.5% or 13 cases, P<0.001), diabetes mellitus(58.4% or 90 vs.20.4% or 10 cases, P<0.001), atrial fibrillation(65.6% or 101 cases vs.12.2% or 6 cases, P<0.001)and chronic obstructive pulmonary disease(COPD)(26.6% or 41 cases vs.4.1% or 2 cases, P=0.001). As compared with HFpEF patients aged 61-85 years group, the same HFpEF patients aged 86-99 years group had significantly increased proportion of atrial fibrillation(P=0.046), of COPD(P=0.002), of senile degenerative heart valvular disease(P=0.009), of chronic myocardial ischemia(P=0.027), of mini-focal old myocardial infarction(P=0.041)and of emphysema(P=0.005). Conclusions The proportion of patients with HFpEF increases along with ageing.Atrial fibrillation and COPD are common geriatric co-morbidities in the elderly especially advanced elderly HFpEF patients.The patients are prone to complicated with atrial fibrillation and COPD, and often have chronic myocardial ischemia.Therefore, we should pay attention to the influences of the above diseases on elderly patients with HFpEF.

Objective: To observe the etiology, comorbidities, clinical features and treatment patterns of hospitalized patients with heart failure (HF) in China. Methods: Data were collected prospectively on hospitalized patients with HF who were enrolled in China Heart Failure Center Registry Study from 169 participating hospitals from January 2017 to August 2018. In this cross-sectional study, patients were stratified by left ventricular ejection fraction (LVEF) category: heart failure with reduced ejection fraction (HFrEF, LVEF<40%); heart failure with mid-ranged ejection fraction (HFmrEF, 40%≤LVEF<50%) and heart failure with preserved ejection fraction (HFpEF, LVEF≥50%). The clinical data were collected, including demographic information, diagnosis, signs, electrocardiogram, echocardiography, laboratory tests, and treatment. Results: A total of 31 356 hospitalized patients with HF were included, 19 072 (60.8%) were males and the average age was (67.9±13.6) years old. The common causes of HF were hypertension (57.2%), coronary heart disease (54.6%), dilated cardiomyopathy (14.7%), valvular heart disease (9.2%). The common complications were atrial fibrillation/atrial flutter (34.1%), diabetes (29.2%), and anemia (26.7%). 32.8% of patients had a history of hospitalization for HF within the previous 12 months. There were 11 034 (35.2%) patients with HFrEF, 6 825 (21.8%) patients with HFmrEF and 13 497 (43.0%) patients with HFpEF. Compared with patients with HFpEF, patients with HFrEF had a lower systolic blood pressure ((124.7±21.1)mmHg(1 mmHg=0.133 kPa) vs. (134.9±22.9)mmHg), faster heart rate ((85±19) beats/minutes vs. (81±19)beats/minutes), and higher percentage of New York Heart Association (NYHA) class Ⅳ, smoking, alcohol, left bundle branch block, and QRS time≥130 ms, and higher levels of blood uric acid, BNP, and NT-proBNP (all P<0.05). Compared with patients with HFmrEF and HFrEF, patients with HFpEF were older, more women, and higher comorbidity burden including hypertension, atrial fibrillation/atrial flutter, anemia and chronic obstructive pulmonary disease (all P<0.05). HFmrEF took a mid-position between HFrEF and HFpEF in age, gender, heart rate, systolic blood pressure, hypertension, atrial fibrillation/atrial flutter, anemia, and chronic obstructive pulmonary disease (all P<0.05). Patients with HFmrEF had the highest proportion of coronary heart disease, myocardial infarction and percutaneous coronary intervention (all P<0.05). During hospitalization, loop diuretics were used in 90.2% of patients, and intravenous inotropics were used in 20.4% of patients. The use of ACEI/ARB/ARNI, β blockers and aldosterone receptor antagonists at discharge were 71.8%, 79.1% and 83.6% in HFrEF and 69.9%, 75.5% and 72.4% in HFmrEF, respectively. The use of digoxin at discharge was 25.3% (HFrEF 36.7%, HFmrEF 23.1%, HFpEF 17.0%). The rates of cardiac resynchronization therapy and implantable cardioverter defibrillator in HFrEF were 2.7% and 2.1%. Conclusions Among the hospitalized patients with HF in China, coronary heart disease and hypertension are the mostly prevalent causes. HFpEF accounts for a large proportion of hospitalized patients with HF. HFrEF, HFmrEF and HFpEF have different etiology and clinical features. In real-world, there are still large gaps in the effective application of the guideline recommended therapies to HF patients, especially the non-pharmacological therapy option, which needs to be improved further in China.

Chinese hamster ovary (CHO) cells are the preferred host cells for the production of complex recombinant therapeutic proteins. Adenine phosphoribosyltransferase (APRT) is a key enzyme in the purine biosynthesis step that catalyzes the condensation of adenine with phosphoribosylate to form adenosine phosphate AMP. In this study, the gene editing technique was used to knock out the aprt gene in CHO cells. Subsequently, the biological properties of APRT-KO CHO cell lines were investigated. A control vector expressed an enhanced green fluorescent protein (EGFP) and an attenuation vector (containing an aprt-attenuated expression cassette and EGFP) were constructed and transfected into APRT-deficient and wild-type CHO cells, respectively. The stable transfected cell pools were subcultured for 60 generations and the mean fluorescence intensity of EGFP in the recombinant CHO cells was detected by flow cytometry to analyze the EGFP expression stability. PCR amplification and sequencing showed that the aprt gene in CHO cell was successfully knocked out. The obtained APRT-deficient CHO cell line had no significant difference from the wild-type CHO cells in terms of cell morphology, growth, proliferation, and doubling time. The transient expression results indicated that compared with the wild-type CHO cells, the expression of EGFP in the APRT-deficient CHO cells transfected with the control vector and the attenuation vector increased by 42%±6% and 56%±9%, respectively. Especially, the EGFP expression levels in APRT-deficient cells transfected with the attenuation vector were significantly higher than those in wild-type CHO cells (P < 0.05). The findings suggest that the APRT-deficient CHO cell line can significantly improve the long-term expression stability of recombinant proteins. This may provide an effective cell engineering strategy for establishing an efficient and stable CHO cell expression system.
Adenine/metabolism* ; Adenine Nucleotides ; Adenine Phosphoribosyltransferase/genetics* ; Adenosine Monophosphate ; Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Recombinant Proteins/genetics*