Objective To investigate the correlation between serum levels of prostaglandin-endoperoxide synthase 2(PTGS2),chitinase-3-like protein 1(CHI3L1)and cognitive impairment caused by cerebrovascular disease.Methods From October 2020 to October 2022,96 inpatients with cerebrovascular diseases admitted to the Third People's Hospital of Chengdu were regarded as the study subjects.The basic clinical data of the patients were recorded,the serum levels of PTGS2 and CHI3L1 were detected by enzyme-linked immunosorbent assay,and these patients were grouped into normal group(n=60)and impaired group(n=36)based on the presence or absence of cognitive impairment.The correlation between serum PTGS2 and CHI3L1 levels and fasting blood glucose(FBG)and homocysteine(Hcy)was analyzed by Pearson method.Logistic regression model was used to determine whether serum PTGS2 and CHI3L1 were independent risk factors for predicting cognitive impairment.Receiver operating characteristic(ROC)curve was drawn,and the predictive value of CHI3L1 and serum PTGS2 expression level in cognitive impairment in patients with cerebrovascular disease was analyzed according to the area under the curve(AUC).Results Compared with the normal group,the levels of serum PTGS2(29.30±9.46 pg/ml vs 17.86±5.40 pg/ml)and CHI3L1(13.04±4.06 pg/ml vs 7.51±2.66 pg/ml)in the disorder group were increased,and the differences were statistically significant(t=7.553,8.065,all P＜0.05).Multivariate Logistic regression analysis showed that FBG(OR=3.612,95%CI:2.324～5.614),Hcy(OR=2.584,95%CI:1.351～4.944),PTGS2(OR=1.964,95%CI:1.194～3.231)and CHI3L1(OR= 1.556,95%CI:1.023～2.367)were independent risk factors of cognitive impairment(all P＜0.05).PTGS2 was positively correlated with FBG and Hcy(r=0.368,0.551,all P＜0.05),and CHI3L1 was positively correlated with FBG and Hcy(r=0.510,0.376,all P＜0.05).The ROC curve showed that the area under curve(AUC)of PTGS2 and CHI3L1 in predicting cognitive impairment was 0.819 and 0.829,respectively.The AUC of the combined prediction of cognitive impairment was 0.902,which was obviously higher than that of the independent prediction of the two(Z =2.089,2.293;P=0.037,0.021),with sensitivity and specificity of 77.78%and 98.33%,respectively.Conclusion PTGS2 and CHI3L1 were highly expressed in the serum of patients with cognitive impairment of cerebrovascular disease,indicating that both were related to cognitive impairment of patients with cerebrovascular disease.

Objective: To observe the effect of lipid regulating therapy on carotid atherosclerotic plaque in diabetic patients. Methods: The REACH study, conducted between March 2009 and February 2012, enrolled asymptomatic patients with magnetic resonance imaging (MRI) confirmed carotid atherosclerotic plaque, who had never taken lipid-lowering drugs. Patients were treated with a moderate dose of rosuvastatin for 24 months. Blood lipid levels were measured and carotid MRI was performed at baseline, 3 and 24 months after treatment. The volume of carotid wall and lipid-rich necrotic core (LRNC) were measured by image analysis software. This study retrospectively analyzed patients in the REACH study. Patients were divided into diabetes group and non-diabetic group. The changes of blood lipid level and MRI parameters of carotid atherosclerotic plaque were compared between the two groups and their correlation was analyzed. Results: A total of 38 patients with carotid atherosclerotic plaque were included in this study, including 13 patients (34.2%) in the diabetic group and 25 patients (65.8%) in the non-diabetic group. Baseline parameters were comparable between the two groups, except higher HbA1c level in diabetes group (P<0.05). Compared with baseline, the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels were significantly decreased at 3 and 24 months in both two groups (P<0.05). The change of high-density lipoprotein cholesterol (HDL-C) in diabetes group was not obvious, while it was significantly increased in non-diabetic group at 24 months ((1.38±0.33) mmol/l vs. (1.26±0.26) mmol/l, P<0.05). MRI results showed that the volume and percentage of LRNC remained unchanged at 3 months, slightly decreased at 24 months (64.86 (45.37, 134.56) mm³ vs. 75.76 (48.20, 115.64) mm³, P>0.05) and (15.84% (11.47%, 24.85%) vs. 16.95% (11.64%, 22.91%), P>0.05) in diabetic group. In non-diabetic group, the volume and percentage of LRNC were significantly decreased at 3 months (63.01 (44.25, 188.64) mm³ vs. 72.49 (51.91, 199.59) mm³, P<0.05) and (13.76% (8.81%, 27.64%) vs. 16.04% (11.18%, 27.05%), P<0.05) respectively. Both parameters further decreased to (55.63 (27.18, 179.40) mm³) and (12.71% (8.39%, 24.41%)) at 24 months (both P<0.05). Wall volume, lumen volume and percent wall volume (PWV) were not affected post therapy in both two groups(P>0.05). There were no correlations between the changes of plaque parameters including volume and percentage of LRNC, wall volume, lumen volume, PWV and the changes of blood lipid parameters (TC, LDL-C, HDL-C and TG) in 3 and 24 months (P>0.05). Conclusion: Lipid-lowering therapy possesses different effects on carotid atherosclerotic plaque in diabetic and non-diabetic patients, and the LRNC improvement is more significant in non-diabetic patients as compared to diabetic patients.
Carotid Arteries/pathology* ; Carotid Artery Diseases/drug therapy* ; Cholesterol, HDL/therapeutic use* ; Cholesterol, LDL ; Diabetes Mellitus ; Humans ; Magnetic Resonance Imaging/methods* ; Necrosis/pathology* ; Plaque, Atherosclerotic/drug therapy* ; Retrospective Studies ; Rosuvastatin Calcium/therapeutic use*

To explore the composition and diversity of the intestinal microflora of Leopoldamys edwardsi in Hainan Island. In November 2019, DNA was extracted from fecal samples of 25 adult Leopoldamys edwardsi (14 males and 11 females) in Hainan Island at the Joint Laboratory of tropical infectious diseases of Hainan Medical College and Hong Kong University. Based on the IonS5TMXL sequencing platform, single-end sequencing (Single-End) was used to construct a small fragment library for single-end sequencing. Based on Reads shear filtration and OTUs clustering. The species annotation and abundance analysis of OTUs were carried out by using mothur method and SSUrRNA database, and further conducted α diversity and β diversity analysis. A total of 1481842 high quality sequences, belonging to 14 Phyla, 85 families and 186 Genera, were obtained from 25 intestinal excrement samples of Leopoldamys edwardsi. At the level of phyla classification, the main core biota of the Leopoldamys edwardsi contained Firmicutes (46.04%),Bacteroidetes (25.34%), Proteobacteria (17.09%), Tenericutes (7.38%) and Actinobacteria (1.67%), these five phyla account for 97.52% of all phyla. The ratio of Helicobacter which occupied the largest proportion at the genus level was 12.44%, followed by Lactobacillus (11.39%), Clostridium (6.19%),Mycoplasma (4.23%) and Flavonifractor (3.52%). High throughput sequencing analysis showed that the intestinal flora of Leopoldamys edwardsi in Hainan Island was complex and diverse, which had the significance of further research.
Adult ; Animals ; Bacteria/genetics* ; Feces/microbiology* ; Female ; Gastrointestinal Microbiome/genetics* ; High-Throughput Nucleotide Sequencing ; Humans ; Intestines ; Male ; Murinae/genetics*

Sleep exerts important functions in the regulation of cognition and emotion. Recent studies have found that sleep disorder is one of the important risk factors for Alzheimer's disease (AD), but the effects of chronic sleep deprivation on the cognitive functions of AD model mice and its possible mechanism are still unclear. In the present study, 8-month-old male APP/PS1/tau triple transgenic AD model (3xTg-AD) mice and wild type (WT) mice (n = 8 for each group) were subjected to chronic sleep deprivation by using the modified multiple platform method, with 20 h of sleep deprivation each day for 21 days. Then, open field test, elevated plus maze test, sugar water preference test, object recognition test, Y maze test and conditioned fear memory test were performed to evaluate anxiety- and depression-like behaviors, and multiple cognitive functions. In addition, the immunohistochemistry technique was used to observe pathological characteristics in the hippocampus of mice. The results showed that: (1) Chronic sleep deprivation did not affect anxiety- (P = 0.539) and depression-like behaviors (P = 0.874) in 3xTg-AD mice; (2) Chronic sleep deprivation exacerbated the impairments of object recognition memory (P < 0.001), working memory (P = 0.002) and the conditioned fear memory (P = 0.039) in 3xTg-AD mice; (3) Chronic sleep deprivation increased amyloid β (Aβ) deposition (P < 0.001) and microglial activation (P < 0.001) in the hippocampus of 3xTg-AD mice, without inducing abnormal tau phosphorylation and neurofibrillary tangles. These results indicate that chronic sleep deprivation exacerbates the impairments of recognition memory, working memory and conditioned fear memory in 3xTg-AD mice by aggravating Aβ deposition and the excessive activation of microglia in the hippocampus.
Alzheimer Disease ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/genetics* ; Animals ; Cognition ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Presenilin-1 ; Sleep Deprivation ; tau Proteins

Objective: To analysis the clinical characteristics and to summarize therapy experience of pediatric patients with cardiac syncope caused by anomalous origin of the left coronary artery from the right sinus (ALCA-R). Methods: We retrospectively analyzed the clinical data including clinical manifestations, myocardial injury biomarkers, radiological features, treatments and prognoses of pediatric patients with ALCA-R who were admitted to Beijing Children's Hospital from November 2015 to June 2018. Results: Four female patients were included in this analysis, age of onset was 7 to 14 years. All the patients presented with exercise-induced syncope and acute myocardial infarction. During the course, three patients presented with acute left heart failure, and one patient had history of sudden cardiac arrest. Laboratory data showed significant elevation of both the creatine kinase and troponin levels in four patients. All electrocardiogram (ECG) showed left main coronary artery occlusion, echocardiography suggested the possible anomalous origin of the left coronary artery in one child. Coronary CT angiography (CTA) revealed there was no coronary ostium in the left coronary sinus, and the left coronary artery had an anomalous origin from the right sinus. The left main coronary artery passed between the ascending artery and the root of the main pulmonary artery, which was compressed by these two large vessels. Two patients underwent cardiac magnetic resonance examination, which detected late gadolinium enhancement in ALCA-R with an interarterial course. Unroofing of the left coronary ostium (cut-back procedure) was performed in two patients, and the other two patients who were not operated were recommended to restrict their physical activities. During a regular follow-up period of 12-43 months, all the children survived without recurrent cardiovascular event. Conclusion: If an adolescent presents with exercise-induced syncope, acute myocardial infarction and even sudden death, and ECG shows left main coronary artery occlusion characteristics, we should consider the possibility of developmental abnormality of coronary artery, particularly the ALCA-R. Once diagnosed as ALCA-R, patients should be recommended to avoid strenuous activities，early recognition and surgical treatment are imperative for these patients.
Adolescent ; Child ; Contrast Media ; Coronary Angiography ; Coronary Vessel Anomalies ; Female ; Gadolinium ; Humans ; Retrospective Studies ; Syncope

OBJECTIVE: To analyze the clinical features of chronic myeloid leukemia (CML) with T315 I mutation (CML-T315I) and compare the effectiveness of different treatments. METHODS: We retrospectively analyzed the clinical data and outcomes of 19 patients with CML-T315I receiving different treatments. The T315 I mutations in these patients were detected by examination of BCR-ABL kinase domain (KD) mutation by RTQ-PCR and Sanger sequencing. The relapse following the treatments, defined as hematological, cytogenetic and molecular biological recurrences, were analyzed in these patients. RESULTS: Of the 19 patients with CML-T315I, 14 (73.7%) were in CML-CP stage at the initial diagnosis, and 13 (81.2%) were high-risk patients based on the Sokal scores. All the 19 patients were treated with TKI after the initial diagnosis, and during the treatment, 15 (78.9%) patients were found to have additional chromosomal aberrations, and 10 (52.6%) had multiple mutations; 13 (68.4%) of the patients experienced disease progression (accelerated phase/blast crisis) before the detection of T315I mutation, with a median time of 40 months (5-120 months) from the initial diagnosis to the mutation detection. After detection of the mutation, 12 patients were treated with ponatinib and 7 were managed with the conventional chemotherapy regimen, and their overall survival rates at 3 years were 83.3% and 14.2%, respectively ( < 0.001). CONCLUSIONS CML patients resistant to TKI are more likely to have T315I mutations, whose detection rate is significantly higher in the progressive phase than in the chronic phase. These patients often have additional chromosomal aberrations and multiple gene mutations with poor prognoses and a high recurrence rate even after hematopoietic stem cell transplantation. Long-term maintenance therapy with ponatinib may improve the prognosis and prolong the survival time of the patients.
Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; Humans ; Imidazoles ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Mutation ; Pyridazines ; Retrospective Studies

OBJECTIVE: The endothelial glycocalyx (eGC) is a dynamic and multicomponent layer of macromolecules found at the surface of vascular endothelium, which is largely underappreciated. It has recently been recognized that eGC is a major regulator of endothelial function and may have therapeutic value in organ injuries. This study aimed to explore the role of the eGC in various pathologic and physiologic conditions, by reviewing the basic research findings pertaining to the detection of the eGC and its clinical significance. We also explored different pharmacologic agents used to protect and rebuild the eGC. DATA SOURCES: An in-depth search was performed in the PubMed database, focusing on research published after 2003 with keywords including eGC, permeability, glycocalyx and injuries, and glycocalyx protection. STUDY SELECTION: Several authoritative reviews and original studies were identified and reviewed to summarize the characteristics of the eGC under physiologic and pathologic conditions as well as the detection and protection of the eGC. RESULTS: The eGC degradation is closely associated with pathophysiologic changes such as vascular permeability, edema formation, mechanotransduction, and clotting cascade, together with neutrophil and platelet adhesion in diverse injury and disease states including inflammation (sepsis and trauma), ischemia-reperfusion injury, shock, hypervolemia, hypertension, hyperglycemia, and high Na as well as diabetes and atherosclerosis. Therapeutic strategies for protecting and rebuilding the eGC should be explored through experimental test and clinical verifications. CONCLUSIONS Disturbance of the eGC usually occurs at early stages of various clinical pathophysiologies which can be partly prevented and reversed by protecting and restoring the eGC. The eGC seems to be a promising diagnostic biomarker and therapeutic target in clinical settings.
Animals ; Databases, Factual ; Endothelium, Vascular ; metabolism ; pathology ; Glycocalyx ; metabolism ; pathology ; Humans ; Shear Strength

Objective: To investigate the relationship between plasma level of pro-protein convertase subtilisin kexin type9 (PCSK9) and coronary artery calcification (CAC). Methods: A total of 380 consecutive chest pain patients without lipid-lowering therapy were enrolled. All patients received CT scan and coronary artery calcification (CAC) score measurement and were divided into 2 groups: CAC group, n=156 patients with CAC score>0 and Non-CAC group, n=224 patients with CAC score=0. CAC group was further classified in 3 subgroups as CAC score (1-100) subgroup, n=53, CAC score (101-400) subgroup, n=64 and CAC score>400 subgroup, n=39. Clinical data was collected, plasma levels of PCSK9 were measured in all patients and the relationship between PCSK9 and CAC score was investigated. Results: Plasma PCSK9 level in CAC group was higher than Non-CAC group (260.23±69.34) ng/ml vs (205.46±53.21) ng/ml, P<0.001; alone with CAC score increasing, PCSK9 level was elevating accordingly as in CAC score (1-100) subgroup, CAC score (101-400) subgroup and CAC score>400 subgroup, PCSK9 levels were (247.38±72.68) ng/ml, (264.87±57.63) ng/ml and (295.33±69.06) ng/ml respectively, all P<0.05. With adjusted traditional cardiovascular risk factors, multivariate regression analysis confirmed that plasma PCSK9 level was independently related to CAC score (β=0.584, P=0.002). In addition, the optimal cut-off value for PCSK9 predicting CAC was 228.58 ng/ml with sensitivity at 67% and specificity at 71%. Conclusion: Plasma PCSK9 level was related to CAC in chest pain patients without lipid-lowering therapy.