Objective: To externally validate and compare the accuracy of the China-PAR (Prediction for ASCVD Risk in China) model and the 2019 World Health Organization (WHO) cardiovascular disease risk charts for East Asian in predicting a 10-year cardiovascular disease in a general Chinese population. Methods: Participants aged 40-79 years without prior cardiovascular disease at baseline in the CHinese Electronic health Records Research in Yinzhou (CHERRY) were analyzed. The Kaplan-Meier analysis estimated the observed cardiovascular events (including non-fatal myocardial infarction, fatal coronary heart disease, and non-fatal or fatal stroke) rate within ten years. The expected risks were calculated using the WHO risk charts for East Asia (including the laboratory-based and non-laboratory-based models) and the China-PAR model. The expected-observed ratios were calculated to evaluate the overestimation or underestimation of the models in the cohort. Model accuracy was assessed by discrimination C-index, calibration χ² value, and calibration plots. Results: During a median of 7.26 years of follow-up, 13 301 cardiovascular events were identified among 225 811 participants. The C-index for the China-PAR model, WHO laboratory-based model and WHO non-laboratory-based model were 0.741 (0.735-0.747), 0.747 (0.740-0.753), and 0.739 (0.733-0.746) for men, and 0.782 (0.776-0.788), 0.789 (0.783-0.795), and 0.782 (0.776-0.787) for women, respectively. The WHO laboratory-based model and non-laboratory-based model underestimated the 10-year ASCVD risk by around 15% in women and underestimated by 0.8% and 4.4% in men, respectively. The China-PAR model underestimated the risks by 19.5% and 42.3% for men and women. Conclusions: The China-PAR and WHO models all have pretty good discriminations for 10-year cardiovascular risk assessment in this general Chinese population. However, the accuracy should be improved in the highest-risk groups, suggesting further specific models are still needed for those with the highest risk, such as patients with diabetes or older persons.
Adult ; Aged ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Female ; Humans ; Male ; Middle Aged ; Risk Assessment ; Risk Factors ; World Health Organization

Currently, the expanding recreational use of synthetic cannabinoids (SCBs) threatens public health. SCBs produce psychoactive effects similar to those of tetrahydrocannabinol, the main component of cannabis, and additionally induce unexpected pharmacological side effects. SCBs are falsely advertised as legal and safe, but in reality, SCB abuse has been reported to cause acute intoxication and addictive disorders. However, because of the lack of scientific evidence to elucidate their dangerous pharmacological effects, SCBs are weakly regulated and continue to circulate in illegal drug markets. In the present study, the intravenous self-administration (IVSA) paradigm was used to evaluate the abuse potential of three SCBs (AM-1248, CB-13, and PB-22) in rats. All three SCBs maintained IVSA with a large number of infusions and active lever presses, demonstrating their reinforcing effects.The increase of active lever presses was particularly significant during the early IVSA sessions, indicating the reinforcementenhancing effects of the SCBs (AM-1248 and CB-13). The number of inactive lever presses was significantly higher in the SCB groups (AM-1248 and CB-13) than that in the vehicle group, indicating their impulsive effects. In summary, these results demonstrated that SCBs have distinct pharmacological properties and abuse potential.

OBJECTIVE: To evaluate the mechanisms underlying the protective effect of Chinese herbal medicine Fructus broussonetiae (FB) in both mouse and cell models of Alzheimer's disease (AD). METHODS: APP/PS1 mice treated with FB for 2 months and vehicle-treated controls were run through the Morris water maze and object recognition test to evaluate learning and memory capacity. RNA-Seq, Western blotting, and immunofluorescence staining were also conducted to evaluate the effects of FB treatment on various signaling pathways altered in APP/PS1 mice. To further explore the mechanisms underlying FB's protective effect, PC-12 cells were treated with Aβ RESULTS: FB-treated mice showed improved learning and memory capacity on both the Morris water maze and object recognition tests. RNA-seq of hippocampal tissue from APP/PS1 mice showed that FB had effects on multiple signaling pathways, specifically decreasing cell apoptotic signaling and increasing AKT and β-catenin signaling. Similarly, FB up-regulated both AKT and β-catenin signaling in PC-12 cells pre-treated with Aβ CONCLUSIONS FB exerted neuroprotective effects on hippocampal cells of APP/PS1 mice, as well as improved cell viability in an in vitro model of AD. The protective actions of FB occurred via the upregulation of AKT/β-catenin signaling.

BACKGROUND: Acute type A aortic dissection (ATAAD) and acute type A intramural hematoma (ATAIMH) are life-threatening diseases with high mortality. To better understand their clinical features in the Chinese population, we analyzed the data from the first Registry of Aortic Dissection in China (Sino-RAD) to promote the understanding and management of the diseases. METHODS: All patients with ATAAD and ATAIMH enrolled in Sino-RAD from January 1, 2012 to December 31, 2016 were involved. The data of patients' selection, history, symptoms, management, outcomes, and postoperation complications were analyzed in the study. The continuous variables were compared using the Student's t test for normal distributions and the Mann-Whitney U test for non-normal distributions. Categorical variables were compared using the Chi-square test or Fisher exact test. RESULTS: A total of 1582 patients with ATAAD and 130 patients with ATAIMH were included. The mean age of all patients was 48.4 years. Patients with ATAAD were significantly younger than patients with ATAIMH (48.9 years vs. 55.6 years, P < 0.001). For the total cohort, males were dominant, but the male ratio of patients with ATAAD was significantly higher compared to those with ATAIMH (P = 0.01). The time range from the onset of symptom to hospitalization was 2.0 days. More patients of ATAIMH had hypertension than that of ATAAD (82.3% vs. 67.6%, P < 0.05). Chest and back pain were the most common clinical symptoms. Computerized tomography (CT) was the most common initial diagnostic imaging modality. 84.7% received surgical treatment and in-hospital mortality was 5.3%. Patients with ATAAD mainly received surgical treatment (89.6%), while most patients with ATAIMH received medical treatment (39.2%) or endovascular repair (35.4%). CONCLUSIONS Our study suggests that doctors should comprehensively use clinical examination and genetic background screening for patients with ATAAD and ATAIMH and further shorten the time range from symptoms onset to intervention, achieving early diagnosis and treatment, thereby reducing the mortality rate of patients with aortic dissection in China. We should standardize the procedures of aortic dissection treatment and improve people's understanding. Meanwhile, the curing and transferring efficiency should also be improved.
Acute Disease ; Aneurysm, Dissecting/diagnosis* ; China ; Hematoma ; Humans ; Male ; Middle Aged ; Registries ; Retrospective Studies ; Time Factors ; Treatment Outcome

Currently, the expanding recreational use of synthetic cannabinoids (SCBs) threatens public health. SCBs produce psychoactive effects similar to those of tetrahydrocannabinol, the main component of cannabis, and additionally induce unexpected pharmacological side effects. SCBs are falsely advertised as legal and safe, but in reality, SCB abuse has been reported to cause acute intoxication and addictive disorders. However, because of the lack of scientific evidence to elucidate their dangerous pharmacological effects, SCBs are weakly regulated and continue to circulate in illegal drug markets. In the present study, the intravenous self-administration (IVSA) paradigm was used to evaluate the abuse potential of three SCBs (AM-1248, CB-13, and PB-22) in rats. All three SCBs maintained IVSA with a large number of infusions and active lever presses, demonstrating their reinforcing effects.The increase of active lever presses was particularly significant during the early IVSA sessions, indicating the reinforcementenhancing effects of the SCBs (AM-1248 and CB-13). The number of inactive lever presses was significantly higher in the SCB groups (AM-1248 and CB-13) than that in the vehicle group, indicating their impulsive effects. In summary, these results demonstrated that SCBs have distinct pharmacological properties and abuse potential.

OBJECTIVE: To evaluate the potential effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population from economically developed area of China. METHODS: Totally 202 179 adults aged 40 to 74 years without cardiovascular diseases at baseline (January 1, 2010) were enrolled from the Chinese electronic health records research in Yinzhou (CHERRY) study. Three scenarios were considered: the screening strategy based on risk charts recommended by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases in Chinese adults aged 40-74 years (Strategy 1); the screening strategy based on the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) models recommended by the 2019 Guideline on the assessment and management of cardiovascular risk in China in Chinese adults aged 40-74 years (Strategy 2); and the screening strategy based on the China-PAR models in Chinese adults aged 50-74 years (Strategy 3). According to the guidelines, individuals who were classified into medium- or high-risk groups after cardiovascular risk assessment by the corresponding strategies would be introduced to lifestyle intervention, while high-risk population would take medication in addition. Markov model was used to simulate different screening scenarios for 10 years (cycles), using parameters mainly from the CHERRY study, as well as published data, Meta-analyses and systematic reviews for Chinese populations. The life year gained, quality-adjusted life year (QALY) gained, number of cardiovascular disease events/deaths could be prevented and number needed to be screened (NNS) were calculated to compare the effectiveness between the different strategies. One-way sensitivity analysis on uncertainty of cardiovascular disease incidence rate and probabilistic sensitivity analysis on uncertainty of distributions for the hazard ratios were conducted. RESULTS: Compared with non-screening strategy, QALYs gained were 1 433 [95% uncertainty interval (UI): 969-1 831], 1 401 (95%UI: 936-1 807), and 716 (95%UI: 265-1 111) for the Strategies 1, 2, and 3; and the NNS per QALY in the above strategies were 141 (95%UI: 110-209), 144 (95%UI: 112-216), and 198 (95%UI: 127-529), respectively. The Strategies 1 and 2 based on different guidelines showed similar effectiveness, while more benefits were found for screening using China-PAR models in adults aged 40-74 years than those aged 50-74 years. The results were consistent in the sensitivity analyses. CONCLUSION Screening for cardiovascular diseases in Chinese adults aged above 40 years seems effective in coastal developed areas of China, and the different screening strategies based on risk charts by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases or China-PAR models by the 2019 Guideline on the assessment and management of cardiovascular risk in China may have similar effectiveness.
Adult ; Cardiovascular Diseases/prevention & control* ; China/epidemiology* ; Cost-Benefit Analysis ; Humans ; Mass Screening ; Primary Prevention ; Quality-Adjusted Life Years

Chinese medicine Buyang Huanwu decoction (BYHW) is widely used in treating cerebral infarction combined with Qi-deficiency and blood-stasis syndrome, but the pharmacological basis is still not clear. This study aims to uncover the biological basis of BYHW therapy for cerebral infarction combined with Qi-deficiency and blood-stasis syndrome using label-free proteomic technology. Using Qi deficiency and blood stasis rat cerebral infarction model as the research object, the protein expression of rat brain tissue was compared among the sham operation group, the model group and the drug group. Quantitative analysis of the 3 groups of tissue samples detected 3 959, 3 996 and 4 055 proteins in the sham operation group, the model group and the drug group, respectively. Take model group as the control group, 391 proteins were identified to be upregulated or downregulated for more than 2 folds. Biological analysis and functional enrichment of the differentially expressed proteins revealed that BYHW may treat cerebral infarction combined with Qi-deficiency and blood-stasis syndrome through energy metabolism, nervous system and several signal pathways. This study preliminarily revealed the pharmacological mechanism of BYHW at the protein level, and provided a molecular basis for clinical treatment and traditional Chinese medicine research on cerebral infarction combined with Qi-deficiency and blood-stasis syndrome.

Background Researches showed that elevatory blood glucose level results in long-term damage of cells and tissue,or metabolic memory phenomenon,and manipulation of hyperglycemic memory is a good approach in the prevention of diabetic complications.However,its mechanism is not clear.It is speculated that the pathogenesis of diabetic retinopathy (DR) in diabetic patients may be associated to related mechanisms.Uncoupling proteins (UCPs) can decrease the production of reactive oxygen species (ROS),which may be related to DR.Objective This study was to explore the association between DR and the single nucleotide polymorphisms (SNPs) of UCP genes in Chinese Han population with type 2 diabetes.Methods A cross-sectional study was performed.This study was approved by Ethic Committee of Affiliated First Hospital of Shanghai Jiao Tong University and complied with Declaration of Helsinki,and written informed consent was obtained from each subject prior to any medical examination.One thousand eight hundreds and seventy-five patients with type 2 diabetes mellitus were enrolled in Xinjing district of Shanghai city by cluster sampling from November 2014 to January 2015.The demographic and medical baseline characteristics,ocular examination and laboratory tests were obtained and periphery blood of 2 ml was collected for extraction of DNA.Eight tag SNPs of UCP1,three tag SNPs of UCP2,and seven tag SNPs of UCP3 were selected as marker locus for the detection of genotype by Sequenom Mass ARRAY.Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry platform were used for genotyping.Hardy-Weinberg equilibrium (HWE) analysis,allele and genotype frequencies,haplotype analysis,and association tests for DR and SNPs were performed by SAS and SHEsis software.Results A total of 530 DR patients were checked out from 1 875 subjects with type 2 diabetes mellitus,with the detection rate of 28.27％.rs660339 locn of UCP2 gene and rs1626521,rs668514 locus of UCP3 gene appeared to have low detectable rates,and the secondary allele base frequency of rs632862 in UCP2 gene was ＜0.01 and rs15763 of UCP3 gene was unmatched with HWE,therefore,these locus analysis was not included.In 13 SNPs locus included in the analysis,only 2 SNPs of UCP1 gene were related to DR.Compared with the non-diabetic retinopathy (NDR) patients,the G allele frequency of rs10011540 was increased (P =0.03,OR =1.31,95 ％ confidence interval[CI] =1.03-1.67,and T allele frequency of rs3811787 was decreased (P=0.04,OR=0.86,95％ CI=0.75-0.99) in DR patients.Genotyping detection showed that the C/C and A/A frequencies of rs3811790 in UCP1 gene were significantly more and C/A frequency was less in DR patients than those in NDR patients (all at P＜0.01).The logistic regression analysis indicated an association of SNPs of rs10011540 and rs3811787 with DR independent from glucose and disease duration.Conclusions The SNPs of rs10011540 and rs3811787 locus in UCP1 gene are associated with DR in Chinese type 2 diabetes patients.

OBJECTIVETo explore the clinical features and prognosis of primary acute myeloid leukemia (AML) with trisomy 8.

METHODSThe clinical data of 24 cases diagnosed as primary AML with trisomy 8 were collected. The clinical characteristics such as sex, age, subtype of FAB, blood routine and bone marrow blast at the first visit were analyzed and the relationship of the characteristics with CR rate and the prognosis was explored.

RESULTS12 out of 24 AML patients were diagnosed as M5 (50%), while M2, M3, M4 and M6 had 3 cases, respectively (12.5%); one case did not receive the chemotherapy. 23 cases received 1-2 cycles of standard induction chemotherapy. Among them 3 cases of M3 achieved complete response (CR) and survived until the last following up with 100% 5-year OS rate. Among 20 cases of non-M3, 12 cases achieved CR1 (60%), 4 cases achieved partial response (PR) (20%), 4 cases did not respond (NR); 5 cases relapsed in follow-up for 3 years after CR1 (41.7%), 3 cases achieved CR2 after re-induction chemotherapy, and 2 cases remained NR. Among 20 cases of non-M3, 1 case failed to be followed-up after diagnosis within 1 month. The mean follow-up time of 19 cases was 26.2 (1.5-84) months, 9 cases died (6 cases of M5, 1 case of M4 and 2 cases of M2), who achieved PR and NR, or relapsed after CR1; the 3-year DFS and OS were 21%, 31.5% respectively. 2 cases of non-M3 accepted allo-HSCT with HLA-matched sibling donor and kept disease-free survival until the last following up, and survived for 58 and 66 months respectively. Except for 3 cases of M3, 2 cases received allo-HSCT and the cases without chemotherapy, the other 18 cases with initial WBC count less than 10×10(9)/L had OS and DFS longer than those of 10 cases with initial WBC count no less than 10×10(9)/L (P<0.05, P<0.01). The OS of 10 cases with CR1 was longer than OS of those cases without CR1 (P<0.01).

CONCLUSIONThe incidence of trisomy 8 in M5 is higher than the other AML subtypes, and the prognosis of M5 is poor. The initial WBC count above 10×10(9)/L is a high-risk factor. M3 with trisomy 8 and RARA gene has a very good prognosis. Trisomy 8 may increase the risk of primary AML except for M3, so allo-HSCT with HLA-matched sibling donor should be carried out as much as possible after CR1. The gene mutation of FLT3, MLL, HOX11, C-kit, NPM1 may possess an important significance on prognosis.

Bone Marrow ; pathology ; Chromosomes, Human, Pair 8 ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; therapy ; Leukocyte Count ; Prognosis ; Remission Induction ; Trisomy