BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

OBJECTIVE: To compare the clinical effect of arsenic-containing Qinghuang Powder (QHP) and low-intensity chemotherapy (LIC) in treatment of elderly acute myeloid leukemia (eAML) patients. METHODS: Clinical data of 80 eAML patients treated at Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2015 to December 2020 were retrospectively analyzed. The treatment scheme was designed by real world study according to patients' preference, and patients were divided into a QHP group (35 cases) and a LIC group (45 cases). The median overall survival (mOS), 1-, 2-, and 3-year OS rates, and incidence of adverse events were compared between the two groups. RESULTS: The mOS of 80 patients was 11 months, and the 1-, 2-, and 3-year OS rates were 45.51%, 17.96%, and 11.05%, respectively. The QHP and LIC groups demonstrated no significant difference in mOS (12 months vs. 10 months), 1- (48.57% vs. 39.65%), 2- (11.43% vs. 20.04%), and 3-year OS rates (5.71% vs. 13.27%, all P>0.05). Moreover, the related factors of mOS demonstrated no significant difference in patients with age>75 years (11 months vs. 8 months), secondary AML (11 months vs. 8 months), poor genetic prognosis (9 months vs. 7 months), Eastern Cooperative Oncology Group performance status score ⩾ 3 (10 months vs. 7 months) and hematopoietic stem cell transplant comorbidity index ⩾ 4 (11 months vs. 7 months) between the QHP and LIC groups (all P>0.05). However, the incidence of myelosuppression was significantly lower in the QHP group than that in the LIC group (28.57% vs. 73.33%, P<0.01). CONCLUSIONS QHP and LIC had similar survival rates in eAML patients, but QHP had a lower myelosuppression incidence. Hence, QHP can be an alternative for eAML patients who do not tolerate LIC.
Humans ; Aged ; Arsenic/therapeutic use* ; Powders/therapeutic use* ; Retrospective Studies ; Leukemia, Myeloid, Acute/drug therapy* ; Prognosis ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

OBJECTIVE: To demonstrate the mechanism of mechanical ventilation (MV) induced endoplasmic reticulum stress (ERS) promoting mechanical ventilation-induced pulmonary fibrosis (MVPF), and to clarify the role of angiotensin receptor 1 (AT1R) during the process. METHODS: The C57BL/6 mice were randomly divided into four groups: Sham group, MV group, AT1R-shRNA group and MV+AT1R-shRNA group, with 6 mice in each group. The MV group and MV+AT1R-shRNA group mechanically ventilated for 2 hours after endotracheal intubation to establish MVPF animal model (parameter settings: respiratory rate 70 times/minutes, tidal volume 20 mL/kg, inhated oxygen concentration 0.21). The Sham group and AT1R-shRNA group only underwent intubation after anesthesia and maintained spontaneous breathing. AT1R-shRNA group and MV+AT1R-shRNA group were airway injected with the adeno-associated virus one month before modeling to inhibit AT1R gene expression in lung tissue. The expressions of AT1R, ERS signature proteins [immunoglobulin heavy chain-binding protein (BIP), protein disulfide isomerase (PDI)], fibrosis signature proteins [collagen I (COL1A1), α-smooth muscle actin (α-SMA)] in lung tissues were detected by immunofluorescence and Western blotting. Hematoxylin-eosin (HE) staining was used to evaluate lung injury and Masson staining was used to evaluate pulmonary fibrosis. RESULTS: Compared with the Sham group, the degree of pulmonary fibrosis and lung injury were more significant in the MV group. In the MV group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were increased (AT1R/β-actin: 1.40±0.02 vs. 1, BIP/β-actin: 2.79±0.07 vs. 1, PDI/β-actin: 2.07±0.02 vs. 1, COL1A1/α-Tubulin: 2.60±0.15 vs. 1, α-SMA/α-Tubulin: 2.80±0.25 vs. 1, all P < 0.01). The number of E-cad⁺/AT1R⁺ and E-cad⁺/BIP⁺ cells in lung tissue increased, and the fluorescence intensity of COL1A1 and α-SMA increased. Compared with the MV group, the degree of pulmonary fibrosis and lung injury were significantly relieved in the MV+AT1R-shRNA group. In the MV+AT1R-shRNA group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were decreased (AT1R/β-actin: 0.53±0.03 vs. 1.40±0.02, BIP/β-actin: 1.73±0.15 vs. 2.79±0.07, PDI/β-actin: 1.04±0.07 vs. 2.07±0.02, COL1A1/α-Tubulin: 1.29±0.11 vs. 2.60±0.15, α-SMA/α-Tubulin: 1.27±0.10 vs. 2.80±0.25, all P < 0.01). The number of E-cad⁺/AT1R⁺ and E-cad⁺/BIP⁺ cells in lung tissue decreased, and the fluorescence intensity of COL1A1 and α-SMA decreased. There was no statistically significant difference in the indicators between AT1R-shRNA group and Sham group. CONCLUSIONS MV up-regulate the expression of AT1R in alveolar epithelial cells, activate the AT1R pathway, induce ERS and promote the progression of MVPF.
Mice ; Animals ; Pulmonary Fibrosis/chemically induced* ; Lung Injury ; Respiration, Artificial/adverse effects* ; Actins/metabolism* ; Tubulin ; Mice, Inbred C57BL ; Endoplasmic Reticulum Stress ; RNA, Small Interfering

Objective: To compare the differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all cause death, thromboembolic events, major bleeding events and composite endpoint in patients with nonvalvular atrial fibrillation. Methods: This is a retrospective cohort study. From the China Atrial Fibrillation Registry cohort study, the patients with atrial fibrillation who were>18 years old were randomly divided into CAS risk score group and CHA₂DS₂-VASc risk score group respectively. According to the anticoagulant status at baseline and follow-up, patients in the 2 groups who complied with the scoring specifications for anticoagulation were selected for inclusion in this study. Baseline information such as age and gender in the two groups were collected and compared. Follow-up was performed periodically to collect information on anticoagulant therapy and endpoints. The endpoints were all-cause death, thromboembolism events and major bleeding, the composite endpoint events were all-cause death and thromboembolism events. The incidence of endpoints in CAS group and CHA₂DS₂-VASc group was analyzed, and multivariate Cox proportional risk model was used to analyze whether the incidence of the endpoints was statistically different between the two groups. Results: A total of 5 206 patients with AF were enrolled, average aged (63.6±12.2) years, and 2092 (40.2%) women. There were 2 447 cases (47.0%) in CAS risk score group and 2 759 cases (53.0%) in CHA₂DS₂-VASc risk score group. In the clinical baseline data of the two groups, the proportion of left ventricular ejection fraction<55%, non-paroxysmal atrial fibrillation, oral warfarin and HAS BLED score in the CAS group were lower than those in the CHA₂DS₂-VASc group, while the proportion of previous diabetes history and history of antiplatelet drugs in the CAS group was higher than that in the CHA₂DS₂-VASc group, and there was no statistical difference in other baseline data. Patients were followed up for (82.8±40.8) months. In CAS risk score group, 225(9.2%) had all-cause death, 186 (7.6%) had thromboembolic events, 81(3.3%) had major bleeding, and 368 (15.0%) had composite endpoint. In CHA₂DS₂-VASc risk score group, 261(9.5%) had all-cause death 209(7.6%) had thromboembolic events, 112(4.1%) had major bleeding, and 424 (15.4%) had composite endpoint. There were no significant differences in the occurrence of all-cause death, thromboembolic events, major bleeding and composite endpoint between anticoagulation in CAS risk score group and anticoagulation in CHA₂DS₂-VASc risk score group (log-rank P =0.643, 0.904, 0.126, 0.599, respectively). Compared with CAS risk score, multivariable Cox proportional hazards regression models showed no significant differences for all-cause death, thromboembolic events, major bleeding and composite endpoint between the two groups with HR(95%CI) 0.95(0.80-1.14), 1.00(0.82-1.22), 0.83(0.62-1.10), 0.96(0.84-1.11), respectively. All P>0.05. Conclusions: There were no significant differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all-cause death, thromboembolic events, and major bleeding events in Chinese patients with non-valvular atrial fibrillation.
Adolescent ; Anticoagulants ; Atrial Fibrillation/drug therapy* ; Cohort Studies ; Female ; Hemorrhage/complications* ; Humans ; Male ; Retrospective Studies ; Risk Assessment ; Stroke/epidemiology* ; Stroke Volume ; Thromboembolism/etiology* ; Ventricular Function, Left

OBJECTIVE: To investigate the effect of exosomal FZD10 derived from non-small cell lung cancer (NSCLC) cells on angiogenesis of human umbilical venous endothelial cells (HUVECs) and explore the possible mechanism. METHODS: We analyzed the expression of FZD10 in two NSCLC cell lines (95D and H1299 cells), normal human bronchial epithelial cells (BEAS-2B cells) and their exosomes isolated by ultracentrifugation. Cultured HUVECs were treated with the exosomes derived from NSCLC cells or NSCLC cells transfected with FZD10-siRNA, and the changes in tube formation ability of the cells were analyzed using an in vitro angiogenesis assay. ELISA was performed to determine the concentration of VEGFA and Ang-1 in the conditioned media of HUVECs, and RT-qPCR was used to analyze the mRNA levels of VEGFA and Ang-1 in the HUVECs. The effects of exosomal FZD10 on the activation of PI3K, Erk1/2 and YAP/TAZ signaling pathways were evaluated using Western blotting. RESULTS: Compared with BEAS-2B cells and their exosomes, 95D and H1299 cells and their exosomes all expressed high levels of FZD10 (P < 0.01). The exosomes derived from 95D and H1299 cells significantly enhanced tube formation ability and increased the expressions of VEGFA and Ang-1 protein and mRNA in HUVECs (P < 0.01), but FZD10 knockdown in 95D and H1299 cells obviously inhibited these effects of the exosomes. Exosomal FZD10 knockdown suppressed the activation of PI3K and Erk1/2 signaling pathways, but had no obvious effect on the activation of YAP/TAZ signaling pathway. CONCLUSION Exosomal FZD10 derived from NSCLC cells promotes HUVEC angiogenesis in vitro, the mechanism of which may involve the activation of PI3K and Erk1/2 signaling pathways.
Carcinoma, Non-Small-Cell Lung/metabolism* ; Cell Proliferation ; Culture Media, Conditioned ; Exosomes ; Frizzled Receptors/metabolism* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Lung Neoplasms/metabolism* ; MicroRNAs/genetics* ; Neovascularization, Pathologic/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; RNA, Messenger/metabolism* ; RNA, Small Interfering/metabolism*

Objective: To investigate the causes of death and predictors in patients with nonvalvular atrial fibrillation (AF) undergoing anticoagulation therapy. Methods: Consecutive anticoagulated nonvalvular AF patients were recruited from the China Atrial Fibrillation Registry (China-AF) Study from August 2011 to December 2018. After exclusion of patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, or loss of follow-up within 1 year, 2 248 patients were included in this analysis. Enrolled patients were followed up were followed up for 3 and 6 months, and then every 6 months. The primary endpoint was death, including cardiovascular death, non-cardiovascular death and undetermined death. The patients were divided into survival group and death group according to the survival status after follow-up. Clinical information such as age and sex was collected. Cox proportional hazards regression was performed to identify associated risk factors for all-cause mortality, and Fine-Gray competing risk model was used to identify associated risk factors for cardiovascular mortality. Results: A total of 2 248 patients with atrial fibrillation receiving anticoagulant therapy died over a mean follow-up of (42±24) months, mean age was (67±10) years old and 41.1% (923/2 248) patients were female. The mortality rate was 2.8 deaths per 100 patient-years. The most common cause of death was cardiovascular deaths, accounted for 55.0% (120/218). Worsening heart failure was the most common cause of cardiovascular deaths (18.3% (40/218)), followed by bleeding events (12.9% (28/218)) and ischemic stroke (8.7% (19/218)). Multivariate Cox regression analysis showed that age (HR = 1.05, 95%CI 1.04-1.07, P<0.001), anemia (HR = 1.81, 95%CI 1.02-3.18, P = 0.041), heart failure (HR=2.40, 95%CI 1.75-3.30, P<0.001), ischemic stroke/transient ischemic attack (TIA)(HR = 1.59, 95%CI 1.21-2.13, P = 0.001) and myocardial infarction (HR = 2.93, 95%CI 1.79-4.81, P<0.001) were independently associated with all-cause death. Fine-Gray competing risk model showed that age (HR=1.05, 95%CI 1.02-1.08, P<0.001), heart failure (HR=2.81, 95%CI 1.79-4.39, P<0.001), ischemic stroke/TIA (HR=1.50, 95%CI 1.02-2.22, P=0.041) and myocardial infarction (HR=3.31, 95%CI 1.72-6.37, P<0.001) were independently associated with cardiovascular death. Conclusions: In anticoagulated nonvalvular AF patients, ischemic stroke represents only a small subset of deaths, whereas worsening heart failure is the most common cause of cardiovascular deaths. Heart failure, ischemic stroke/TIA, and myocardial infarction are associated with increased mortality.
Aged ; Anticoagulants/therapeutic use* ; Atrial Fibrillation/drug therapy* ; Cause of Death ; China ; Female ; Humans ; Male ; Middle Aged ; Risk Factors ; Stroke

OBJECTIVE: To analyze the overall survival (OS) of elderly acute myeloid leukemia (AML) patients treated with oral arsenic-containing Qinghuang Powder (, QHP) or low-intensity chemotherapy (LIC). METHODS: Forty-two elderly AML patients treated with intravenous or subcutaneous LIC (1 month for each course, at least 3 courses) or oral QHP (3 months for each course, at least 2 courses) were retrospectively analyzed from January 2015 to December 2017. The main endpoints of analysis were OS and 1-, 2-, 3-year OS rates of patients, respectively. And the adverse reactions induding bone marrow suppression, digestive tract discomfort and myocardia injury were observed. RESULTS: Out of 42 elderly AML patients, 22 received LIC treatment and 20 received QHP treatment, according to patients' preference. There was no significant difference on OS between LIC and QHP patients (13.0 months vs. 13.5 months, >0.05). There was no significant difference on OS rates between LIC and QHP groups at 1 year (59.1% vs. 70.0%), 2 years (13.6% vs. 15%), and 3 years (4.6% vs. 5.0%, all >0.05). Furthermore, there was no significant difference of OS on prognosis stratification of performance status > 2 (12 months vs. 12 months), age> 75 year-old (12.0 months vs. 12.5 months), hematopoietic stem cell transplant comorbidity index >2 (12 months vs. 13 months), poor cytogenetics (12 months vs. 8 months), and diagnosis of secondary AML (10 months vs. 14 months) between LIC and QHP patients (>0.05). CONCLUSION QHP may be an alternative treatment for elderly AML patients refusing LIC therapy.
Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Arsenicals ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; Male ; Middle Aged ; Powders ; Retrospective Studies

OBJECTIVE: To provide reference of the ideal entry point for antegrade femoral nailing according to analysis correlation between highest point of greater trochanter and the middle line of the medullary cavity in adults by three-dimensional images. METHODS: From January 2016 to January 2017, 107 adults who underwent continuous computed tomography (CT) scans were ultimately enrolled, including 64 males and 43 females with an average age of (51.7±16.4) years old;54 patients on the left side and 53 patients on the right side. Three-dimensional images were built by using image-processing software (Volume Viewer) to reconstruct geometry of cortex and medullary canal. All people weregrouped according to different femoral greater trochanter morphology, such as anterior apex (AA), posterior apex (PA), middle apex (MA) and none apex (NA). Forwards inclination was adjusted to apparent neck shaft angle (ANSA) and true neck shaft angle (TNSA) on the coronal and saggittal view, recorded as C-ANSA, C-TNSA, S-ANSA, S-TNSA respectively, vertical distance from the middle line of femur medullary cavity to the highest point of greater trochanter of femur on the 4 positions were measured and performed statistical analysis, multiple linear regression was applied to analysis relationship between clinical data and VD value. RESULTS: (1)Comparison of VD value among 4 groups on the 4 positions, there were no difference in VD value between AA and MA groups on the S-ANSA position;and no differences in VD value among AA, MA and NA groups on the C-ANSA and C-TNSA position. (2)There were differences in VD value among AA, MA and NA groups on the sagittal plane;while had difference in VD value between PA and NA group on the coronal plane. (3)Prediction equation of VD value on S-ANSA and S-TNSA position by multiple linear regression showed R=0.343, F=3.409, =0.012 on the S-ANSA position;R=0.317, F=2.846, =0.028 on the S-TNSA position; neck shaft angle and sex were risk factors of VD value on the sagittal plane, while no difference in VD value on the coronal position. CONCLUSION (1)When indentify insertion point in adult femoral nail according to the highest point of greater trochanter as anatomic landmark, the morphology of greater trochanter of femur should be distinguished to certain observation position, then evaluate migration before and after on the sagttial plane and lateral offset on the coronal plane. (2)Migration before and after on the sagttial plane is increase with increase of neck shaft angle, and the degree of migration of female before and after is less than that of male.
Adult ; Aged ; Female ; Femur ; Fracture Fixation, Intramedullary ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; Male ; Middle Aged ; Tomography, X-Ray Computed

Objective: This study explored the thromboembolism risk of low-risk atrial fibrillation (AF) patients (CHA₂DS₂-VASc score of 0 or 1 for male and 1 or 2 for female) with different clinical characteristics to provide the basis for anticoagulation decision-making in these patients. Methods: We prospectively enrolled consecutive 2 862 nonvalvular low-risk AF patients between August 2011 to December 2018 in China-AF (China Atrial Fibrillation Registry) Study, their CHA₂DS₂-VASc score was 0 or 1 for male and 1 or 2 for female. According to their age, sex, presence or absence of hypertension, diabetes mellitus, congestive heart failure, and vascular disease at the time of enrolling, patients were divided into CHA₂DS₂-VASc score 0 score group, 1 score group, and 2 score group. Patients were followed up every 6 months by outpatient clinic visit or telephone interview. The outcome was a thromboembolic event, including ischemic stroke and systemic embolism. Univariate Cox regression analysis was used to compare the thromboembolism risk between the patients with different risk factors and CHA₂DS₂-VASc score 0 group. Results: A total of 2 862 low-risk atrial fibrillation patients were enrolled in this study. 915 patients (32.0%) were female, and age was (55.0±10.7) years old. There were 933 patients (32.6%) in CHA₂DS₂-VASc score 0 group, 1 401 patients (49.0%) in score 1 group and 528 patients (18.5%) in score 2 group. During follow-up (median 1.5 years, 5 811.82 person-years), 33 cases of thromboembolic events were recorded, the annual rate of thromboembolism was 0.57% (95%CI 0.40%~0.80%). The number of thromboembolic events in patients with CHA₂DS₂-VASc score 0, 1 and 2 were 8, 11 and 14, respectively, and the annual thromboembolism event rates were 0.40% (95%CI 0.20%-0.81%), 0.39% (95%CI 0.22%-0.71%) and 1.34% (95%CI 0.80%-2.27%), respectively. The risk of thromboembolism of CHA₂DS₂-VASc score 2 group (HR=3.53, 95%CI 1.48-8.44; P=0.005), especially female patients aged 65-74 years in CHA₂DS₂-VASc score 2 group (HR=2.67, 95%CI 1.63-4.38; P<0.000) was significantly higher than that in patients of CHA₂DS₂-VASc score 0 group. Conclusion: Low-Risk Atrial Fibrillation patients with CHA₂DS₂-VASc score 2, especially female patients aged 65-74 years old with CHA₂DS₂-VASc score 2 are at higher risk of thromboembolism in low-risk AF patients. For such patients, intensified oral anticoagulant therapy might be helpful to reduce the risk of thrombolism.
Adult ; Aged ; Anticoagulants ; Atrial Fibrillation ; China ; Female ; Humans ; Male ; Middle Aged ; Risk Assessment ; Risk Factors ; Stroke ; Thromboembolism

Objective: Taking electronic-eye (visual analyzer) technique,based on the powder color of Andrographis Herba,to investigate the applicability of electronic-eye technique and evaluate the quality of Andrographis Herba with different commercial specifications. Method: HPLC was employed to determine contents of andrographolide,dehydroandrographolide,14-deoxyandrographolide,neoandrographolide in 50 batches of Andrographis Herba with different commercial specifications(stems,leaves and aerial parts).Color of these samples were measured by electronic-eye technique.The data were analyzed by principal component analysis(PCA) and Pearson correlation analysis.The ability of electronic-eye to distinguish the different commercial specifications of Andrographis Herba was investigated and the correlation of chroma space system parameters (L^*,a^*,b^*) with active components was investigated. Result: There was remarkable difference in contents of 4 diterpenoids in Andrographis Herba from different parts,their contents in leaves was the highest,followed by the aerial parts(mixture of stems and leaves),and their contents in stems was the lowest.The results of PCA was divided into two classes,namely the stem part,leaf and aerial parts,indicating that electronic-eye could be used to distinguish the quality of Andrographis Herba.The correlation results showed that there were significant negative correlation(P<0.01) between L^*(lightness value) and the contents of andrographolide,dehydroandrographolide,14-deoxyandrographolide,neoandrographolide and the total content of these 4 components.In addition,L^* of samples that did not conform to the lower limit of determination in the 2015 edition of Chinese Pharmacopeia was ≥ 69.5,and the L^* of more than 90% of the samples in accordance with the requirements was <69.5. Conclusion: Electronic-eye technique provides a new method and idea for the quality evaluation of Andrographis Herba.