[Clinical value of focused ultrasound ablation surgery in the treatment of abdominal wall endometriosis].

Objective: To explore the effectiveness and safety of focused ultrasound ablation surgery (FUAS) for abdominal wall endometriosis. Methods: From November 2019 to October 2022, a total of 34 patients with abdominal wall endometriosis who underwent FUAS were collected, and their clinical features, imaging features, intraoperative treatment and side effects after treatment were analyzed retrospectively, and the improvement of symptoms and re-intervention were followed up. Results: (1) Characteristics of clinical data: the average age of 34 patients with abdominal wall endometriosis was (32.8±3.8) years old. The largest diameter of the lesion was 48 mm, and the median lesion diameter was 24 mm. Thirty cases (88%, 30/34) had moderate to severe periodic pain in abdominal incision before FUAS. All patients were diagnosed by preoperative magnetic resonance imaging, including 19 cases (56%, 19/34) of superficial type, 8 cases (24%, 8/34) of intermediate type and 7 cases (21%, 7/34) of deep type. (2) FUAS treatment parameters: ablation was completed with average operation time of (64±18) minutes, average sonication time was (385±108) s, (103±11) W of average power, (38 819±16 309) J of average total energy, the average treatment area volume of (3.11±1.42) cm3, and (377.79±106.34) s/h of average treatment intensity. (3) Efficiency: the pain of patients after FUAS was significantly relieved, and the pain scores of patients after 1 month, 3 months, 6 months and 1 year after FUAS were significantly decreased (Z=-4.66, -5.13, -5.11 and -4.91, all P<0.01). One year after FUAS, the near relief and effective pain relief rate was 74% (25/34), and the clinical effective rate was 85% (29/34). Five patients recurred after one year, including 3 patients who underwent abdominal wall endometriosis lesion resection and 2 patients who received drug treatment. One month after FUAS, the size of the lesion did not change significantly compared with that before FUAS (P>0.05), and the size of the lesion decreased significantly after FUAS at 3 months, 6 months and 1 year (Z=-2.15, -2.67 and -3.41, all P<0.05). It has no difference in pain relief among different types (P>0.05), but has significant difference in focus reduction among three types (P<0.01). (4) Safety: there were 34 cases (100%, 34/34) of skin burning sensation, 19 cases (56%, 19/34) of pain in the treatment area and 2 cases (6%, 2/34) of hematuria. All patients got better after corresponding treatments. Conclusion: FUAS is safe and effective for the treatment of abdominal wall endometriosis, which has clinical application value.

[Early experience with mechanical hemodynamic support for catheter ablation of malignant ventricular tachycardia].

Objective: To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice. Methods: This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed. Results: A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up. Conclusions: MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.

[Analysis of factors associated with anxiety in patients with atrial fibrillation and their caregivers].

Objective: To explore the risk factors of anxiety in patients with atrial fibrillation and their caregivers. Methods: From September 2020 to March 2021, patients with atrial fibrillation and one primary family member as caregiver of each patient from Beijing Anzhen Hospital were enrolled. Basic data of patients and their caregivers were collected, and anxiety of patients and caregivers were evaluated by Generalized Anxiety Disorder-7 scale (GAD-7). A total of 374 patients with atrial fibrillation and their caregivers were included in this study. Multivariate logistic regression analysis was used to analyze the risk factors of anxiety of patients and their caregivers. Results: The mean age of the patients was (58.3±10.6) years, and 124 (33.2%) were female. The caregivers were (53.6±11.6) years old, and 247 (66%) were female. 69 (18.4%) patients and 38 (10.2%) caregivers had mild anxiety (GAD-7:5-9 scores), 13 (3.5%) patients and 9 (2.4%) caregivers had moderate or higher anxiety (GAD-7:10-21 scores). Multivariate analysis showed that the risk factors of anxiety in patients with atrial fibrillation included EHRA score≥3 (OR=1.73,95%CI:1.03-2.89,P=0.039) and female sex (OR=1.90,95%CI:1.06-3.40,P=0.032). EHRA score of patients≥3 (OR=2.11,95%CI:1.05-4.24, P=0.036) or anxiety of patients (OR=2.76,95%CI:1.36-5.60,P=0.005) were associated with higher anxiety of caregivers. Moreover, age of≥65 years old (OR=3.97,95%CI:1.68-9.38,P=0.002), female sex (OR=3.83,95%CI:1.64-8.93,P=0.002) and number of comorbidities of caregivers≥2 (OR=2.57,95%CI:1.03-6.41,P=0.043) were also associated with anxiety of caregivers. Conclusions: Patients with severe symptoms have a higher proportion of anxiety, and their caregivers are more likely to experience anxiety. Anxiety rate is higher in caregivers of patients with anxiety.

[Low-frequency fluctuation amplitude changes in resting-state brain functional magnetic resonance imaging and its correlation with clinical hearing levels in patients with unilateral hearing impairment].

Objective: To investigate low-frequency fluctuation amplitude changes in resting-state brain fMRI and its correlation with clinical hearing levels in patients with clinical hearing level in patients with unilateral hearing impairment. Methods: Forty-five patients with unilateral hearing impairment[12 males and 33 females, aged 36-67 (46.0±9.7) years], and 31 controls with normal hearing[9 males and 22 females, aged 36-67 (46.0±10.1) years], were retrospectively included. All subjects underwent blood oxygen level-dependent (BOLD) resting-state functional magnetic resonance imaging and high-resolution T1-weighted imaging. The patients were divided into the left-sided hearing impaired group(24 cases), and the right-sided hearing impaired group(21 cases). After data being preprocessed, differences in low frequency amplitude (ALFF) metrics between the evaluated patients and controls were calculated and analyzed, and the statistics were corrected for Gaussian random field (GFR). Results: Overall comparative analysis of patients with hearing impairment showed that one-way ANOVA among the three groups showed abnormal ALFF values only in the right anterior cuneiform lobe (GRF adjusted P=0.002). The ALFF value of the hearing impaired group was higher than that of the control group in one cluster (peak coordinates: X=9, Y=-72, Z=48, T=5.82), involving the left occipital gyrus, right anterior cuneiform lobe, left superior cuneiform lobe, left superior parietal gyrus, and left angular gyrus (GRF adjusted P=0.031). The ALFF value of the hearing impaired group was lower than that of the control group in three clusters (peak coordinates: X=57, Y=-48, Z=-24; T=-4.99; X=45, Y=-66, Z=0, T=-4.06; X=42, Y=-12, Z=36, T=-4.03), involving the right inferior temporal gyrus, the right middle temporal gyrus, and the right precentral gyrus (GRF adjusted P=0.009). Compared with the control group, the ALFF value of the left hearing impairment group was significantly higher than that of the control group in one cluster (peak coordinates: X=-12, Y=-75, Z=45, T=5.78), involving the left anterior cuneiform lobe, right anterior cuneiform lobe, left middle occipital gyrus, left superior parietal gyrus, left superior occipital gyrus, left cuneiform lobe, and right cuneiform lobe (P=0.023 after GRF correction). Compared with the control group, the right hearing impairment group had a significantly higher ALFF value in one cluster (peak coordinates: X=9, Y=-46, Z=22, T=6.06), involving the left middle occipital gyrus, right anterior cuneiform lobe, left cuneiform lobe, right cuneiform lobe, left superior occipital gyrus, and right superior occipital gyrus (GRF adjusted P=0.022); The brain area with reduced ALFF values is located in the right inferior temporal gyrus (GRF adjusted P=0.029). Spearman's two-tailed correlation analysis between ALFF values and pure tone average in the abnormal brain regions showed that ALFF values in the abnormal brain regions correlated to some extent with the pure tone average (PTA) only in the left-sided hearing impaired group(PTA=2 000 Hz, r=0.318,P=0.033;PTA=4 000 Hz,r=0.386,P=0.009). Conclusion: The abnormal neural activity within the brain are different in patients with left-sided and right-sided hearing impairment, and the severity of hearing impairment is related to the difference in functional integration of brain regions.

[Association between atrial fibrillation reoccurrence and new-onset ischemic stroke among patients with nonvalvular atrial fibrillation].

Objective: Explore the association between atrial fibrillation (AF) reoccurrence and new-onset ischemic stroke (IS) in patients with nonvalvular AF, and explore whether there is a high-risk period of IS after recurrent episodes of AF. Methods: A nested case-control study design was used. A total of 565 nonvalvular AF patients with new-onset IS after a follow-up of at least 2 years in the China-AF cohort were enrolled as the case group, and 1 693 nonvalvular AF patients without new-onset IS were matched as the control group at a ratio of 1∶3. Frequency and types of recurrent AF in the previous 1 or 2 years were compared between two groups, and the adjusted associations of AF reoccurrence with new onset IS were explored using conditional logistic regression analysis. The proportion of recurrent AF was compared between the case period and control period, and conditional logistic regression analysis was performed to calculate adjusted associations of case-period AF with IS. Results: The nested case-control study design results showed that the proportion of at least one record of recurrent AF in the previous 1 year was higher in the case group than in the control group (72.0% vs. 60.8%, P<0.05), and the recurrent AF was positively correlated with new-onset IS (adjusted OR=1.80, P<0.001). Similar results were also observed in the previous 2 years period. The case-crossover study design analysis showed that among 565 patients with new-onset IS, recurrent AF in the case period was positively correlated with IS (adjusted OR=1.61, P=0.003). Conclusion: Recurrent AF is associated with IS, and there may be a high-risk period of IS after recurrent episodes of AF.

[Current use of oral anticoagulation therapy and influencing factors among coronary artery disease patients with nonvalvular atrial fibrillation in China].

Objective: To investigate current use of oral anticoagulant (OAC) therapy and influencing factors among coronary artery disease (CAD) patients with nonvalvular atrial fibrillation (NVAF) in China. Methods: Results of this study derived from "China Atrial Fibrillation Registry Study", the study prospectively enrolled atrial fibrillation (AF) patients from 31 hospitals, and patients with valvular AF or treated with catheter ablation were excluded. Baseline data such as age, sex and type of atrial fibrillation were collected, and drug history, history of concomitant diseases, laboratory results and echocardiography results were recorded. CHA2DS2-VASc score and HAS-BLED score were calculated. The patients were followed up at the 3rd and 6th months after enrollment and every 6 months thereafter. Patients were divided according to whether they had coronary artery disease and whether they took OAC. Results: 11 067 NVAF patients fulfilling guideline criteria for OAC treatment were included in this study, including 1 837 patients with CAD. 95.4% of NVAF patients with CAD had CHA2DS2-VASc score≥2, and 59.7% of patients had HAS-BLED≥3, which was significantly higher than NVAF patients without CAD (P<0.001). Only 34.6% of NVAF patients with CAD were treated with OAC at enrollment. The proportion of HAS-BLED≥3 in the OAC group was significantly lower than in the no-OAC group (36.7% vs. 71.8%, P<0.001). After adjustment with multivariable logistic regression analysis, thromboembolism(OR=2.48,95%CI 1.50-4.10,P<0.001), left atrial diameter≥40 mm(OR=1.89,95%CI 1.23-2.91,P=0.004), stain use (OR=1.83,95%CI 1.01-3.03, P=0.020) and ß blocker use (OR=1.74,95%CI 1.13-2.68,P=0.012)were influence factors of OAC treatment. However, the influence factors of no-OAC use were female(OR=0.54,95%CI 0.34-0.86,P=0.001), HAS-BLED≥3 (OR=0.33,95%CI 0.19-0.57,P<0.001), and antiplatelet drug(OR=0.04,95%CI 0.03-0.07,P<0.001). Conclusion: The rate of OAC treatment in NVAF patients with CAD is still low and needs to be further improved. The training and assessment of medical personnel should be strengthened to improve the utilization rate of OAC in these patients.

[Analysis of cerebral blood perfusion changes in patients with unilateral sudden sensorineural hearing loss based on three-dimensional pseudo-continuous arterial spin labeling].

Objective: To explore the changes of cerebral blood perfusion in patients with unilateral sudden sensorineural hearing loss (SSNHL) by using the three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) technique. Methods: The clinical characteristics and ASL data of the 32 patients with unilateral SSNHL were retrospectively collected from November 2020 to June 2021 in Beijing Fuxing Hospital of Capital Medical University, among them, there were 7 males and 25 females, aged from 17 to 73 (44.9±14.4) years. According to the location of SSNHL, they were divided into the left SSNHL (L-SSNHL) group (18 cases) and the right SSNHL (R-SSNHL) group (14 cases). A total of 34 healthy volunteers, which including 14 males and 20 females, aged from 24 to 68 (46.2±14.4) years were enrolled from the local community. The parameter of cerebral blood flow (CBF) of each brain area was obtained using the CereFlow software. The Brainnetome Atlas software package based on MATLAB was used for visualization. The independent-samples t test was conducted to compare the difference of cerebral blood perfusion between the unilateral SSNHL group and healthy control (HC) group. Pearson correlation analysis was used to evaluate the correlation between changes in cerebral blood perfusion and clinical scale scores. Results: The CBF of left orbital gyrus part 5, left inferior temporal gyrus part 7, right orbital gyrus part 5, right inferior temporal gyrus part 1, right inferior temporal gyrus part 7, and right parahippocampal gyrus part 3 of the L-SSNHL group were higher than that in the HC group[(49.1±8.8) vs (31.6±10.9)ml·100g-1·min-1;(42.8±14.3) vs (27.1±13.6)ml·100g-1·min-1;(51.8±9.4) vs (27.2±11.2)ml·100g-1·min-1;(38.8±5.7) vs (28.0±9.2)ml·100g-1·min-1;(38.4±13.8) vs (23.6±10.3)ml·100g-1·min-1;(42.4±9.4) vs (30.1±12.6)ml·100g-1·min-1; all P<0.05]. The CBF of left superior frontal gyrus part 7 and left middle frontal gyrus part 3 of the L-SSNHL group were lower than that in the HC group[(48.2±7.9) vs (59.3±13.7)ml·100g-1·min-1;(46.4±10.3) vs (59.3±16.9)ml·100g-1·min-1;all P<0.05]. The CBF of left orbital gyrus part 5, right orbital gyrus part 5, right inferior temporal gyrus part 1, and right inferior temporal gyrus part 7 of the R-SSNHL group were higher than that in the HC group[(50.6±7.0) vs (31.6±10.9)ml·100g-1·min-1;(50.9±8.8) vs (27.2±11.2)ml·100 g-1·min-1;(38.0±7.2) vs (28.0±9.2)ml·100g-1·min-1;(35.7±8.5) vs (23.6±10.3)ml·100g-1·min-1;all P<0.05]; the CBF of right insular part 4 was lower than that in the HC group [(44.2±6.1) vs (54.4±11.3) ml·100 g-1·min-1, P=0.018]. In the L-SSNHL group, the CBF of left superior frontal gyrus part 7 and right orbital gyrus part 5 were negatively correlated with the VAS score(r=-0.83, -0.81, all P<0.05), and the CBF of right orbital gyrus part 5 was negatively correlated with the THI score(r=-0.75, P=0.013). There was no statistically significant correlation between the remaining differences in brain regions and clinical scale scores(all P>0.05). Conclusion: Changes in cerebral blood perfusion in multiple brain regions were found in patients with unilateral SSNHL by using the 3D pCASL technique.

[Efficacy and safety of radiofrequency catheter ablation of septal hypertrophy guided by intracardiac echocardiography in hypertrophic obstructive cardiomyopathy].

Nine patients identified as hypertrophic obstructive cardiomyopathy (HOCM) in Beijing Anzhen Hopspital who underwent ablation from March to July 2019 were included in the study. All patients had left ventricular outflow tract gradient (LVOTG) over 50 mmHg(1 mmHg=0.133 kPa)with significant symptoms despite not optimal drug therapy. Intracardiac echocardiography (ICE) was used to reconstruct septum and surrounding structures, and monitor the effect of ablation during procedure. Nine patients with HOCM were included,.of which 6 men and 3 women. The average age was (51.7±12.2) years. All patients underwent successful ablation after a mean of procedural time of (152.2±31.9) minutes and ablation time of (838.4±227.3) seconds. Except for one patients, all other patients had significant LVOTG reduction(P=0.001)within 50 mmHg after the procedure. Systolic anterior motion of the mitral valve disappeared in all patients after the procedure without major periprocedural complications. The LVOTG of these patients remained stable during follow-up. Radiofrequency ablation using ICE guidance is feasible in treating HOCM with promising efficacy and safety.

[Pregnancy outcomes in patients with adenomyosis with fertility requirements: retrospective analysis of clinical data from real world].

Objective: To retrospectively analyze the pregnancy outcomes of patients with adenomyosis requiring fertility in a single center under real world condition. Methods: From June 2015 to May 2020, 231 cases of pregnancy complicated with adenomyosis diagnosed by ultrasound with fertility requirements were treated in the Women's and Children's Hospital Affiliated to Qingdao University with complete clinical data. And they were divided into three groups according to the treatment of adenomyosis before pregnancy: expectation group, drug group and operation group. The relevant data before pregnancy of the three groups were analyzed, and the pregnancy outcomes of the patients were summarized. According to whether the early pregnancy was treated with medication, the patients who were naturally conceived without symptoms of threatened abortion were divided into observation group and fetus protection group, and the pregnancy outcomes of the two groups were compared. Results: (1) Compared with the expectation group, the ages of patients in the drug group and the operation group were larger [(31.5±1.8) vs (34.1±3.7) vs (36.9±3.6) years old], and the difference was statistically significant (P<0.05). Only 9 patients (11.5%, 9/78) had clinical symptoms in the expectation group, while the patients in the drug group and the operation group had a higher proportion of dysmenorrhea and increased menstrual volume. The uterine volume of the drug group and the operation group were larger than that of the expectation group [(151±46) vs (166±27) vs (97±18) cm3], the difference was statistically significant (P<0.05). 78.6% (33/42) of the operation group were focal adenomyosis. The proportion of natural pregnancy in the expectation group was 97.4% (76/78), and in vitro fertilization and embryo transfer was mainly used in the drug group and the operation group. (2) The abortion rates of the three groups were 48.7% (26/111), 4/17, 67.5% (27/78) respectively. Compared with the drug group and the operation group, the preterm birth rate was lower [55.9% (33/111) vs 11/17 vs 12.5% (5/78)] and the natural delivery rate was higher [44.1% (26/111) vs 4/17 vs 67.5% (27/78)] in the expectation group. (3) There were 89 cases of spontaneous pregnancy without threatened abortion symptoms, including 31 cases in the observation group and 58 cases in the fetus protection group. Compared with the observation group, the abortion rate of patients in the fetus protection group was lower [41.9% (13/31) vs 34.5% (20/58)], and the difference was statistically significant (P<0.05). Conclusions: Patients with adenomyosis who have fertility requirements should be comprehensively evaluated and individualized treatment plans should be given. Pregnancy patients with adenomyosis have a high rate of miscarriage, and they should be included in the management of high-risk pregnant women. Active fetal protection treatment during early pregnancy might improve pregnancy outcomes.

[A comparison of CAS risk model and CHA2DS2-VASc risk model in guiding anticoagulation treatment in Chinese patients with non-valvular atrial fibrillation].

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.

BGL3 inhibits papillary thyroid carcinoma progression via regulating PTEN stability.

PURPOSE: BGL3, a novel long non-coding RNA (lncRNA) that plays a crucial role in several human malignancies. However, the clinical significance and biological function of BGL3 in papillary thyroid carcinoma (PTC) have not been explored. Herein, we aimed to investigate the role of BGL3 in human PTC. METHODS: A total of 85 pairs of PTC and normal tissues were collected for clinicopathological analysis. Expression of BGL3 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of BGL3 on PTC cells ware determined by CCK-8, colony formation, EdU and wound healing assays. The molecular mechanism underlying BGL3 was tested by ChIP, Co-IP, RNA pull-down and luciferase reporter assays. In vivo experiments were conducted using xenografts in nude mice. RESULTS: BGL3 was significantly decreased in PTC tissues compared to adjacent normal thyroid tissues, and it was transcriptionally repressed by oncogene Myc. Low BGL3 is positively related to larger tumor size, lymph node metastasis, later TNM stage and poor prognosis. Overexpression of BGL3 inhibited PTC cell proliferation and migration in vitro, and reduced tumor size and lung metastasis nodules in vivo. BGL3 was mainly located in the cytoplasm, in which interacted with PTEN and recruited OTUD3, enhancing the de-ubiquitination effect of OTUD3 on PTEN, resulting in increasing PTEN protein stability and inactivating carcinogenic PI3K/AKT signaling. CONCLUSIONS: Our data underscore the critical tumor-inhibiting role of BGL3 in PTC via post-translational regulation of PTEN protein stability, which may serve as a novel therapeutic target and prognostic biomarker in human PTC.

Effect of macro-calcification on the failure mechanics of intracranial aneurysmal wall tissue.

BACKGROUND: Calcification was recently found to be present in the majority of cerebral aneurysms, though how calcification and the presence or absence of co-localized lipid pools affect failure properties is still unknown. OBJECTIVE: The primary objective is to quantify the biomechanical effect of a macro-calcification with surrounding Near-Calcification Region (NCR) of varying mechanical properties on tissue failure behavior. METHODS: We utilized a structurally informed finite element model to simulate pre-failure and failure behavior of a human cerebral tissue specimen modeled as a composite containing a macro-calcification and surrounding NCR, embedded in a fiber matrix composite. Data from multiple imaging modalities was combined to quantify the collagen organization and calcification geometry. An idealized parametric model utilizing the calibrated model was used to explore the impact of NCR properties on tissue failure. RESULTS: Compared to tissue without calcification, peak stress was reduced by 82% and 49% for low modulus (representing lipid pool) and high modulus (simulating increase in calcification size) of the NCR, respectively. Failure process strongly depended on NCR properties with lipid pools blunting the onset of complete failure. When the NCR was calcified, the sample was able to sustain larger overall stress, however the failure process was abrupt with nearly simultaneous failure of the loaded fibers. CONCLUSIONS: Failure of calcified vascular tissue is strongly influenced by the ultrastructure in the vicinity of the calcification. Computational modeling of failure in fibrous soft tissues can be used to understand how pathological changes impact the tissue failure process, with potentially important clinical implications.

Adaptive Remodeling in the Elastase-induced Rabbit Aneurysms.

BACKGROUND: Rupture of brain aneurysms is associated with high fatality and morbidity rates. Through remodeling of the collagen matrix, many aneurysms can remain unruptured for decades, despite an enlarging and evolving geometry. OBJECTIVE: Our objective was to explore this adaptive remodeling for the first time in an elastase induced aneurysm model in rabbits. METHODS: Saccular aneurysms were created in 22 New Zealand white rabbits and remodeling was assessed in tissue harvested 2, 4, 8 and 12 weeks after creation. RESULTS: The intramural principal stress ratio doubled after aneurysm creation due to increased longitudinal loads, triggering a remodeling response. A distinct wall layer with multi-directional collagen fibers developed between the media and adventitia as early as 2 weeks, and in all cases by 4 weeks with an average thickness of 50.6 ± 14.3 µm. Collagen fibers in this layer were multi-directional (AI = 0.56 ± 0.15) with low tortuosity (1.08 ± 0.02) compared with adjacent circumferentially aligned medial fibers (AI = 0.78 ± 0.12) and highly tortuous adventitial fibers (1.22 ± 0.03). A second phase of remodeling replaced circumferentially aligned fibers in the inner media with longitudinal fibers. A structurally motivated constitutive model with both remodeling modes was introduced along with methodology for determining material parameters from mechanical testing and multiphoton imaging. CONCLUSIONS: A new mechanism was identified by which aneurysm walls can rapidly adapt to changes in load, ensuring the structural integrity of the aneurysm until a slower process of medial reorganization occurs. The rabbit model can be used to evaluate therapies to increase aneurysm wall stability.

[The impact of digoxin on the long-term outcomes in patients with coronary artery disease and atrial fibrillation].

Objective: To investigate the long-term safety of digoxin in patients with coronary artery disease (CAD) and atrial fibrillation (AF). Methods: This was a prospective study, in which 25 512 AF patients were enrolled from China Atrial Fibrillation Registry Study. After exclusion of patients receiving ablation therapy at the enrollment, 1 810 CAD patients [age: (71.5±9.3)years] with AF were included. The subjects were grouped into the digoxin group and non-digoxin group, and were followed up for a period of 80 months. Long-term outcomes were compared between the groups and an adjusted Cox regression analysis was applied to evaluate the risk of digoxin on the long-term outcomes. The primary endpoint was all-cause mortality. Results: The patients were followed up for a median period of 3.05 years. After multivariable adjustment, the Cox regression analysis showed that digoxin significantly increased the risk of all-cause mortality (HR=1.28, 95%CI 1.01-1.61, P=0.038), cardiovascular mortality (HR=1.48,95%CI 1.10-2.00,P=0.010), cardiovascular hospitalization (HR=1.67,95%CI 1.35-2.07,P=0.008) and the composite endpoints (HR=2.02,95%CI 1.71-2.38,P<0.001). In the subgroup of patients with heart failure (HF), digoxin was not associated with the risk of all-cause mortality, but was still associated with the increased risk of cardiovascular mortality (HR=1.44,95%CI 1.05-1.98,P=0.025), cardiovascular hospitalization (HR=1.44,95%CI 1.09-1.90,P=0.010) and the composite endpoints (HR=1.37, 95%CI 1.01-1.70, P=0.004). However, in the subgroup of patients without HF, digoxin was only associated with all-cause mortality (HR=2.56,95%CI 1.44-4.54,P=0.001). Conclusion: Digoxin significantly increased the risk of all-cause mortality in CAD patients with AF, especially in patients without HF.

[Causes of death and influencing factors of atrial fibrillation patients undergoing anticoagulation therapy].

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.

[Efficacy and safety of catheter ablation in patients with new-onset atrial arrhythmia after surgical excision of left atrial myxoma].

Objective: To evaluate the safety and efficacy of catheter ablation in patients with new-onset atrial arrhythmia after surgical excision of left atrial myxoma. Methods: Nine patients with new onset atrial arrhythmia and a prior history of left atrial myxoma, who received surgical myxoma excision and catheter ablation between September 2014 and November 2019, were included in the present study. Baseline characteristics, procedural parameters during catheter ablation, severe perioperative adverse events, recurrence rate of arrhythmia and clinical prognosis were analyzed. Kaplan Meier survival analysis was used to define the maintenance rate of sinus rhythm after catheter ablation in this patient cohort. Results: Nine patients were included. The average age was (55.8 ± 9.1) years old (3 male), there were 3 patients (3/9) with paroxysmal atrial fibrillation (PAF) and 6 patients (6/9) with atrial flutter or atrial tachycardia (AFL or AT). Ablation was successful in all patients, there were no perioperative complications such as stroke, pericardial effusion, cardiac tamponade, vascular complications or massive hemorrhage. During a mean follow-up time of 40.0 (27.5, 55.5) months, sinus rhythm was maintained in six patients (6/9) after the initial catheter ablation. The overall sinus rhythm maintenance rate was 2/3. In addition, 1 out of the 3 AF patients (1/3) developed recurrence of AF at 3 month after ablation, and 2 out of the 6 AFL or AT patients (2/6) developed late recurrence of AF or AFL (19 months and 29 months after ablation), two out of three patients with recurrent AFs or AFL received repeated catheter ablation and one patient remained sinus rhythm post repeat ablation. Meanwhile, there was no recurrence of atrial myxoma, no death, stroke, acute myocardial infarction and other events during the entire follow-up period. Conclusions: Catheter ablation is a safe and feasible therapeutic option for patients with new-onset atrial arrhythmia after surgical excision of left atrial myxoma.

[Feasibility and safety of intracardiac ultrasound-assisted atrial septal puncture during radiofrequency ablation for atrial fibrillation].

Objective: To explore the feasibility and safety of intracardiac ultrasound-assisted atrial septal puncture (ASP) during radiofrequency ablation for atrial fibrillation. Methods: We enrolled 241 consecutive patients scheduled to radiofrequency ablation for atrial fibrillation in Beijing Anzhen Hospital from July to September 2020. Inclusion criteria: patients aged over 18 years with a clear electrocardiogram record of atrial fibrillation. Patients were divided into 2 groups: ASP with ultrasound-assisted X-ray (ultrasound group, n=123), ASP under X-ray alone (X-ray group, n=118). Clinical features of patients including age, sex, percent of paroxysmal atrial fibrillation, and repeat ablation, CHA2DS2-VASc score and past history (hypertension, diabetes mellitus, coronary artery disease, stroke/transient ischemic attack (TIA), valve diseases) and echocardiographic parameters (left atrial dimension, left ventricular ejection fraction, left ventricular end-diastolic dimension) were obtained and compared. The first-pass rate, radiation exposure time, duration of ASP, and complications of ASP were also compared between the two groups. Results: The age of patients in this cohort was (62.5±8.0) years, and the proportion of males was 57.0% (n=138). Among them, the proportion of paroxysmal atrial fibrillation was 56.0% (n=135), and the ratio of repeat ablation was 17.8% (n=43). Age, sex, percent of paroxysmal atrial fibrillation, history of hypertension, diabetes mellitus were similar between the two groups. The first-pass rate was significantly higher in the ultrasound group than in the X-ray group (94.3% (116/123) vs. 79.7% (94/118), P=0.001); the exposure time of X-ray was significantly shorter in the ultrasound group than in the X-ray group ((31.3±7.9) s vs. (124.8±35.7) s, P<0.001), while the duration of ASP was longer in the ultrasound group ((10.1±1.8) minutes vs. (8.2±1.3) minutes, P<0.001). In terms of complications, the incidence of puncture into the pericardium was lower in the ultrasound group (0 vs.3.4% (4/118), P=0.039); the rate of transient ST-segment elevation post ASP was similar between the ultrasound group and X-ray group (2.4% (3/123) vs. 1.7% (2/118), P=0.999). Conclusion: Intracardiac ultrasound-assisted atrial septal puncture can effectively improve the accuracy of atrial septal puncture, shorten the radiation exposure time, and reduce the complications related to atrial septal puncture.

[The thromboembolism risk of low-risk atrial fibrillation patients with different clinical characteristics].

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.

[Association between weight control and recurrence of atrial fibrillation after catheter ablation in overweight and obese patients].

Objectives: This study explored the relationship between weight control and atrial fibrillation (AF) recurrence after catheter ablation in overweight and obese patients. Methods: We prospectively enrolled consecutive 333 overweight and obese patients aged 28 to 87 years old, who underwent catheter ablation for AF in Beijing Anzhen Hospital between October 2015 and February 2016. Data of patients' characteristics, laboratory examination and treatment were collected at baseline. Each patient was followed up at 3, 6 and 12 months after ablation to collect information on weight, AF recurrence, stroke, major bleeding, hospitalization for cardiovascular reasons and death, etc. Patients were divided into weight controlled group (ΔBMI<-1 kg/m(2)) and weight uncontrolled group (ΔBMI≥-1 kg/m(2)), according to the changes in the most recent exposure BMI before AF recurrence in patients with recurrence or the BMI at 12 months' follow-up in patients without recurrence and the BMI at baseline. Multivariate logistic regression was performed to adjust other known risk factors of AF recurrence and to explore the association between weight control and AF recurrence after catheter ablation. Results: There were 54 patients in weight controlled group and 279 patients in weight uncontrolled group. There were no significant differences in age, gender, education level, left atrial size and history of hypertension between the two groups (all P>0.05). The proportion of patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was higher in the weight controlled group (50.0%(27/54) vs. 34.8%(97/279), P=0.034). However, there was no significant difference in the proportion of patients with obesity (33.3% (18/54) vs. 29.7% (83/279)), paroxysmal AF (59.3% (32/54) vs. 56.6% (158/279)) and AF duration less than 5 years (76.9% (40/52) vs. 65.4% (178/272)) between the weight controlled group and the uncontrolled group. During 1-year follow-up after ablation, the recurrence rate of AF was significantly lower in the weight controlled group than that in the weight uncontrolled group (14.8% (8/54) vs. 32.6%(91/279), P=0.009). Multivariable logistic regression analysis shows that weight control is independently associated with a lower postoperative AF recurrence rate (OR=0.40, 95%CI 0.18-0.90, P=0.026). Conclusion: Weight control is strongly associated with a lower AF recurrence rate after catheter ablation in overweight and obese patients.