As a new clinical trial mode,decentralized & digitalized clinical trial(DCT)is based on digital health equipment and uses internet and artificial intelligence technologies to complete the screening,registration,randomization,intervention,evaluation and follow-up of subjects,which is helpful to improve efficiency and reduce trial costs.The DCT mode has been applied to evaluate the treatment and management effects of cardiovascular diseases such as atrial fibrilla-tion,heart failure,coronary heart disease,and hypertension,showing broad development prospects and application space.This article will provide a brief introduction to representative DCT in the global cardiovascular disease field,and look for-ward to the application prospects of this model,providing reference and guidance for accelerating the development of cardio-vascular DCT in China.

Objective:To investigate the effects of Apelin-13 regulatory peptide on neuronal cell pyroptosis in mice modeled with cerebral ischemia-reperfusion(I/R).Methods:We prepared a mouse cerebral I/R model using middle cerebral artery embolization and Reperfusion(MCAO/R).The HT22 cell injury model was prepared by the oxygen glu-cose deprivation/reoxygenation(OGD/R),and Apelin-13 treatment was also given.Neurological function was assessed by neurological deficit score;hematoxylin-eosin(HE)staining and Nissl staining were used to observe the morphologic changes of the infarcted area of the mice;and 2,3,5triphenyltetrazolium chloride(TTC)staining was used to observe the volume of cerebral infarcts;The expression of NOD-like receptor thermoprotein structural domain-related protein 3(NLRP3),gasdermin D(GSDMD),caspase-1,apoptosis-associated speck-like protein(ASC),interleukin 1β(IL-1β),and interleukin 18(IL-18)in brain tissues from infarcted areas or HT22 cells was detected by Western Blot,and IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA)in serum of mice and culture supema-tants;The cell viability and cell damage of HT22 were detected by CCK-8 kit and lactate dehydrogenase(LDH)assay kit,respectively;caspase-1 activity was measured by caspase-1 activity kit in HT22 cells;and the expression of caspase-1 and GSDMD was observed by immunofluorescence staining in HT22 cells.Results:Apelin-13 significantly improved neurological function and cerebral infarct volume in I/R mice,and attenuated pathological damage in the in-farcted area.It also reduced the serum levels of IL-1β and IL-18.In addition,Apelin-13 reduced the expression of mol-ecules such as NLRP3,GSDMD,caspase-1,IL-1β,and IL-18 in the cerebral infarct area of mice.In vitro experiments showed that Apelin-13 significantly increased the viability of OGD/R-treated HT22 cells,decreased caspase-1 activity,and reduced the LDH content,as well as decreased the expression of molecules such as NLRP3,GSDMD,caspase-1,IL-1β,IL-18,and so on,in OGD/R-treated HT22 cells.Conclusion:Apelin-13 inhibits pyroptosis through the NL-RP3/caspase-1/GSDMD pathway in cerebral ischemia/reperfusion mice and thus exerts neuroprotective effects.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

BACKGROUND: The age, biomarkers, and clinical history (ABC)-atrial fibrillation (AF)-Stroke score have been proposed to refine stroke risk stratification, beyond what clinical risk scores such as the CHA2DS2-VASc score can offer. This study aimed to identify risk factors associated with thromboembolism and evaluate the performance of the ABC-AF-Stroke score in predicting thromboembolism in non-anticoagulated AF patients following successful ablations. METHODS: A total of 2692 patients who underwent successful ablations with discontinued anticoagulation after a 3-month blanking period in the Chinese Atrial Fibrillation Registry (CAFR) between 2013 and 2019 were included. Cox regression analysis was conducted to present the association of risk factors with thromboembolism risk. The ABC-AF-Stroke score was evaluated in terms of discrimination, including concordance index (C-index), net reclassification improvement (NRI) and integrated discrimination improvement (IDI), clinical utilization by decision curve analysis (DCA), and calibration by comparing the predicted risk with the observed annualized event rate. RESULTS: After a median follow-up of 3.5 years, 64 patients experienced thromboembolism events. Age, prior history of stroke/transient ischemic attack (TIA), high-sensitivity cardiac troponin T (cTnT-hs), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were independently associated with thromboembolism risk. The ABC-AF-Stroke score performed statistically significantly better than the CHA2DS2-VASc score in terms of C-index (0.67, 95% confidence interval [CI]: 0.59-0.74 vs. 0.60, 95% CI: 0.52-0.67, P = 0.030) and reclassification capacity. The DCA implied that the ABC-AF-Stroke score could identify more thromboembolism events without increasing the false positive rate compared to the CHA2DS2-VASc score. The calibration curve showed that the ABC-AF-Stroke score was well calibrated in this population. CONCLUSIONS In this real-world study enrolling non-anticoagulated AF patients following successful ablations, age, prior history of stroke/TIA, level of NT-proBNP, and cTnT-hs were independently associated with an increased risk of thromboembolism. The ABC-AF-Stroke score was well-calibrated and statistically significantly outperformed the CHA2DS2-VASc score in predicting thromboembolism risk.
Humans ; Anticoagulants/therapeutic use* ; Atrial Fibrillation/complications* ; East Asian People ; Ischemic Attack, Transient ; Registries ; Risk Assessment ; Risk Factors ; Stroke/etiology* ; Thromboembolism/etiology* ; Troponin T

Objective:To examine the effectiveness of thin struct bare stents for the treatment of spontaneous isolated dissection of the superior mesenteric artery (SIDSMA).Methods:The data of 32 patients admitted to First Hospital of Jiaxing (20 cases) and Jinling Hospital (12 cases) with SIDSMA from January 2016 to January 2021 were retrospectively analyzed. There were 27 males and 5 females, aging (54.8±9.4) years (range: 36 to 75 years). All patients were treated with thin struct bare stents. Controllable spring coils were used to fulfill the false lumen in 2 cases. Symptoms, vascular remodeling pattern at the SIDSMA lesion, and patency of the stents were observed during follow-up.Results:The surgical success rate was 100%. According to the length of the lesions and stents, the number of stents implanted was 1 in 17 cases, 2 in 11 cases and 3 in 4 cases. The angiography showed that blood flow in the stent was smooth. The numerical rating scale for abdominal pain decreased from 6.1±1.5 (range: 4 to 10) preoperatively to 1.0 (1.0) (range: 0 to 3) 1 hour postoperatively ( W=528, P<0.01). The compression rate of the true lumen of the superior mesenteric artery decreased from (92.3±6.7)% (range: 25% to 94%) preoperatively to 0.8 (1.2)% (range: 0 to 3.2%) 1 month postoperatively ( W=528, P<0.01). The primary patency rate of CT angiography at 1 month postoperatively was 100%. The vascular remodeling rate was (92.3±6.7)% (range: 80% to 100%). All patients were followed for (46.3±17.0) months (range: 24 to 76 months). The cumulative patency rates in 1, 2 and 5 years were all 100%. Conclusion:The use of thin struct bare stents for SIDSMA could obtained the expected safety and efficacy.

Objective:To examine the effectiveness of thin struct bare stents for the treatment of spontaneous isolated dissection of the superior mesenteric artery (SIDSMA).Methods:The data of 32 patients admitted to First Hospital of Jiaxing (20 cases) and Jinling Hospital (12 cases) with SIDSMA from January 2016 to January 2021 were retrospectively analyzed. There were 27 males and 5 females, aging (54.8±9.4) years (range: 36 to 75 years). All patients were treated with thin struct bare stents. Controllable spring coils were used to fulfill the false lumen in 2 cases. Symptoms, vascular remodeling pattern at the SIDSMA lesion, and patency of the stents were observed during follow-up.Results:The surgical success rate was 100%. According to the length of the lesions and stents, the number of stents implanted was 1 in 17 cases, 2 in 11 cases and 3 in 4 cases. The angiography showed that blood flow in the stent was smooth. The numerical rating scale for abdominal pain decreased from 6.1±1.5 (range: 4 to 10) preoperatively to 1.0 (1.0) (range: 0 to 3) 1 hour postoperatively ( W=528, P<0.01). The compression rate of the true lumen of the superior mesenteric artery decreased from (92.3±6.7)% (range: 25% to 94%) preoperatively to 0.8 (1.2)% (range: 0 to 3.2%) 1 month postoperatively ( W=528, P<0.01). The primary patency rate of CT angiography at 1 month postoperatively was 100%. The vascular remodeling rate was (92.3±6.7)% (range: 80% to 100%). All patients were followed for (46.3±17.0) months (range: 24 to 76 months). The cumulative patency rates in 1, 2 and 5 years were all 100%. Conclusion:The use of thin struct bare stents for SIDSMA could obtained the expected safety and efficacy.

Objective:To investigate the compliance of oral anticoagulant(OAC) medication and influencing factors among nonvalvular atrial fibrillation(NVAF) patients with new-onset acute ischemic stroke (AIS).Methods:A total of 396 NVAF patients, who initiated OAC therapy after a new-onset AIS from August 2011 to December 2020 were enrolled from China Atrial Fibrillation Registry (China-AF). The demographic characteristics, medical history, comorbid diseases and medication of patients were collected before and after the index stroke, and the influencing factors of compliance of OAC medication were analyzed.Results:Patients were followed up for a mean of 26.9 months. Among 396 patients, 228 (57.6%) had continuous anticoagulant medication (persistent OAC group);while 168 (42.4%) discontinued OAC therapy within 2 years after the index stroke (non-persistent OAC group). Patients on persistence OAC had a higher proportion of atrial fibrillation episodes than patients on non-persistent OAC [83.3% (190/228) vs. 73.8% (126/168); χ 2=5.34, P=0.021], while lower proportion of radiofrequency ablation(RFA)[18.9% (43/228) vs. 32.1% (43/228); χ 2=9.22, P=0.002]. Multivariate Cox regression modelshowed that history of RFA ( HR=1.77, 95% CI: 1.25-2.50; P=0.001) was positively associated with non-persistence of OAC. Conclusion:The study indicates that quite large proportion of NVAD patients with a new-onset of AIS discontinued OAC therapy during 2 years of follow up, and a history of RFA procedure might be an independent factor associated with discontinuing of anticoagulant therapy.

【Objective】 To study the yielding rate and distribution of unexpected antibodies in blood transfusion children with thalassemia in Yunnan province, and to explore the blood transfusion strategies. 【Methods】 From January 2016 to December 2021, 298 children with thalassemia, who received blood transfusion treatment in Kunming, Xishuangbanna, Wenshan, Dehong, Yuxi and Baoshan hospitals across Yunnan Province, were selected. The unexpected antibodies of blood plasma were screened by microcolumn gel card. The samples with positive antibodies were identified for alloantibody specificity. 【Results】 Unexpected antibodies were yielded in 67 out of 298(22.48%) transfused children with thalassemia. The positive rates of unexpected antibodies in boys and girls were 16.55%(24/145) and 28.10%(43/153), respectively. The positive rates of unexpected antibodies in Han, Dai, Zhuang, Yi, Bulang, Jinuo and Miao people were 14.06%(18/128), 30.80%(32/104), 35.71%(10/28), 36.36%(8/22), 50.00%(4/8), 60.00%(3/5)and 66.67%(2/3), respectively, with statistically significant differences between each other. The positive rate of unexpected antibodies in ethnic minorities was higher than that in Han. The positive rates of unexpected antibodies in children who received the first transfusion at birth-one year old, 1~3 years old, 3~6 years old and above 6 years old were 12.50%(3/24), 10.14%(7/69), 24.54%(40/163)and 40.48%(17/42), respectively. The positive rates of unexpected antibodies in children with first transfusion after 3 years old were significantly higher than those before 3 years old. The positive rates of unexpected antibodies in children with one transfusion, 1~3, 3~10, 10~20 and more than 20 transfusions were 4.76%(1/21), 12.07%(7/58), 23.71%(23/97), 28.16%(29/103)and 36.84%(7/19), respectively, with statistically significant differences between each other. The number of blood transfusions was positively correlated with the unexpected antibody yielding. The yielding rate of unexpected antibodies in children with α thalassemia, βthalassemia, δ+ βthalassemia and untyped thalassemia was 7.50%(3/40), 17.62%(34/193), 53.70%(29/54)and 9.09%(1/11), respectively(P<0.05). The yielding rate of unexpected antibodies in transfused children with δ+ βthalassemia was the highest. And 57 unexpected antibodies of Rh blood group system were yielded, 6 anti-M antibodies, 2 anti-N antibodies and 2 undetermined. 【Conclusion】 The positive rate of unexpected antibodies in transfused children with thalassemia in Yunnan province is high. Routine antibody screening should be carried out for transfusion children with thalassemia, and blood units, compatible with ABO, Rh and MNS typing results, should be selected to ensure the safety and effectiveness of clinical blood use.

Background: Antimicrobial peptides (AMPs) have been identified as promising compounds for consideration as novel antimicrobial agents. Objectives: This study analyzed the efficacy of cecropin B against Haemophilus parasuis isolates through scanning electron microscopy (SEM) and atomic force microscopy (AFM) experiments. Results: Cecropin B exhibited broad inhibition activity against 15 standard Haemophilus parasuis (HPS) strains and 5 of the clinical isolates had minimum inhibition concentrations (MICs) ranging from 2 to 16 μg/mL. Microelectrophoresis and hexadecane adsorption assays indicated that the more hydrophobic and the higher the isoelectric point (IEP) of the strain, the more sensitive it was to cecropin B. Through SEM, multiple blisters of various shapes and dents on the cell surface were observed. Protrusions and leakage were detected by AFM. Conclusions Based on the results, cecropin B could inhibit HPS via a pore-forming mechanism by interacting with the cytoplasmic membrane of bacteria. Moreover, as cecropin B concentration increased, the bacteria membrane was more seriously damaged. Thus, cecropin B could be developed as an effective anti-HPS agent for use in clinical applications.

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.