This study explored a novel digital design and fabrication method for a double constrained split orthodontic miniscrew guide to improve the accuracy and safety of clinical miniscrew implantation and reduce related complications. A patient requiring miniscrew implantation was selected, and data were acquired using cone beam computed tomography (CBCT) and intraoral optical scanning. For the construction of a double constrained split guide including a screw-hole guide and an insertion rod guide, different types of software such as Mimics 24.0, Geomagic wrap 2021, and Materialise magics 21.0 were utilized for 3D reconstruction, model integration, and guide design. The guide was then fabricated via laser metal 3D printing. Model and intraoral try-in results demonstrated that the guide fitted well and was stable. Postoperative CBCT verified that the final miniscrew implantation site was consistent with the preoperative design, and no related complications occurred. This double constrained split orthodontic miniscrew guide provides a precise and safe digital solution for clinical miniscrew implantation.
Humans ; Bone Screws ; Cone-Beam Computed Tomography ; Printing, Three-Dimensional ; Orthodontic Anchorage Procedures/instrumentation* ; Imaging, Three-Dimensional ; Computer-Aided Design

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin apioside,alibiflorin,swertiamarin,methyl gallate,benzoylpaeoniflorin,sweroside,6′-O-β-D-glucosylgentiopicroside,isoliquiritigenin,loganic acid,liquiritigenin,gallic acid,paeoniflorin,oxypaeoniflorin,gentiopicroside,glycyrrhizic acid,isoliquiritoside and liquiritin in Yangxue Ruanjian Capsules.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18column(2.1 mm×100 mm,1.7 μm),with the mobile phase comprising of 2 mmol/L ammonium acetate(containing 0.1%formic acid)-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Seventeen constituents showed good linear relationships within their own ranges(r>0.999 6),whose average recoveries were 91.33%-104.03%with the RSDs of 1.58%-3.50%.CONCLUSION This rapid,accurate and stable method can be used for the quality control of Yangxue Ruanjian Capsules.

Aim To investigate the protective effect of total flavonoids of Dracocephalum moldavica(TFDM)on atherosclerosis in rats and the inflammation of mouse macrophage RAW264.7 aggravated by trimeth-ylamine N-oxide(TMAO)and its possible mecha-nism.Methods The AS model of SD rats was estab-lished by high-fat diet feeding combined with intraper-itoneal injection of vitamin D3.The rats were divided into control group,model group,simvastatin group(15 mg·kg-1)and TFDM group(60,30,15 mg·kg-1).Biochemical method was used to detect the levels of se-rum total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C).HE staining was used to detect the pathological changes of aortic tissue.ELISA kit was used to detect the expression of TMAO,IL-1β,IL-6 in serum and TNF-α in liver tis-sue.Western blot was used to detect the expression of JAK,STAT and TNF-α protein in aorta.In addition,RAW264.7 macrophages were cultured in vitro,and LPS+TMAO was used to establish a macrophage in-flammation model,which was intervened by TFDM(100,50,25 mg·L-1).CCK-8 was used to determine cell viability and proliferation,and RT-qPCR was used to detect the expression of TNF-α,IL-6,JAK and STAT mRNA in cells.Results TFDM could significantly down-regulate the levels of serum TC,TG,LDL-C,ser-um TMAO,IL-1β,IL-6 and liver TNF-α,reduce aortic plaque deposition,and down-regulate the protein ex-pression of TNF-α,JAK and STAT in aorta.In addi-tion,TFDM intervention can significantly down-regulate the expression of TNF-α,IL-6,JAK,STAT mRNA and the expression of JAK,STAT protein.Conclusion TFDM can reduce the content of TMAO in serum,in-hibit JAK/STAT inflammatory signaling pathway and slow down the occurrence of inflammation,playing an anti-AS role.

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 β 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.
Humans ; Female ; Male ; Atrial Fibrillation/drug therapy* ; Coronary Artery Disease/complications* ; Anticoagulants/therapeutic use* ; Platelet Aggregation Inhibitors/therapeutic use* ; Risk Factors ; China ; Administration, Oral ; Stroke

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: 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.
Humans ; Atrial Fibrillation/epidemiology* ; Case-Control Studies ; Cross-Over Studies ; Ischemic Stroke ; China/epidemiology*

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.
Humans ; Atrial Fibrillation/epidemiology* ; Case-Control Studies ; Cross-Over Studies ; Ischemic Stroke ; China/epidemiology*

COVID-19/genetics* ; Genome, Viral/genetics* ; Humans ; RNA, Viral/genetics* ; RNA-Seq ; SARS-CoV-2/genetics* ; Whole Genome Sequencing

Objective: To explore the relationship between fasting blood glucose level and thromboembolism events in patients with non-valvular atrial fibrillation (NVAF). Methods: This was an observational study based on data from a multicenter, prospective Chinese atrial fibrillation registry cohort, which included 18 703 consecutive patients with atrial fibrillation (AF) in 31 hospitals in Beijing from August 2011 to December 2018. Patients were divided into 5 groups according to status of comorbid diabetes and fasting glucose levels at admission: normal blood glucose (normal glucose group), pre-diabetes group, strict glycemic control group, average glycemic control group and poor glycemic control group. Patients were followed up by telephone or outpatient service every 6 months. The primary follow-up endpoint was thromboembolic events, including ischemic stroke and systemic embolism. The secondary endpoint was the composite endpoint of cardiovascular death and thromboembolic events. Kaplan-Meier survival analysis and multifactorial Cox regression were used to analyze the correlation between fasting glucose levels and endpoint events. Results: The age of 18 703 patients with NVAF was (63.8±12.0) years, and there were 11 503 (61.5%) male patients. There were 11 877 patients (63.5%) in normal blood glucose group, 2 023 patients (10.8%)in pre-diabetes group, 1 131 patients (6.0%) in strict glycemic control group, 811 patients in average glycemic control group and 2 861 patients(4.3%) in poor glycemic control group. Of the 4 803 diabetic patients, 1 131 patients (23.5%) achieved strict glycemic control, of whom 328 (29.0%) were hypoglycemic (fasting blood glucose level<4.4 mmol/L at admission). During a mean follow-up of (51±23) months (up to 82 months), thromboembolic events were reported in 984 patients (5.3%). The survival curve analysis of Kaplan Meier showed that the incidence rates of thromboembolic events in normal glucose group, pre-diabetes group, strict glycemic control group, average glycemic control group and poor glycemic control group were 1.10/100, 1.41/100, 2.09/100, 1.46/100 and 1.71/100 person-years, respectively (χ²=53.0, log-rank P<0.001). The incidence rates of composite endpoint events were 1.86/100, 2.17/100, 4.08/100, 2.58/100, 3.16/100 person-years (χ²=72.3, log-rank P<0.001). The incidence of thromboembolic events and composite endpoint events in the other four groups were higher than that in the normal blood glucose group (P<0.001). Multivariate Cox regression analysis showed that compared with normal glucose group, the risk of thromboembolism increased in pre-diabetes group(HR=1.23, 95%CI 1.00-1.51, P=0.049), strict glycemic control group(HR=1.32, 95%CI 1.06-1.65, P=0.013) and poor glycemic control group(HR=1.26, 95%CI 1.01-1.58, P=0.044). Conclusion: Both high or low fasting glucose may be an independent risk factor for thromboembolic events in patients with NVAF.
Aged ; Atrial Fibrillation/complications* ; Blood Glucose/analysis* ; Fasting ; Humans ; Male ; Middle Aged ; Prospective Studies ; Thromboembolism/etiology*

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome