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Abstract Aims/Introduction We investigated the relationship of circulating TSP‐1 mRNA and miR‐194 with diabetic kidney disease’s degree. Materials and Methods We enrolled 167 hospitalized type 2 diabetes patients in the endocrinology department. Patients were split into three groups according to urinary microalbumin: A, B and C. The control group comprised healthy outpatients (n = 163). The quantities of microribonucleic acid (miR)‐194 and thrombospondin‐1 (TSP‐1) messenger ribonucleic acid (mRNA) in the participants’ circulation were measured using a quantitative real‐time polymerase chain reaction. Results Circulating TSP‐1 mRNA (P = 0.024) and miR‐194 (P = 0.029) expressions significantly increased in type 2 diabetes patients. Circulating TSP‐1 mRNA (P = 0.040) and miR‐194 (P = 0.007) expression levels differed significantly among the three groups; circulating TSP‐1 mRNA expression increased with urinary microalbumin. However, miR‐194 declined in group B and increased in group C. Circulating TSP‐1 mRNA was positively correlated with cystatin‐c (r = 0.281; P = 0.021) and microalbumin/creatinine ratio (UmALB/Cr; r = 0.317; P = 0.009); miR‐194 was positively correlated with UmALB/Cr (r = 0.405; P = 0.003). Stepwise multivariate linear regression analysis showed cystatin‐c (β = 0.578; P = 0.021) and UmALB/Cr (β = 0.001; P = 0.009) as independent factors for TSP‐1 mRNA; UmALB/Cr (β = 0.005; P = 0.028) as an independent factor for miR194. Areas under the curve for circulating TSP‐1 mRNA and miR194 were 0.756 (95% confidence interval 0.620–0.893; sensitivity 0.69 and specificity 0.71, P

Transcriptional dysregulation of genes is a hallmark of tumors and can serve as targets for cancer drug development. However, it is extremely challenging to develop small-molecule inhibitors to target abnormally expressed transcription factors (TFs) except for the nuclear receptor family of TFs. Little is known about the interaction between TFs and transcription cofactors in gastroesophageal adenocarcinoma (GEA) or the therapeutic effects of targeting TF and transcription cofactor complexes. In this study, we found that ETS homologous factor (EHF) expression is promoted by a core transcriptional regulatory circuitry (CRC), specifically ELF3-KLF5-GATA6, and interference with its expression suppressed the malignant biological behavior of GEA cells. Importantly, we identified Ajuba LIM protein (AJUBA) as a new coactivator of EHF that cooperatively orchestrates transcriptional network activity in GEA. Furthermore, we identified KRAS signaling as a common pathway downstream of EHF and AJUBA. Applicably, dual targeting of EHF and AJUBA by lipid nanoparticles cooperatively attenuated the malignant biological behaviors of GEA in vitro and in vivo. In conclusion, EHF is upregulated by the CRC and promotes GEA malignancy by interacting with AJUBA through the KRAS pathway. Targeting of both EHF and its coactivator AJUBA through lipid nanoparticles is a novel potential therapeutic strategy.

ObjectiveThis study aimed to evaluate the efficacy of cyclic cryotherapy and vitamin D administration on early rehabilitation after total knee arthroplasty (TKA), as its efficacy remains unclear.MethodsWe divided 150 patients (three groups) who underwent TKA into those treated with or without cyclic cryotherapy and vitamin D.ResultsCompared with patients who did not receive cyclic cryotherapy, those who received postoperative cyclic cryotherapy and vitamin D supplementation had significantly higher American Knee Society Scores (AKSS) on postoperative day (POD) 7 and at 1 month postoperatively; higher visual analogue scale (VAS) values on POD1–3 and POD7; reduced thigh swelling on POD3 and POD7; increased range of motion (ROM) on POD3, POD7, and at 1 month postoperatively; and reduced postoperative length of stay (PLOS). However, no significant difference in patient satisfaction was observed between the patient groups. At 1 and 3 months postoperatively, patients administered cyclic cryotherapy and vitamin D had significantly higher AKSS, ROM, and vitamin D levels than those who did not receive vitamin D. No perioperative complications such as surgical site infection, skin frostbite, or vitamin D intoxication were observed.ConclusionCyclic cryotherapy post-TKA had short-term advantages in terms of AKSS, VAS, thigh swelling, ROM, PLOS, and accelerated rehabilitation, but did not improve patient satisfaction. Cyclic cryotherapy combined with vitamin D improved AKSS and ROM at 1 and 3 months postoperatively.

Abstract This study aimed to evaluate the optimal frequency of dexamethasone (DEX) administration and the efficacy of DEX with aggressive warming in total hip arthroplasty (THA), which remains unclear. A total of 150 patients were treated with DEX (10 mg) once before and once or twice after surgery with or without intraoperative aggressive warming. On postoperative day 3, the dynamic visual analogue scale scores and C-reactive protein (CRP) and interleukin-6 (IL-6) levels in participants administered with DEX twice after surgery were significantly lower than those who did not receive the second dose. The range of motion (ROM), postoperative fatigue based on Identity-Consequence-Fatigue Scale, average temperature at different stages, intraoperative blood loss, and postoperative drainage volume in patients who were subjected to warming were significantly higher than those who were not. The degree of satisfaction was also higher in the patients who received both second dose and warming than those who received neither. No differences in complications were observed based on the treatments. An additional dose of DEX at 48 h post-surgery has short-term advantages in terms of analgesia, anti-inflammatory effects, and accelerated rehabilitation after THA. DEX combined with aggressive warming further optimises short-term ROM and fatigue and improves the degree of satisfaction. Clinical trial was registered in the International Clinical Trial Registry, and the date of registration is 2/12/2020 (ChiCTR2000040560).

The “quality project” is an objective need to promote the comprehensive and coordinated development of higher education and cultivate high-quality talents. Based on the fuzzy clustering maximum tree algorithm, this paper first generates the maximum tree for a similar matrix and then clusters the maximum tree to find the clustering results. Then the idea of fuzzy clustering maximum tree algorithm is introduced into the management of “quality engineering” in Heilongjiang province colleges and universities, and the necessity of project management in the management of “quality engineering” in colleges and universities is analyzed, so that the knowledge related to project management can be applied in the construction of “quality engineering” in colleges and universities. “The results show that project quality management has a lot of advantages and disadvantages. The results show that there are problems such as weak awareness of quality management among all staff, unclear construction objectives and quality construction standards, and a lack of effective project monitoring and evaluation mechanism in project quality management. During the experimental period, the groundwater level was 0.4~0.7m below the surface, and the global risk level decreased from 5 to 3 along with the deep excavation of the foundation pit, and the risk probability of the foundation pit project became larger with time and finally stabilized at 60%. The research of this paper is helpful to improve the project management level of “quality engineering” in universities and promote the transformation of “quality engineering” results, which has certain practicality and guidance.

Abstract Background The triglyceride-glucose (TyG) index and the stress hyperglycaemia ratio (SHR) are both positively associated with cardiovascular (CV) risk in patients with coronary heart disease. However, the prognostic value of these two biomarkers has not been well elucidated in patients with chronic total occlusion (CTO). Therefore, this study aims to evaluate the association of the TyG index and the SHR with long-term prognosis in patients with CTO. Methods This prospective cohort study consecutively included 2740 angina patients with CTO from January 2017 to December 2018 at Fuwai Hospital. The outcomes are a composite of CV death and target vessel myocardial infarction (TVMI) and major CV cerebrovascular adverse events (MACCEs, including all-cause death, nonfatal MI, ischaemia-driven target vessel revascularization, and stroke). The association between biomarkers and prognosis was analysed by multivariable Cox proportional hazard models, and the predictive value was determined by a receiver-operating characteristic (ROC) curve. Results During the follow-up with a median time of 3 years, 179 (6.5%) cases of MACCEs and 47 (1.7%) cases of CV death or TVMI were recorded. Patients with a high TyG index (> 9.10) and a high SHR (> 0.87) showed a significantly increased risk of CV death/TVMI (TyG index: HR 4.23, 95% CI 1.58–11.37; SHR: HR 5.14, 95% CI 1.89–13.98) and MACCEs (TyG index: HR 2.47, 95% CI 1.54–3.97; SHR: HR 2.91, 95% CI 1.84–4.60) compared with those with a low Tyg index and a low SHR (TyG

Abstract Background Stress hyperglycemia was positively associated with poor prognosis in individuals with acute myocardial infarction (AMI). However, admission glucose and stress hyperglycemia ratio (SHR) may not be the best indicator of stress hyperglycemia. We performed this study to evaluate the comparative prognostic value of different measures of hyperglycemia (fasting SHR, fasting plasma glucose [FPG], and hemoglobin A1c [HbA1c]) for in-hospital mortality in AMI patients with or without diabetes. Methods In this prospective, nationwide, multicenter China Acute Myocardial Infarction (CAMI) registry, 5,308 AMI patients including 2081 with diabetes and 3227 without diabetes were evaluated. Fasting SHR was calculated using the formula [(first FPG (mmol/l))/(1.59×HbA1c (%)-2.59)]. According to the quartiles of fasting SHR, FPG and HbA1c, diabetic and non-diabetic patients were divided into four groups, respectively. The primary endpoint was in-hospital mortality. Results Overall, 225 (4.2%) patients died during hospitalization. Individuals in quartile 4 had a significantly higher rate of in-hospital mortality compared with those in quartile 1 in diabetic cohort (9.7% vs. 2.0%; adjusted odds ratio [OR] 4.070, 95% CI 2.014–8.228) and nondiabetic cohort (8.8% vs. 2.2%; adjusted OR 2.976, 95% CI 1.695–5.224). Fasting SHR was also correlated with higher in-hospital mortality when treated as a continuous variable in diabetic and nondiabetic patients. Similar results were observed for FPG either as a continuous variable or a categorical variable. In addition, fasting SHR and FPG, rather than HbA1c, had a moderate predictive value for in-hospital mortality in patients with diabetes (areas under the curve [AUC] for fasting SHR: 0.702; FPG: 0.689) and without diabetes (AUC for fasting SHR: 0.690; FPG: 0.693). The AUC for fasting SHR was not significantly different from that of FPG in diabetic and nondiabetic patients. Moreover, adding fasting SHR or FPG to the original model led to a significant improvement in C-statistic regardless of diabetic status. Conclusions This study indicated that, in individuals with AMI, fasting SHR as well as FPG was strongly associated with in-hospital mortality regardless of glucose metabolism status. Fasting SHR and FPG might be considered as a useful marker for risk stratification in this population. Trial registration: ClinicalTrials.gov NCT01874691.

Abstract The occurrence and development of coronary heart disease (CHD) are closely linked to fluctuations in blood glucose levels. While the efficacy of intensified treatment guided by HbA1c levels remains uncertain for individuals with diabetes and CHD, this review summarizes the findings and conclusions regarding HbA1c in the context of CHD. Our review showed a curvilinear correlation between regulated level of HbA1c and therapeutic effectiveness of intensified glycemic control among patients with type 2 diabetes and coronary heart disease. It is necessary to optimize the dynamic monitoring indicators of HbA1c, combine genetic profiles, haptoglobin phenotypes for example and select more suitable hypoglycemic drugs to establish more appropriate glucose-controlling guideline for patients with CHD at different stage of diabetes.

Background Serum uric acid (UA) is correlated closely with traditional cardiovascular risk factors, which might interfere with the action of UA, in patients with coronary artery disease. We performed this study to evaluate the prognostic effect of UA levels in individuals with different numbers of standard modifiable cardiovascular risk factors (SMuRFs). Methods and Results In this prospective study, we consecutively enrolled 10 486 patients with coronary artery disease. They were stratified into 3 groups according to the tertiles of UA concentrations and, within each UA tertile, further classified into 3 groups by the number of SMuRFs (0–1 versus 2–3 versus 4). The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including death, myocardial infarction, stroke, and unplanned revascularization. Over a median follow‐up of 2.4 years, 1233 (11.8%) MACCEs were recorded. Patients with high UA levels developed significantly higher risk of MACCEs than those with low UA levels. In addition, UA levels were positively associated with MACCEs as a continuous variable. More importantly, in patients with 0 to 1 SMuRF, the risks of MACCEs were significantly higher in the high‐UA‐level group (adjusted hazard ratio [HR], 1.469 [95% CI, 1.197–1.804]) and medium‐UA‐level group (adjusted HR, 1.478 [95% CI, 1.012–2.160]), compared with the low‐UA‐level group, whereas no significant association was found between UA levels and the risk of MACCEs in participants with 2 to 3 or 4 SMuRFs. Conclusions In patients with coronary artery disease who received evidence‐based secondary prevention therapies, elevated UA levels might affect the prognosis of individuals with 0 to 1 SMuRF but not that of individuals with ≥2 SMuRFs.

Summary: Background: Social isolation and loneliness pose significant public health challenges globally. The objective of this study is to investigate the association between social isolation, loneliness, and the risk of type 2 diabetes mellitus (T2DM). Methods: 423,503 UK adults from the UK Biobank (UKB) and 13,800 Chinese adults from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. The exposures of interest were social isolation and loneliness. Social isolation was evaluated based on the number of household members, frequency of social activities, contact with others, and marriage status (CHARLS only). Loneliness was evaluated by the subjective feeling of loneliness and the willingness to confide in others (UKB only). The primary endpoint was incident T2DM. The two-sample Mendelian randomization (MR) analysis was based on the genome-wide association studies of UKB (n = 463,010) and the European Bioinformatics Institute (n = 655,666). Findings: The UKB cohort study documented 15,072 T2DM cases during a mean follow-up of 13.5 years, and the CHARLS cohort study recorded 1,249 T2DM cases during a mean follow-up of 5.8 years. Social isolation and loneliness showed significant associations with an elevated risk of T2DM in both UKB (social isolation [most vs least]: HR 1.17, 95% CI 1.11–1.23; loneliness [yes vs no]: HR 1.21, 95% CI 1.13–1.30) and CHARLS cohorts (social isolation [yes vs no]: HR 1.22, 95% CI 1.06–1.40; loneliness [yes vs no]: HR 1.21, 95% CI 1.07–1.36). These associations remained significant after accounting for baseline glucose status and genetic susceptibility to T2DM. Two-sample MR analyses determined that feeling lonely (OR 1.04, 95% CI 1.02–1.06) and engaging in fewer leisure/social activities (OR 1.03, 95% CI 1.02–1.05) were associated with increased T2DM risk, whereas more contact with friends or family (OR 0.99, 95% CI 0.98–0.99) was associated with reduced T2DM risk. Interpretation: Social isolation and loneliness are each associated with an elevated risk of T2DM, with MR analyses suggesting potential causal links. These associations remain significant after considering genetic susceptibility to T2DM. The findings highlight the importance of promoting initiatives to address social isolation and loneliness as part of T2DM prevention strategies. Funding: CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-008) and National Natural Science Foundation of China (No. 72103187).

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is a malignant disease characterized by onset occult, rapid progression, high relapse rate, and high mortality. However, data on how the tumor microenvironment (TME) regulates ICC metastasis at the transcriptomic level remains unclear. This study aimed to explore the mechanisms and interactions between hepatocytes and ICC cells. Methods We analyzed the interplay between ICC and liver microenvironment through cytokine antibody array analysis. Then we investigated the role of N6-methyladenosine (m6A) modification and the downstream target in vitro, in vivo experiments, and in clinical specimens. Results Our study demonstrated that cytokine CCL3, which is secreted by hepatocytes, promotes tumor metastasis by regulating m6A modification via vir-like m6A methyltransferase associated (VIRMA) in ICC cells. Moreover, immunohistochemical analyses showed that VIRMA correlated with poor outcomes in ICC patients. Finally, we confirmed both in vitro and in vivo that CCL3 could activate VIRMA and its critical downstream target SIRT1, which fuels tumor metastasis in ICC. Conclusions In conclusion, our results enhanced our understanding of the interaction between hepatocytes and ICC cells, and revealed the molecular mechanism of the CCL3/VIRMA/SIRT1 pathway via m6A-mediated regulation in ICC metastasis. These studies highlight potential targets for the diagnosis, treatment, and prognosis of ICC.

Abstract Background Inflammation plays a crucial role in the pathogenesis and progression of coronary artery disease (CAD). The neutrophil to lymphocyte ratio (NLR) is a novel inflammatory biomarker and its association with clinical outcomes in CAD patients with different glycemic metabolism after percutaneous coronary intervention (PCI) remains undetermined. Therefore, this study aimed to investigate the effect of NLR on the prognosis of patients undergoing PCI with or without type 2 diabetes mellitus (T2DM). Methods We consecutively enrolled 8,835 patients with CAD hospitalized for PCI at Fuwai hospital. NLR was calculated using the following formula: neutrophil (*109/L)/lymphocyte (*109/L). According to optimal cut-off value, study patients were categorized as higher level of NLR (NLR-H) and lower level of NLR (NLR-L) and were further stratified as NLR-H with T2DM and non-T2DM, and NLR-L with T2DM and non-T2DM. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as all-cause mortality, myocardial infarction (MI), stroke and target vessel revascularization. Results A total of 674 (7.6%) MACCEs were recorded during a median follow-up of 2.4 years. The optimal cut-off value of NLR was 2.85 determined by the surv_cutpoint function. Compared to those in the NLR-H/T2DM groups, patients in the NLR-L/non-T2DM, NLR-H/non-T2DM and NLR-L/T2DM groups were at significantly lower risk of 2-year MACCEs [adjusted hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.52 to 0.87, P = 0.003; adjusted HR: 0.62, 95%CI: 0.45 to 0.85, P = 0.003; adjusted HR: 0.77, 95%CI: 0.61 to 0.97, P = 0.025; respectively]. Remarkably, patients in the NLR-L/non-T2DM group also had significantly lower risk of a composite of all-cause mortality and MI than those in the NLR-H/T2DM group (adjusted HR: 0.57, 95%CI: 0.35 to 0.93, P = 0.024). Multivariable Cox proportional hazards model also indicated the highest risk of MACCEs in diabetic patients with higher level of NLR than others (P for trend = 0.009). Additionally, subgroup analysis indicated consistent impact of NLR on MACCEs across different subgroups. Conclusions Presence of T2DM with elevated NLR is associated with worse clinical outcomes in CAD patients undergoing PCI. Categorization of patients with elevated NLR and T2DM could provide valuable information for risk stratification of CAD patients.

Objective To investigate the clinical effects of microwave ablation (MWA) in addition to open surgery for the treatment of lung cancer‐derived thoracolumbar metastases. Methods This was a single‐institution, retrospective, cohort study. From January 2019 to December 2020, a total of 47 patients with lung cancer‐derived thoracolumbar metastases underwent posterior spinal canal decompression and fixation surgery in our hospital. Two independent surgical teams treated these patients. One group underwent open surgery combined with MWA therapy, while the other had open surgery only (control). The pre‐ and post‐operative visual analog scale (VAS) scores and the overall survival (OS) were compared between the MWA and control groups. The Frankel Grade classification was applied for the evaluation of the post‐surgical spinal cord function. Improvement was defined as an increase of at least one rank from the pre‐operative scores. Each patient was evaluated pre‐ and post‐operatively at 48 h, 1 month, and 3‐month intervals. Data on surgical‐related complications were recorded. Results Thirty men and 17 women were included, with an average age of 57.9 ± 11.4 years (range, 26–81 years). Twenty‐eight patients underwent MWA and were in the MWA group, and 19 patients were included in the control group. Post‐operatively all patients were followed up regularly; the median follow‐up time was 12 months (range, 3–24 months), and their median OS was 14 months. Patients in the MWA group had a lower VAS score than those in the control group at the 48‐h (1.75 ± 1.01 vs 2.47 ± 0.96, P = 0.01) and 1‐month (1.79 ± 0.92 vs 2.53 ± 1.35, P = 0.048) check‐ups. At the 3‐month evaluation, the VAS score differences between the two groups were not significant (P = 0.133). After surgery, spinal cord function improvement was not significantly different between the MWA and control groups (P = 0.515). MWA therapy combined with open surgery was not associated with increased OS compared with the control group (P = 0.492). Conclusion MWA can be an effective and safe pain‐relief method but may not extend the OS of patients with lung cancer.

Background The PRAISE (Prediction of Adverse Events Following an Acute Coronary Syndrome) score is a machine‐learning‐based model for predicting 1‐year all‐cause death, myocardial infarction, and Bleeding Academic Research Consortium (BARC) type 3/5 bleeding. Its utility in an unselected Asian population undergoing percutaneous coronary intervention for acute coronary syndrome remains unknown. We aimed to validate the PRAISE score in a real‐world Asian population. Methods and Results A total of 6412 consecutive patients undergoing percutaneous coronary intervention for acute coronary syndrome were prospectively included. The PRAISE scores were compared with established scoring systems (GRACE [Global Registry of Acute Coronary Events] 2.0, PRECISE‐DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy), and PARIS [Patterns of Non‐Adherence to Anti‐Platelet Regimen in Stented Patients]) to evaluate their discrimination, calibration, and reclassification. The risk of all‐cause mortality (hazard ratio [HR], 12.24 [95% CI, 5.32–28.15]) and recurrent acute myocardial infarction (HR, 3.92 [95% CI, 1.76–8.73]) was greater in the high‐risk group than in the low‐risk group. The C‐statistics for death, myocardial infarction, and major bleeding were 0.75 (0.67–0.83), 0.61 (0.52–0.69), and 0.62 (0.46–0.77), respectively. The observed to expected ratio of death, myocardial infarction, and major bleeding was 0.427, 0.260, and 0.106, respectively. Based on the decision curve analysis, the PRAISE score displayed a slightly greater net benefit for the 1‐year risk of death (5%–10%) than the GRACE score did. Conclusions The PRAISE score showed limited potential for risk prediction in our validation cohort with acute coronary syndrome. As a result, new prediction models or model refitting are required with improved discrimination and accuracy in risk prediction.

Collaborative autonomous landing of a quadrotor Unmanned Aerial Vehicle (UAV) on a moving Unmanned Ground Vehicle (UGV) presents challenges due to the need for accurate real-time tracking of the UGV and the adjustment for the landing policy. To address this challenge, we propose a progressive learning framework for generating an optimal landing policy based on vision without the need of communication between the UAV and the UGV. First, we propose the Landing Vision System (LVS) to offer rapid localization and pose estimation of the UGV. Then, we design an Automatic Curriculum Learning (ACL) approach to learn the landing tasks under different conditions of UGV motions and wind interference. Specifically, we introduce a neural network-based difficulty discriminator to schedule the landing tasks according to their levels of difficulty. Our method achieves a higher landing success rate and accuracy compared with the state-of-the-art TD3 reinforcement learning algorithm.

Background: Recommendations for drug treatment of left ventricular thrombus (LVT) are based on the ST-segment elevation myocardial infarction (STEMI) guidelines; however, the etiology of LVT has changed. Due to the lack of evidence regarding LVT treatment in the heart failure population, current heart failure guidelines do not cover LVT treatment. We sought to review the etiology of LVT and changes in antithrombotic therapy over the previous 12 years and explore the impact of anticoagulation treatment from a single center’s experience. Methods: From January 2009 to June 2021, we studied 1675 patients with a discharge diagnosis of LVT at a single center to investigate the clinical characteristics, incidence of all-cause death, cardiovascular death, ischemic stroke, major adverse cardiac and cerebrovascular events (MACCE), systemic embolism (SE), and major bleeding events. Patients were divided into an anticoagulant group and a non-anticoagulant group according to whether they received oral anticoagulant therapy at discharge. Results: The study included 909 patients (anticoagulation, 510; no anticoagulation, 399). While overall antiplatelet therapy dramatically decreased, more patients with LVT received oral anticoagulation in 2021 (74.0%) than in 2009 (29.6%). In addition, more than half of the patients had heart failure with reduced ejection fraction (HFrEF) each year. The all-cause mortality was 17.3% during 3.8 years of follow-up. The incidences of cardiovascular death, stroke, MACCE, SE, and major bleeding were 16.0%, 3.3%, 19.8%, 5.1%, and 1.7%, respectively. The anticoagulation group had a significantly higher proportion of dilated cardiomyopathy than the non-anticoagulation group (24.7% vs. 5.5%, p < 0.001), and a lower LVEF (34.0 vs. 41.0, p < 0.001). The anticoagulation group also had a higher probability of adverse events on long-term follow-up (p > 0.05). A multivariable competing risk regression model found no significant difference in all six endpoints between the groups (all p > 0.05). Similar results were found by matched and weighted data analysis. Diabetes mellitus (hazard ratio (HR), 1.42; 95% confidence interval (CI), 1.04–1.93; p = 0.027), renal insufficiency (HR, 2.36; 95% CI, 1.60–3.50; p < 0.001), history of previous stroke (HR, 1.60; 95% CI, 1.13–2.29; p = 0.009), and HFrEF (HR, 2.54; 95% CI, 1.78–3.64; p < 0.001) were predictors of increased risk of MACCE. Conclusions: Heart failure, rather than acute myocardial infarction, is currently the primary cause of LVT. A trend towards better prognosis in the no anticoagulation group was noted. Multivariable, matching and weighting analysis showed no improvement in prognosis with anticoagulant therapy. Our study does not negate the efficacy of anticoagulation but suggests the need to strengthen the management of anticoagulation in order to achieve better efficacy.

Background: Drug-coated balloons (DCB) have been evaluated to be safe and practical in treating coronary small vessel disease (SVD). However, evidence about the practicality and safety of DCB in treating coronary lesions with diameters greater than 3.0 mm is limited. Methods: 1166 patients who received DCB angioplasty were enrolled and divided into groups of SVD or large vessel disease (LVD) according to the target vessel diameters (

Abstract Background The recombinant human bone morphogenetic protein (rhBMP) is a common graft substitute for treating cases of long bone nonunion. However, the feasibility of combining an autologous bone graft (ABG) with rhBMPs remains uncertain. Thus, this systematic review and meta-analysis aimed to evaluate the synergistic effect of ABG and rhBMPs on the healing of long bone nonunion. Methods A systematic literature search was performed on PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure. Two authors independently screened the studies, extracted data, and assessed the quality of the trials. Statistical analyses were performed using Stata 12.0. Results Of the 202 citations, five studies involving a total of 394 cases met the eligibility criteria; thus, they were included in this study. The pooled data revealed no significant differences among the groups in terms of postoperative healing rate (risk ratio [RR] = 1.01, 95% confidence interval [CI] = 0.96–1.06, P = 0.744), healing time (standardised mean difference = − 0.20, 95% CI = − 0.95–0.56, P = 0.610), and pain (RR = 1.44, 95% CI = 0.25–8.29, P = 0.681). The combination of ABG and rhBMPs resulted in good limb function (RR = 1.31, 95% CI = 1.04–1.66, P = 0.023). Conclusions The combination of ABG and rhBMPs did not result in the healing of long bone nonunion and pain reduction. Nevertheless, it conferred good limb function. Thus, the findings in this study are insufficient to support the use of rhBMPs as an adjuvant to ABG.

Abstract Background Complex lower limb reconstruction due to severe trauma remains a challenge for reconstructive surgeons. Here, we introduce a modified donor blood flow-preserved cross-leg anterolateral thigh flap procedure and evaluate its clinical efficacy. Methods Between January 2013 and December 2019, 22 patients (range 10 to 64 years old) with unilateral lower limb injury underwent modified donor blood flow-preserved cross-leg anterolateral thigh flap procedures. Among them, 16 cases were traffic accidents, 5 cases were persistent ulcers, and 1 case was a degloving injury. The arterial pedicle of the flap was prepared in a Y-shaped fashion and microanastomosed to the posterior tibial artery of intact leg in a flow-through style. A split-thickness skin graft was applied to wrap the vascular pedicle after anastomosis. The flap was designed in a single or bilobed fashion according to the shape of the tissue defect. The operation time, the intraoperative blood loss and the length of hospital stays were recorded. The vascular pedicle was divided 4 weeks after anastomosis. Doppler ultrasound was performed to evaluate the blood flow of the donor posterior tibial artery during postoperative follow-up. Results All 22 flaps survived. The tissue defects ranged from 12 × 6 to 21 × 18 cm2. The flap sizes ranged from 14 × 7.5 to 24 × 21 cm2. The average operation time, intraoperative blood loss and length of hospital stays were 6.73 ± 1.49 h, 280.95 ± 59.25 ml and 30.55 ± 2.52 days, respectively. Eighteen flaps were designed in a single fashion, while four were in bilobed fashion. Twenty patients underwent fasciocutaneous flap transplantations, while two underwent musculocutaneous flap transplantations. Two cases developed local lysis of the flap which healed after further debridement. Direct suture of the incision after flap harvest was performed in 16 cases, while additional full-thickness skin grafting was performed in the remaining 6 cases. Further bone transport procedures were performed in 15 patients who had severe tibia bone defects. The blood flow of donor posterior tibial artery was confirmed in all patients during follow-ups. All patients recovered flap sensation at the final follow-up. The postoperative follow-ups ranged from 18 to 84 months, and no long-term complications were observed. Conclusions The modified donor blood flow-preserved cross-leg anterolateral thigh flap procedure is an ideal method to repair severe lower limb trauma with tibial artery occlusion which avoids sacrificing the major artery of the uninjured lower limb.

MEX3A is an RNA-binding protein that mediates mRNA decay through binding to 3′ untranslated regions. However, its role and mechanism in clear cell renal cell carcinoma remain unknown. In this study, we found that MEX3A expression was transcriptionally activated by ETS1 and upregulated in clear cell renal cell carcinoma. Silencing MEX3A markedly reduced clear cell renal cell carcinoma cell proliferation in vitro and in vivo. Inhibiting MEX3A induced G1/S cell-cycle arrest. Gene set enrichment analysis revealed that E2F targets are the central downstream pathways of MEX3A. To identify MEX3A targets, systematic screening using enhanced cross-linking and immunoprecipitation sequencing, and RNA-immunoprecipitation sequencing assays were performed. A network of 4,000 genes was identified as potential targets of MEX3A. Gene ontology analysis of upregulated genes bound by MEX3A indicated that negative regulation of the cell proliferation pathway was highly enriched. Further assays indicated that MEX3A bound to the CDKN2B 3′ untranslated region, promoting its mRNA degradation. This leads to decreased levels of CDKN2B and an uncontrolled cell cycle in clear cell renal cell carcinoma, which was confirmed by rescue experiments. Our findings revealed that MEX3A acts as a post-transcriptional regulator of abnormal cell-cycle progression in clear cell renal cell carcinoma.

The identification model of chlorpyrifos pesticide residues in wheat was established based on near infrared spectroscopy and stoichiometry. Wheat samples with different chlorpyrifos residues were prepared by spraying method. Near infrared diffuse reflectance spectra of samples were collected, and qualitative prediction models of factorization method, Euclidean distance method and quantitative prediction model of partial least squares method were established. The results showed that: The qualitative discrimination rate of factorization method was higher than that of Euclidean distance method, the characteristic bands of construction conditions were 5543.68~4643.72, 7582.43~6510.28 cm−1, the preprocessing method was second derivative+vector normalization+5-point smoothing, the discrimination rate could reach 96%. The characteristic bands of the construction conditions of partial least squares quantitative discrimination model were 5543.68~4643.72 cm−1, 7582.43~6510.28 cm−1, the preprocessing method was to eliminate the constant offset, the main component fraction was 7, the cross validation coefficient (R2) was 99.46, and the mean square residual (RMSECV) was 1.15. The correlation between the actual value and the predicted value was good, and the minimum detection limit was 1 mg/kg, which could accurately determine the pesticide of Chlorpyrifos in wheat. The above results showed that the discrimination rate of the qualitative analysis model established by the factorization method was as high as 96%, which could realize the qualitative analysis and identification of chlorpyrifos pesticide residues in wheat, and the partial least squares method could realize the quantitative analysis and identification with good reproducibility.

Abstract Background Coronary artery ectasia (CAE) is a rare finding in coronary angiography and associated with poor clinical outcomes. Unlike atherosclerosis, diabetes mellitus (DM) is not commonly associated with CAE. This study aims to investigate the effect of type 2 diabetes mellitus (DM2) on coronary artery ectasia, especially the differences in angiographic characteristics and clinical outcomes. Methods Patients with angiographically confirmed CAE from 2009 to 2015 were included. Quantitative coronary angiography (QCA) was performed to measure the diameter and length of the dilated lesion. The primary endpoint was the maximum diameter and maximum length of the dilated lesion at baseline coronary angiography. The secondary endpoint was 5-year major adverse cardiovascular events (MACE), which was a component of cardiovascular death and nonfatal myocardial infarction (MI). Propensity score weighting (PSW) and propensity score matching (PSM) were used to balance covariates. Kaplan–Meier method and Cox regression were performed to assess the clinical outcomes. Results A total of 1128 patients were included and 258 were combined with DM2. In the DM2 group, the maximum diameter of dilated lesion was significantly lower (5.26 mm vs. 5.47 mm, P = 0.004) and the maximum length of the dilated lesion was significantly shorter (25.20 mm vs. 31.34 mm, P = 0.002). This reduction in dilated lesion diameter (5.26 mm vs. 5.41 mm, P = 0.050 in PSW; 5.26 mm vs. 5.46 mm, P = 0.007 in PSM, respectively) and length (25.17 mm vs. 30.17 mm, P = 0.010 in PSW; 25.20 mm vs. 30.81 mm, P = 0.012 in PSM, respectively) was consistently observed in the propensity score analysis. A total of 27 cardiovascular deaths and 41 myocardial infarctions occurred at 5-year follow-up. Compared with non-DM group, there were similar risks of MACE (6.02% vs. 6.27%; HR 0.96, 95% CI 0.54–1.71, P = 0.894), cardiovascular death (2.05% vs. 2.61%; HR 0.78, 95% CI 0.29–2.05, P = 0.605) and MI (4.07% vs. 3.72%; HR 1.11, 95% CI 0.54–2.26, P = 0.782) in patients with DM2. Consistent result was observed in multivariable regression. Conclusions Compared to non-DM patients, patients with CAE and type 2 diabetes were associated with a smaller diameter and shorter length of dilated vessels, suggesting the important effect of DM2 on the pathophysiological process of CAE. Similar risks of MACE were found during 5-year follow up among diabetic and non-DM patients.

Traditional percutaneous coronary intervention (T-PCI) has long been an effective method for treating coronary heart disease (CHD), but the radiation hazards and orthopedic injuries among T-PCI operators are concerning. These problems have been mitigated with the emergence of robotic percutaneous coronary intervention (R-PCI), which is expected to increase intervention accuracy and safety. In this review, we first summarize the current status of PCI development, including robot systems, and PCI application and evaluation. Second, we compare T-PCI and R-PCI to identify the benefits for patients and physicians. In addition, we describe a new R-PCI system, R-PCI WSER-CD01, which incorporates multi-instrument collaborative delivery and provides full-process assistance in minimally invasive vascular intervention. This system introduces three key innovations that address safety concerns, and improve the accuracy, wire compatibility, and remote operation capabilities of existing of vascular intervention robot systems. Finally, we discuss prospects for the development of R-PCI. As an emerging technology, R-PCI aligns well with the trends of precision medicine and telemedicine, and therefore warrants continued innovation.

Dual antiplatelet therapy (DAPT) score emerged as a tool for quantification of ischemia and bleeding risks. However, there was discrepancy of the prediction ability of DAPT score in previous studies. We aimed to assess the utility of DAPT score in a large-scale cohort of consecutive percutaneous coronary intervention (PCI) patients. This study enrolled 9,114 patients who had undergone PCI at Fuwai Hospital in 2013, adhered to DAPT and were event-free within the first 12 months following PCI. The endpoints included primary ischemic endpoints (major adverse cardiovascular and cerebrovascular events, and myocardial infarction and/or stent thrombosis), and bleeding endpoint from 12 through 24 months after PCI. Patients were classified into low (score

Abstract Background The main cause of death in colorectal cancer patients is metastasis. Accumulating evidences suggest that circRNA plays pivotal roles in cancer initiation and development. However, the underlying molecular mechanisms of circRNAs that orchestrate cancer metastasis remain vague and need further clarification. Methods Two paired CRC and adjacent normal tissues were used to screen the upregulated circRNAs by circRNA-seq; then, cell invasion assay was applied to confirm the functional invasion-related circRNAs. According to the above methods, circHERC4 (hsa_circ_0007113) was selected for further research. Next, we investigated the clinical significance of circHERC4 in a large cohort of patients with CRC. The oncogenic activity of circHERC4 was investigated in both CRC cell lines and animal xenograft studies. Finally, we explored the molecular mechanisms underlying circHERC4 as a malignant driver. Results We demonstrated that circHERC4 was aberrantly elevated in CRC tissues (P

Abstract Background Long noncoding RNAs (lncRNAs) play important roles in many physiological and pathological processes, this indicates that lncRNAs can serve as potential targets for gene therapy. Stable expression is a fundamental technology in the study of lncRNAs. The lentivirus is one of the most widely used delivery systems for stable expression. However, it was initially designed for mRNAs, and the applicability of lentiviral vectors for lncRNAs is largely unknown. Results We found that the lentiviral vector produces lncRNAs with improper termination, appending an extra fragment of ~ 2 kb to the 3ʹ-end. Consequently, the secondary structures were changed, the RNA–protein interactions were blocked, and the functions were impaired in certain lncRNAs, which indicated that lentiviral vectors are not ideal delivery systems of lncRNAs. Here, we developed a novel lncRNA delivery method called the Expression of LncRNAs with Endogenous Characteristics using the Transposon System (ELECTS). By inserting a termination signal after the lncRNA sequence, ELECTS produces transcripts without 3ʹ-flanking sequences and retains the native features and function of lncRNAs, which cannot be achieved by lentiviral vectors. Moreover, ELECTS presents no potential risk of infection for the operators and it takes much less time. ELECTS provides a reliable, convenient, safe, and efficient delivery method for stable expression of lncRNAs. Conclusions Our study demonstrated that improper transcriptional termination from lentiviral vectors have fundamental effects on molecular action and cellular function of lncRNAs. The ELECTS system developed in this study will provide a convenient and reliable method for the lncRNA study. Graphic Abstract

BackgroundThe objective of our study was to assess whether calculated low-density lipoprotein cholesterol (LDL-C) is inferior to direct LDL-C (dLDL-C) in identifying patients at higher risk of all-cause mortality, recurrent acute myocardial infarction (AMI), and major adverse cardiovascular event (MACE).MethodsA total of 9,751 patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) in the Fuwai PCI registry were included. DLDL-C was measured by the selective solubilization method (Kyowa Medex, Tokyo, Japan). Correct classification was defined as the proportion of estimated LDL-C in the same category as dLDL-C based on dLDL-C levels: less than 1.4, 1.4–1.8, 1.8–2.6, 2.6–3.0, and 3.0 mmol/L or greater.ResultsUnderestimation of LDL-C was found in 9.7% of patients using the Martin/Hopkins equation, compared with 13.9% using the Sampson equation and 24.6% with the Friedewald equation. Cox regression analysis showed compared the correct estimation group, underestimation of LDL-C by the Martin/Hopkins equation did not reduce all-cause mortality (HR 1.26, 95% CI: 0.72–2.20, P = 0.4), recurrent AMI (HR 1.24, 95% CI: 0.69–2.21, P = 0.5), and MACE (HR 1.02, 95% CI: 0.83–1.26, P = 0.9). Similarly, the overestimated group did not exacerbate all-cause mortality (HR 0.9, 95% CI: 0.45–1.77, P = 0.8), recurrent AMI (HR 0.63, 95% CI: 0.28–1.44, P = 0.3), and MACE (HR 1.07, 95% CI: 0.86–1.32, P = 0.6). The results of the diabetes subgroup analysis were similar to those of the whole population.ConclusionCompared with dLDL-C measurement, misclassification by the Martin/Hopkins and Sampson equations was present in approximately 20% of patients. However, directly measured vs. calculated LDL-C did not identify any more individuals in the PCI population with increased risk of all-cause mortality, recurrent AMI, and MACE, even in high-risk patients such as those with diabetes.

BackgroundThe optimal treatment strategy for patients with coronary intermediate lesions, defined as diameter stenosis of 50–70%, remains a great challenge for cardiologists. Identification of potential biomarkers predictive of major adverse cardiovascular events (MACEs) risk may assist in risk stratification and clinical decision.MethodsA total of 1,187 patients with intermediate coronary lesions and available N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were enrolled in the current study. A baseline NT-proBNP level was obtained. The primary endpoint was defined as MACEs, the composite endpoint of all-cause death and non-fatal myocardial infarction. A multivariate Cox regression model was used to explore the association between NT-proBNP level and MACE risk.ResultsThe mean age of the study cohort was 59.2 years. A total of 68 patients experienced MACE during a median follow-up of 6.1 years. Restricted cubic spline analysis delineated a linear relationship between the baseline NT-proBNP level and MACE risk. Both univariate and multivariate analyses demonstrated that an increased NT-proBNP level was associated with an increased risk of MACE [adjusted hazard ratio (HR) per doubling: 1.412, 95% confidence interval (CI): 1.022–1.952, p = 0.0365]. This association remains consistent in clinical meaningful subgroups according to age, sex, body mass index (BMI), and diabetes.ConclusionAn increased NT-proBNP level is associated with an increased risk of MACE in patients with intermediate coronary lesions and may serve as the potential biomarker for risk stratification and treatment decision guidance.

The benefits and harms of dual antiplatelet therapy (DAPT) continuation with aspirin and clopidogrel beyond 1 year after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation for high ischemic or bleeding risk patients remain unclear. All consecutive patients undergoing PCI were prospectively included in the Fuwai PCI Registry from January 2013 to December 2013. We evaluated 7521 patients who were at high risk for thrombotic or hemorrhagic complications and were events free at 1 year after the index procedure. “TWILIGHT-like” patients with high risk of bleeding or ischemic events were defined by clinical and angiographic criteria. The primary ischemic outcome was major adverse cardiac and cerebrovascular events [MACCE] (a composite of all-cause death, myocardial infarction, or stroke). Median follow-up duration was 2.4 years. The risk of MACCE was significantly lower in DAPT>1-year group (n = 5252) than DAPT≤1-year group (n = 2269) (1.5% vs. 3.8%; hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.27–0.50; P

BackgroundThe prognostic effect of admission blood glucose (ABG) for patients with acute myocardial infarction (AMI) has not been well validated, especially in patients with diabetes. We performed this study to assess the predictive value of ABG for all-cause mortality in AMI patients with different glucose metabolism status.MethodsWe evaluated a total of 6,892 AMI patients from the prospective, nationwide, multicenter CAMI registry, of which 2,820 had diabetes, 2,011 had pre-diabetes, and 2,061 had normal glucose regulation (NGR). Patients were divided into high ABG and low ABG groups according to the optimal cutoff values of ABG to predict 2-year mortality for patients with diabetes, pre-diabetes and NGR, respectively. The primary endpoint was all-cause mortality.ResultsThe optimal cutoff values of ABG for predicting 2-year mortality was 9.0mmol/l, 7.2mmol/l and 6.2mmol/l for patients with diabetes, pre-diabetes and NGR, respectively. Overall, the risk of all-cause mortality in high ABG group was significantly increased compared with that in low ABG group among patients with diabetes (15.2% vs. 8.9%; hazard ratio [HR] 1.787, 95% confidence interval [CI] 1.413-2.260; P

Background Lp(a) (lipoprotein[a]) plays an important role in predicting cardiovascular events in patients with coronary artery disease through its proatherogenic and prothrombotic effects. We hypothesized that prolonged dual antiplatelet therapy (DAPT) might be beneficial for patients undergoing percutaneous coronary intervention who had elevated Lp(a) levels. This study aimed to evaluate the effect of Lp(a) on the efficacy and safety of prolonged DAPT versus shortened DAPT in stable patients with coronary artery disease who were treated with a drug‐eluting stent. Methods and Results We selected 3201 stable patients with CAD from the prospective Fuwai Percutaneous Coronary Intervention Registry, of which 2124 patients had Lp(a) ≤30 mg/dL, and 1077 patients had Lp(a) >30 mg/dL. Patients were divided into 4 groups according to Lp(a) levels and the duration of DAPT therapy (≤1 year versus >1 year). The primary end point was major adverse cardiovascular and cerebrovascular event, defined as a composite of all‐cause death, myocardial infarction, or stroke. The median follow‐up time was 2.5 years. Among patients with elevated Lp(a) levels, DAPT >1 year presented lower risk of major adverse cardiovascular and cerebrovascular event and definite/probable stent thrombosis compared with DAPT ≤1 year. In contrast, in patients with normal Lp(a) levels, the risks of major adverse cardiovascular and cerebrovascular event and definite/probable stent thrombosis were not significantly different between the DAPT >1 year and DAPT ≤1 year groups. Prolonged DAPT had 2.4‐times higher risk of clinically relevant bleeding than shortened DAPT in patients with normal Lp(a) levels, although without statistical difference. Conclusions In stable patients with coronary artery disease, who underwent percutaneous coronary intervention with a drug‐eluting stent, prolonged DAPT was associated with reduced risk of cardiovascular events among those with elevated Lp(a) levels, whereas it did not show statistically significant evidence of benefit for reducing ischemic events and tended to increase clinically relevant bleeding among those with normal Lp(a) levels.

Considering the fact that only pores can transport water, pores in the homogeneous control volume are conceptualized as a three-dimensional orthogonal network of line elements, which is in contrast to the continuum hypothesis in traditional numerical approaches. The related flow velocity, hydraulic conductivity and continuity equation equivalent to the continuum model are formulated based on the principle of flow balance. Subsequently, the unified form for flow velocity and continuity equation is established based on the local coordinate system, and a finite line-element method is developed, in which three-dimensional steady free surface flow is reduced to one-dimensional form, and the numerical difficulty is greatly decreased. The proposed line-element model is validated by the good agreements of free surface locations with other methods through steady flow in a rectangular dam and a right trapezoidal dam, respectively. It is found that the proposed line-element model is not heavily dependent on the mesh size and penalty parameter. Steady free surface flow on the left bank abutment slope of the Kajiwa Dam in Southwestern China is further evaluated, and a parabolic variational inequality algorithm based on the continuum model is also employed for comparison. The consistent results indicate that the proposed line-element model can capture the steady free surface flow behavior as well as the continuum-based method. Moreover, the proposed line-element model can rapidly achieve accurate solutions whether for simple examples or for complicated engineering applications.

Path planning using handcrafted waypoints is inefficient for a multi-task UAV operating in dynamic environments with potential risks such as bad weather, obstacles, or forbidden zones, among others. In this paper, we propose an automatic path planning method through natural language that instructs the UAV with compound commands about the tasks and the corresponding regions in a given map. First, we analyze the characteristics of the tasks and we model each task with a parameterized zone. Then, we use deep neural networks to segment the natural language commands into a sequence of labeled words, from which the semantics are extracted to select the waypoints and trajectory patterns accordingly. Finally, paths between the waypoints are generated using rapidly exploring random trees (RRT) or Dubins curves based on the task requirements. We demonstrate the effectiveness of the proposed method using a simulated quadrotor UAV that follows sequential commands in four typical tasks with potential risks.

Background: The focus of this investigation into the impact of type 2 diabetes mellitus (T2DM) on left ventricular thrombus (LVT) is (a) the differences in LVT characteristics, (b) long-term clinical outcomes, and (c) differential effects of direct oral anticoagulants (DOAC) among patients with T2DM and without diabetes. Methods: Patients with confirmed LVT from 2009 to 2021 were included. The primary endpoints were major adverse cardiac and cerebrovascular events (MACCE), composite of cardiovascular death, ischemic stroke, and acute myocardial infarction (AMI). The secondary endpoints were all-cause death and cardiovascular death. Multivariable competing-risk regression and cumulative incidence functions (CIF) were used to evaluate the adverse consequences. Results: In total, 1675 patients were assessed initially. Follow-up data were available for 91.1% of the participants. Median follow-up was 3.8 years. This retrospective study ultimately comprised 1068 participants, of which 429 had T2DM. Significantly higher proportions of comorbidities were observed in the T2DM group. The location, morphology, and size of LVT were similar in the two groups. Multivariable analysis suggested a higher risk of MACCE among patients with T2DM. The difference in risk between the two groups after matching and weighting was not statistically significant. Among the whole sample (n = 638) or the just the non-diabetic patients with LVT and anticoagulation (n = 382), the incidence of MACCE did not differ between DOAC treatment and warfarin treatment. In the diabetic LVT population with anticoagulation (n = 256), DOAC treatment was associated with a significantly higher risk of MACCE than was warfarin treatment. Conclusions: The location and morphology of LVT are similar in T2DM and non-diabetic patients. A higher risk of MACCE was found among patients with diabetes.

Abstract Background A large number of pig breeds are distributed around the world, their features and characteristics vary among breeds, and they are valuable resources. Understanding the underlying genetic mechanisms that explain across-breed variation can help breeders develop improved pig breeds. Results In this study, we performed GWAS using a standard mixed linear model with three types of genome variants (SNP, InDel, and CNV) that were identified from public, whole-genome, sequencing data sets. We used 469 pigs of 57 breeds, and we identified and analyzed approximately 19 million SNPs, 1.8 million InDels, and 18,016 CNVs. We defined six biological phenotypes by the characteristics of breed features to identify the associated genome variants and candidate genes, which included coat color, ear shape, gradient zone, body weight, body length, and body height. A total of 37 candidate genes was identified, which included 27 that were reported previously (e.g., PLAG1 for body weight), but the other 10 were newly detected candidate genes (e.g., ADAMTS9 for coat color). Conclusion Our study indicated that using GWAS across a modest number of breeds with high density genome variants provided efficient mapping of complex traits.

Super-enhancers (SEs) comprise large clusters of enhancers that highly enhance gene expression. Long non-coding RNAs (lncRNAs) tend to be dysregulated in cases of stomach adenocarcinoma (STAD) and are vital for balancing tumor immunity. However, whether SE-associated lncRNAs play a role in the immune infiltration of STAD remains unknown. In the present study, we identified SE-associated lncRNAs in the H3K27ac ChIP-seq datasets from 11 tumor tissues and two cell lines. We found that the significantly dysregulated SE-associated lncRNAs were strongly correlated with immune cell infiltration through the application of six algorithms (ImmuncellAI, CIBERSORT, EPIC, quantiSeq, TIMER, and xCELL), as well as immunomodulators and chemokines. We found that the expression of SE-associated lncRNA TM4SF1-AS1 was negatively correlated with the proportion of CD8+ T cells present in STAD. TM4SF1-AS1 suppresses T cell-mediated immune killing function and predicts immune response to anti-PD1 therapy. ChIP-seq, Hi-C and luciferase assay results verified that TM4SF1-AS1 was regulated by its super-enhancer. RNA-seq data showed that TM4SF1-AS1 is involved in immune and cancer-related processes or pathways. In conclusion, SE-associated lncRNAs are involved in the tumor immune microenvironment and act as indicators of clinical outcomes in STAD. This study highlights the importance of SE-associated lncRNAs in the immune regulation of STAD.

ObjectiveJailed balloon technique (JBT) is an active side branch (SB) protection strategy and is considered to be superior to the jailed wire technique (JWT) in reducing SB occlusion. However, no randomized trials have proved that. We aim to investigate whether JBT could decrease the SB occlusion rate.MethodsConventional versus Intentional straTegy in patients with high Risk prEdiction of Side branch OccLusion in coronary bifurcation interVEntion (CIT-RESOLVE) (NCT02644434, registered on December 31, 2015) (https://clinicaltrials.gov) is a randomized trial that assessed the effects of different strategies on SB occlusion rate in patients with a high risk of SB occlusion. The present subgroup analysis enrolled bifurcation lesions (2 mm ≤ reference vessel diameter of SB < 2.5 mm) with Visual estimation for Risk prEdiction of Side branch OccLusion in coronary bifurcation intervention (V-RESOLVE) score ≥ 12 points. The primary endpoint is SB occlusion. One-year clinical events were compared.ResultsA total of 284 subjects at 16 sites were randomly assigned to the JBT group (n = 143) or the JWT group (n = 141). The rate of SB occlusion (9.1 vs. 19.9%, p = 0.02) and periprocedural myocardial infarction (defined by WHO, 7 vs. 14.9%, p = 0.03) is significantly lower in the JBT group than in the JWT group. The JBT and JWT groups showed no significant differences in cardiac death (0.7 vs. 0.7%, p = 1), myocardial infarction (MI, 6.3 vs. 7.1%, p = 0.79), target lesion revascularization (TLR, 1.4 vs. 2.1%, p = 0.68), and major cardiac adverse events (MACE, a composite of all-cause death, MI, or TLR, 8.4 vs. 10.6%, p = 0.52) during a 1-year follow-up.ConclusionIn patients with a high risk of SB occlusion (V-RESOLVE score ≥ 12 points), JBT is superior to JWT in reducing SB occlusion. However, no significant differences were detected in 1-year MACE.

Background: The relative benefit of immediate complete revascularization, staged complete revascularization, and culprit-only percutaneous coronary intervention (PCI) remains unclear in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. The aim of this study was to compare the clinical outcomes of the 3 PCI strategies in this population.Methods: We followed a pre-specified protocol (PROSPERO number: CRD42020183801). A comprehensive search of the electronic databases including PubMed, EMBASE and Cochrane Library from inception through February 21, 2020 was conducted. Randomized trials evaluating the comparative efficacy and safety of at least 2 of the 3 PCI strategies were identified. The primary endpoint was the composite of cardiovascular mortality or myocardial infarction (MI) during the longest follow-up. Pairwise and network meta-analyses were performed with random-effects model.Results: Eleven trials including 6,942 patients were analyzed. Pairwise meta-analysis noted that immediate complete revascularization and staged complete revascularization were respectively associated with a 52 and 27% reduction in the risk of cardiovascular death or MI (relative risk [RR] 0.48, 95% confidence interval [CI] 0.32–0.73, I2 = 0%; and RR 0.73, 95% CI 0.61–0.88, I2 = 0%, respectively), compared with culprit-only PCI. The risk of cardiovascular death or MI was not statistically different in staged and immediate complete revascularization groups (RR 0.88, 95% CI 0.45–1.72, I2 = 0%). Network meta-analysis obtained almost similar results compared with pairwise meta-analysis, and immediate complete revascularization had a 77% probability of being the best strategy for reducing cardiovascular death or MI among the 3 PCI strategies.Conclusion: The current evidence suggests that both immediate and staged complete revascularization were associated with a reduction of cardiovascular death or MI compared with culprit-only PCI. Further trials are warranted to directly compare immediate vs. staged complete revascularization in this population.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, PROSPERO [CRD42020183801].

Abstract Background Whether the underlying risk of high bleeding risk (HBR) influences the relationship of high thrombotic risk (HTR) features with adverse events after drug-eluting stent implantation remains unclear. The purpose of this study was to evaluate (1) the prognostic effect of ESC guideline-endorsed HTR features on long-term clinical outcomes and (2) whether the outcomes of HTR versus non-HTR features vary by HBR status. Methods Ten thousand one hundred sixty-seven consecutive patients who underwent percutaneous coronary intervention between January 2013 and December 2013 were prospectively enrolled in Fuwai PCI Registry. Patients who are at HTR were defined as: diffuse multivessel disease in diabetic patients, chronic kidney disease, at least three stents implanted, at least three stents lesions treated, bifurcation with two stents implanted, total stent length > 60 mm, or treatment of chronic total occlusion. The definition of HBR was based on the Academic Research Consortium for HBR criteria. The primary ischemic outcome was major adverse cardiac event (MACE), a composite of cardiac death, myocardial infarction, target vessel revascularization and stent thrombosis. The primary bleeding outcome was clinically relevant bleeding, defined according to Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. Results With a 2.4-year median follow-up, 4430 patients (43.6%) having HTR experienced a significantly higher risk of MACE (hazard ratio [HR] adjust: 1.56, 95% confidence interval [CI]: 1.34–1.82; P 0.05); however, adverse event rates were highest among subjects with both HTR and HBR. Conclusions ESC guideline-endorsed HTR was associated with significantly increased risk of MACE without any significant differences in clinically relevant bleeding. The presence of HBR does not emerge as a modifier of cardiovascular risk for patients at HTR, suggesting more potent and longer antiplatelet therapy may be beneficial for this patient population.

Abstract Background Thoracolumbar burst fractures can be treated with posterior short-segment fixation. However, no classification can help to estimate whether the healed vertebral body will have sufficient stability after implant removal. We aimed to develop a Healing Pattern Classification (HPC) to evaluate the stability of the healed vertebra based on cavity size and location. Methods Fifty-two thoracolumbar burst fracture patients treated with posterior short-segmental fixation without fusion and followed up for an average of 3.2 years were retrospectively studied. The HPC was divided into 4 types: type I - no cavity; type II - a small cavity with or without the violation of one endplate; type III - a large cavity with or without the violation of one endplate; and type IV - a burst cavity with the violation of both endplates or the lateral cortical shell. The intraobserver and interobserver intraclass correlation coefficients (ICCs) of the HPC were assessed. The demographic characteristics and clinical outcomes of the cohort were compared between the stable group (types I and II) and the unstable group (types III and IV). Logistic regression was conducted to evaluate risk factors for unstable healing. Results The intraobserver and interobserver ICCs of the HPC were 0.86 (95% CI = 0.74–0.90) and 0.77 (95% CI = 0.59–0.86), respectively. While the unstable healing group (types III and IV) accounted for 59.6% of the patients, most of these patients were asymptomatic. The preoperative Load Sharing Classification (LSC) comminution score may predict the occurrence of unstable healing (OR = 8.4, 95% CI = 2.4–29.7). Conclusions A reliable classification for assessing the stability of a healed vertebra was developed. With type I and II healing, the vertebra is considered stable, and the implant can be removed. With type III healing, the vertebra may have healing potential, but the implant should not be removed unless type II healing is achieved. With type IV healing, the vertebra is considered extremely unstable, and instrumentation should be maintained. Assessing the LSC comminution score preoperatively may help to predict unstable healing after surgery.

Abstract Background The main objectives of this study were as follows: (1) evaluate the prevalence of burnout syndrome among doctors, (2) establish associations with demographic factors in China, and (3) examine the mediating role of psychological attachment in the relationship between job burnout and career calling. Methods This cross-sectional survey was conducted by administering an online questionnaire in May 2016. The survey was performed across Thirty provinces. In total, A total of 3016 Chinese doctors were selected as participants, of which 2617 completed valid questionnaires (effective response rate: 86.77%). Results The overall prevalence of burnout symptoms among Chinese doctors was 85.79%. Little variance was reported for burnout symptoms according to age (Waldχ 2 = 6.843, P 1), and daily working hours (Waldχ 2 = 7.226, P 1). However, the burnout of Chinese doctors was found to be associated with psychological attachment (B = − 0.6433, P

Abstract Background Recent evidences have shown that circular RNAs (circRNAs) are frequently dysregulated and play paramount roles in various cancers. circRNAs are abundant in central nervous system (CNS); however, few studies describe the clinical significance and role of circRNAs in gliomas, which is the most common and aggressive primary malignant tumor in the CNS. Methods A bioinformatics analysis was performed to profile and screen the dyregulated circRNAs during early neural development. Quantitative real-time PCR was used to detect the expression of circ-MAPK4 and target miRNAs. Glioma cells were transfected with circ-MAPK4 siRNAs, then cell proliferation, apoptosis, transwell assays, as well as tumorigenesis and TUNEL assays, were performed to examine effect of circ-MAPK4 in vitro and vivo. Biotinylated-circ-MAPK4 probe based pull-down assay was conducted to confirm the relationship between circ-MAPK4 and miR-125-3p. Results In this study, we identified a circRNA, circ-MAPK4 (has_circ_0047688), which was downregulated during early neural differentiation. In gliomas, circ-MAPK4 acted as an oncogene, was inversely upregulated and linked to clinical pathological stage of gliomas (P

Reports indicate that the mechanism of doxorubicin (Dox)-induced cardiotoxicity is very complex, involving multiple regulatory cell death forms. Furthermore, the clinical intervention effect is not ideal. Iron dependence, abnormal lipid metabolism, and excess reactive oxygen species generation, three characteristics of ferroptosis, are potential therapeutic intervention targets. Here, we confirmed in vitro and in vivo that at least autophagy, apoptosis, and ferroptosis are involved in Dox cardiotoxicity-induced damage. When the neonatal rat cardiomyocytes and H9C2 cells or C57BL/6 mice were subjected to Dox-induced cardiotoxicity, epigallocatechin-3-gallate pretreatment could effectively decrease iron accumulation, inhibit oxidative stress and abnormal lipid metabolism, and thereby alleviate Dox cardiotoxicity-induced ferroptosis and protect the myocardium according to multiple functional, enzymatic, and morphological indices. The underlying mechanism was verified to involve the upregulation and activation of AMP-activated protein kinase α2, which promoted adaptive autophagy, increased energy supply, and maintained mitochondrial function. We believe that epigallocatechin-3-gallate is a candidate phytochemical against Dox-induced cardiotoxicity.

Background: Lipoprotein(a) is positively related to cardiovascular events in patients with coronary artery disease (CAD). Given that lipoprotein(a) has a prothrombotic effect, prolonged dual antiplatelet therapy (DAPT) might have a beneficial effect on reducing ischemic events in patients with elevated lipoprotein(a) levels after percutaneous coronary intervention (PCI). We performed this study to assess the efficacy and safety of prolonged DAPT (>1 year) in this population.Methods: We evaluated a total of 3,025 CAD patients with elevated lipoprotein(a) levels who were event-free at 1 year after PCI from the prospective Fuwai PCI Registry, of which 913 received DAPT ≤ 1 year and 2,112 received DAPT>1 year. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction or stroke.Results: After a median follow-up of 2.4 years, patients who received DAPT>1 year were associated with lower risks of MACCE compared with DAPT ≤ 1 year (1.6 vs. 3.8%; hazard ratio [HR] 0.383, 95% confidence interval [CI] 0.238–0.616), which was primarily driven by the lower all-cause mortality (0.2 vs. 2.3%; HR 0.078, 95% CI 0.027–0.227). In addition, DAPT>1 year was also associated with lower risks of cardiac death, and definite/probable stent thrombosis than those who received DAPT ≤ 1 year (P < 0.05). Conversely, no difference was found between the two groups in terms of clinically relevant bleeding. Similar results were observed in multivariate Cox regression analysis and inverse probability of treatment weighting analysis.Conclusions: In patients with elevated lipoprotein(a) concentrations after PCI, prolonged DAPT (>1 year) reduced ischemic cardiovascular events, including MACCE, all-cause mortality, cardiac mortality, and definite/probable stent thrombosis, without increase in clinically relevant bleeding risk compared with ≤ 1-year DAPT. Lipoprotein(a) levels might be a new important consideration when deciding the duration of DAPT after PCI.

Background: Coronary artery ectasia (CAE) is found in about 1% of coronary angiography and is associated with poor clinical outcomes. The prognostic value of plasma big Endothelin-1 (ET-1) in CAE remains unknown.Methods: Patients with angiographically confirmed CAE from 2009 to 2015, who had big ET-1 data available were included. The primary outcome was 5-year major adverse cardiovascular events (MACE), defined as a component of cardiovascular death and non-fatal myocardial infarction (MI). Patients were divided into high or low big ET-1 groups using a cut-off value of 0.58 pmol/L, according to the receiver operating characteristic curve. Kaplan-Meier method, propensity score method, and Cox regression were used to assess the clinical outcomes in the 2 groups.Results: A total of 992 patients were included, with 260 in the high big ET-1 group and 732 in the low big ET-1 group. At 5-year follow-up, 57 MACEs were observed. Kaplan-Meier analysis and univariable Cox regression showed that patients with high big ET-1 levels were at increased risk of MACE (9.87 vs. 4.50%; HR 2.23, 95% CI 1.32–3.78, P = 0.003), cardiovascular death (4.01 vs. 1.69%; HR 2.37, 95% CI 1.02–5.48, P = 0.044), and non-fatal MI (6.09 vs. 2.84%; HR 2.17, 95% CI 1.11–4.24, P = 0.023). A higher risk of MACE in the high big ET-1 group was consistent in the propensity score matched cohort and propensity score weighted analysis. In multivariable analysis, a high plasma big ET-1 level was still an independent predictor of MACE (HR 1.82, 95% CI 1.02–3.25, P = 0.043). A combination of high plasma big ET-1 concentrate and diffuse dilation, when used to predict 5-year MACE risk, yielded a C-statistic of 0.67 (95% CI 0.59–0.74).Conclusion: Among patients with CAE, high plasma big ET-1 level was associated with increased risk of MACE, a finding that could improve risk stratification.

BackgroundIn China, ischemic heart disease is the main cause of mortality. Having cardiac rehabilitation and a secondary prevention program in place is a class IA recommendation for individuals with coronary artery disease. WeChat-based interventions seem to be feasible and efficient for the follow-up and management of chronic diseases. ObjectiveThis study aims to evaluate the effectiveness of a tertiary A-level hospital, WeChat-based telemedicine intervention in comparison with conventional community hospital follow-up on medication adherence and risk factor control in individuals with stable coronary artery disease. MethodsIn this multicenter prospective study, 1424 patients with stable coronary artery disease in Beijing, China, were consecutively enrolled between September 2018 and September 2019 from the Fuwai Hospital and 4 community hospitals. At 1-, 3-, 6-, and 12-month follow-up, participants received healthy lifestyle recommendations and medication advice. Subsequently, the control group attended an offline outpatient clinic at 4 separate community hospitals. The intervention group had follow-up visits through WeChat-based telemedicine management. The main end point was medication adherence, which was defined as participant compliance in taking all 4 cardioprotective medications that would improve the patient’s outcome (therapies included antiplatelet therapy, β-blockers, statins, and angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers). Multivariable generalized estimating equations were used to compare the primary and secondary outcomes between the 2 groups and to calculate the relative risk (RR) at 12 months. Propensity score matching and inverse probability of treatment weighting were performed as sensitivity analyses, and propensity scores were calculated using a multivariable logistic regression model. ResultsAt 1 year, 88% (565/642) of patients in the intervention group and 91.8% (518/564) of patients in the control group had successful follow-up data. We matched 257 pairs of patients between the intervention and control groups. There was no obvious advantage in medication adherence with the 4 cardioprotective drugs in the intervention group (172/565, 30.4%, vs 142/518, 27.4%; RR 0.99, 95% CI 0.97-1.02; P=.65). The intervention measures improved smoking cessation (44/565, 7.8%, vs 118/518, 22.8%; RR 0.48, 95% CI 0.44-0.53; P

Objective: MicroRNAs (miRNAs) regulate gene expression and are involved in diabetic kidney disease (DKD) pathogenesis. We investigated circulating miRNA-194 levels as a biomarker of DKD prevalence and incidence, and the relationship between miRNA-194 and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP). Methods: We recruited 136 type-2 diabetes mellitus (T2DM) patients at the First People’s Hospital of Lianyungang and 127 healthy individuals. Circulating miRNA-194 and CHOP levels were measured using quantitative reverse transcription qRT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Anthropometric and biochemistry measurements were also made. Results: T2DM patients showed higher circulating miRNA-194 ( p = 0.029) and lower circulating CHOP ( p 300 ( p = 0.030, 0.013,

Background: Clinical guidelines recommend surgical intervention when left ventricular thrombus (LVT) is complicated with left ventricular aneurysm (LVA). Objectives: This study aimed to review the changes in the treatment of LVT combined with LVA over the past 12 years at our center and to compare the efficacy of medical therapy and surgical treatment on patient outcomes. Methods: Between January 2009 and June 2021, 723 patients with LVT combined with LVA were enrolled, of whom 205 received surgical ventricular reconstruction (SVR) therapy and 518 received medical therapy. The following clinical outcomes were gathered via observation: all-cause death, cardiovascular death, and major adverse cardiovascular and cerebrovascular events (MACCEs; defined as the composite of cardiovascular death, ischemic stroke, and acute myocardial infarction). The median follow-up time was 1403 [707, 2402] days. Results: The proportion of SVR dropped yearly in this group of patients, from a peak of 64.5% in 2010 to 7.5% in 2021 (p for trend < 0.001). Meanwhile, the proportion of anticoagulant use increased quickly, from 8.0% in 2016 to 67.9% in 2021 (p for trend < 0.001). The incidence rates of all-cause mortality, cardiovascular death, and MACCEs were 12.9% (n = 93), 10.5% (n = 76), and 14.7% (n = 106), respectively. In the multivariable analysis, there were no significant differences in all-cause death (HR of 0.60, 95% CI of 0.32–1.13, p = 0.11), cardiovascular death (HR of 0.79, 95% CI of 0.41–1.50, p = 0.5), and MACCEs (HR of 0.82, 95% CI of 0.49–1.38, p = 0.5) between the two groups. The competing risk regression performed in the propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses was in line with the unmatched analysis. Conclusions: The rate of SVR dropped significantly among patients with both LVT and LVA, while there was an improvement in oral anticoagulant utilization. SVR with thrombus removal did not improve all-cause mortality and cardiovascular outcomes in patients with LVT and LVA. Ventricular aneurysm with thrombus may not be an indication for surgery.

Background and aims: Our goals in the study were to (1) quantify the discordance in LDL-C levels between equations (the Friedewald, Sampson, and Martin/Hopkins equations) and compare them with direct LDL-C (dLDL-C); and (2) explore the proportion of misclassified patients by calculated LDL-C using these three different equations. Methods: A total of 30,349 consecutive patients with angiographically confirmed coronary artery disease (CAD) were prospectively enrolled. Concordance was defined as if the LDL-C was Results: The concordance was 96.3% (Sampson vs. Martin/Hopkins), 95.0% (Friedewald vs. Sampson), and 91.4% (Friedewald vs. Martin/Hopkins), respectively. This proportion fell to 82.4% in those with hypertriglyceridemia (TG ≥ 1.7 mmol/L). With an accurate classification rate of 73.6%, the Martin/Hopkins equation outperformed the Sampson equation (69.5%) and the Friedewald equation (59.3%) by a wide margin. Conclusions: Comparing it to the validated Martin/Hopkins equation, the Friedewald equation produced the lowest levels of LDL-C, followed by the Sampson equation. In the classification of LDL-C, the Martin/Hopkins equation has also been shown to be more accurate. There is a significant difference between the equations and the direct measurement method, which may lead to overtreatment or undertreatment.

Background: Transradial artery (TRA) access for percutaneous coronary intervention (PCI) was associated with lower risks of major bleeding and vascular complications compared to transfemoral artery access. Use of large-bore (≥7-Fr) guiding catheters through TRA approach increased the likelihood of radial artery occlusion (RAO). This study aimed to investigate whether use of the thin-walled 7-Fr Glidesheath Slender, allowing PCI with large-caliber guiding catheters, is superior to standard 7-Fr Cordis sheath with respect to periprocedural RAO within 24 hours after transradial coronary intervention (TRI) in complex lesions. Methods: A prospective randomized, controlled, single-blinded (patient-blinded) trial was conducted, randomizing 504 patients with TRI for complex lesions to either 7-Fr Glidesheath Slender or conventional 7-Fr Cordis sheath. The primary outcome was defined as the incidence of periprocedural RAO with Doppler ultrasound during the first 24 hours after TRI. Results: The incidence of early RAO was 10.3% for 7-Fr Glidesheath Slender and 13.5% for conventional 7-Fr sheath (p = 0.271). The procedural success rate for Glidesheath Slender was 92.9% and for Cordis sheath was 93.7% (p = 0.722). There was no signficiant difference between treatment arms in terms of local hematoma and radial spasm, whereas use of the Glidesheath Slender was associated with significantly less pain during the procedure (numeric rating scale [NRS], 2.27 ± 0.75 vs. 2.45 ± 0.95, p = 0.017). The assessment of radial artery in ultrasound parameters after complex TRI was improved with Glidesheath Slender. Conclusions: Among patients with complex coronary lesions undergoing TRI, 7-Fr Glidesheath Slender was not superior to conventional 7-Fr in the prevention of periprocedural RAO within 24 hours following complex PCI, without reducing RAO occurrence. Clinical Trial Registration: NCT04748068.