Amentoflavone alleviated cartilage injury and inflammatory response of knee osteoarthritis through PTGS2.

The role of amentoflavone on cartilage injury in knee osteoarthritis (KOA) rats and the underlying mechanism were explored. KOA rat and IL-1ß-stimulated chondrocyte models were constructed. MTT, colony formation, and ELISA were performed to determine the cytotoxicity, cell proliferation, and inflammatory factors. The role of PTGS2 in IL-1ß-stimulated chondrocytes was also confirmed through transfecting PTGS2 overexpression and silencing plasmids. Further, we analyzed how amentoflavone regulated PTGS2 to improve IL-1ß-stimulated chondrocytes in vitro. Additionally, we analyzed the expression of PTGS2 after amentoflavone treatment. In vivo, HE and Safranin-O staining were carried out, and the inflammatory response was detected by ELISA and HE staining. In addition, we also analyzed the regulatory effect of amentoflavone on PTGS2 and explored the mechanism effect of PTGS2 in vitro and in vivo. The results indicated that PTGS2 was the downstream molecule of amentoflavone, which was highly expressed in IL-1ß-stimulated chondrocytes and KOA rats, and amentoflavone decreased PTGS2 expression. We also confirmed the potential role of amentoflavone on KOA, which was also characterized by the repair of cartilage injury, reduction of inflammatory infiltration, and improvement of functional disability. Consistent with in vivo results, in vitro experiments gave the same conclusions. Amentoflavone reduced PTGS2 expression in IL-1ß-stimulated chondrocytes and inhibited inflammation of chondrocytes via PTGS2. Collectively, the results confirmed that this drug was the potential targeted drug for KOA, whose repair effect on cartilage injury was partly related to PTGS2.

Naps and cardiovascular disease risk in different age and sex groups: evidence from a large community cohort.

STUDY OBJECTIVES: This study examined the relationship between naps and cardiovascular disease (CVD) events or death in different age and sex groups. METHODS: A total of 3069 participants stratified by age (<65, 65-74, and ≥75 years old) and sex, underwent Cox regression analysis to assess nap's impact on CVD risk. Restricted cubic spline plots (RCS) were used for dose-response relationships. RESULTS: Significant age-stratified interactions were found when exploring the associations between nap frequency or duration and CVD events (P interaction = 0.001, 0.036 respectively). Individuals younger than 65 years with higher nap frequency or longer nap duration had a significantly increased risk of CVD events (P < 0.001, P = 0.001 respectively). The age group of 65-74 years showed significant associations between CVD events and nap frequency or nap duration (P = 0.017, 0.016 respectively), together with nap duration and CVD deaths (P = 0.008). In the subgroup of females aged 65-74, significant associations were found between nap frequency or duration and CVD events (P = 0.006, 0.002 respectively). Nap frequency or duration was also significantly associated with CVD deaths (P =0.005, 0.010 respectively). CONCLUSIONS: This study underscores a noteworthy correlation between a higher frequency or longer duration of daytime nap and an increased susceptibility to CVD among individuals aged 65-74 years, particularly in females. However, further research is needed to better understand the underlying mechanisms.

The influence of pressure injury risk on the association between left ventricular ejection fraction and all-cause mortality in patients with acute myocardial infarction 80 years or older.

BACKGROUND: We aimed to investigate whether the pressure injury risk mediates the association of left ventricular ejection fraction (LVEF) with all-cause death in patients with acute myocardial infarction (AMI) aged 80 years or older. METHODS: This retrospective cohort study included 677 patients with AMI aged 80 years or older from a tertiary-level hospital. Pressure injury risk was assessed using the Braden scale at admission, and three risk groups (low/minimal, intermediate, high) were defined according to the overall score of six different variables. LVEF was measured during the index hospitalization for AMI. All-cause death after hospital discharge was the primary outcome. RESULTS: Over a median follow-up period of 1,176 d (interquartile range [IQR], 722-1,900 d), 226 (33.4%) patients died. Multivariate Cox regression analysis showed that reduced LVEF was associated with an increased risk of all-cause death only in the high-risk group of pressure injury (adjusted hazard ratios [HR]=1.81, 95% confidence interval [CI]: 1.03-3.20; P=0.040), but not in the low/minimal- (adjusted HR=1.29, 95%CI: 0.80-2.11; P=0.299) or intermediate-risk groups (adjusted HR=1.14, 95%CI: 0.65-2.02; P=0.651). Significant interactions were detected between pressure injury risk and LVEF (adjusted P=0.003). The cubic spline with hazard ratio plot revealed a distinct shaped curve relation between LVEF and all-cause death among different pressure injury risk groups. CONCLUSIONS: In older patients with AMI, the risk of pressure injury mediated the association between LVEF and all-cause death. The classification of older patients for both therapy and prognosis assessment appears to be improved by the incorporation of pressure injury risk assessment into AMI care management.

Risk factors, clinical features, and outcomes of premature acute myocardial infarction.

Aims: To investigate the risk factors, clinical features, and prognostic factors of patients with premature acute myocardial infarction (AMI). Materials and methods: A retrospective cohort study of patients with AMI included in data from the West China Hospital of Sichuan University from 2011 to 2019 was divided into premature AMI (aged < 55 years in men and < 65 years in women) and non-premature AMI. Patients' demographics, laboratory tests, Electrocardiography (ECG), cardiac ultrasound, and coronary angiography reports were collected. All-cause death after incident premature MI was enumerated as the primary endpoint. Results: Among all 8,942 AMI cases, 2,513 were premature AMI (79.8% men). Compared to the non-premature AMI group, risk factors such as smoking, dyslipidemia, overweight, obesity, and a family history of coronary heart disease (CHD) were more prevalent in the premature AMI group. The cumulative survival rate of patients in the premature AMI group was significantly better than the non-premature AMI group during a mean follow-up of 4.6 years (HR = 0.27, 95% CI 0.22-0.32, p < 0.001). Low left ventricular ejection fraction (LVEF) (Adjusted HR 3.00, 95% CI 1.85-4.88, P < 0.001), peak N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (Adjusted HR 1.34, 95% CI 1.18-1.52, P < 0.001) and the occurrence of in-hospital major adverse cardiovascular and cerebrovascular events (MACCEs) (Adjusted HR 2.36, 95% CI 1.45-3.85, P = 0.001) were predictors of poor prognosis in premature AMI patients. Conclusion: AMI in young patients is associated with unhealthy lifestyles such as smoking, dyslipidemia, and obesity. Low LVEF, elevated NT-proBNP peak level, and the occurrence of in-hospital MACCEs were predictors of poor prognosis in premature AMI patients.

The Value of Different Short-Term Risk Scoring Models in Predicting Long-Term Death of Acute Myocardial Infarction.

Background and aims: To compare the value of three commonly used cardiovascular short-term risk scoring models, the GRACE score, TIMI score, and HEART score, in predicting the long-term prognosis of patients with acute myocardial infarction. Methods: The hospitalization data of patients who were hospitalized in West China Hospital of Sichuan University from 2011 to 2013 and diagnosed with acute myocardial infarction (AMI) were collected. The patients were scored by GRACE score, TIMI score, and HEART score. The long-term follow-up of patients was conducted until the end of January 2021. All-cause death and time of death of patients were confirmed by telephone follow-up, electronic medical record query, and household registration information. The predictive ability of different risk scores for long-term prognosis was compared according to the receiver operating characteristic (ROC) area under the curve (AUC), and the ability to distinguish patients with different risk levels was compared according to Kaplan−Meier survival curves. Results: The study ultimately included 2220 patients, with a median follow-up of 8 years and 454 (20.5%) deaths until the end of follow-up. Whether in ST-segment elevation myocardial infarction (STEMI) patients or non-ST-segment elevation myocardial infarction (NSTEMI) patients, the AUC value of the GRACE score (both AUC = 0.734) was significantly higher than the TIMI score (AUC = 0.675, p < 0.01; AUC = 0.665, p < 0.01) and HEART score (AUC = 0.632, p < 0.01; AUC = 0.611, p < 0.01) until the end of follow-up. In terms of risk stratification, the Kaplan−Meier survival curve shows that both THE GRACE score and TIMI score can distinguish AMI patients with different risk levels (p < 0.01), but the risk stratification ability of the HEART score in AMI patients was poor (p > 0.05). Conclusion: The GRACE risk score could represent a more accurate model to assess long-term death of acute myocardial infarction, but further studies are required.

Exosomes derived from fibrinogen-like protein 1-overexpressing bone marrow-derived mesenchymal stem cells ameliorates rheumatoid arthritis.

Rheumatoid arthritis (RA) is a most common chronic joint disease belonging to inflammatory autoimmune disease. The aim of this study was to determine the role and mechanism of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes and fibrinogen-like protein 1 (FGL1) overexpression exosomes shuttled by BMSCs (FGL1-Exos) on RA. All of the exosomes were visualized by transmission electron microscope (TEM) and the characteristic proteins were detected by western blot. To investigate the therapeutic effect of FGL1-Exos, RA-FLSs were activated by TNF-α and RA rat model was established by collagen incomplete Freund's adjuvant. Cell viability, apoptosis, inflammation factors, and protein levels were detected by CCK-8, flow cytometry, enzyme-linked immunosorbent assay and western blot, respectively. Hematoxylin and eosin and safranin O staining were used to detect the histopathology changes. Cell apoptosis and FGL1 expression in knee joint were detected by immunofluorescence. The results showed that FGL1-Exos could inhibit the cell viability meanwhile increase the cell apoptosis in RA-FLSs. Meanwhile, FGL1-Exos could effectively suppress the inflammation score, joint destruction, and inflammatory response in RA rat model. FGL1-Exos directly inhibited cell apoptosis of RA-FLSs and RA rat model by suppressing the inflammatory cytokines, specific rheumatoid markers, immunological markers meanwhile meditating the NF-κB pathway. Our results indicate that FGL1 was a therapeutic potential target in RA therapy.

Angiotensin-converting enzyme inhibitor for post-transcatheter aortic valve implantation patients: study protocol for a multicenter randomized, open-label blinded endpoint control trial.

BACKGROUND: With the expanded utilization of transcatheter aortic valve implantation (TAVI) to younger and lower surgical risk patients with severe aortic stenosis (AS), optimal medical therapy after TAVI procedure has become the main concern. Renin-angiotensin system inhibitors (RASi) are widely utilized in the area of cardiovascular disease including heart failure and myocardial infarction and revealed the ability to reverse left ventricular (LV) remodeling. Interests have, thus, been drawn in investigating whether the prescription of RASi after the TAVI procedure can prevent or reverse cardiac remodeling and improve long-term clinical outcomes. No recommendation regarding the prescription of RASi after TAVI is proposed yet due to the lack of evidence from randomized controlled trials, especially in the Chinese population. We, therefore, designed this randomized controlled trial to explore the effect of adding fosinopril to standard care in patients who underwent a successful TAVI procedure on the LV remodeling. METHODS: A total of 200 post-TAVI patients from seven academic hospitals across China will be recruited and randomized with a ratio of 1:1 to receive standard care or standard care plus fosinopril. Follow-up visits will take place at 30 days, 3 months, 6 months, 12 months, and 24 months from randomization to assess the clinical symptoms, any adverse events, cardiac function, and quality of life. Cardiac magnetic resonance will be performed at baseline and repeated at the 24-month follow-up visit to assess LV remodeling. DISCUSSION: This study will provide evidence regarding medical therapy for AS patients who underwent TAVI and filling the gap in the Chinese population. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100042266 . Registered on 17 January 2021.

A fibular notch approach for the treatment of ankle fractures involving the distal tibial plafond.

BACKGROUND: Although efficacy is related to many factors, the surgical approach is one of the most important intervention factors for complex ankle fractures. Ankle fractures involving the distal tibial plafond frequently present a surgical challenge in choosing which incisions will be best for surgical treatment. Here, we present an innovative fibular notch approach for the treatment of some specific ankle fractures and present a series of patients with either functional or radiographic outcomes. METHODS: Twenty-two patients with distal tibial plafond fractures with concomitant fibular and distal tibiofibular syndesmosis injuries were treated through a fibular notch approach in this retrospective study. The details of the surgical technique were reviewed from the operative notes. Relevant data were reviewed from the medical records. The quality of fractures and syndesmosis reduction was examined using CT scans, and lateral stability of the ankle was assessed by physical examination and stress radiographs. The American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS) score was implemented for clinical functional assessment. RESULTS: All surgeries were successfully performed via the fibular notch approach as the primary approach with excellent intraoperative visualization. Postoperative radiography revealed satisfying restoration of all fractures and syndesmosis. All fractures healed with an average time of 17.3 ± 3.6 weeks. Mild posttraumatic osteoarthritis (PTOA) was present in 4 patients. The average AOFAS score was 88.8 at the last follow-up. CONCLUSIONS: The fibular notch approach is a safe and reliable approach for the treatment of specific ankle fractures involving the distal tibial plafond. This approach provides excellent direct visualization of the fragments and articular surface without significantly increasing iatrogenic injuries. Satisfactory radiographic and clinical results were observed, and further clinical and anatomical studies are recommended to ascertain the feasibility of this approach in the treatment of complex distal tibial fractures.

Tibial Nail Combined with Vacuum Sealing Drainage for Gustilo Grade IIIB Open Tibial Fractures: A Patient Series.

Gustilo grade IIIB open tibial fractures are relatively difficult to treat. We investigated the treatment effects of tibial intramedullary nails combined with vacuum sealing drainage (VSD) for Gustilo grade IIIB open tibial fractures. From March 2015 to March 2017, 13 cases of Gustilo grade IIIB open tibial fractures were treated with Expert Tibial Nails combined with VSD. Causes of injury included falls from a height (n = 9, 69.2%) and road accidents (n = 4, 30.8%). The duration from time of injury to hospital intake was 7.3 hours (range 5 to 9.5), and the time between injury and operation was 6.7 days (range 3 to 11). Six months after the operation, overall patient general health was investigated via the American Orthopaedic Foot and Ankle Society (AOFAS) ankle score and the physical and mental health dimensions of the Short-Form Health Survey 36 (SF-36). Postoperative complications and infections also were recorded. The results indicated that the median AOFAS score was 93.7 (range 89 to 97), with all individuals having either excellent (90 to 100; n = 10, 76.9%) or good (80 to 89; n = 3, 23.1%) outcomes. The median physical SF-36 score was 83.1 (range 72.5 to 93.0), and the median mental SF-36 score was 80.6 (range 69.7 to 92.0). Moreover, there were no instances of tibial shortening, neurovascular injury, postoperative complications, implant failure, malunion, or serious infections. In conclusion, intramedullary tibial nail combined with VSD is a safe and effective method to treat type grade IIIB open tibial fractures.

Expert Tibial Nails for Treating Distal Tibial Fractures With Soft Tissue Damage: A Patient Series.

Distal tibial fractures with soft tissue damage are relatively difficult to treat. We assessed the outcomes of patients with these fractures treated with the Expert Tibial Nail® (DePuy Synthes, Raynham, MA) from March 2012 to December 2014. At 6 months postoperatively, the general health quality of patients was assessed using operative time, interval to return to work, American Orthopaedic Foot and Ankle Society ankle scale score, pain measured using a visual analog scale, and short-form health outcomes 36-item survey physical functioning and mental health dimension scores. Of 11 cases, 7 (63.6%) were open fractures (3 [27.3%] Gustilo-Anderson type II, 3 [27.3%] type IIIA, and 1 [9.1%] type IIIB) and 4 (36.4%) were closed fractures with Tscherne-Oestern type II tissue damage. Their mean age was 52.2 (range 28 to 66) years. The mean operative time was 83 (range 65 to 105) minutes. The mean follow-up period was 16.3 (range 14 to 18) months. The median short-form 36-item survey scores were 79.1 (range 68.9 to 89.0) for the physical function dimension and 77.0 (range 64.3 to 90.0) for the mental health dimension. The mean postoperative ankle score was 88.6 (range 84 to 94). The mean pain score was 1.6 (range 0 to 4) mm. The mean interval to return to work was 14 (range 11 to 17) months. No patient showed evidence of neurovascular damage, malunion, nonunion, or shortening of the tibia. Taken together, we have confirmed that Expert Tibial Nails can effectively treat distal tibial fractures with soft tissue damage.

Severe open Lisfranc injuries: one-stage operation through internal fixation associated with vacuum sealing drainage.

BACKGROUND: This study aimed to investigate the clinical feasibility of treating severe open Lisfranc injuries by means of one-stage internal fixation with k-wires associated with vacuum sealing drainage (VSD). METHODS: The clinical outcomes of 20 cases of severe open Lisfranc joint fracture-dislocation treated by using one-stage internal fixation with k-wires associated with VSD, after debridement and suturing during emergency treatment, were reviewed. RESULTS: At 6 and 12 months after surgery, the American Orthopaedic Foot and Ankle Society midfoot scores were 69.2 and 78.2, the positive rates were 75 and 85 %, and the average visual analogue scale scores were 4.3 and 1.3, respectively. The average time of internal fixation surgery was 47 min (30-70 min). There were three cases of wound-edge necrosis; however, there were no cases of skin necrosis around the incision, or deep infection. The mean time of first hospital stay was 16.1 days (10-23 days). CONCLUSIONS: Treatment of severe open Lisfranc fracture and dislocation through one-stage internal fixation with k-wires in association with VSD led to fast anatomical reduction, stabilized bony structure, fast soft tissue recovery, and good short-term follow-up results.