Objective To develop a novel transcatheter tricuspid valve replacement device and test its performance. Methods The transcatheter tricuspid valve stent consisted of double-layer self-expanding nitinol stent, biotissue-derived bovine pericardial leaflets, and PTFE woven. The delivery system, mainly consisting of a handle control unit and a delivery sheath, was sent to the correct position via right atrium or jugular vein. The sheath had a visualization feature, and the handle control unit could realize the functions of stable release and partial recovery of the interventional valve. In addition, this study performed animal survival experiments on the basis of in vitro experiments. A large-white pig was used as the experimental animal. Cardiopulmonary bypass was established through median thoracotomy, then the right atrium was opened, and the interventional valve was released under direct vision without cardiac arrest. Approximately 1 month after interventional valve implantation, the maneuverability and stability of the interventional tricuspid device were evaluated by autopsy. Results Through the animal experiment, the interventional valve was successfully released, and the anchoring was satisfactory. Postoperative transthoracic echocardiography showed that the interventional valve opened and closed well, the flow rate of tricuspid valve was 0.6 m/s, and there was no obvious tricuspid regurgitation. One month after the operation, we dissected the large-white pig and found the interventional valve was not deformed or displaced, the leaflets were well aligned, and there was thrombus attachment in the groove between the inner and outer layers of the interventional valve. Conclusion Animal experiment shows that the novel device can stably and firmly attach to the tricuspid annulus, with good anchoring effect, and effectively reduce paravalvular leakage.

Objective:To explore the prognostic factors of elderly patients with community-acquired pneumonia-related sepsis and to construct a prediction model.Methods:The clinical data of elderly patients with community-acquired pneumonia-associated sepsis from October 2020 to October 2022 in the General Hospital of Ningxia Medical University from October 2020 to October 2022 were retrospectively included, and the clinical data of the two groups were divided into the modeling population and the validation population in the ratio of 7:3 by random number table method, and the clinical data of the two groups were compared. According to the 30-day outcomes of admission, the patients were divided into survival group and death group, and the independent risk factors for the prognosis of elderly patients with community-acquired pneumonia-related sepsis were screened out by LASSO regression and multivariate logistic regression analysis, and the nomogram prediction model was constructed by R software. The area under the curve (AUC), calibration curve and decision curve of the receiver operating characteristic curve were used to validate the nomogram prediction model in the modeling population and the validation population to judge its discrimination, calibration and clinical practicability.Results:A total of 472 patients were included, with 331 and 141 models and validations, respectively, indicating that the clinical data were comparable between the modeled and validated populations. LASSO regression and multivariate logistic regression analysis showed that pneumonia severity index (PSI) score and sequential organ failure assessment (SOFA) score were independent risk factors for the prognosis of elderly patients with community-acquired pneumonia-associated sepsis. The AUC of the modeled population prediction model was 0.984 (95% CI: 0.975-0.994), and the AUC of the validated population prediction model was 0.961 (95% CI: 0.926-0.996). The nomogram prediction model has good discrimination, calibration and clinical practicability in both the modeled and validated populations. Conclusions:The nomogram prediction model established in the study has high accuracy for early identification and risk of sepsis in elderly patients with CAP and can guide for clinicians to formulate personalized interventions.

Objective:To assess the consistency of ultrasound and dual-energy computed tomography (DECT) in the diagnosis of gouty arthritis(GA), reasons of the differences were further analyzed.Methods:The ultrasound and DECT images of 150 knee joints from 147 patients diagnosed with gout at the Gout Specialty Clinic of Qingdao University Affiliated Hospital from February 2022 to October 2023 were retrospectively analyzed. According to anatomy, the knee joint was anatomically segmented into five regions: intra-articular, anterior, posterior, medial, and lateral.Location of monosodium urate (MSU) deposition was meticulously recorded. The Kappa consistency test was employed to assess the consistency of the two examination results in different regions of the knee joint. The McNemar chi-square test was utilized to conduct a differential analysis between DECT and ultrasound results.Results:Double contour sign(DCS) (81.2%, 92/112) was the most common intra-articular ultrasound sign in knee joints with GA. In the extra-articular region, MSU was commonly deposited in and around the popliteal tendon (ultrasound: 51.6%, 66/128; DECT: 54.7%, 70/128). Corresponding MSU deposits on DECT were found in 9 of 92 joints with DCS and in 9 of 49 joints with aggregates detected on ultrasound.In the assessment of MSU deposits, ultrasound showed an overall higher positive rate than DECT (87.3% vs. 72.3%, P=0.001), with poor consistency between the two examinations (Kappa=0.153). In distinct anatomical regions, ultrasound and DECT showed high consistency in the medial (Kappa=0.697) and lateral (Kappa=0.718) sides and the difference was not statistically significant ( P>0.05). Intra-articular (Kappa=0.289) and anterior (Kappa=0.303) regions exhibited only fair consistency, with statistically significant diagnostic differences ( P<0.05). When exclusively assessing cases with tophus, ultrasound and DECT demonstrated high consistency in the medial and lateral aspects(Kappa=0.685, 0.748) without statistical difference ( P>0.05). In the anterior region, the consistency between the two examinations was moderate (Kappa=0.256), while in the intra-articular region, the consistency of the two methods was lower (Kappa=0.147), and the differences was statistically significant ( P<0.001). Conclusions:Both ultrasound and DECT exhibit good diagnostic capabilities for gouty knee arthritis.However, the consistency between the two techniques varies in different anatomical locations. Clinical assessment should be tailored based on the specific anatomical position. DECT has an advantage in evaluating intra-articular MSU deposits, while ultrasound is more sensitive to detect early and scattered MSU deposits.

Objective:To assess the discriminatory value of the Thyroid Follicular Tumor Ultrasound Risk Stratification System (F-TIRADS) in differentiating follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA), and to compare its performance with other risk stratification systems(RSS).Methods:A retrospective analysis was conducted on 325 patients (327 thyroid nodules) diagnosed postoperatively as FTC or FTA at Affiliated Hospital of Qingdao University from January 2016 to December 2023. The cases were divided into FTC group (81 nodules) and FTA group (246 nodules). The nodules were classified based on F-TIRADS, the 2020 Chinese Thyroid Imaging Reporting and Data System (C-TIRADS), the 2015 American Thyroid Association guidelines (ATA guidelines), and the 2017 European Thyroid Association Thyroid Imaging Reporting and Data System (EU-TIRADS) by two ultrasound physicians. Multivariate Logistic regression analysis was used to identify independent predictors associated with FTC. Diagnostic performance of the 4 RSS was compared using postoperative pathological results as the gold standard.Results:Multivariate Logistic regression analysis showed maximum diameter, solid composition, hypoechogenicity, unclear or angular margins, marginal or ring calcifications, trabecular structure, and central blood flow were independent predictors of FTC( OR=1.914, 3.427, 9.926, 9.163, 45.918, 3.191, 8.936, respectively; all P<0.05). Within each RSS, the actual malignancy rate increased with higher risk categories, aligning closely with the recommended malignancy rates (except for ATA guidelines). The optimal cut-off values for distinguishing FTC from FTA were FTC risk 50%-90% in F-TIRADS, C-TIRADS 4B, moderately suspicious nodules in ATA guidelines, and EU-TIRADS 4, with areas under the curve of 0.916, 0.808, 0.827, and 0.836, respectively. F-TIRADS demonstrated the best overall performance (sensitivity: 82.72%, specificity: 82.93%), with significant differences compared with C-TIRADS, ATA guidelines, and EU-TIRADS (all P<0.05). Conclusions:F-TIRADS is highly effective in distinguishing FTA from FTC, outperforming C-TIRADS, ATA Guidelines, and EU-TIRADS. Clinicians should pay close attention to solid hypoechoic nodules with unclear or angular margins, marginal or ring calcifications, central blood flow, or a trabecular structure.

OBJECTIVES: To investigate the effect of oral microscope-assisted surface decontamination on implants in vitro. METHODS: Twelve implants that fell off because of severe peri-implantitis were collected, and decontamination was carried out on the surfaces of implants through curetting, ultrasound, titanium brushing, and sandblasting at 1×, 8×, or 12.8× magnifications. The number and sizes of residues on the implants' surfaces after decontamination were determined, and the decontamination effect was analyzed according to the thread spacing in the different parts of the thread. RESULTS: 1) The 8× and 12.8× groups scored lower for implant surface residues than the 1× group (P<0.000 1), and the 12.8× group scored lower than the 8× group (P<0.001); 2) no difference in residue score was found between the wide and narrow thread pitch (P>0.05), and the 8× and 12.8× groups had lower scores than the 1× group (P<0.001); 3) the lowest number of contaminants was observed at the tip of the thread, whereas the highest was observed below the thread, and the difference was significant (P<0.001). However, the thread pitch had no effect on the number of contaminants in different areas (P>0.05); 4) the residue scores of the 8× and 12.8× groups were lower than those of the 1× group at the thread tip and above, sag, and below the thread of the implants (P<0.05). CONCLUSIONS Residues on the surfaces of contaminated implants can be effectively removed by using an oral microscope. After decontamination, the residues of pollutants were mainly concentrated below the thread of the implants, and the thread pitch of the implants had no significant effect on the residues.
Humans ; Dental Implants ; Decontamination ; Surface Properties ; Peri-Implantitis ; Titanium

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Objective    To summarize the early outcomes of totally thoracoscopic minimally invasive aortic valve replacement (AVR) and double valve replacement (DVR). Methods    The clinical data of patients who underwent totally thoracoscopic minimally invasive AVR or DVR in Guangdong Provincial People’s Hospital from April 2020 to January 2021 were retrospectively analyzed. The patients were divided into an AVR group and a DVR group according to the surgical method, and the clinical data of the two groups were compared. Results    Finally 22 patients were enrolled, including 14 males and 8 females with an average age of 50.0±11.2 years at operation. Eight patients were degenerative disease, 8 were rheumatic heart disease combined with valvular disease, and 6 were bicuspid aortic valve. Out of the 22 patients, 16 underwent AVR alone, and 6 underwent DVR. All patients completed the operation successfully, and there was no death. Perivalvular leakage during surgery occurred in 2 patients. The average cardiopulmonary bypass time was 187.0±39.9 minutes, and aortic cross-clamping time was 117.0 (99.0, 158.0) minutes. Duration of mechanical ventilation and intensive care unit stay was 9.5 (4.8, 18.3) hours and 41.0 (34.0, 64.0) hours, respectively. The volume of chest drainage at the first 24 hours after surgery was 214.0±124.6 mL, and the postoperative hospital stay was 5.5 (4.0, 8.3) days. The cardiopulmonary bypass time and aortic cross-clamping time in the DVR group were longer than those in the AVR group, and the volume of chest drainage at 24 hours after surgery was more than that in the AVR group, with a statistical difference (P<0.05). Echocardiography before hospital discharge showed paravalvular leakage in 1 patient. There was no death during follow-up of 5.9±3.0 months. Conclusion    The early outcome of totally thoracoscopic minimally invasive AVR and DVR is satisfactory, and the approach of surgery is worth exploring.

Objective    To investigate the predictive value of right atrial myocardial fibrosis in the prognosis of isolated tricuspid regurgitation surgery after left heart valve surgery. Methods    The patients who underwent tricuspid valvuloplasty by the same operator in Guangdong Provincial People's Hospital from April 2016 to August 2021 due to long-term isolated severe tricuspid regurgitation after left heart valve surgery were included in the study. According to the degree of right atrial myocardial fibrosis, the patients were divided into three groups: a mild group, a moderate group, and a severe group. The clinical data of these patients were compared and analyzed. Results    A total of 75 patients were enrolled, including 16 males and 59 females with an average age of 57.0±8.4 years. There were 30 patients in the mild group, 29 patients in the moderate group and 16 patients in the severe group. In terms of the preoperative data, there were statistical differences in cardiac function grade, right atrial diameter, tricuspid incompetence area among the three groups (P<0.05). In terms of the postoperative data, there were statistical differences among the three groups in the cardiopulmonary bypass time, mechanical ventilation time, ICU monitoring time, complication rate and mortality (P<0.05). Further pairwise comparison showed that, compared with the mild group, the severe group had longer mechanical ventilation time (P=0.024), longer ICU monitoring time (P=0.003) and higher incidence of postoperative complications (P=0.024), while the moderate group had no statistical difference in all aspects (P>0.05); compared with the moderate group, the severe group had longer ICU monitoring time (P=0.021) and higher incidence of complications (P=0.006). Conclusion    The early outcome of tricuspid valvuloplasty in patients with isolated tricuspid regurgitation after left heart valve surgery with severe right atrial myocardial fibrosis is worse than that in the patients with mild and moderate fibrosis, suggesting that the degree of myocardial fibrosis in the right atrium can be a predictor of the effect of tricuspid regurgitation surgery and a judgement indicator of the surgery timing.

Objective: To explore the activity of auranofin against ovarian cancer cells and its possible molecular mechanism． Methods : The dose-response survival curve and IC50 of auranofin on ovarian cancer cell lines ，SKOV3，Caov3 and SW626 cells and immortalized normal human embryonic kidney HEK-293T cells were determined by CCK-8 method．Cell cycle was determined by flow cytometry．The levels of total glutathione ( GSH) ，reduced GSH and glutathione disulfide ( GSSG) ，thioredoxin reductase (TrxR) and reactive oxygen species (ROS) in cells were determined by microplate reader，and the reduced GSH / GSSG ratio was calculated．Western blot was used to determine the expression of cyclin dependent kinases( CDK) 4，CDK6，Cyclin D1，P53，p-P53 and MDM2 in SKOV3 and Caov3 ovarian cancer cells. Results : Compared with HEK-293T cells，the dose-response survival curves and IC50 values of SKOV3，Caov3 and SW626 cells showed that ovarian cancer cells were more sensitive to auranofin (P＜0. 05) ．After SKOV3 and Caov3 cells were treated with the dose of respective IC50 concentrations of auranofin，compared with the untreated cells group，the Auranofin IC50 group cells' intracellular levels of GSH，the ratio of reduced GSH / GSSG and the activity of TrxR decreased (t = 25. 11 /31. 18，14. 72 /19. 92，43. 30 /10. 74， all P＜0. 05) ，and the levels of ROS increased (t = 23. 82 /27. 71，P＜0. 05) ; cells number at G0 / G1 phases increased，with cells number at S and G2 phases decreased (P＜0. 05) ; and the expression levels of cell cycle-related proteins CDK4，CDK6，Cyclin D1 and the P53-specific E3 ubiquitin ligase MDM2 were down-regulated (t = 7. 51 /15. 59，17. 32 /11. 26，20. 78 /20. 78，24. 25 /17. 32，all P＜0. 05) ，while the expression levels of P53 and p-P53 were up-regulated (t = 17. 32 /24. 25，12. 12 /10. 39，all P ＜0. 05) ． Conclusion Auranofin causes oxidative stress in ovarian cancer cells by inhibiting TrxR activity，and by partially degrading MDM2 to stabilize and acti- vate P53，so as to block the cancer cells in G0 / G1 phase，and exert anti-ovarian cancer activities.

Objective:To investigate the relationship between hyperuricemia and outcome in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke admitted to Department of Neurology, Putuo Hospital, Shanghai University of Tranditional Chinese Medicine between January 2020 and September 2020 were enrolled retrospectively. The modified Rankin Scale (mRS) score was used to evaluate the clinical outcome 3 months after the onset. ≤2 was considered as good outcome, and >2 was considered as poor outcome. The demography and baseline characteristics were compared between the good outcome group and the poor outcome group. Multivariate logistic regression analysis was used to determine the independent influencing factors of the outcome. Results:A total of 210 patients were included, their age was 69.87±62.62 years. There were 125 males (59.52%) and 85 females (40.48%). The baseline median National Institutes of Health Stroke Scale (NIHSS) score was 4. The serum uric acid level in 169 patients (80.48%) was normal and 41 (19.52%) had hyperuricemia; 120 patients (57.14%) had a good outcome, and 90 (42.86%) had a poor outcome. Blood glucose level, serum uric acid level, baseline NIHSS score and the proportions of diabetes mellitus, history of stroke or transient ischemic attack, hyperuricemia in the poor outcome group were significantly higher than those in the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that diabetes mellitus (odds ratio [ OR] 2.735, 95% confidence interval [ CI] 1.461-5.121; P=0.002), hyperuricemia ( OR 2.400, 95% CI 1.102-5.228; P=0.027), and higher baseline NIHSS score ( OR 1.233, 95% CI 1.118-1.360; P<0.001) were the independent risk factors for poor outcome in patient with acute ischemic stroke. Conclusion:Hyperuricemia is an independent risk factor for poor outcome in patients with acute ischemic stroke.