Type 1 diabetes, its complications, and non-ischemic cardiomyopathy: a mendelian randomization study of European ancestry.

BACKGROUND: Type 1 diabetes (T1D) is a significant risk factor for a range of cardiovascular diseases. Nonetheless, the causal relationship between T1D and non-ischemic cardiomyopathy (NICM) remains to be elucidated. Furthermore, the mechanisms responsible for the progression from T1D to NICM have not been definitively characterized. OBJECTIVE: The aim of this study was to conduct a Mendelian randomization (MR) study to investigate the causal effects of T1D and its complications on the development of NICM. Additionally, this study aimed to conduct a mediation analysis to identify potential mediators within this correlation. METHODS: Genetic variants were used as instrumental variables for T1D. The summary data for T1D were obtained from two genome-wide association study datasets. The summary data for T1D with complications and NICM were obtained from the Finnish database. Two-sample MR, multivariable MR and mediation MR were conducted in this study. RESULTS: The study revealed a causal association between T1D, T1D with complications, and NICM (with odds ratios of 1.02, 95% CI 1.01-1.04, p = 1.17e-04 and 1.03, 95% CI 1.01-1.05, p = 3.15e-3). Even after adjusting for confounding factors such as body mass index and hypertension, T1D remained statistically significant (with odds ratio of 1.02, 95% CI 1.01-1.04, p = 1.35e-4). Mediation analysis indicated that monokine induced by gamma interferon may play a mediating role in the pathogenesis of T1D-NICM (mediation effect indicated by odds ratio of 1.005, 95% CI 1.001-1.01, p = 4.9e-2). CONCLUSION: The study demonstrates a causal relationship between T1D, its complications, and NICM. Additionally, monokine induced by gamma interferon may act as a potential mediator in the pathogenesis of T1D-NICM.

VEGFR2 targeted microbubble-based ultrasound molecular imaging improving the diagnostic sensitivity of microinvasive cervical cancer.

BACKGROUND: The current diagnostic methods of microinvasive cervical cancer lesions are imaging diagnosis and pathological evaluation. Pathological evaluation is invasive and imaging approaches are of extremely low diagnostic performance. There is a paucity of effective and noninvasive imaging approaches for these extremely early cervical cancer during clinical practice. In recent years, ultrasound molecular imaging (USMI) with vascular endothelial growth factor receptor type 2 (VEGFR2) targeted microbubble (MBVEGFR2) has been reported to improve the early diagnosis rates of breast cancer (including ductal carcinoma in situ), pancreatic cancer and hepatic micrometastases. Herein, we aimed to assess the feasibility of MBVEGFR2-based USMI in extremely early cervical cancer detection to provide an accurate imaging modality for microinvasive cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) Stage IA1 and IA2). RESULTS: We found MBVEGFR2-based USMI could successfully distinguish extremely early lesions in diameter < 3 mm from surrounding normal tissues (all P < 0.05), and the sensitivity gradually decreased along with increasing tumor diameter. Moreover, normalized intensity difference (NID) values showed a good linear correlation with microvessel density (MVD) (R2 = 0.75). In addition, all tumors could not be identified from surrounding muscles in subtracted ultrasound images when mice were administered MBCon. CONCLUSIONS: Overall, MBVEGFR2-based USMI has huge potential for clinical application for the early detection of microinvasive cervical cancer (FIGO Stage IA1 and IA2), providing the foothold for future studies on the imaging screening of this patient population.

Removable partial prosthesis combined with swallowing training is an efficient clinical solution for oral cancer post-operation patients with palatal defect and dysphagia: a prospective study.

OBJECTIVE: Dysphagia is one of the major complications of oral cancer patients, and is disturbing thousands of patients worldwide. Our study aim to evaluate the clinical efficacy of prosthesis combined with swallowing training on palatal defect and dysphagia in post-operative oral cancer patients. MATERIALS AND METHODS: Sixteen oral cancer patients with palatal defect and dysphagia post-operation were treated with removable prosthesis and individualized swallowing function training. Swallowing function of patients before and after treatment was analyzed and compared by videofluoroscopic swallowing examination. The severity of depression and life quality were evaluated by Depression Scale (SDS) and Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) scores, respectively. RESULTS: Oral transit time (OTT) significantly shortened after treatment (P < 0.01), and Penetration-Aspiration Scale (PAS) scores was significantly higher after treatment (P < 0.001). Different consistency bolus showed different risk of aspiration. Thickened liquids were related to lower PAS scores (P < 0.001). SDS standard score was significantly lower after treatment (P < 0.05). The total score of FACT-H&N after treatment was significantly higher (P < 0.05). No patients came back for regressed swallowing function during the follow-up period (17.06 ± 2.376 months). CONCLUSION: Removable prosthesis and swallowing training can significantly improve swallowing function, reduce depression degree, and improve quality of life (QOL). CLINICAL RELEVANCE: Removable prosthesis combined with swallowing training is a cheap and effective method to improve QOL in patients with palate defect and dysphagia after oral cancer.

Reconstruction of Acquired Segmental Mandibular Defects Using Pedicled Mandibular Muscle Flap and Evaluation of Speech Function and Aesthetic Outcomes.

PURPOSE: The purpose of this study was to investigate the clinical effect of pedicled mandibular osteomuscular flap in the reconstouring of repair of acquired segmental mandibular defects. PATIENTS AND METHODS: Thirteen patients with acquired segmental mandibular defects requiring secondary repair were included into the study. Pedicled mandibular osteomuscular flap was applied with strong internal fixation to repair the mandibular defects. The patients' speech, swallowing function, and aesthetic changes were evaluated upon follow-up. RESULTS: The flaps were viable in all patients. Average speech function score was 7.6±0.6. All patients had a drinking test rating of grade I or II with good masticatory efficiency. The postoperative self-assessment Visual Analog Scale score of appearance was 7.8±0.8. CONCLUSIONS: Pedicled mandibular osteomuscular flap is a viable choice in the secondary repair and reconstruction of mandibular acquired segmental defects. This flap could achieve better oral function with good aesthetic results.

Reconstruction of Large Acquired Palatal Defects Using Facial-Submental Artery Island Flap.

OBJECTIVE: To evaluate the feasibility and clinical effect of facial-submental artery island flap (FSAIF) in the repair of palatal defects, and to provide reference for the clinical application of submental artery island flap. METHODS: Nine patients with palatal defects, the range of nasal palatal perforation defects were 3 cm × 4cm to 3 cm × 6 cm (median 3 cm × 5.4 cm), were repaired by FSAIF, and the sizes of FSAIF were 4 cm × 9cm to 4 cm × 12 cm (median 4 cm × 10.4 cm,). Postoperative clinical efficacy was evaluated, including infection and necrosis of mucosal flap and postoperative palatal fistula perforation. Patients were followed up to evaluate their chewing, swallowing, speech function, and satisfaction of appearance. RESULTS: All patients were successfully repaired with FSAIF. Followed up 13∼35 months, there was no palatal fistula perforation in all patients. The speech, agitation, and swallowing function were not affected and the patients were satisfied with the appearance. CONCLUSION: FSAIF is a safe and reliable method for palatal defect repair.

Monocyte to High-Density Lipoprotein Cholesterol Ratio Is Associated with Subclinical Left Cardiac Remodeling and Dysfunction in Type 2 Diabetes Mellitus.

Chronic inflammation is involved in the development of heart failure (HF) in type 2 diabetes mellitus (T2DM). However, reliable and easily accessible biomarker of subclinical left cardiac remodeling and dysfunction remains a challenge.Overall, 1020 patients with T2DM without overt HF were enrolled from May 2019 to April 2020. Monocyte to high-density lipoprotein ratio (MHR) was calculated by blood monocyte count divided by high-density lipoprotein cholesterol. Left cardiac structure and function were assessed using transthoracic echocardiography. Univariate and multivariate linear regression analyses were used to estimate the association of MHR (Lg transferred) with echocardiographic parameters. We found that septal wall thickness (SWT), left ventricular internal end-diastole dimension (LVIDd), and left ventricular mass index (LVMI) raised with increasing MHR (P = 0.002 for SWT, P < 0.001 for LVIDd, and P = 0.001 for LVMI). Declined trends were shown in ejection fraction (EF) (P = 0.016), E velocity (P = 0.037), E/A ratio (P = 0.009), and tissue Doppler e' (P < 0.001), and elevating trend was observed in E/e' (P < 0.001). In multivariate regression analysis, MHR (Lg transferred) was positively associated with LVIDd (ß = 0.031; P = 0.016), LVMI (ß = 0.073; P = 0.014), and E/e' (ß = 0.331; P < 0.001), whereas it was negatively associated with EF (ß = -0.086; P = 0.007), E/A (ß = -0.072; P = 0.009), and e' (ß = -0.332; P < 0.001).MHR could be a practical biomarker for indicating subclinical cardiac remodeling and dysfunction in T2DM, due to low cost and easy availability.

Treatment of donor site wounds using facial skin remaining in the scar area.

Reconstruction of cheek skin defects is surgically challenging. We evaluated the outcomes of using cheek skin remaining in the scar area for treating donor site wounds following the repair of cheek skin defects using full-thickness skin. We conducted a retrospective case series study that included 12 patients with a scar of the cheek. The patients included seven females and five males. The donor site was treated using the cheek skin remaining in the scar area following repair of the cheek skin defect with a full-thickness skin graft from the inner side of the upper arm. Minor flap necrosis of the full-thickness skin graft in the cheek developed in one patient. The postoperative esthetic results were excellent and satisfactory in 11 and 1 patient, respectively. Patients were followed up for 18-32 months; no lagophthalmos or ectropion was noted. However, there were two cases of hyperpigmentation in cheek grafts, and two of graft hypertrophy in the arm. The facial skin remaining in the scar area can be used to treat donor site wounds following a full-thickness skin graft from the inner side of the upper arm to repair a large cheek skin defect.

Impact of long-term glucose variability on coronary atherosclerosis progression in patients with type 2 diabetes: a 2.3 year follow-up study.

BACKGROUND: Glycemic variability (GV) confers a risk of cardiovascular events. In this study, we aimed to investigate whether long-term GV has an impact on coronary atherosclerosis progression in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 396 patients with T2DM who had coronary computed tomography angiography and laboratory data available at baseline and for follow-up evaluations [median 2.3 (1.8-3.1) years] were included. Fasting plasma glucose (FPG) was measured every 1-3 months, and HbA1c was measured quarterly. The coefficient of variation (CV) of HbA1c and FPG were calculated as measures of GV. Quantitative assessment of coronary plaques was performed by measuring the annual change and progression rate of total plaque volume (TPV). Significant progression was defined as annual TPV progression ≥ 15%. Multivariable regression analyses were used to assess the effects of GV on atherosclerosis progression. RESULTS: In the 396 patients, the annual change in TPV was 12.35 ± 14.23 mm3, and annual progression rate was 13.36 ± 12.69%. There were 143 (36.11%) patients with significant progression, and they had a significantly higher CV-HbA1c (P < 0.001) and CV-FPG (P < 0.001) than those without significant progression. In multivariable regression analyses, both CV-HbA1c and CV-FPG were independent predictors of annual change in TPV [CV-HbA1c: ß = 0.241 (0.019-0.462), P = 0.034; CV-FPG: ß = 0.265 (0.060-0.465), P = 0.012], annual TPV progression [CV-HbA1c: ß = 0.214 (0.023-0.405), P = 0.029; CV-FPG: ß = 0.218 (0.037-0.399), P = 0.019], and significant atherosclerosis progression [CV-HbA1c: odds ratio [OR] = 1.367 (1.149-1.650), P = 0.010; CV-FPG: OR = 1.321 (1.127-1.634), P = 0.013]. CONCLUSIONS: Long-term GV is associated with accelerated progression of coronary atherosclerosis independent of conventional risk factors in patients with T2DM. Trial registration ClinicalTrials.gov (NCT02587741), October 27, 2015; retrospectively registered.

Predictive value of P wave terminal force in lead V1 for atrial fibrillation: A meta-analysis.

BACKGROUND: Several studies have explored the association between P wave terminal force in lead V1 (PTFV1) and risk of atrial fibrillation (AF) occurrence, but the results were controversial. This meta-analysis aimed to examine whether abnormal PTFV1 could predict AF occurrence. METHODS: We searched PubMed, Embase, and Cochrane Library databases for articles published before August 25, 2018. Pooled odds ratios (ORs) of AF occurrence were calculated using random-effects models to explore the significance of PTFV1. RESULTS: A total of 12 studies examining 51,372 participants were included, with 9 studies analyzing PTFV1 as a categorical variable and 4 studies analyzing PTFV1 as a continuous variable. As a categorical variable, abnormal PTFV1 (>0.04 mm s) was significantly associated with AF occurrence with a pooled OR of 1.39 (95% confidence interval [CI] 1.08-1.79, p = .01). Subgroup analysis found that ORs of studies in hemodialysis patients (OR = 4.89, 95% CI 2.54-9.90, p < .001) and acute ischemic stroke patients (OR = 1.60, 95% CI 1.14-2.25, p = .007) were higher than general population (OR = 1.15, 95% CI 1.03-1.29, p = .01). Studies from Europe (OR = 1.05, 95% CI 0.91-1.20, p = .51) yielded lower OR of endpoints compared with Asia (OR = 1.89, 95% CI 1.38-2.60, p < .001) and United States (OR = 1.43, 95% CI 1.19-1.72, p < .001). As a continuous variable, PTFV1 was also significantly associated with AF occurrence with a polled OR per 1 standard deviation (SD) change of 1.27 (95% CI 1.02-1.59, p = .03). CONCLUSIONS: PTFV1 was significantly associated with the risk of AF and was considered to be a good predictor of AF occurrence in population with or without cardiovascular diseases.

Prevalence of sleep-disordered breathing in acute coronary syndrome: a systemic review and meta-analysis.

PURPOSE: This study aimed to review the literature on the prevalence of sleep-disordered breathing (SDB) in patients with acute coronary syndrome (ACS). METHODS: Relevant studies were searched on PubMed, EMBASE, and Cochrane Library through December 2014. Data were extracted using standardized forms. Pooled prevalence of all SDB (apnea-hypopnea index (AHI) > 5), moderate-to-severe SDB (AHI > 15), and severe SDB (AHI > 30) in ACS patients was calculated using DerSimonian-Laird random-effects model. Sensitivity analysis was performed based on races and diagnostic methods of SDB. RESULTS: A total of 32 studies were included in the present meta-analysis, examining 3360 patients. The meta-analysis indicated that pooled prevalence of all SDB (AHI > 5), moderate-to-severe SDB (AHI > 15), and severe SDB (AHI > 30) in ACS patients were 69 % (95 % confidence interval (CI) = 61, 77 %), 43 % (95 % CI = 36, 49 %), and 25 % (95 % CI = 17, 33 %), respectively. Sensitivity analysis indicated that the pooled prevalence of SDB in Western population was similar to that in Asian population. However, diagnostic methods of SDB seemed to have various impacts on the prevalence of all SDB (AHI > 5), moderate-to-severe SDB (AHI > 15), and severe SDB (AHI > 30). CONCLUSIONS: High prevalence of all SDB, moderate-to-severe SDB, and severe SDB was found in ACS patients. It is clinically important to screen for SDB in patients with ACS.

Dysphagia in Tongue Cancer Patients Before and After Surgery.

PURPOSE: To define factors influencing postoperative aspiration in tongue cancer patients and to analyze the characteristics of dysphagia before and after surgery. MATERIALS AND METHODS: A total of 112 tongue cancer patients participated in this work. Videofluoroscopic swallowing studies were performed in all patients before and after surgery. A Penetration-Aspiration Scale score of 3 or greater was defined as an aspiration risk. Qualitative data were collected on a frame-by-frame basis from each videofluoroscopic swallowing study and analyzed. RESULTS: Smoking (58.14%, P < .01), tongue resection greater than 50% (38.71%, P < .05), and advanced tumor stage (49.18%, P < .01) were strong risk factors for aspiration. High incidences of inadequate tongue movement, delayed oral transit time, reduced hyoid bone elevation, poor aspiration or penetration, vallecula epiglottica, and residual material in the pyriform sinuses were evident after surgery (all P < .001). The Penetration-Aspiration Scale score was significantly higher after surgery than before surgery. The incidence of silent aspiration increased to 6.25% postoperatively. CONCLUSIONS: Smoking, larger tongue resection, and advanced tumor stage were strong risk factors for postoperative aspiration and dysphagia complications in tongue cancer patients. The aspiration rate was higher after surgery. Further studies should focus on the prevention and early treatment of dysphagia, especially postoperative aspiration, in tongue cancer patients.

Lipotoxicity induces cardiomyocyte ferroptosis via activating the STING pathway.

Objective Lipotoxicity is a well-established contributor to cardiomyocyte death and heart damage, with ferroptosis being identified as a crucial death mode in cardiomyocyte disease. This study aims to explore the potential role and mechanism of ferroptosis in lipotoxicity-induced myocardial injury. Methods Eight-weeks high-fat diet (HFD) SD rat and H9c2 cardiomyocytes treated with palmitic acid (PA) were established for in vivo and in vitro lipotoxic model. Ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) were used to inhibit ferroptosis. Myocardial-specific STING knockdown rat (Stingmyo-KD) with HFD was further introduced. Rat cardiac structure and function, cell viability, the level of lipid peroxidation, malondialdehyde (MDA), glutathione (GSH), mitochondrial function, ferroptosis related proteins and STING pathway related proteins in H9c2 cells/myocardium were detected. Results HFD rats with ferroptosis inhibitor showed improved cardiac structure and function, reduced lipid peroxidation and restored GSH, which was further confirmed in H9c2 cell. The time-dependent activation of the STING pathway following PA stimulation was observed. Knockdown the expression of STING could reduce PA-induced cell death, lipid peroxidation and MDA levels while restoring the GSH. In addition, both HFD Stingmyo-KD rats and HFD rats with systematic inhibited by STING inhibitor exhibited mitigating lipotoxicity-induced myocardial ferroptosis and reducing myocardial injury. Innovation and conclusion These findings suggest that lipotoxicity can induce ferroptosis in cardiomyocytes through the activation of the STING pathway, providing new targets, and strategies for the treatment of lipotoxicity cardiomyopathy.

Interplay of heart rate variability and resting heart rate on mortality in type 2 diabetes.

AIMS: Heart rate variability (HRV) and resting heart rate (RHR) are usually analyzed and interpreted separately. We aimed to assess the interplay of HRV and RHR on mortality in type 2 diabetes. METHODS: The study included 7,529 participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. HRV metrics included standard deviation of all normal-to-normal intervals (SDNN) and root mean square of successive differences between normal-to-normal intervals (rMSSD). Abnormal values were defined based on <25th percentile for HRV and >75th percentile for RHR. Interactions of HRV status and RHR status were tested on multiplicative and additive scales. Results were validated in a subset of patients with type 2 diabetes (n = 745) from the Multi-Ethnic Study of Atherosclerosis. RESULTS: Low SDNN was associated with increased all-cause mortality in the high RHR group (HR 1.60; 95% CI 1.29-1.97), but not in the normal RHR group. Compared with those who had neither low SDNN nor high RHR, the presence of either low SDNN or high RHR was not significantly associated with an increased risk of all-cause mortality. In contrast, the combination of low SDNN and high RHR was associated with a significantly increased risk of all-cause mortality (HR 1.68; 95% CI 1.43-1.97). Significant multiplicative and additive interactions were found between HRV status and RHR status on risk of all-cause mortality (all Pinteraction < 0.05). Similar findings were observed for cardiovascular mortality, in analyses using rMSSD, and in the Multi-Ethnic Study of Atherosclerosis. CONCLUSIONS: The association between HRV and mortality risk is modified by RHR levels. Furthermore, low HRV and high RHR have interdependent and synergistic associations with mortality risk.

Coronary Sinus Metabolite 12,13-diHOME Is a Novel Biomarker for Left Atrial Remodeling in Patients With Atrial Fibrillation.

BACKGROUND: 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) has shown potential in protecting against heart disease, but its relationship with atrial fibrillation (AF) remains unknown. METHODS: Coronary sinus (CS) and femoral vein blood samplings were synchronously collected from AF and non-AF subjects (paroxysmal supraventricular tachycardia or idiopathic premature ventricular complexes) who underwent catheter ablation. First, untargeted metabolomic profiling was performed in a discovery cohort (including 12 AF and 12 non-AF subjects) to identify the most promising CS or femoral vein metabolite. Then, the selected metabolite was further measured in a validation cohort (including 119 AF and 103 non-AF subjects) to confirm its relationship with left atrium remodeling and 1-year postablation recurrence of AF. Finally, the biological function of the selected metabolite was validated in a rapid-paced cultured HL-1 atrial cardiomyocytes model. RESULTS: Metabolomic analysis identified CS 12,13-diHOME as the most pronounced change metabolite correlated with left atrium remodeling in the discovery cohort. In the validation cohort, CS 12,13-diHOME was significantly lower in patients with AF than non-AF controls (84.32±20.13 versus 96.24±23.56 pg/mL; P<0.01), and associated with worse structural, functional, and electrical remodeling of left atrium. Multivariable regression analyses further demonstrated that decreased CS 12,13-diHOME was an independent predictor of 1-year postablation recurrence of AF (odds ratio, 0.754 [95% CI, 0.648-0.920]; P=0.005). Biological function validations showed that 12,13-diHOME treatment significantly protect the cell viability, improved the expression of MHC (myosin heavy chain) and Cav1.2 (L-type calcium channel α1c), and attenuated mitochondrial damage in the rapid-paced cultured HL-1 cardiomyocytes model. CONCLUSIONS: CS metabolite 12,13-diHOME is decreased in patients with AF and can serve as a novel biomarker for left atrium remodeling.

Nanoparticles (NPs)-mediated systemic mRNA delivery to reverse trastuzumab resistance for effective breast cancer therapy.

Monoclonal antibody-based therapy has achieved great success and is now one of the most crucial therapeutic modalities for cancer therapy. The first monoclonal antibody authorized for treating human epidermal growth receptor 2 (HER2)-positive breast cancer is trastuzumab. However, resistance to trastuzumab therapy is frequently encountered and thus significantly restricts the therapeutic outcomes. To address this issue, tumor microenvironment (TME) pH-responsive nanoparticles (NPs) were herein developed for systemic mRNA delivery to reverse the trastuzumab resistance of breast cancer (BCa). This nanoplatform is comprised of a methoxyl-poly (ethylene glycol)-b-poly (lactic-co-glycolic acid) copolymer with a TME pH-liable linker (Meo-PEG-Dlink m -PLGA) and an amphiphilic cationic lipid that can complex PTEN mRNA via electrostatic interaction. When the long-circulating mRNA-loaded NPs build up in the tumor after being delivered intravenously, they could be efficiently internalized by tumor cells due to the TME pH-triggered PEG detachment from the NP surface. With the intracellular mRNA release to up-regulate PTEN expression, the constantly activated PI3K/Akt signaling pathway could be blocked in the trastuzumab-resistant BCa cells, thereby resulting in the reversal of trastuzumab resistance and effectively suppress the development of BCa.

Cancer-associated fibroblasts in the invasive tumour front promote the metastasis of oral squamous cell carcinoma through MFAP5 upregulation.

Cancer-associated fibroblasts (CAFs) are widely involved in the development and progression of tumours. As a direct junction between tumour and normal host tissue, the invasive tumour front can remodel host tissue to generate a microenvironment more suitable for tumour invasion. However, whether CAFs derived from the invasive front (CAFs-F) have a greater ability to promote tumour invasion than CAFs derived from the superficial tumour (CAFs-S) is unclear. In this study, we characterized primary CAFs from different spatial locations of tumours. We demonstrated that CAFs-F had an increased ability to promote oral squamous cell carcinoma (OSCC) proliferation and invasion in vitro and significantly enhanced tumour growth in vivo compared to CAFs-S. Mechanistically, transcriptome profiling analysis revealed that the expression of MFAP5, encoding microfibril associated protein 5, was dramatically increased in CAFs-F compared to CAFs-S, which further confirmed that the MFAP5 protein level was elevated in head and neck squamous cell carcinoma (HNSCC) and that this increase was correlated with poor survival. Genetic ablation of MFAP5 impaired the preinvasive capabilities of CAFs-F. Together, our findings demonstrated that CAFs-F had a greater ability to promote tumour invasion than CAFs-S and that MFAP5 might be involved in this process.

Alirocumab effect on preventing periprocedural ischaemic events in coronary heart disease patients undergoing coronary stenting (APPEASE trial): study protocol of a multicentre, open-label, randomised controlled trial.

INTRODUCTION: Percutaneous coronary intervention (PCI)-related myocardial infarction (type 4a MI) and major periprocedural myocardial injury have been demonstrated leading to poor prognosis of patients with coronary heart disease (CHD) undergoing elective PCI and still remain high occurrence even after the therapy of dual antiplatelet agents and statins. Proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has been shown to be effectively in reducing the risk of acute MI (AMI). However, the effect of alirocumab on preventing PCI-related MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI remains uncertain. METHODS AND ANALYSIS: Alirocumab effect on Preventing Periprocedural ischaemic Events in coronary heart diseAse patients undergoing coronary StEnting trial is a multicentre, open-label, randomised controlled trial aiming to determine whether alirocumab could reduce the incidence of type 4a MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI. In total, 422 non-AMI CHD patients planned to undergo elective PCI will be randomly assigned to receive standard pharmacotherapy of CHD (control group) or additional use of subcutaneous alirocumab 75 mg 1 day before procedure (alirocumab group). The primary outcome is type 4a MI or major periprocedural myocardial injury defined as high-sensitivity cardiac troponin elevating above 5×99 th percentile upper reference limit in 48 hours after PCI. Patients will continue receiving standard pharmacotherapy or additional biweekly subcutaneous alirocumab 75 mg for 3 months according to the initial randomisation group. We will follow up for 3 months and record all the major adverse cardiovascular events (MACEs). Incidence of PCI-related MI or major periprocedural myocardial injury, and MACE in 3 months after PCI will be compared between control group and alirocumab group. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University with approval number: (2022)02-140-01. The results of this study will be reported through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200063191.

Tooth Loss after Jaw Curettage Surgery: Associated Factors and Potential Benefit of Splint Application.

BACKGROUND: This retrospective study is aimed at (I) assessment of tooth loss and related parameters after jaw curettage of benign lesions and (II) assessment of the outcome of jaw curettage supported by splint insertion after at least six months of follow-up. Material and Methods. For (I), patients who had jaw curettage surgery in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University (Guangzhou, China) from July 2015 to June 2019 were included. For part (II), consecutive patients who came to the department from July to December 2019 that were additionally treated with dental splinting were involved in this study. Based on the patient records, age, gender, initial tooth mobility, follow-up outcome, and potential tooth loss (intra- or postoperatively) were recorded. Based on available radiographs, alveolar crest bone loss and root surface area supported by bone (RSA) were determined. RESULTS: (I) 128 patients with 305 teeth were included, of which 40 teeth were lost (success rate 86.9%), without statistical difference in gender, age, or tooth type (P > 0.05). Tooth mobility, RSA, and the presence of alveolar crest bone defects were associated to tooth loss (P < 0.001). (II) 17 patients with a medium follow-up period of 11 months (range 9 to 13 months) were enrolled. All lesion-involving teeth supported by splint treatment at risks of loss were preserved, showing an effective tooth retention rate in 17/17 cases (74/74 teeth, success rate: 100%). CONCLUSIONS: Tooth mobility and bone loss (lesion-related and/or periodontal) are potential risk predictors for tooth loss in the first year after jaw curettage surgery. Dental splints could be recommendable for teeth involved by jaw benign lesions with little bone support.

Nucleus-specific RNAi nanoplatform for targeted regulation of nuclear lncRNA function and effective cancer therapy.

In the context of cancer therapy, a recently identified therapeutic target is represented by the essential subtype of RNA transcripts - the long noncoding RNAs (lncRNA). While this is the case, it is especially difficult to successfully regulate the expression of this subtype in vivo, particularly due to the protection granted by the nuclear envelope of nuclear lncRNAs. This study documents the development of a nucleus-specific RNA interference (RNAi) nanoparticle (NP) platform for the targeted regulation of the nuclear lncRNA function, in order to effectuate successful cancer therapy. An NTPA (nucleus-targeting peptide amphiphile) and an endosomal pH-responsive polymer make up the novel RNAi nanoplatform in development, which is capable of complexing siRNA. The nanoplatform is capable of accumulating greatly in the tumor tissues and being internalized by tumor cells, following intravenous administration. The exposed complexes of the NTPA/siRNA may conveniently escape from the endosome with the pH-triggered NP disassociation, following which it can target the nucleus by specifically interacting with the importin α/ß heterodimer. In orthotopic and subcutaneous xenograft tumor models, this would result in a notable suppression of the expression of nuclear lncNEAT2 as well as greatly impede the growth of tumors in liver cancer.