Stability between single and segmental maxillary osteotomies in bimaxillary surgery for cleft-associated class III deformity: a CBCT study.

OBJECTIVE: Segmental Le Fort I osteotomy through the cleft is a common strategy to narrow the alveolar cleft in adults. This study compared skeletal stability between single and segmental Le Fort I osteotomies in patients with unilateral cleft lip and palate (UCLP). MATERIALS AND METHODS: This retrospective analysis examined 45 adults with complete UCLP-associated class III deformities who underwent bimaxillary surgery with either single (n = 30) or segmental (n = 15) Le Fort I advancement. Cone beam computed tomography (CBCT) scans of the facial skeleton were acquired before surgery, 1-week postsurgery, and at follow-up. Measures of landmarks from the CBCT images for the two treatment groups were compared for translation (left/right, posterior/anterior, superior/inferior) and rotation (yaw, roll, pitch). RESULTS: Postsurgery, the downward movement of the maxilla was larger in the segmental group than the single group. At follow-up, the maxilla moved backward in both groups, and upward in the segmental group. The mandible moved forward and upward and rotated upward in both groups. The amount of upward movement and rotation was larger in the segmental group than the single group. CONCLUSIONS: Two years after bimaxillary surgery in patients with UCLP-associated class III deformity, greater relapse was found after segmental Le Fort I osteotomies in vertical translation of the maxilla and mandible, and pitch rotation of the mandible compared with single Le Fort I osteotomies. CLINICAL RELEVANCE: The vertical relapse of the maxilla was larger after segmental Le Fort I advancement compared with single Le Fort I advancement in clefts.

Site and severity of facial asymmetry after bimaxillary surgery for class III deformity: a case-control study.

OBJECTIVES: The study aimed (1) to evaluate the site and severity of facial asymmetry in Class III patients before and after bimaxillary surgery, and (2) to identify the influence of initial severity and positional jaw asymmetry on residual facial asymmetry. MATERIALS AND METHODS: Preoperative and postoperative cone-beam computed tomography of 65 patients with Class III facial asymmetry who underwent bimaxillary surgery were evaluated. Five midline and 14 paramedian facial soft tissue landmarks were identified to assess facial asymmetry. The outcomes were compared to a control group consisting of 30 age- and gender-matched Class I subjects. The postoperative positional jaw asymmetry (i.e., shift, roll, yaw) of each osteotomy segment (maxilla, mandible, chin, ramus) was also measured. RESULTS: Before surgery, the asymmetry was more severe at the chin, middle and lower contour. Bimaxillary surgery effectively corrected facial asymmetry, particularly in achieving normalization of chin deviation. However, significant asymmetry persisted postoperatively in the middle and lower contour (p < 0.001 and p < 0.01, respectively), which was affected by the positional ramus asymmetry in the roll and shift. CONCLUSIONS: Deviation of the chin, middle and lower contour contributed significantly to overall facial asymmetry in Class III asymmetry. Despite normalization of the chin deviation after bimaxillary surgery, asymmetry persisted at the middle and lower contour, primarily as the result of insufficient correction of the positional ramus asymmetry. CLINICAL RELEVANCE: Understanding the residual asymmetry after bimaxillary surgery is important for minimizing deviation and optimizing the surgical planning for its correction.

Role of low-density lipoprotein electronegativity and sexual dimorphism in contributing early ventricular tachyarrhythmias following ST-elevation myocardial infarction.

Background: Early ventricular tachycardia/fibrillation (VT/VF) in patients with ST-elevation myocardial infarction (STEMI) has higher morbidity and mortality. This study examines gender-differentiated risk factors and underlying mechanisms for early onset VT/VF in STEMI. Methods: We analyzed data from 2,964 consecutive STEMI patients between January 1, 2008 and December 31, 2021. Early VT/VF was defined as occurrence of spontaneous VT/VF of ≥30 s or requirement of immediate cardioversion/defibrillation within the first 48 h after symptoms. An ex vivo ischemic-reperfusion experiments were conducted in 8-week-old ApoE-/- mice fed a high-fat diet to explore the underlying mechanisms of early VT/VF. Results: In 255 of out 2,964 STEMI patients who experienced early VT/VF, the age was younger (58.6 ± 13.8 vs. 61.0 ± 13.0 years old, P = 0.008) with a male predominance. The plasma levels of L5, the most electronegative subclass of low-density lipoprotein, was higher in early VT/VF patients compared to those without early VT/VF (n = 21, L5: 14.1 ± 22.6% vs. n = 46, L5: 4.3 ± 9.9%, P = 0.016). In the experimental setup, all male mice (n = 4) developed VT/VF post sham operation, whereas no such incidence was observed in the female mice (n = 3). Significantly, male mice exhibited considerably slower cardiac conduction velocity as compared to their female counterparts in whole heart preparations (25.01 ± 0.93 cm/s vs.42.32 ± 5.70 cm/s, P < 0.001), despite analogous action potential durations. Furthermore, isolated ventricular myocytes from male mice showed a distinctly lower sodium current density (-29.20 ± 3.04 pA/pF, n = 6) in comparison to female mice (-114.05 ± 6.41 pA/pF, n = 6, P < 0.001). This decreased sodium current density was paralleled by a reduced membrane expression of Nav1.5 protein (0.38 ± 0.06 vs. 0.89 ± 0.09 A.U., P < 0.001) and increased cytosolic Nav1.5 levels (0.59 ± 0.06 vs. 0.29 ± 0.04 A.U., P = 0.001) in male mice. Furthermore, it was observed that the overall expressions of sorting nexin 27 (SNX27) and vacuolar protein sorting 26 (VPS26) were significantly diminished in male mice as compared to female littermates (0.91 ± 0.15 vs. 1.70 ± 0.28, P = 0.02 and 0.74 ± 0.09 vs. 1.57 ± 0.13, P < 0.01, respectively). Conclusions: Our findings reveal that male STEMI patients with early VT/VF are associated with elevated L5 levels. The gender-based discrepancy in early VT/VF predisposition might be due to compromised sodium channel trafficking, possibly linked with increased LDL electronegativity.

Three-dimensional evaluation of skeletal stability after surgery-first bimaxillary surgery for class III asymmetry in 70 consecutive patients.

Background/purpose: Skeletal stability after orthognathic surgery is essential for positive treatment outcome. This study evaluated the stability of osteotomy segments after surgery-first bimaxillary surgery for class III asymmetry. Materials and methods: Seventy adults with class III asymmetry consecutively corrected through surgery-first Le Fort I and bilateral sagittal split osteotomies were investigated. Cone-beam computed tomography before treatment (T0), 1-week after surgery (T1), and after all treatment (T2, ≥1-year after surgery) was used to assess surgical movement (T0 to T1) and skeletal stability (T1 to T2) regarding the translation and rotation of the maxillary, mandibular distal, and proximal segments. Results: At T1, the maxillary segment had moved forward and upward, turned to the deviated side, and rotated downward (all P < 0.01). The distal segment of mandible had moved forward and upward and rotated upward (all P < 0.001). The deviated proximal segment had moved upward, tilted to the opposite side, and rotated upward (all P < 0.001). The opposite proximal segment had moved upward and tilted to the deviated side (both P < 0.01). At T2, significant relapse occurred in the mandible. The distal segment moved forward and upward and rotated upward (all P < 0.001). The deviated proximal segment moved upward, tilted to the opposite side, and rotated upward (all P < 0.001). The opposite proximal segment moved upward and tilted to the deviated side (both P < 0.01). Conclusion: Clinically significant relapse of class III asymmetry was discovered on the mandibular distal and opposite proximal segments.

2α, 3α, 24-Thrihydroxyurs-12-en-24-ursolic acid enhances the cytotoxic effect of cisplatin on oral cancer cells by down-regulating autophagy.

This study aimed to investigate the effect and mechanism of 2α, 3α, 24-thrihydroxyurs-12-en-24-ursolic acid (TEOA) alone or in combination with cisplatin on oral cancer. TEOA, a pentacyclic triterpenoid compound isolated from the roots of Actinidia eriantha, has demonstrated antitumor activity in preclinical experiments. However, its role in oral cancer remains poorly understood. Our findings revealed that a low concentration of TEOA did not exhibit significant cytotoxicity against oral squamous cell carcinoma cells. However, when combined with cisplatin, TEOA showed a significant therapeutic effect. The combined treatments resulted in a significant inhibition of proliferation and migration and a significant increase in apoptosis of squamous cell carcinoma cells. Cisplatin exposure increased autophagy levels, which may contribute to chemoresistance. Of note, the presence of TEOA significantly inhibited cisplatin-induced autophagy, leading to improved chemotherapy efficacy. Our findings indicate that a mild low dosage of TEOA may enhance the cytotoxic effect of cisplatin by downregulating autophagy in oral cancer cells.

Surgery-First Orthognathic Approach for Correction of Dentofacial Deformity in Unilateral Cleft Lip and Palate.

BACKGROUND: Although several studies have reported the advantages of the surgery-first approach for orthognathic correction of class III deformity, there is no report of the success of this approach for patients with cleft lip and palate. Therefore, the purpose of this study was to evaluate the stability and outcome of bimaxillary surgery for cleft-related dentofacial deformity using a surgery-first approach. METHODS: Forty-one patients with unilateral cleft lip and palate who consecutively underwent Le Fort I and bilateral sagittal split osteotomies for skeletal class III deformity were included. Cone-beam computed tomographic scans before surgery, 1 week after surgery, and after orthodontic treatment were used to measure the surgical and postsurgical changes in jaw position by landmarks, and outcomes of jaw protrusion and relation, incisor angle and occlusion, and menton deviation after treatment. Self-report questionnaires regarding satisfaction with overall appearance of the face and seven facial regions were administered after treatment. RESULTS: A clinically insignificant relapse was found in the maxilla (<1 mm) and mandible (<2 mm). There was a significant improvement in the jaw protrusion and relation, incisor angle and occlusion, and menton deviation. Responses from the self-report questionnaires completed after treatment indicated that patient satisfaction was high. CONCLUSION: These findings demonstrate surgical-orthodontic treatment with a surgery-first approach can successfully improve cleft-related dentofacial deformity in patients with unilateral cleft lip and palate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Luteolin suppresses oral carcinoma 3 (OC3) cell growth and migration via modulating polo-like kinase 1 (PLK1) expression and cellular energy metabolism. / æœ¨çŠ€è‰ç´ é€šè¿‡è°ƒèŠ‚PLK1è¡¨è¾¾å’Œç»†èƒžèƒ½é‡ä»£è°¢æŠ‘åˆ¶å£è ”ç™Œç»†èƒžOC3的生长和迁移.

Oral squamous cell carcinoma (OSCC) is a prevalent malignant tumor affecting the head and neck region (Leemans et al., 2018). It is often diagnosed at a later stage, leading to a poor prognosis (Muzaffar et al., 2021; Li et al., 2023). Despite advances in OSCC treatment, the overall 5-year survival rate of OSCC patients remains alarmingly low, falling below 50% (Jehn et al., 2019; Johnson et al., 2020). According to statistics, only 50% of patients with oral cancer can be treated with surgery. Once discovered, it is more frequently at an advanced stage. In addition, owing to the aggressively invasive and metastatic characteristics of OSCC, most patients die within one year of diagnosis. Hence, the pursuit of novel therapeutic drugs and treatments to improve the response of oral cancer to medication, along with a deeper understanding of their effects, remains crucial objectives in oral cancer research (Johnson et al., 2020; Bhat et al., 2021; Chen et al., 2023; Ruffin et al., 2023).

Surgical occlusion setup and skeletal stability of correcting cleft-associated class III deformity using surgery-first bimaxillary surgery.

BACKGROUND: This study aimed to assess the three-dimensional (3D) quantitative characteristics of the surgical occlusion setup in surgery-first cleft orthognathic surgery, and to evaluate its influence on post-surgical skeletal stability. METHODS: This prospective study was comprised of 35 patients with unilateral cleft lip and palate and class III deformity who consecutively underwent two-jaw surgery with surgery-first approach. Digitized dental models were analyzed to quantify the 3D characteristics of the final surgical occlusion setup. Cone-beam computed tomography was used to measure the 3D surgical skeletal movement and post-surgical skeletal stability. The correlation between skeletal stability and surgical occlusal contact or surgical skeletal movement was also evaluated. RESULTS: The surgical occlusion setup had a large incisor overjet and positive overbite, and buccal cross bite and open bite on second molars. Occlusal contact on three segments was present in 51.4% of the patients, and the average number for tooth contact was 4.3 teeth. No correlation was found between maxillary or mandibular stability and surgical occlusal contact. However, a significant correlation was found between maxillary and mandibular stability and the surgical skeletal movement. CONCLUSIONS: The surgical occlusion for correction of cleft-associated class III deformity using the surgery-first approach was characterized with large overjet and positive overbite, and posterior cross bite and open bite. On average, there was occlusal contact on four to five teeth; half of surgical occlusion setups had contact on three segments. The post-surgical skeletal stability was not related to the surgical occlusal contact but to the surgical skeletal movement.

TGF-ß promotes the proliferation and osteogenic differentiation of dental pulp stem cells a systematic review and meta-analysis.

BACKGROUND: Dental pulp stem cells (DPSCs) are adult stem cells with multi-directional differentiation potential derived from ectoderm. Vitro experiments have shown that adding cytokines can help DPSCs to be transformed from multipotent stem cells to osteoblasts. TGF-ß has been proved to have an effect on the proliferation and mineralization of bone tissue, but its effect on the osteogenesis and proliferation of dental pulp stem cells is still uncertain. We aim to determine the effect of TGF-ß on the osteogenesis and proliferation of dental pulp stem cells. METHODS: We have identified studies from the Cochrane Central Register of Controlled Trials, PubMed, Embase, and China national knowledge infrastructure (CNKI) for studies interested in TGF-ß and proliferation and differentiation of dental pulp stem cells in the following indicators: A490 (an index for evaluating cell proliferation), bone sialoprotein (BSP), Col plasmid-1 (Col-1), osteocalcin (OCN), runt-related transcription factor 2 (Runx-2); and the number of mineralized nodules. Any language restrictions were rejected. Furthermore, we drew a forest plot for each outcome. We conducted a sensitivity analysis, data analysis, heterogeneity, and publication bias test. We evaluate the quality of each study under the guidance of Cochrane's tool for quality assessment. RESULTS: The pooled data showed that TGF-ß could promote the proliferation and ossification of dental pulp stem cells. All the included results support this conclusion except for the number of mineralized nodules: TGF-ß increases the A490 index (SMD 3.11, 95% CI [0.54-5.69]), promotes the production of BSP (SMD 3.11, 95% CI [0.81-6.77]), promotes the expression of Col-1 (SMD 4.71, 95% CI [1.25-8.16]) and Runx-2 (SMD 3.37, 95% CI [- 0.63 to 7.36]), increases the content of OCN (SMD 4.32, 95% CI [1.20-7.44]) in dental pulp, and has no significant effect on the number of mineralized nodules (SMD 3.87, 95% CI [- 1.76 to 9.51]) in dental pulp stem cells. CONCLUSIONS: TGF-ß promotes the proliferation and osteogenesis of dental pulp stem cells.

Alveolar ridge preservation in sockets with severe periodontal destruction using autogenous partially demineralized dentin matrix: A randomized controlled clinical trial.

BACKGROUND: The preservation and reconstruction of alveolar ridge volume in extraction sockets of molars affected by severe periodontitis is a critical challenge that requires clinical attention. PURPOSE: This randomized controlled clinical trial was designed to evaluate the efficiency of autogenous partially demineralized dentin matrix (APDDM) for alveolar ridge preservation (ARP) in severely periodontally compromised sockets compared to spontaneous healing (SH) on radiographic and histomorphometric outcomes. MATERIALS AND METHODS: Thirty-two patients with 32 periodontally compromised molars were randomized into either the test group, which received ARP using APDDM covered with a collagen sponge, or the control group, which underwent SH. Linear and volumetric changes were assessed using superimposed cone-beam computed tomography (CBCT) acquired pre-extraction and after a 4-month healing time. Histomorphometric evaluation was performed on trephine cores harvested during implant placement. RESULTS: All sites healed uneventfully. The ridge width at 1 mm apical to the bone crest increased by 5.03, 4.50, and 5.20 mm in the mesial, middle, distal area in the APDDM group, while decreasing by -1.98, -2.19, and -1.98 mm in the SH group, respectively (p < 0.05). The height increase of the central bone was significantly higher in the APDDM group than in the SH group (p < 0.05). The height decrease of the buccal (mesial, middle, distal) bone plate was lower in the APDDM group than in the SH group (p < 0.05). After a 4-month healing time, bone volume increased by 37.07% in the APDDM group and by only 2.33% in the SH group (p < 0.05). Histomorphometric analysis revealed that APDDM particles were surrounded by newly formed bone, with partially absorbed residual APDDM materials observed. New bone, APDDM remnants, and connective tissue occupied 39.67 ± 8.28%, 23.66 ± 9.22%, and 36.67 ± 17.05% of the areas in the APDDM group, respectively. CONCLUSIONS: ARP using APDDM was effective, resulting in a significant increase in both linear and volumetric changes in severely periodontally compromised extraction sockets compared to SH. These findings suggest that APDDM may serve as a promising new clinical option for the reconstruction of alveolar ridge dimensions.

A Common East Asian aldehyde dehydrogenase 2*2 variant promotes ventricular arrhythmia with chronic light-to-moderate alcohol use in mice.

Chronic heavy alcohol use is associated with lethal arrhythmias. Whether common East Asian-specific aldehyde dehydrogenase deficiency (ALDH2*2) contributes to arrhythmogenesis caused by low level alcohol use remains unclear. Here we show 59 habitual alcohol users carrying ALDH2 rs671 have longer QT interval (corrected) and higher ventricular tachyarrhythmia events compared with 137 ALDH2 wild-type (Wt) habitual alcohol users and 57 alcohol non-users. Notably, we observe QT prolongation and a higher risk of premature ventricular contractions among human ALDH2 variants showing habitual light-to-moderate alcohol consumption. We recapitulate a human electrophysiological QT prolongation phenotype using a mouse ALDH2*2 knock-in (KI) model treated with 4% ethanol, which shows markedly reduced total amount of connexin43 albeit increased lateralization accompanied by markedly downregulated sarcolemmal Nav1.5, Kv1.4 and Kv4.2 expressions compared to EtOH-treated Wt mice. Whole-cell patch-clamps reveal a more pronounced action potential prolongation in EtOH-treated ALDH2*2 KI mice. By programmed electrical stimulation, rotors are only provokable in EtOH-treated ALDH2*2 KI mice along with higher number and duration of ventricular arrhythmia episodes. The present research helps formulate safe alcohol drinking guideline for ALDH2 deficient population and develop novel protective agents for these subjects.

Comparison of regional soft tissue changes after bimaxillary rotational surgery between class III deformity with overbite and open bite: A 3D imaging analysis.

BACKGROUND: This prospective study aimed to compare regional soft tissue changes between patients with class III overbite and open bite deformities treated with bimaxillary surgery involving clockwise and counter-clockwise mandibular setback, respectively. MATERIAL AND METHODS: Class III deformity adults receiving Le Fort I and bilateral sagittal split osteotomies were grouped according to the incisal occlusion: overbite (n = 30) and open bite (n = 30). Combined cone-beam CT scans and 3D facial photographs preoperative and at least 1-year postoperative were taken to assess the soft tissue changes. RESULTS: Postoperative changes for the overbite and open bite groups included anterior repositioning of nose (-0.8 ± 1.2 mm and -1.1 ± 1.1 mm, respectively) and cheek (-1.9 ± 1.3 mm and -1.7 ± 2.6 mm, respectively), posterior repositioning of chin (5.2 ± 4.0 mm and 4.9 ± 3.2 mm, respectively), and medial (-1.7 ± 2.0 mm and -1.9 ± 2.1 mm, respectively) and posterior (2.7 ± 1.4 mm and 2.8 ± 2.3 mm, respectively) repositioning of bilateral angles. Posterior (1.2 ± 2.0 mm and 5.1 ± 3.3 mm) and inferior (-1.4 ± 2.2 mm and -2.4 ± 2.7 mm) repositioning of upper lip and lower lip occurred in overbite group. Inferior (-2.3 ± 2.4 mm) and superior (3.7 ± 3.4 mm) repositioning of chin occurred in the overbite and open bite groups, respectively. CONCLUSIONS: Treatment of class III overbite and open bite deformities with bimaxillary rotational surgery resulted in comparable regional soft tissue changes, except for upper lip, lower lip and chin.

PD-L1 and AKT Overexpressing Adipose-Derived Mesenchymal Stem Cells Enhance Myocardial Protection by Upregulating CD25+ T Cells in Acute Myocardial Infarction Rat Model.

This study explores the synergistic impact of Programmed Death Ligand 1 (PD-L1) and Protein Kinase B (Akt) overexpression in adipose-derived mesenchymal stem cells (AdMSCs) for ameliorating cardiac dysfunction after myocardial infarction (MI). Post-MI adult Wistar rats were allocated into four groups: sham, MI, ADMSC treatment, and ADMSCs overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) treatment. MI was induced via left anterior descending coronary artery ligation, followed by intramyocardial AdMSC injections. Over four weeks, cardiac functionality and structural integrity were assessed using pressure-volume analysis, infarct size measurement, and immunohistochemistry. AdMSC-PDL1-Akt exhibited enhanced resistance to reactive oxygen species (ROS) in vitro and ameliorated MI-induced contractile dysfunction in vivo by improving the end-systolic pressure-volume relationship and preload-recruitable stroke work, together with attenuating infarct size. Molecular analyses revealed substantial mitigation in caspase3 and nuclear factor-κB upregulation in MI hearts within the AdMSC-PDL1-Akt group. Mechanistically, AdMSC-PDL1-Akt fostered the differentiation of normal T cells into CD25+ regulatory T cells in vitro, aligning with in vivo upregulation of CD25 in AdMSC-PDL1-Akt-treated rats. Collectively, PD-L1 and Akt overexpression in AdMSCs bolsters resistance to ROS-mediated apoptosis in vitro and enhances myocardial protective efficacy against MI-induced dysfunction, potentially via T-cell modulation, underscoring a promising therapeutic strategy for myocardial ischemic injuries.

Shegan Mahuang Decoction May Reduce Airway Inflammation in Neutrophilic Asthmatic Mice by Improving the Mitochondrial Function of Bronchoalveolar Lavage Fluid Exosomes.

Asthma is a common pulmonary disease mainly caused by the infiltration of neutrophils. There is a limit to the therapeutic effects of the available asthma drugs on neutrophilic asthma. Shegan Mahuang Decoction (SMD) is one of the representative traditional Chinese medicine (TCM) prescriptions for asthma, and it can effectively relieve the clinical symptoms of patients. However, the effect of SMD on the treatment of neutrophilic asthma remains unknown. In this study, a mouse model of neutrophilic asthma induced by lipopolysaccharide (LPS)/ovalbumin (OVA) was established, and the effect of a modified SMD prescription on the model was evaluated. After treatment, SMD was demonstrated to be therapeutically effective on asthmatic mice via airway resistance detection and lung pathology and was able to affect cytokine levels in vivo. Further experiments verified that SMD regulated the expression of mitochondrial function proteins in bronchoalveolar lavage fluid (BALF) exosomes. The results demonstrate that SMD confers a therapeutic effect on a neutrophilic asthma mouse model, and it may reduce neutrophil airway inflammation by regulating myeloid-derived regulatory cell (MDRC) function and airway exosome mitochondrial function.

Research on the temporal evolution track and influence of green development from 2010 to 2019.

This study aims to analyze the balance and coordination during green and sustainable development and estimates the evolution track of the green development system from 2010-2019. The projection pursuit model (PPM), as well as the system gray prediction model GM (1, N) and other measurement methods, were used to construct an evaluation system accounting for green fortune, growth, and benefits to analyze the temporal evolution, developmental trends, and influencing factors of the ecological engineering construction area in Baoshan, Yunnan Province. The results revealed a relatively good green development system, with an upward trend, an average growth rate of 18.3%, and a synergistic coupling effect among the three subsystems. Regional green development has achieved remarkable progress, but challenges and pressure among the three subsystems remain. The prediction analysis also showed that the green development index in Baoshan will continue to increase over the next two years, suggesting that the regional green development system is effective. Green development is primarily affected by environmental pollution, industrial structure, urbanization, population, market, and other factors from the three subsystems of ecology, economy, and social benefits. This study provides practical reference values for prompting regional ecological advancement and green development, along with regional support for the post-2020 Global Biodiversity Framework and the achievement of the United Nations Sustainable Development Goals.

Acute and Subacute Toxicity of Fluorescent Gold Nanoclusters Conjugated with α-Lipoic Acid.

Fluorescent gold nanoclusters conjugated with α-lipoic acid (FANC) is a promising biocompatible fluorescent nanomaterial with a high potential for drug development. However, there is still no FANC-related research on toxicology, which is very important for future research and the development of healthy food supplements or drugs. This study uses oral administration of FANC to determine the most appropriate dose range in ICR mice for further evaluation. The in vivo acute and subacute toxicity study was conducted by oral administration of FANC to male and female ICR mice. Animal survival, body weight, daily food consumption, hematological profile, organ coefficient, serum biochemistry profile, and histopathological changes were analyzed. FANC did not show any form of morbidity or mortality at acute and subacute toxicity in both male and female ICR mice. Animal behavior, daily food consumption, hematological profile, organ coefficient, and histopathology showed no treatment-related malignant changes at single and repeated doses. Furthermore, serum glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and creatinine (CRE) levels showed no significant malignant changes, which indicated that FANC does not cause liver and renal damage. The only change observed in this study was the change in body weight. The body weight of the FANC-treated group was slightly decreased in female mice but increased in male mice; however, the body weight decreases were below the threshold of concern, and there was no dose-response effect. In conclusion, no observed adverse effect level (NOAEL) in repeated doses was considered in 20 µM/100 µL/25 g male and female ICR mice.

Effect of the prosthetic index on stress distribution in Morse taper connection implant system and peri-implant bone: a 3D finite element analysis.

BACKGROUND: The combination of a prosthetic index with Morse taper connection was developed, with the purpose of making prosthetic procedures more precise. However, the presence of the index may compromise the mechanical performance of the abutment. The aim of this study is to evaluate the effect of prosthetic index on stress distribution in implant-abutment-screw system and peri-implant bone by using the 3D finite element methodology. METHODS: Two commercial dental implant systems with different implant-abutment connections were used: the Morse taper connection with platform switching (MT-PS) implant system and the internal hex connection with platform matching (IH-PM) implant system. Meanwhile, there are two different designs of Morse taper connection abutment, namely, abutments with or without index. Consequently, three different models were developed and evaluated: (1) MT-PS indexed, (2) MT-PS non-indexed, and (3) IH-PM. These models were inserted into a bone block. Vertical and oblique forces of 100 N were applied to each abutment to simulate occlusal loadings. RESULTS: For the MT-PS implant system, the maximum stress was always concentrated in the abutment neck under both vertical and oblique loading. Moreover, the maximum von Mises stress in the neck of the MT-PS abutment with index even exceed the yield strength of titanium alloy under the oblique loading. For the IH-PM implant system, however, the maximum stress was always located at the implant. Additionally, the MT-PS implant system has a significantly higher stress level in the abutment neck and a lower stress level around the peri-implant bone compared to the IH-PM implant system. The combined average maximum stress from vertical and oblique loads is 2.04 times higher in the MT-PS indexed model, and 1.82 times for the MT-PS non-indexed model than that of the IH-PM model. CONCLUSIONS: MT-PS with index will cause higher stress concentration on the abutment neck than that of without index, which is more prone to mechanical complications. Nevertheless, MT-PS decreases stress within cancellous bone and may contribute to limiting crestal bone resorption.

Efficacy and safety of anlotinib combined with carboplatin and pemetrexed as first-line induction therapy followed by anlotinib plus pemetrexed as maintenance therapy in EGFR/ALK wild-type advanced non-squamous non-small cell lung cancer in China: a multicenter, single-arm trial.

Background: The efficacy and safety of chemotherapy strategies combining the multi-target receptor tyrosine kinase inhibitor in patients with advanced EGFR/ALK wild-type non-squamous non-small-cell lung cancer (nsq-NSCLC) are undetermined. We aimed to investigate the efficacy and safety of anlotinib combined with carboplatin/pemetrexed-based chemotherapy followed by maintenance therapy (anlotinib plus pemetrexed) in advanced EGFR/ALK wild-type nsq-NSCLC. Methods: Eligible patients with wild-type EGFR/ALK advanced nsq-NSCLC who received first-line therapy in Henan Province from March 2019 to February 2021 were recruited. All patients were treated with anlotinib in combination with carboplatin/pemetrexed-based chemotherapy, followed by maintenance therapy (anlotinib plus pemetrexed). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), disease control rate (DCR), objective response rate (ORR), and adverse events (AEs). Response and AEs were assessed based on the Response Evaluation Criteria in Solid Tumors (1.1) and National Cancer Institute - Common Terminology Criteria for Adverse Events v.4.0.3, respectively. The follow-up interval for survival was 6 weeks and the safety follow-up was performed until the end of treatment. Kaplan-Meier analysis was used to calculate the median PFS and OS. Results: Thirty-eight participants with median age of 62 (range, 33-75) years were evaluated. Five participants were still on maintenance therapy until the end of the study. The majority were non-smokers (68.4%). The median follow-up was 13.6 (range, 12.3-14.9) months. The median PFS (mPFS) was 10.5 (95% CI: 4.1, 17.0) months, and the median OS was 23.4 [95% CI: not evaluable (NE), NE] months. The DCR and ORR were 94.7% and 60.5%, respectively. Grade 3 and above treatment-related adverse events (TRAEs) happened to 12 participants. The most common TRAEs were hypertension (23.7%), neutropenia (19.4%), and bone marrow toxicity (10.5%). Seven patients discontinued treatment, including two patients during induction and five patients during maintenance treatment. No grade 5 TRAE was reported. In the non-smoker participants, the mPFS was 14.5 (95% CI: 4.0-25.0) months. Conclusions: Anlotinib in combination with carboplatin/pemetrexed-based chemotherapy followed by anlotinib plus pemetrexed as maintenance therapy might be an effective choice in treating patients with wild-type EGFR/ALK advanced nsq-NSCLC.

Abutment mechanical complications of a Morse taper connection implant system: A 1- to 9-year retrospective study.

BACKGROUND: The fracture of a Morse tapered abutment connection in an osseointegrated implant is one of the most serious mechanical complications, and it is extremely hard to deal with this complication in clinical practice. PURPOSE: The aim of this study was to explore the cumulative mechanical complications focus on abutment of a platform switching Morse taper connection implant system after loading, and to perform a retrospective, approximately 1- to 9-year follow-up study to identify the predisposing factors. MATERIALS AND METHODS: A total of 495 patients with 945 fitted implants were enrolled in this study with a follow-up from January 2012 to January 2020. The data of mechanical complications of the abutment, including abutment fracture (AF) and abutment screw loosening (ASL), and possible causative factors were extracted and evaluated statistically. RESULTS: A total of 25 out of 945 (2.65%) cumulative abutment mechanical complications occurred. AF was the most common complication (n = 13, 1.38%), followed by ASL (n = 12, 1.27%). For AF, gender, type of prosthesis, abutment design, and implant diameter were identified as the causative factors. AF was mostly observed in the single crown of males in molar areas, while ASL was more likely to occur on an angled abutment than on a non-angled abutment. Moreover, the abutment with the positioning index (/X) had a higher incidence of fracture than the abutment without the positioning index (C/). CONCLUSIONS: This study shows that the Morse taper connection is a safe abutment connection. AF occurs more frequently within single crowns in molar area of males, especially with the positioning index (/X), while ASL is more likely to occur in an angled abutment.

tert-Butylhydroquinone-induced formation of high-molecular-weight p62: A novel mechanism in the activation of Nrf2-Keap1.

The respiratory system is always exposed to air and is most vulnerable to attack by environmental free radicals. The nuclear factor E2-related factor 2-Kelch-like ECH-associated protein 1-antioxidant response element (Nrf2-Keap1-ARE) pathway and p62 are both involved in the oxidative stress response. However, the interplay between these two systems remains largely unknown. This study shows that treatment of L2 cells with tert-Butylhydroquinone (tBHQ) generates a high-molecular-weight (HMW) form of p62, leading to activation of the Nrf2-Keap1-ARE pathway. The levels of HMW-p62 increased as the tBHQ concentration increased, with concomitant decreases seen in the classical form of p62. Moreover, small interfering RNA targeting p62 increases Keap1 protein levels and inactivates the Nrf2-Keap1-ARE pathway. These results demonstrate that the Nrf2-Keap1 pathway is partially regulated by p62. tBHQ-induced HMW-p62 production may be a novel mechanism in the activation of the Nrf2-Keap1-ARE pathway.