Extracellular vesicles promote silica nanoparticle aggregation that inhibits silica-induced cytotoxicity.

Amorphous silica has been approved as a food and pharmaceutical additive. However, its potential to enhance the carcinogenicity of epithelial cells is incontrovertible. With their expanded surface area per unit mass and distinctive cellular incorporation, nano-sized silica particles (nSPs) exhibit heightened cytotoxicity compared to micrometer-sized counterparts. The precise effect of nSPs on the generation of small extracellular vesicles (sEVs) within endosomes after cellular uptake remains unclear. In the present study, we explored the secretion of sEVs from cells and their functional implications following exposure to nSPs. Our findings demonstrate that nSP50 exposure not only induced epithelial-mesenchymal transition (EMT) but also promoted the maturation of multivesicular endosomes (MVEs) along with the secretion of sEVs in A549 cells. Inhibition of sEV secretion using GW4869 and apoptosis activator 2 exacerbated nSP50-induced EMT, indicating that sEV secretion may suppress EMT. Analysis of the function of sEV in a cell-free system revealed that co-incubation of sEVs with nSP50 led to the formation of micrometer-sized aggregates, which exhibited limited uptake efficiency within A549 cells. These results strongly suggest that the secretion of sEVs plays a protective role against the cytotoxicity attributed to nSP50 exposure.

Right versus left coronary artery involvement in patients with type A acute aortic dissection.

BACKGROUND: Type A acute aortic dissection (AAD) complicated by coronary malperfusion is a life-threatening disease. In the present study, we compared the clinical characteristics and prognostic impact of treatment strategies including surgical treatment and percutaneous coronary intervention (PCI) in type A AAD patients with RCA and LCA involvement. METHODS: This multicenter registry included 220 patients with type A AAD and either RCA or LCA involvement. Treatment strategies were left to treating physicians. The primary endpoint was in-hospital death. RESULTS: Of 220 patients, 115 (52.3%) and 105 (47.7%) had RCA and LCA involvement. Patients with LCA involvement were more1 likely to present with Killip class IV on admission than those with RCA involvement. Coronary angiography was performed in 52 of 220 (23.6%) patients, among whom 39 (75.0%) underwent subsequent PCI. During the hospitalization, 93 (42.3%) patients died. Patients with LCA involvement had an increased risk of in-hospital mortality compared to those with RCA involvement (54.3% vs. 31.3%, p < 0.001). In patients with RCA involvement, multivariable analysis identified Killip class IV and no surgical treatment as predictors of in-hospital death, while PCI and surgical treatment were indicated as factors associated with lower in-hospital mortality in patients with LCA involvement. CONCLUSIONS: The rates of RCA and LCA involvement were similar in type A AAD. Immediate PCI as a bridge to subsequent surgical treatment might improve survival in patients with type A AAD complicated by coronary malperfusion, especially in those with LCA involvement.

Skin, Liver, and Kidney Interactions Contribute to Skin Dryness in Aging KK-Ay/Tajcl Mice.

Type 2 diabetes is a lifestyle-related disease that affects people worldwide and is especially prevalent in the elderly. Many elderly people with diabetes also complain of dry skin; however, the relationship between aging and dry skin in type 2 diabetes is unknown. The purpose of this study was to examine the interaction between aging and dry skin using the specific pathogen-free KK-Ay/TaJcl type 2 diabetes mouse model. Skin dryness in this model increases with age and was evaluated at 10, 27, 40, and 50 weeks. We observed increased mast cell expression, increased histamine and matrix metalloproteinase-1 levels, and decreased collagen expression in the skin of aging KK-Ay/TaJcl mice. In addition, the increased expression of angiopoietin 2, interleukin-6, tumor necrosis factor-α, and endostatin in the blood indicated kidney damage in this model. Aging KK-Ay/TaJcl mice also showed fatty liver pathology, which led to increased reactive oxygen species in the blood and liver, as well as the increased expression of M1 macrophages in the liver. These results showed that dry skin is associated with skin, kidney, and liver interactions in an aging type 2 diabetes mouse model.

Relationships of pain-causing substances with dry skin and effects of zaltoprofen on alleviation of symptoms in arthritis model mice.

Purpose: Skin dryness is a symptom of rheumatoid arthritis (RA). However, the mechanisms through which dry skin is induced in RA are unclear. Accordingly, in this study, we characterized substances related to pruritus and pain and then evaluated whether oral administration of zaltoprofen (ZLT) alleviated the symptom of dry skin induced by RA in model mice.Material and Methods: DBA/1JJmsSlc collagen-induced arthritis model mice were treated with ZLT, and transepidermal water loss (TEWL), capacitance, and inflammation-, pruritus-, and pain-related markers were assessed.Results: Our findings demonstrated that arthritis model mice treated with ZLT exhibited suppression of increases in TEWL and decreases in capacitance. Furthermore, ZLT also blocked the increase in mast cell numbers, substance P expression, and cyclo-oxygenase-2 expression in the skin and prevented enhancement of plasma levels of thymic stromal lymphopoietin, tumour necrosis factor-α, interleukin-6, histamine, and bradykinin. No changes in plasma levels of corticosterone or reactive oxygen species or skin levels of glucocorticoid receptor were observed in ZLT-treated arthritis model mice.Conclusions: Overall, these findings suggested that patients with RA may benefit from biopharmacy to alleviate joint symptoms and nonsteroidal anti-inflammatory drugs for pain relief and alleviation of skin symptoms.

Influence of Smoking in the Clinical Outcomes of Distal Radius Fractures.

Introduction There are various studies that reviewed the effect of cigarette smoking in fracture healing process. Nonunion, delayed union, and residual pain are the significant risk factors associated with smoking and fracture healing. Little has been known about the impact of smoking in distal radius fracture healing. We intend to explore in brief the effect of smoking in distal radius fracture healing and comparing it with nonsmokers having the same fracture fixation and analyze the outcomes with respect to fracture healing and return of function. Materials and Methods Of the total 186 patients, 92 were included in the study with ( n = male: 31, female: 61) mean age of 60.2 years. They were divided into two groups: smoking ( n = 43) and nonsmoking ( n = 49). All had surgical fixation of the distal radius with volar locking plate and started on early mobilization. The range of motion of the wrist, grip, visual analog scale, quick disabilities of the arm and shoulder and hand score, Mayo wrist score, and bone healing period were noted between these two groups and compared with statistical analysis. Results The mean follow-up period was 8.7 months. There was a significant association of young age and male patients having distal radius fractures in the smoking group ( p < 0.05). All fractures healed well in both groups without complications. There was no significant difference between these two groups in terms of range of motion, grasp, bone healing period, and functional outcomes. Conclusion Despite the well-known fact that, smoking has negative implications in the fracture healing process, we found group of patients (smoking and nonsmoking) with distal radius fractures treated by volar locking plates healed well with good radiological union and excellent functional outcome There is no significant influence of smoking in distal radius fracture fixation.

Glycyrrhizin ameliorates melanoma cell extravasation into mouse lungs by regulating signal transduction through HMGB1 and its receptors.

Metastasis, which accounts for the majority of all cancer-related deaths, occurs through several steps, namely, local invasion, intravasation, transport, extravasation, and colonization. Glycyrrhizin has been reported to inhibit pulmonary metastasis in mice inoculated with B16 melanoma. This study aimed to identify the mechanism through which glycyrrhizin ameliorates the extravasation of melanoma cells into mouse lungs. Following B16 melanoma cell injection, mice were orally administered glycyrrhizin once every two days over 2 weeks; lung samples were then obtained and analyzed. Blood samples were collected on the final day, and cytokine plasma levels were determined. We found that glycyrrhizin ameliorated the extravasation of melanoma cells into the lungs and suppressed the plasma levels of interleukin-6, tumor necrosis factor-α, and transforming growth factor-ß. Furthermore, glycyrrhizin ameliorated the lung tissue expression of high mobility group box-1 protein (HMGB1), receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)-4, RAS, extracellular signal-related kinase, NF-κB, myeloid differentiation primary response 88, IκB kinase complex, epithelial-mesenchymal transition markers, and vascular endothelial growth factor-A. Our study demonstrates that glycyrrhizin ameliorates melanoma metastasis by regulating the HMGB1/RAGE and HMGB1/TLR-4 signal transduction pathways.

[The Mid-term Results of Transapical Transcatheter Aortic Valve Implantation for Aortic Stenosis].

We aimed to evaluate the results of transapical transcatheter aortic valve implantation (TAVI) for aortic stenosis. Thirty patients who had aortic stenosis and underwent transapical TAVI between 2016 and 2020 were enrolled. Medical records were reviewed, and the following data were retrieved and analyzed:basic demographic data, and intraoperative data and postoperative outcomes. Mean age was 85.8 years. There were 3 intraoperative complications (1 apex bleeding, 1 coronary stenosis and 1 mitral regurgitation). Extracorporeal membrane oxygenation was initiated due to unstable hemodynamics in two patients. One patient was converted to mitral valve replacement due to severe mitral regurgitation. There were 2 in-hospital complications (1 with sick sinus syndrome and 1 with cerebral infarction). One patient died of cerebral infarction and eventually, the 30-day mortality was 3%. Median observational period was 1.3 years. Three-year survival was 87.3%. Left ventricular ejection fraction increased by six months after the procedure and then, reached plateau. Left ventricular mass index decreased constantly throughout the observational period. Both parameters at one year after the procedure were significantly higher than preoperative ones. In conclusion, survival after transapical TAVI was favorable because of the low critical complication rate. Both left ventricular functional improvement and reverse remodeling were obtained.

Outcomes of conservative treatment for bony mallet fingers.

BACKGROUND: The treatment strategy for bony mallet fingers remains controversial. The outcomes of conservative treatment were investigated in this study. In addition, the time to bone union, and gap between the bone fragment and distal phalanx are discussed. METHODS: The subjects were 26 patients (27 fingers) with bony mallet fingers (20 males and 6 females, mean age: 46.0 years old, the mean limitation of extension of the distal interphalangeal (DIP) joint: - 20.2°). In conservative treatment, splinting was applied for 6 weeks, followed by 2-week taping. The time to bone union, range of motion of the DIP joint, and the Crawford classification on the final follow-up were investigated. In addition, the bone fragment occupation rate was evaluated on plain radiography on the first examination. Furthermore, the gap on the first examination and after splinting. The relationship between the gap and bone union period was also investigated. RESULTS: The mean time from injury to bone union was 170.2 days, the mean range of motion of the DIP joint was - 8.5° in extension and 60.9° in flexion, and the Crawford classification was Excellent for 22 fingers, Good for 2, Fair for 2, and Poor for 1. On the first examination, the mean bone fragment occupation rate was 44.0%. The mean gap on the first examination was 1.1 mm and this was significantly narrowed to 0.8 mm after splinting (p < 0.01). No significant correlation was noted between the time to bone union and gap on the first examination (p = 0.16), however, a significant positive correlation was noted between them after splinting (p < 0.01). CONCLUSIONS: This study suggested that a favorable clinical outcome can be achieved by conservative treatment. Moreover, the bone union period decreased as the gap after splinting decreased, being significantly correlated.

Correction of humpback and DISI deformities by vascularized bone grafting in patients with scaphoid nonunion.

INTRODUCTION: Although vascularized bone grafting (VBG) using 1, 2 intercompartmental supraretinacular artery (1, 2 ICSRA) is effective for scaphoid nonunion, dorsal intercalated segment instability (DISI) deformity persists even after correction of humpback deformity (HD). The purpose of this retrospective study was to evaluate the correction of HD and DISI deformity after 1, 2 ICSRA VBG for scaphoid nonunion. METHODS: We treated 18 patients (mean age: 25.8, 16 males and 2 females) with scaphoid nonunion using a 1, 2-ICSRA VBG between January 2010 and December 2018. The average time from injury to surgery was 20.0 (3-120) months. The nonunions were located at the waist in all patients. The correction of HD and DISI deformity was investigated on the preoperative images and images at the last examination. RESULTS: In all patients, the correction of HD was positively correlated with that of DISI deformity. Moreover, we focused on the time from injury to surgery and evaluated changes in HD and DISI deformity according to the time to surgery. As a result, changes in HD and DISI deformity were positively correlated in patients with a shorter time to surgery but were not correlated when the time to surgery exceeded 5 months. CONCLUSIONS: These results suggest that DISI deformity can be corrected by correcting HD when the time from injury to surgery is short, but that correction is difficult if the time to surgery is prolonged.

Comparison of clinical outcomes with and without volar lunate facet fragments in dorsal displaced distal radius fractures.

INTRODUCTION: Although many clinical studies about distal radius fracture (DRF) accompanied by volar lunate facet fragments (VLFF) have recently been reported, none focus on the direction of displacement of distal fragments. Many previous cases with difficulty in treating DRF with VLFF were volar-displaced fractures. Thus, the postoperative risk for re-displacement is different between volar- and dorsal-displaced fractures with VLFF. The aim of this study is to compare the outcome of dorsal-displaced fractures treated using proximal volar locking plates (PVLP) between those with VLFF and those without, in order to reconsider the indications of distal volar locking plates (DVLP) and investigate the possibility of treating dorsal-displaced DRF with VLFF using PVLP. METHODS: The subjects were 122 patients with dorsal-displaced DRFs treated using PVLP (42 males and 80 females, mean age: 59.2 years old). The patients were divided into 13 patients with VLFF group and 109 patients without VLFF group, and the clinical outcomes at 12 months after surgery were compared. RESULTS: No significant difference was noted on any evaluation between the groups. In addition, no postoperative re-displacement of VLFF was observed and bone union was confirmed. Furthermore, no osteoarthritic change was noted in all patients. CONCLUSIONS: We confirmed that surgical treatment for dorsal-displaced DRF using PVLP is possible even in cases of DRF with VLFF. In addition, DVLP is an implant with a high complication risk; therefore, it may be necessary to reconsider the use of DVLP for dorsal-displaced DRF with VLFF treatable by PVLP.

Influence of aging on the peripheral nerve repair process using an artificial nerve conduit.

The influence of aging on the induction of nerve regeneration in artificial nerve conduits has yet to be clarified. In the present study, artificial nerve conduit transplantation and histological analysis using the sciatic nerve of young and elderly mice were performed. Using 20 male C57BL/6 mice, an artificial nerve conduit was transplanted to the sciatic nerve at 8 weeks (Young group) or 70 weeks of age (Aged group), and the sciatic nerve was evaluated histologically at 1, 4 and 12 weeks after surgery. Using hematoxylin and eosin staining, the state of induction of nerve regeneration in the artificial nerve conduit was evaluated. Additionally, immunohistochemical staining was used to investigate an angiogenic marker [vascular endothelial growth factor A (VEGFA)], Schwann cell markers [sex determining region Y-box 10 (SOX10) and S100 calcium-binding protein ß (S100ß)] and a nerve damage marker [nerve growth factor (NGF)]. The results revealed that the induction of nerve regeneration was significantly higher in the Young group than in the Aged group. In addition, VEGFA and SOX10 expression at 1 week, SOX10 expression at 4 weeks and SOX10, S100ß and NGF expression at 12 weeks in the proximal stump were significantly higher in the Young group than in the Aged group. At the center of the artificial nerve conduit, S100ß and NGF expression at 4 weeks, and VEGFA, SOX10, S100ß and NGF expression at 12 weeks were significantly higher in the Young group than in the Aged group. In the distal stump, no significant difference was noted in immunostaining at any week between the two groups. The present study suggested that the nerve regeneration-inducing functions decrease due to aging.

Intratendinous ganglion in the extensor digitorum communis.

We encountered a patient with intratendinous ganglion which developed in the extensor digitorum communis tendon. Although its developmental mechanism is unclear, synovitis is considered the cause. For treatment, it may be necessary to prepare for tendon transfer and tendon grafting in consideration of the risk of tendon injury.

Treatment for a Metacarpal Shaft Fracture using Locked Wire Fixator: A Case Report of New Surgical Technique.

INTRODUCTION: This article reports a case of metacarpal shaft fracture using a low-invasive simple locked wires fixator with a high degree of flexibility. A new surgical technique for this injury will also be presented. CASE REPORT: A 27-year-old female with the right 3rd metacarpal shaft fracture caused by falling down while riding a bicycle. The patient was a professional ballet dancer and requested treatment enabling an early return to exercise and non-noticeable wound. Pins were percutaneously inserted antegradely and retrogradely to the metacarpal bone as intramedullary pinning, then were connected using locked wires fixator. Post-operative immobilization was not necessary. The locked wire fixator was removed 6 weeks after surgery. Postoperatively, there were no limitations of the range of motion of the finger joints and the operative scar was almost unrecognizable. CONCLUSION: This is a new breakthrough procedure facilitating. Furthermore, this surgical procedure may be selected as an esthetically useful method making a small wound because it can be percutaneously applied.

Characteristics of sagittal spine alignment in female patients with distal radius fractures due to fall.

OBJECTIVES: Distal radius fractures occur due to reflex clasp when falling. Recently, attention has been focused on the strong relationship between sagittal spine alignment and falls. Therefore, we investigated the parameters of sagittal spinal alignment in distal radius fractures in female patients. PATIENTS AND METHODS: The subjects were group D: 28 female patients with distal radius fractures aged 50 years or older (mean age: 69.3 years), and group C: 26 healthy female patients without a history of fragility fractures (mean age: 70.5 years). Height, body weight, and body mass index (BMI) were measured as physical indices. As parameters of sagittal spinal alignment, the sagittal vertical axis (SVA), pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), lumber lordosis (LL), and thoracic kyphosis (TK) were measured on lateral whole-spine plain radiographs in a standing position. The measured physical indices and sagittal spinal alignment parameters were compared between groups. RESULTS: Height, weight, and BMI did not differ significantly between the two groups. Among the sagittal spinal alignment parameters, PT, PI, SS, LL, and TK did not differ significantly between groups, whereas SVA was significantly higher in group D than in group C (P < 0.05). CONCLUSION: In this study, SVA was significantly higher in group D than in group C. As SVA increased, the center of gravity of the body shifts forward, which can cause the body to lose balance and fall. This study suggested that an increase in SVA is associated with distal radius fractures.

Robot-assisted Intercostal Nerve Harvesting: A Technical Note about the First Case in Japan.

Recently, surgical robotic systems have been used to perform microsurgery. Surgical robots have certain properties that make them well suited to microsurgery; for example, they possess 3-dimensional vision, which can be magnified up to 25 times; their movements are up to 5 times more precise than those of surgeons; they possess 7 degrees of wrist articulation; they do not suffer from physiologic tremors; and they can achieve ergonomic surgical positions. The purpose of this study was to report the feasibility of robot-assisted intercostal nerve harvesting in a clinical case. A healthy 57-year-old man suffered a left plexus injury. On diagnosis of clavicular brachial plexus injury, the intercostal nerve transfer to the muscular cutaneous nerve to restore elbow flexion was performed with Da Vinci Xi robot. The harvesting of intercostal nerves using the conventional open approach involves significant surgical exposure, which can lead to perioperative complications. Robot-assisted intercostal nerve harvesting might reduce postoperative pain, shorten patients' hospital stays, lower complication rates, and produce better quality-of-life outcomes. There are many issues to be solved when performing robotic surgery on peripheral nerves in Japan. However, robot-assisted intercostal nerve harvesting was a feasible surgical procedure, and patient satisfaction was high.

A Survey of the Median Nerve Elasticity after Volar Locking Plate Fixation Using Ultrasound Elastography.

Introduction Median nerve disorder is one of the complications after surgery using volar locking plate (VLP) for distal radius fracture (DRF). In this study, elasticity of the median nerve was quantified using ultrasound elastography (EG) (real-time tissue EG) and compared between the operation and healthy sides in patients after surgery for DRF using VLP. Materials and Methods The subjects of this study were 28 patients (4 males and 24 females; mean age: 58.5 years) who could be followed up for more than 6 months after surgery for DRF and were able to be examined by EG. We evaluated median nerve elasticities on the operation and healthy sides using EG on the final follow-up. Results The median nerve strain ratios were 3.97 ± 2.99 on the operation side and 3.91 ± 1.51 on the healthy side, showing no significant difference in elasticity of the median nerve between the operation and healthy sides. Conclusion Median nerve disorder, which is a complication after surgery with VLP, can be objectively detected using EG capable of evaluating median nerve elasticity externally to detect medial nerve degeneration while degeneration of the median nerve. Thus, EG may be used as a useful diagnostic tool to prevent complications and decide on appropriate timing of VLP extraction.

Evaluation of Patient-Reported and Clinician-Reported Outcomes of Volar Locking Plate Fixation for Distal Radius Fractures.

Background: Postoperative evaluation of wrist joint trauma is divided into patient-reported outcomes (PROs) and clinician-reported outcomes (CROs). We investigated the association of the Q-DASH score as the postoperative PROs and the Mayo wrist score as the postoperative CROs with clinical evaluation in patients with distal radius fractures surgically treated using a volar locking plate (VLP). Moreover, whether PROs and CROs are correlated to the clinical evaluation was investigated. Methods: The subjects were 109 patients surgically treated for distal radius fractures at our hospital between June 2013 and May 2017. Forty-one patients were male, 68 patients were female, and the mean age was 61.4 (19-86) years old. The fracture type was AO classification A type in 30 patients (A2: 25, A3: 5), B type in 5 (B2: 1, B3: 4), and C type in 74 (C1: 50, C2: 11, C3: 13). All patients were surgically treated using VLP. The range of motion of the wrist, grip strength the Visual Analog Scale (VAS), the Q-DASH score (PROs), and the Mayo wrist score (CROs) were investigated. Each evaluation was compared as the clinical outcome between at 3 months after surgery and the final follow-up. In addition, the correlations of the postoperative PROs and CROs with the clinical evaluation were analyzed. Results: Each evaluation was significantly improved compared with that at 3 months after surgery. There was a significant correlation between PROs and CROs at 3 months after surgery and the final follow-up. However, the range of motion of the wrists was not significantly correlated with PROs or CROs at 3 months after surgery or at the final follow-up. Conclusions: On evaluation after surgery for distal radius fractures, PROs and CROs improved early after surgery (3 months after surgery) before the final follow-up, and an inverse correlation was present between these scores.

Locked wires fixator for fractures of the distal third of the radius and ulna in children.

BACKGROUND: Prevention of redisplacement is an issue after the treatment of fractures of the distal third of the radius in children. In this study, we used a locked wires fixator for this type of fracture and achieved favorable treatment outcomes. METHODS: The subjects were 8 children with fractures of the distal third of the radius (male: 7, female: 1, mean age: 9.0 years old) who underwent surgery with locked wires fixators and were able to be evaluated 12 months after surgery. Immobilization was not applied after surgery. The locked wires fixator or K-wire was removed when the bridging callus was observed on plain radiography 4-6 (mean 5.5) weeks after surgery in all patients. The presence of bone union, functional outcomes, and complications were investigated postoperatively. RESULTS: All patients achieved bone union without redisplacement excellent function. The pin site infection was observed in two patients. CONCLUSIONS: The locked wires fixator may be a new useful treatment method for fractures likely to cause postoperative redisplacement.

The interference with transapical transcatheter aortic valve implantation by the anterior chordae tendineae preserved at previous mitral valve replacement.

Preserved anterior chordae tendineae is a possible risk factor for disturbing delivery of a transcatheter heart valve. Inserting a sheath just below the aortic valve for delivery of the transcatheter heart valve might be proposed as an alternative to avoid the chordae tendineae.