Enhancing calvarial defects repair with PDGF-BB mimetic peptide hydrogels.

Addressing bone defects represents a significant challenge to public health. Localized delivery of growth factor has emerged as promising approach for bone regeneration. However, the clinical application of Platelet-Derived Growth Factor (PDGF) is hindered by its high cost and short half-life. In this work, we introduce the application of PDGF-mimicking peptide (PMP1) hydrogels for calvarial defect restoration, showcasing their remarkable effectiveness. Through osteogenic differentiation assays and q-PCR analyses, we demonstrate PMP1's substantial capacity to enhance osteogenic differentiation of bone marrow mesenchymal stem cell (BMSC), leading to increased expression of crucial osteogenic genes. Further molecular mechanistic investigations reveal PMP1's activation of the PI3K-AKT-mTOR signaling pathway, a key element of its osteogenic effect. In vivo experiments utilizing a rat calvaria critical-sized defect model underscore the hydrogels' exceptional ability to accelerate new bone formation, thereby significantly advancing the restoration of calvaria defects. This research provides a promising bioactive material for bone tissue regeneration.

Experimental study and finite element analysis of heavy-duty escalator truss under full load conditions.

The performance of the heavy-duty escalator truss greatly affects the stability and service life of the whole escalator system, and the manufacturing cost of truss structure accounts for more than 1/5. Thus, how to design the truss structure reasonably is a pivotal issue drawing the attention of numerous engineers and researchers. In this work, the experimental research of heavy-duty escalators under full load conditions were performed in terms of the end restraints, the docking port clearances, and the deflection. Based on the experimental results, the three-dimensional simulation model of truss structure was created, and the influences of various factors such as the internal chamfer of truss member, the lower deviation of truss member, the dead weight of escalator, and the pretension force of each bolt at the docking port were analyzed and quantified. Finally, the finite element model which can almost completely characterize the actual structure was obtained with slight difference. The conclusions drawn in this work provide the basis for the efficient design, correct simulation, low cost production and rapid installation of the heavy-duty escalator truss.

Early endovascular approaches for treating acute mesenteric arterial occlusive disease in hemodialysis patients.

BACKGROUND: Among hemodialysis patients, acute superior mesenteric artery (SMA) thrombosis a condition with a high mortality rate. Very few larger case series have been reported. METHOD: We reviewed eight hemodialysis patients with diabetes mellitus and SMA thrombosis managed with endovascular therapy in our institution. Demographic, clinical, and radiological data were described. The patency of the SMA was assessed by computed tomography angiography (CTA) at one month after the endovascular procedure. At the last visit, clinical symptoms and check of mortality were recorded. RESULTS: Multidetector CTA scan revealed severe stenosis of SMA in 6 patients and SMA occlusion in the other two patients. The severe stenosis of SMA were verified by angiography. Balloon angioplasty without stenting was performed to obtain satisfactory patency of SMA. Seven of eight patients achieved resolution of abdominal pain after the endovascular procedure. One patient died of suspected intestinal necrosis after 6 days of balloon angioplasty. All seven surviving patients did not experience a recurrence of symptoms with a median follow-up of 2 years. No significant residual stenotic or occlusive lesions were noted in follow-up CTA at one month after the endovascular procedure. CONCLUSION: SMA thrombosis should be systematically suspected in hemodialysis patients experiencing abdominal pain. Prompt diagnosis of SMA thrombosis as soon as possible and early endovascular therapy are required to obtain a favorable prognosis in the hemodialysis patient with SMA thrombosis.

A hydrogel optical fibre sensor for rapid on-site ethanol determination.

Ethanol plays a critical role in the modern chemical industry, food production, and medical research. Given its wide applications, the detection of ethanol concentration is very necessary. In this paper, a fibre device for rapid ethanol detection is proposed. The sensing head was fabricated with multimode fibre. The hydrogel was photo-cured on the fibre tip from polyethylene glycol diacrylate (PEGDA). In the hydrogel, rhodamine 6G (R6G) was immobilized as the fluorescent indicator. The sensor was designed based on the swelling behaviour of the hydrogel in liquid. The transparency of the hydrogel was modulated by the component of the water-ethanol mixture, thus, the fluorescence intensity of R6G was monitored for the determination of ethanol. Within the range of 0-62.2 vol%, the detection limit (LOD) was 0.4 vol%. A detailed comparison with other detection methods showed that the proposed sensor has the advantages of being single-ended, low LOD, cost-effective, and easy to prepare. It has great potential for on-site ethanol detection applications.

Membrane-Free Electrosynthesis of Epichlorohydrins Mediated by Bromine Radicals over Nanotips.

The industrial manufacture of epichlorohydrin (ECH) often suffers from excessive corrosive chlorine and multistep processes. Here, we report a one-pot membrane-free Br radical-mediated ECH electrosynthesis. Bromine radicals electro-oxidized from Br- ions initiate the reaction and then eliminate HBr from bromohydrin to give ECH and release Br- ions for reuse. A high energy barrier for *OH oxidation and isolated Br adsorption sites enables NiCo2O4 to suppress the competitive oxygen and bromine evolution reactions. The high-curvature nanotips with an increased electric field concentrate Br- and OH- ions to accelerate ECH electrosynthesis. This strategy delivers ECH with a Faradaic efficiency of 47% and a reaction rate of 1.4 mol h-1 gcat-1 at a high current density of 100 mA cm-2, exceeding the profitable target from the techno-economic analysis. Economically profitable electrosynthesis, methodological universality, and the extended synthesis of epoxide-drug blocks highlight their promising potential.

Structural properties of Kudzu protein enzymatic hydrolysate and its repair effect on HepG2 cells damaged by H2O2 oxidation.

We investigated the structural properties, foaming capacity and foaming stability, antioxidant activity, and amino acid composition of Kudzu protein (KP) and Kudzu protein hydrolysate (KPH). The peptide sequence of KPH was analyzed using ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS), and the binding ability of the peptide sequence to Keap1 was predicted through molecular docking simulations. The electrophoresis and molecular weight distribution analysis results showed that the molecular weight of KPH was significantly lower than that of KP, with a mean molecular weight of approximately 2000-5000 Da. The structures and properties were characterized using Fourier transform infrared spectroscopy, relative fluorescence, and circular dichroism. The results showed that KP exposed a large number of hydrophobic groups after enzymatic hydrolysis, and its structure changed from α-helical to random coils. KPH has a higher foaming capacity (200%) and foaming stability (97.5%) than KP, which may be related to the change in structure. These results indicate that moderate hydrolysis can improve the functional properties of KP, providing a new opportunity for its application as a food ingredient. The antioxidant assay results showed that KP and KPH had a good hydroxyl radical, superoxide anion, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging capacity and a high reducing capacity. KPH exerted better antioxidant effects than KP. The scavenging rates for DPPH, ABTS, hydroxyl radicals, and superoxide anions were 89.31%, 93.14%, 85.74%, and 58.29%, respectively, and its reducing capacity was 2.191, which may be related to the increase in amino acids with antioxidant activity after enzymolysis. In vitro, KP and KPH could significantly repair H2O2-induced oxidative damage in HepG2 cells, reduce the apoptosis rate, activate the Nrf2-Keap1 signaling pathway, reduce the accumulation of reactive oxygen species and malondialdehyde after oxidative damage, increase the activities of superoxide dismutase and glutathione (GSH) peroxidase, and increase the content of GSH and the total antioxidant capacity. Twenty-one peptide components were identified in KPH using UPLC-MS/MS, and the binding ability of 21 peptide components to Keap1 was analyzed through molecular docking technology. The results showed that all 21 peptides in KPH had good antioxidant activity, and real-time quantitative PCR (qRT-PCR) analysis was conducted to further explain the high antioxidant activity of KPH at the genetic level. These results show that KP and KPH are suitable for preparing antioxidant foods and related health foods to prevent oxidation-related diseases. KPH has more beneficial effects than KP.

Ethnic, Botanic, Phytochemistry and Pharmacology of the Acorus L. Genus: A Review.

The genus Acorus, a perennial monocotyledonous-class herb and part of the Acoraceae family, is widely distributed in the temperate and subtropical zones of the Northern and Southern Hemispheres. Acorus is rich in biological activities and can be used to treat various diseases of the nervous system, cardiovascular system, and digestive system, including Alzheimer's disease, depression, epilepsy, hyperlipidemia, and indigestion. Recently, it has been widely used to improve eutrophic water and control heavy-metal-polluted water. Thus far, only three species of Acorus have been reported in terms of chemical components and pharmacological activities. Previously published reviews have not further distinguished or comprehensively expounded the chemical components and pharmacological activities of Acorus plants. By carrying out a literature search, we collected documents closely related to Acorus published from 1956 to 2022. We then performed a comprehensive and systematic review of the genus Acorus from different perspectives, including botanical aspects, ethnic applications, phytochemistry aspects, and pharmacological aspects. Our aim was to provide a basis for further research and the development of new concepts.

Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database.

Background and purpose: Testosterone is an essential sex hormone in maintaining masculine characteristics, which is prescribed for male hypogonadism as testosterone replacement treatment (TRT). Herein, we investigated long-standing controversies about the association between TRT and major adverse cardiovascular events (MACEs), based on real world adverse event (AE) reports, registered in the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Publicly available FAERS data from 1 January 2004 to 31 December 2022 were retrieved from the Food and Drug Administration (FDA) website. The data mining protocol including the reporting odds ratio (ROR) and the Bayesian confidence propagation neural network (BCPNN) was applied to analyze overreporting caused by risk factors and MACEs, including TRT, morbidities, and ages. The ROR and the BCPNN were also applied to investigate the annually developing trend of pharmacovigilance (PV) signals in the real world, retrospectively. Results: A total of 3,057 cases referring to MACEs, with a median age of 57 years old (yo), were identified from 28,921 cases of testosterone users. MACEs related to PV signals have emerged since 2014, including cardiac death, non-fatal myocardial infarction, and non-fatal stroke. Myocardial infarction (MI) (ROR: 9.46; IC025: 3.08), acute myocardial infarction (AMI) (ROR: 16.20; IC025: 3.72), ischemic cardiomyopathy (ROR: 11.63; IC025: 2.20), and cardiomyopathy (ROR: 5.98; IC025: 1.96) were the most significant signals generated, and weaker signals included cardiac failure acute (ROR: 4.01; IC025: 0.71), cardiac arrest (ROR: 1.88; IC025: 0.56), and ventricular fibrillation (VF) (ROR: 2.38; IC025: 0.38). The time-to-onset (TTO) of MACEs was calculated with a median of 246 days for AMI. Conclusion: For myocardial infarction and cardiomyopathy, TRT statistically tended to increase the risk of MACEs, while for cardiac arrhythmia, cardiac failure, and stroke, TRT demonstrated beneficial effects among the population with morbidities, such as testosterone deficiency (TD), diabetes mellitus (DM), and hypertension. MACEs were rare but led to serious outcomes including significant increase in death and disability. Since 2018, and before 2014, reports referring to TRT associated with MACEs were relatively scarce, which indicated that there might be a considerable number of cases that went unrecorded, due to neglection. Health workers and testosterone users might pay more attention to testosterone-induced MACEs.

Immunomodulatory activity of semen Ziziphi Spinosae protein: a potential plant protein functional food raw material.

Semen Ziziphi Spinosae protein (SZSP) is a new plant protein resource with good food functional properties and health care function. However, the biological activity of SZSP has not been further studied, which greatly limits the development and utilization of SZSP in the food industry. The aim of this study was to investigate the protective effect of SZSP on immunosuppressed mice and its inhibitory effect on immune-stimulated RAW264.7 cells. The results demonstrated that SZSP remarkably improved the immunomodulatory secretion in serum (interleukin-2, tumor necrosis factor-α [TNF-α], interferon-γ, immunoglobulin-A, immunoglobulin-G, immunoglobulin-M) and primary macrophages (nitric oxide, interleukin-1ß, TNF-α) and promoted the NK-cell killing activity of primary splenocytes in CTX-induced immunosuppression mice. Immunohistochemical analysis results indicated that the secretion of CD4+ and CD8+ in the spleen and thymus can be regulated by SZSP, leading to inhibition of the damage induced by cyclophosphamide in mice. Meanwhile, in order to clarify the immunomodulatory mechanism of SZSP, we showed that SZSP significantly inhibited the secretion of NO, interleukin-6, and TNF-α and reduced the phosphorylation expression of p-ERK, p-JNK, and p-IκBα in lipopolysaccharide-stimulated RAW264.7 cells. Therefore, the immunomodulatory effect of SZSP may be related to the activation of MAPKs and NF-κB signaling pathways. Based on the above studies, the preliminary purification of SZSP was continued, and S1F2G1 with immunomodulatory activity was obtained. Taken together, SZSP has an immunoregulatory effect in vivo and in vitro and may be a favorable candidate of functional food raw material for regulating immune responses.

Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicentre cohort study.

BACKGROUND: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. METHODS: The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity. RESULTS: The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P <0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) ( P <0.001). The IR of Gram-positive (GP) and Gram-negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP vs. GN's composition did not show any significance (Z=±1.1918, P >0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. CONCLUSIONS: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).

Sodium-glucose co-transporter-2 inhibitor (SGLT2i) treatment and risk of osteomyelitis: A pharmacovigilance study of the FAERS database.

Background and purpose: Several clinical trials have indicated that the use of canagliflozin increases the risk of lower extremity amputation. Although the US Food and Drug Administration (FDA) has withdrawn its black box warning about amputation risk for canagliflozin, the risk still exists. We sought to estimate the association between hypoglycemic medications, especially sodium-glucose co-transporter-2 inhibitors (SGLT2is), and adverse events (AEs) before the irreversible outcome of amputation as a promising early warning, based on the FDA Adverse Event Reporting System (FAERS) data. Methods: Publicly available FAERS data were analyzed using a reporting odds ratio (ROR) method and validated by a Bayesian confidence propagation neural network (BCPNN) method. The developing trend of the ROR was investigated by a series of calculations based on the accumulation of data in the FAERS database quarter by quarter. Results: Ketoacidosis, infection, peripheral ischemia, renal impairment, and inflammation including osteomyelitis might be more likely to occur among users of SGLT2is, especially canagliflozin. Osteomyelitis and cellulitis are AEs unique to canagliflozin. Among 2,888 osteomyelitis-related reports referring to hypoglycemic medications, 2,333 cases were associated with SGLT2is, with canagliflozin accounting for 2,283 of these cases and generating an ROR value of 360.89 and a lower limit of information component (IC025) of 7.79. No BCPNN-positive signal could be generated for drugs other than insulin and canagliflozin. Reports suggesting that insulin could generate BCPNN-positive signals span from 2004 to 2021, whereas reports with BCPNN-positive signals emerged only since the second quarter (Q2) of 2017, 4 years since the approval of SGLT2is in Q2 of 2013, for canagliflozin and drug groups containing canagliflozin. Conclusion: This data-mining investigation revealed a strong association between canagliflozin treatment and developing osteomyelitis that might be a crucial forewarning to lower extremity amputation. Further studies with updated data are needed to better characterize the risk of osteomyelitis associated with SGLT2is.

Yuhong ointment ameliorates inflammatory responses and wound healing in scalded mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Yuhong ointment (YHO) is famous for its efficacy in clearing away heat and dampness, reducing swelling and relieving pain, and it has been used for more than 600 years. Scalding damages the skin's defense function, resulting in a large number of necrotic tissues and cells on the wound surface, which favors bacterial growth and inflammation. If the inflammation reaction is not controlled on time, it may lead to reduced immunity and cause complications such as infection. Yuhong ointment can promote wound healing in scalded mice, but its potential pharmacological mechanism is still unclear. AIM OF THE STUDY: This study focused on identifying the active ingredients of YHO and on investigating the performance of YHO in terms of anti-inflammatory activity and scald wound healing activity. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) and high-performance liquid chromatography-mass spectrometry (HPLC-MS) were performed to identify the active ingredients of YHO. The performance of transdermal delivery of YHO was studied via HPLC for analyzing the ingredients of the exposed skin liquid of mice. Enzyme-linked immunosorbent assay (ELISA) analysis, immunohistochemistry, and real-time fluorescence quantitative PCR (qRT-PCR) were used to investigate the anti-inflammatory and scald wound healing activity of YHO. RESULTS: A total of 41 components of YHO were identified via HPLC and HPLC-MS for the first time. In the transdermal delivery experiment, the cumulative amounts of chlorogenic acid, sesamol, ferulic acid, and L-shikonin were calculated to be 342.28, 567.89, 384.54, and 528.67 µg/cm2, respectively. Pharmacological activity experiments indicated that these four kinds of drugs exhibited different degrees of therapeutic effects on scald. Specifically, YHO high-dose (YHO-H) group showed better therapeutic ability (P < 0.01) than FN and MB group. Furthermore, the immune function of the YHO group was enhanced due to the continuous increment of the levels of Hydroxyproline (HYP), Immunoglobulin G (IgG), and vascular endothelial growth factor (VEGF) and simultaneous decrement of the levels of TNF-α, TNF-ß, IL-10, and IL-6 in the skin wound. Histological results showed that the thickening of skin tissue was alleviated after treatment with YHO. Moreover, the expression of substance P (SP), calcitonin gene related peptide (CGRP) and transient receptor potential vanilloid-1 (TRPV1) was inhibited, and the expression of VEGF was promoted by YHO (P < 0.01). The qRT-PCR test results indicated that the YHO group exhibited better inhibitory effect on interleukin 6 (IL-6), interleukin 10 (IL-10), transforming growth factor-beta (TGF-ß), and Smad-3 mRNA expression levels than the other groups. CONCLUSIONS: In this work, the active ingredients of YHO were identified via HPLC and HPLC-MS analysis. Importantly, YHO showed great advantages in transdermal delivery and scald wound healing, which can be attributed to the both anti-inflammatory and tissue regeneration mechanisms. Therefore, this work not only identified the active ingredients of YHO but also revealed the potential pharmacological mechanism of YHO for the healing of scald.

Sequential treatment of rituximab and belimumab in thrombotic thrombocytopenia purpura associated with systemic lupus erythematous: A respective case series and literature review.

INTRODUCTION: Thrombotic thrombocytopenia purpura (TTP) associated with systemic lupus erythematous (SLE), features the appearance of inhibitory autoantibodies against ADAMTS13. Rituximab and belimumab (BEL), as both targeting B cells, seem to be an optimal therapy to induce clinical remission, prevent relapse of disease and contribute to glucocorticoid induction. However, the clinical outcome of SLE-TTP treated with sequential therapy between rituximab and BEL remain elusive. CASE SERIES: We reported the clinical outcomes of 4 patients diagnosed with SLE-TTP who were administrated a combination of corticosteroids, plasma exchange, and rituximab at stage of induction. BEL was utilized to rapidly reduce the reliance on these agents and prevent relapse of TTP at maintenance stage. Ultimately, 4 patients fully recovered with a SLE Disease Activity Index score of 0 and reached the goal at dose of prednisolone <7.5 mg/d without relapse. CONCLUSION: Sequential treatment of rituximab and BEL could be an encouraging approach in treatment of SLE-TTP and rapid glucocorticoid reduction.

Three-Dimensional Printing Model Enhances Correct Identification and Understanding of Pelvic Fracture in Medical Students.

OBJECTIVE: Understanding the anatomy behind a pelvic fracture can be a significant challenge to medical students. Recent advances in three-dimensional printing technology offers a novel approach to facilitate the learning of complex fracture. We have described here how the 3-dimension printing (3Dp) models can help medical students improve their understanding in and identification of pelvic fractures. DESIGN: One hundred students were randomized into 2 teaching module groups (with or without 3Dp models). Prior to randomization assignment, a 50-minute didactic lecture covering elementary knowledge of anatomy, Young-Burgess classification, and traumatic mechanism of pelvic fracture was delivered to all students. The 3Dp group received X-rays, CT images, and 3Dp models of the eight pelvic fractures during presentation, while the students in the control group only obtained X-rays and CT scans of the same 8 pelvic fractures. Young-Burgess classification system and injury mechanism of pelvic fracture, time for evaluation, and subjective questions were conducted to assess the learning outcomes. SETTING: A medical student program based in a LevelⅠtrauma center PARTICIPANTS: One hundred students in their 4th year of a 5-year clinical medicine program (for a medical bachelor degree) RESULTS: Students receiving 3Dp model had a higher rate of identifying the correct pelvic fracture via Young-Burgess identification compared to these without 3Dp model. Moreover, the accuracy of identifying the injury mechanism was significantly higher in the 3Dp group than that in group without 3Dp model. Participant in 3Dp group had faster assessment time compared to the control group. Subjective survey results suggested that 3Dp model would increase the learning interest and enhance the understanding of pelvic fracture. In addition, majority of students (83%) reported that they would like to use 3Dp model in other surgical course education. CONCLUSIONS: 3Dp model increased the perceived accuracy of pelvic fracture identification and understanding of injury mechanism. Moreover, 3Dp model promoted the subjective interest and motivation of students in pelvic fracture learning. Therefore, 3Dp model can be considered as a valuable educational tool for learning pelvic fracture in medical students.

A dual-mode optical fiber sensor for SERS and fluorescence detection in liquid.

The in vivo detection of biomarkers in a liquid environment is very important for the early diagnosis of diseases. Spectroscopy methods are employed in ultraviolet-visible-infrared wavelengths, fluorescence or Raman spectra are detected for clinical diagnose. The dual-mode image can provide more diagnostic information and has been realized in some research work. However, there is still lacking simple and sensitive dual-mode sensors to satisfy the in vivo detecting demands. In this paper, a dual-mode fiber sensor for Surface-enhanced Raman Scattering (SERS) and fluorescence detection is proposed. The sensor is formed by a tapered optical fiber, half of the fiber tip surface is coated with Ag nanoparticles. In the detection of Rhodamine 6G (R6G) aqueous solution, the minimum detectable concentrations in SERS and fluorescence tests are of the same order of magnitude. By combining the Raman spectral features and the fluorescence intensity, the recognition and quantitation of target molecules were obtained reliably. It is the first time, to our knowledge, that the Raman-fluorescence dual-mode detection is realized in one single fiber, which was manufactured with micro-machinery techniques. It is a label-free, general-purpose fiber sensor, which can be applied for liquid biopsy, helping to diagnose and treat diseases in vivo.

Skin cancer signal associated with phosphodiesterase inhibitors: gaining insight through the FDA pharmacovigilance database.

BACKGROUND: Panoramic views of post-marketing safety profiles, such as cancer signal, of phosphodiesterase 5A (PDE5A) inhibitors have yet to be fully evaluated. RESEARCH DESIGN AND METHODS: Data from the FDA Adverse Event Reporting System (FAERS) concerning the timeframe between January 1st, 2004 to 30 June 2022 was analyzed through a disproportionality study to understand the association between sildenafil, tadalafil, and vardenafil and cancer. This association was identified using the Reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) approaches. RESULTS: Sildenafil associated ROR values and IC025 ranged from 9.19 (95% CI 7.72-10.94, IC025 2.77) for metastatic malignant melanoma to 132.23 (95% CI 95.49-183.11, IC025 4.69) for malignant melanoma stage II. Tadalafil associated ROR and IC025 ranged from 6.79 (95% CI 5.41-8.54, IC025 2.27) for metastatic malignant melanoma to 180.17 (95% CI 130.11-249.50, IC025 4.89) for malignant melanoma stage II. Vardenafil associated ROR and IC025 ranged from 23.38 (95% CI 15.20-35.96, IC025 2.63) for metastatic malignant melanoma to 245.77 (95% CI 154.42-391.16, IC025 2.10) for malignant melanoma stage III. CONCLUSIONS: This study supports the association between sildenafil, tadalafil, and vardenafil with skin cancer signal in erectile dysfunction (ED) patients.

Finite element analysis of 3 internal fixations for distal type C3 femur fractures with medial wall bone defects. / æœ‰é™å ƒåˆ†æž3ç§å† å›ºå®šæ–¹å¼æ²»ç–—ä¼´æœ‰å† ä¾§éª¨ç¼ºæŸçš„C3型股骨远端骨折.

OBJECTIVES: Managing 33-C3 femur fractures with medial wall bone defects poses a significant challenge for orthopedic surgeons. The gold standard treatment for arbeitsgemeinschaftfür osteosynthesefragen (AO)/orthopedic trauma association (OTA) 33-C3 distal femur fractures with medial wall bone defects remains elusive. This study employs finite element analysis to compare the stability and mechanical behavior of 3 internal fixation patterns (single lateral distal locking plate, retrograde intramedullary nail, and dual plates) for 33-C3 femur fractures with medial wall bone defects. The aim is to provide a theoretical basis for the selection of internal fixation modalities in clinical practice. METHODS: Enrollment included a 43-year-old male volunteer weighing 60 kg, without a history of femur fracture. Bilateral femur normality was verified through X-ray and CT scan assessments. A finite element simulation model of AO/OTA 33-C3 distal femur fracture with medial wall bone defect was established. Three fixation methods, named single lateral locking plate (single-plate group), retrograde intramedullary nail (retrograde intramedullary nail group), and dual plates (dual-plate group), were evaluated using finite element analysis under an axial load of 300 N. The assessment included an examination of von Mises stress distribution, shear stress, and displacement patterns at the internal fixation and femur fracture sites. RESULTS: The finite element analysis revealed that dual-plate fixation effectively reduced the concentration of von Mises stress at the plate on the fracture site. Under full weight-bearing conditions, the maximum von Mises stress in the implants occurred at the distal femur defect level, with values of 149.30, 59.281, and 58.03 MPa for single-plate fixation, retrograde intramedullary nail, and dual-plate fixation methods, respectively. Similarly, the maximum shear stress in the implants was 77.867, 30.136, and 33.505 MPa for single-plate fixation, retrograde intramedullary nail, and dual-plate fixation methods, respectively, all presenting at the distal femur defect level. The maximum relative displacements of implants during compressive loading were 1.34, 1.25, and 0.83 mm for the single-plate , retrograde intramedullary nail, and dual-plate groups, respectively. Consistently, the maximum loading-point displacements of fracture sites were 1.529, 1.264, and 0.880 mm for the single-plate fixation group, retrograde intramedullary nail group, and dual-plate fixation group, respectively. Furthermore, at the distal femur defect level, the maximum von Mises stress was 72.682, 112.430, and 40.716 MPa for the single-plate, retrograde intramedullary nail, and dual-plate fixation groups, respectively. CONCLUSIONS: Dual-plate fixation demonstrates superior biomechanical outcomes and exhibites the lowest maximum von Mises stress and shear stress, along with minimal relative movements between fracture fragments. This configuration offers optimal mechanical stability for managing AO/OTA 33-C3 distal femur fractures with medial wall bone defects. Consequently, dual-plate fixation emerges as a better treatment strategy for patients presenting with comminuted intra-articular distal femur fractures accompanied by medial wall bone defects.

Neuroprotective effect of Ziziphi Spinosae Semen on rats with p-chlorophenylalanine-induced insomnia via activation of GABAA receptor.

Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F.Chow [Rhamnaceae; Ziziphi Spinosae Semen (ZSS)] has attracted extensive attention as the first choice of traditional Chinese medicine in the treatment of insomnia. However, recent studies on the sleep-improving mechanism of ZSS have mainly focused on the role of single components. Thus, to further reveal the potential mechanism of ZSS, an assessment of its multiple constituents is necessary. In this study, ZSS extract (ZSSE) was obtained from ZSS via detailed modern extraction, separation, and purification technologies. The chemical constituents of ZSSE were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). For in vivo experiments, a rat model of insomnia induced by p-chlorophenylalanine (PCPA) was established to investigate the potential effect and corresponding mechanism of ZSSE on improving sleep. Hematoxylin-eosin staining (HE) results revealed that the drug group showed prominent advantages over the model group in improving sleep. Moreover, the brain levels of γ-aminobutyric acid (GABA), glutamic acid (Glu), 5-hydroxytryptamine (5-HT), and dopamine (DA) were monitored via enzyme-linked immunosorbent assay (ELISA) to further study the sleep-improving mechanism of ZSSE. We found that sleep was effectively improved via upregulation of GABA and 5-HT and downregulation of Glu and DA. In addition, molecular mechanisms of ZSSE in improving sleep were studied by immunohistochemical analysis. The results showed that sleep was improved by regulating the expression levels of GABA receptor subunit alpha-1 (GABAARα1) and GABA acid receptor subunit gamma-2 (GABAARγ2) receptors in the hypothalamus and hippocampus tissue sections. Therefore, this work not only identified the active ingredients of ZSSE but also revealed the potential pharmacological mechanism of ZSSE for improving sleep, which may greatly stimulate the prospective development and application of ZSSE.

Serious adverse reaction associated with the COVID-19 vaccines of BNT162b2, Ad26.COV2.S, and mRNA-1273: Gaining insight through the VAERS.

Background and purpose: Serious adverse events following immunization (AEFI) associated with the COVID-19 vaccines, including BNT162b2 (Pfizer-BioNTech), Ad26.COV2.S (Janssen), and mRNA-1273 (Moderna), have not yet been fully investigated. This study was designed to evaluate the serious AEFI associated with these three vaccines. Methods: A disproportionality study was performed to analyze data acquired from the Vaccine Adverse Event-Reporting System (VAERS) between 1 January 2010 and 30 April 2021. The reporting odds ratio (ROR) method was used to identify the association between the COVID-19 vaccines BNT162b2, Ad26.COV2.S, and mRNA-1273 and each adverse event reported. Moreover, the ratio of the ROR value to the 95% CI span was applied to improve the credibility of the ROR. The median values of time from vaccination to onset (TTO) for the three vaccines were analyzed. Results: Compared with BNT162b2 and mRNA-1273, Ad26.COV2.S vaccination was associated with a lower death frequency (p < 0.05). Ad26.COV2.S vaccination was associated with a lower birth defect and emergency room visit frequency than BNT162b2 (p < 0.05). There were 6,605, 830, and 2,292 vaccine recipients who suffered from COVID-19-related symptoms after vaccination with BNT162b2, Ad26.COV2.S, and mRNA-1273, respectively, including people who were infected by COVID-19, demonstrated a positive SARS-CoV-2 test, and were asymptomatic. Serious AEFI, including thromboembolism, hemorrhage, thrombocytopenia, cardiac arrhythmia, hypertension, and hepatotoxicity, were associated with all three vaccines. Cardiac failure and acute renal impairment events were associated with BNT162b2 and mRNA-1273, while seizure events were associated with BNT162b2 and Ad26.COV2.S. The median values of TTO associated with the three vaccinations were similar. Conclusion: These findings may be useful for health workers and the general public prior to inoculation, especially for patients with underlying diseases; however, the risk/benefit profile of these vaccines remains unchanged. The exact mechanism of SARS-CoV-2 vaccine-induced AEFI remains unknown, and further studies are required to explore these phenomena.

Rapid determination of ethanol content based on an optical fiber-device and R6G-indicator.

A rapid method for the determination of ethanol content is proposed and tested. A fluorescence detecting system, with a multimode fiber (MMF) sensing head, is employed. Rhodamine 6G (R6G) is applied as the fluorescent indicator. In the R6G aqueous solution, the molecules aggregate at high concentration, causing fluorescence quenching. Nevertheless, aggregation and quenching rarely occur in ethanol. Taking an ethanol and water mixture as the solvent, the photoluminescence (PL) intensity reflects the aggregation degree and the ethanol content. Based on this phenomenon, the contents of the ethanol-water mixture were measured through PL intensity detection. A limit of detection (LOD) at ∼0.1 vol% level was obtained in the range of 0-100%. Commercial Chinese baijiu and rubbing alcohol were tested and the results obtained were consistent with the label values. The detecting system is compact and of low-cost, and the detecting method is rapid, accurate and repeatable. There is good prospect of applications for the determination of ethanol content on-site.