High-performance liquid chromatography-tandem mass spectrometry was used to measure 20 antidepressants in human serum.

Aim: This study used high performance liquid chromatography-tandem mass spectrometry to quantify the blood concentrations of 20 antidepressants, such as bupropion and fluoxetine, in human serum samples.Methods: After direct precipitation with a 1:9 protein precipitant of methanol and acetonitrile, serum samples were examined using high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The material was separated using a Poroshell 120 EC-C18 column (3.0 mm × 50 mm, 2.7 µm) and gradient elution. The mobile phases were phase A 0.01% formic acid aqueous solution (containing 2 mmol/ml ammonium acetate) and phase B methanol solution. A 0.45 ml/min flow rate was used to divide the sample and inject 5 µl. Electrospray ionization source positive ion mode and multiple reaction monitoring modes were used for analysis. Measurement was quantified using an internal standard technique.Results: Accuracy ranged from 90.3 to 114.3%, intra-day precision from 100.1 to 112.3%, inter-day precision from 100.4 to 112.6%, extraction recoveries from 85.5 to 114.5% and matrix effect from 85.6 to 98.7%.Conclusion: This approach is fast, accurate, sensitive and repeatable. It can identify 20 antidepressants in blood simultaneously. This can be used to monitor blood drug levels and medication metabolism.

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Unlocking the potential of stimuli-responsive biomaterials for bone regeneration.

Bone defects caused by tumors, osteoarthritis, and osteoporosis attract great attention. Because of outstanding biocompatibility, osteogenesis promotion, and less secondary infection incidence ratio, stimuli-responsive biomaterials are increasingly used to manage this issue. These biomaterials respond to certain stimuli, changing their mechanical properties, shape, or drug release rate accordingly. Thereafter, the activated materials exert instructive or triggering effects on cells and tissues, match the properties of the original bone tissues, establish tight connection with ambient hard tissue, and provide suitable mechanical strength. In this review, basic definitions of different categories of stimuli-responsive biomaterials are presented. Moreover, possible mechanisms, advanced studies, and pros and cons of each classification are discussed and analyzed. This review aims to provide an outlook on the future developments in stimuli-responsive biomaterials.

Potential increased propofol sensitivity in cognitively impaired elderly: a controlled, double-blind study.

Background: Cognitive impairment in the elderly may lead to potential increased sensitivity to anesthetic agents targeting receptors associated with cognition. This study aimed to explore the effect of cognitive status on propofol consumption during surgery in elderly patients. Methods: Sixty elderly patients scheduled for laparoscopic radical prostatectomy were allocated to either a cognitively normal [CogN, Montreal Cognitive Assessment (MoCA) score ≥26] or cognitively impaired (CogI, MoCA <26) group. Propofol was administered via target-controlled infusion to maintain a bispectral index (BIS) between 55-65 during surgery. Propofol consumption was recorded at three time points: T1 (abolished eyelash reflex), T2 (BIS = 50), T3 (extubation). BIS values at eyelash reflex abolition were also recorded. Postoperative MoCA, Visual Analogue Scale (VAS) scores, and remifentanil/sufentanil consumption were assessed. Results: BIS values before induction were similar between CogN and CogI groups. However, at eyelash reflex abolition, BIS was significantly higher in CogI than CogN (mean ± SD: 65.3 ± 7.2 vs. 61.1 ± 6.8, p = 0.031). Propofol requirement to reach BIS 50 was lower in CogI vs. CogN (1.24 ± 0.19 mg/kg vs. 1.46 ± 0.12 mg/kg, p = 0.003). Postoperative MoCA, VAS scores, and remifentanil/sufentanil consumption did not differ significantly between groups. Conclusion: Compared to cognitively intact elderly, those with cognitive impairment exhibited higher BIS at eyelash reflex abolition and required lower propofol doses to achieve the same BIS level, suggesting increased propofol sensitivity. Cognitive status may impact anesthetic medication requirements in the elderly.

Association between dietary fiber to carbohydrate ratio and risk of dental caries in diabetic patients: an analysis of the National Health and Nutrition Examination Survey 2015-2020.

Aim: People with diabetes mellitus have a higher risk of dental caries than the general population. Diet is one of the most important factors affecting the risk of dental caries. This study aimed to evaluate the effect of dietary fiber to carbohydrate ratio (FCR) on the risk of dental caries in diabetic patients. Methods: Data of this cross-sectional study were extracted from the 2015-2020 cycle of the National Health and Nutrition Examination Survey (NHANES) database. FCR levels were divided into two categories based on the median (0.13). The outcomes were untreated dental caries and dental caries experience. The associations of FCR with untreated dental caries and dental caries experience were assessed using multivariable logistic regression analysis and reported as odds ratio (OR) and 95% confidence interval (CI). Stratified analyses were performed according to age (<65 and ≥ 65 years), gender (female and male), hypertension (yes and no), and the ratio of family income to poverty (PIR, <1 and ≥ 1). Results: A total of 2,412 patients diagnosed with diabetes were included, of whom 728 (30.18%) had untreated dental caries and 2,104 (87.23%) had dental caries experience. Patients with FCR ≥0.13 were correlated with lower odds of untreated dental caries (OR = 0.72, 95%CI: 0.52-0.99) and dental caries experience (OR = 0.63, 95%CI: 0.42-0.93) compared to patients with FCR <0.13. Stratified analyses demonstrated that patients with FCR ≥0.13 were found to be related to lower odds of untreated dental caries in those aged <65 years (OR = 0.64, 95%CI: 0.42-0.97), female (OR = 0.57, 95%CI: 0.35-0.93), with hypertension (OR = 0.66, 95%CI: 0.45-0.96), and PIR ≥1 (OR = 0.64, 95%CI: 0.42-0.99). Similar results to untreated dental caries were observed in the analysis of dental caries experience (p < 0.05). Conclusion: High levels of FCR may be associated with a lower risk of dental caries in patients with diabetes. Increasing the proportion of dietary fiber intake among diabetic patients may help prevent the occurrence of dental caries.

Single cell RNA-sequencing in uveal melanoma: advances in heterogeneity, tumor microenvironment and immunotherapy.

Uveal melanoma (UM) is a highly aggressive and fatal tumor in the eye, and due the special biology of UM, immunotherapy showed little effect in UM patients. To improve the efficacy of immunotherapy for UM patients is of great clinical importance. Single-cell RNA sequencing(scRNA-seq) provides a critical perspective for deciphering the complexity of intratumor heterogeneity and tumor microenvironment(TME). Combing the bioinformatics analysis, scRNA-seq could help to find prognosis-related molecular indicators, develop new therapeutic targets especially for immunotherapy, and finally to guide the clinical treatment options.

An electrochemical ratiometric immunosensor for the detection of NMP22 based on ZIF-8@MWCNTs@Chit@Fc@AuNPs and AuPt-MB.

Nuclear matrix protein 22 (NMP22) is one of the most important tumor markers of bladder cancer and is significantly elevated in the urine of bladder cancer patients. Therefore, in this work, a highly sensitive ratiometric electrochemical immunosensor was constructed to detect NMP22 based on ZIF-8@MWCNTs@Chit@Fc@AuNPs composites. ZIF-8 had a large surface area and good adsorption ability. Multi-Walled Carbon Nanotubes (MWCNTs) can optimize the electrical conductivity of ZIF-8, so that the electrode surface of ferrocene (Fc) obtains a stable and strong electrochemical signal. In addition, AuPt-MB provided another strong detection signal methylene blue (MB) while immobilizing the secondary antibody (Ab2) through Au-N and Pt-N bonds. A ratiometric electrochemical sensor was formed based on ZIF-8@MWCNTs@Chit@Fc@AuNPs and AuPt-MB, which showed a great linear connection between IMB/IFc and the logarithmic concentration of NMP22 with a detection limit of 3.33 fg mL-1 (S/N = 3) under optimized specifications in the concentration interval of 0.01 pg mL-1 to 1000 ng mL-1. In addition, the ratiometric immunosensor showed good selectivity and stability.

Gut microbiota dysbiosis links chronic apical periodontitis to liver fibrosis in nonalcoholic fatty liver disease: Insights from a mouse model.

AIM: In this study, we investigated the systemic implications of chronic apical periodontitis (CAP). CAP may contribute to the nonalcoholic fatty liver disease (NAFLD) progression through the gut microbiota and its metabolites, which are related to the degree of fibrosis. METHODOLOGY: Sixteen 7-week-old male apolipoprotein E knockout (apoE-/-) mice were randomly divided into two groups: the CAP and Con groups. A CAP model was established by sealing the first- and second-maxillary molars with bacterium-containing cotton balls. Apical lesions were evaluated by micro-CT. Histological evaluations of NAFLD were performed using second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) assays. Additionally, we comprehensively analyzed the gut microbiota using 16S rRNA gene sequencing and explored metabolic profiles by liquid chromatography-mass spectrometry (LC-MS). Immunofluorescence analysis was used to examine the impact of CAP on tight junction proteins and mucin expression. Transcriptome assays have elucidated gene expression alterations in liver tissues. RESULTS: Micro-CT scans revealed an evident periapical bone loss in the CAP group, and the total collagen percentage was increased (Con, 0.0361 ± 0.00510%, CAP, 0.0589 ± 0.00731%, p < .05). 16S rRNA sequencing revealed reduced diversity and distinct taxonomic enrichment in the CAP group. Metabolomic assessments revealed that differentially enriched metabolites, including D-galactosamine, were enriched and that 16-hydroxyhexadecanoic acid and 3-methylindole were depleted in the CAP group. Immunofluorescence analyses revealed disruptions in tight junction proteins and mucin production, indicating intestinal barrier integrity disruption. Liver transcriptome analysis revealed upregulation of Lpin-1 expression in the CAP group. CONCLUSION: This study provides comprehensive evidence of the systemic effects of CAP on liver fibrosis in NAFLD patients by elucidating alterations in the gut microbiota composition and metabolism.

Fabrication of a Triple-Layer Bionic Vascular Scaffold via Hybrid Electrospinning.

Tissue engineering aims to develop bionic scaffolds as alternatives to autologous vascular grafts due to their limited availability. This study introduces a novel wet-electrospinning fabrication technique to create small-diameter, uniformly aligned tubular scaffolds. By combining this innovative method with conventional electrospinning, a bionic tri-layer scaffold that mimics the zonal structure of vascular tissues is produced. The inner and outer layers consist of PCL/Gelatin and PCL/PLGA fibers, respectively, while the middle layer is crafted using PCL through Wet Vertical Magnetic Rod Electrospinning (WVMRE). The scaffold's morphology is analyzed using Scanning Electron Microscopy (SEM) to confirm its bionic structure. The mechanical properties, degradation profile, wettability, and biocompatibility of the scaffold are also characterized. To enhance hemocompatibility, the scaffold is crosslinked with heparin. The results demonstrate sufficient mechanical properties, good wettability of the inner layer, proper degradability of the inner and middle layers, and overall good biocompatibility. In conclusion, this study successfully develops a small-diameter tri-layer tubular scaffold that meets the required specifications.

The safety, immunogenicity, and efficacy of heterologous boosting with a SARS-CoV-2 mRNA vaccine (SYS6006) in Chinese participants aged 18 years or more: a randomized, open-label, active-controlled phase 3 trial.

Continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enhanced transmissibility, significant immune escape, and waning immunity call for booster vaccination. We evaluated the safety, immunogenicity, and efficacy of heterologous booster with a SARS-CoV-2 mRNA vaccine SYS6006 versus an active control vaccine in a randomized, open-label, active-controlled phase 3 trial in healthy adults aged 18 years or more who had received two or three doses of SARS-CoV-2 inactivated vaccine in China. The trial started in December 2022 and lasted for 6 months. The participants were randomized (overall ratio: 3:1) to receive one dose of SYS6006 (N = 2999) or an ancestral receptor binding region-based, alum-adjuvanted recombinant protein SARS-CoV-2 vaccine (N = 1000), including 520 participants in an immunogenicity subgroup. SYS6006 boosting showed good safety profiles with most AEs being grade 1 or 2, and induced robust wild-type and Omicron BA.5 neutralizing antibody response on Days 14 and 28, demonstrating immunogenicity superiority versus the control vaccine and meeting the primary objective. The relative vaccine efficacy against COVID-19 of any severity was 51.6% (95% CI, 35.5-63.7) for any variant, 66.8% (48.6-78.5) for BA.5, and 37.7% (2.4-60.3) for XBB, from Day 7 through Month 6. In the vaccinated and infected hybrid immune participants, the relative vaccine efficacy was 68.4% (31.1-85.5) against COVID-19 of any severity caused by a second infection. All COVID-19 cases were mild. SYS6006 heterologous boosting demonstrated good safety, superior immunogenicity and high efficacy against BA.5-associated COVID-19, and protected against XBB-associated COVID-19, particularly in the hybrid immune population.Trial registration: Chinese Clinical Trial Registry: ChiCTR2200066941.

Imaging extended single crystal lattice distortion fields with multi-peak Bragg ptychography.

Recent advances in phase-retrieval-based x-ray imaging methods have demonstrated the ability to reconstruct 3D distortion vector fields within a nanocrystal by using coherent diffraction information from multiple crystal Bragg reflections. However, these works do not provide a solution to the challenges encountered in imaging lattice distortions in crystals with significant defect content that result in phase wrapping. Moreover, these methods only apply to isolated crystals smaller than the x-ray illumination, and therefore cannot be used for imaging of distortions in extended crystals. We introduce multi-peak Bragg ptychography which addresses both challenges via an optimization framework that combines stochastic gradient descent and phase unwrapping methods for robust image reconstruction of lattice distortions and defects in extended crystals. Our work uses modern automatic differentiation toolsets so that the method is easy to extend to other settings and easy to implement in high-performance computers. This work is particularly timely given the broad interest in using the increased coherent flux in fourth-generation synchrotrons for innovative material research.

Functionalized BP@(Zn+Ag)/EPLA Nanofibrous Scaffolds Fabricated by Cryogenic 3D Printing for Bone Tissue Engineering.

This study fabricates a functionalized scaffold by cryogenic three-dimensional (3D) printing using an aminated poly-L-lactic acid (EPLA) solution containing nanosilver/zinc-coated black phosphorus (BP@(Zn+Ag)) nanocomposites. The nanocomposites are prepared by a green method of in situ photodeposition of silver and zinc nanoparticles (AgNPs and ZnNPs) on BP nanosheets (BPNs) under visible light irradiation without any chemical reductant. Scanning electron microscope (SEM) and X-ray energy dispersive spectrometer (EDS) confirm the uniform distribution of BP@(Zn+Ag) nanoparticles in the EPLA nanofibrous matrix. The in vitro tests show that the fabricated BP@(Zn+Ag)/EPLA nanofibrous scaffold exhibits excellent antibacterial activity (over 96%) against E. coli and S. aureus, as well as enhanced cell viability and osteogenic activity to facilitate the growth and differentiation of osteoblasts. The in vivo rat calvarial defect model also demonstrates that the BP@(Zn+Ag)/EPLA nanofibrous scaffold promotes new bone tissue formation around the implant site. Therefore, the prepared multifunctional 3D printed BP@(Zn+Ag)/EPLA nanofibrous scaffold has great potential for bone tissue engineering (BTE) applications.

Unveiling the oral-gut connection: chronic apical periodontitis accelerates atherosclerosis via gut microbiota dysbiosis and altered metabolites in apoE-/- Mice on a high-fat diet.

The aim of this study was to explore the impact of chronic apical periodontitis (CAP) on atherosclerosis in apoE-/- mice fed high-fat diet (HFD). This investigation focused on the gut microbiota, metabolites, and intestinal barrier function to uncover potential links between oral health and cardiovascular disease (CVD). In this study, CAP was shown to exacerbate atherosclerosis in HFD-fed apoE-/- mice, as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining. 16S rRNA sequencing revealed significant alterations in the gut microbiota, with harmful bacterial species thriving while beneficial species declining. Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis, leading to elevated levels of taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and tauroursodeoxycholic acid (TDCA). These metabolic shifts may contribute to atherosclerosis development. Furthermore, impaired intestinal barrier function, characterized by reduced mucin expression and disrupted tight junction proteins, was observed. The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions, highlighting the importance of the intestinal barrier in cardiovascular health. In conclusion, this research underscores the intricate interplay among oral health, gut microbiota composition, metabolite profiles, and CVD incidence. These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues, as well as the need for further investigations into the intricate mechanisms linking oral health, gut microbiota, and metabolic pathways in CVD development.

Mechanochemically Robust LiCoO2 with Ultrahigh Capacity and Prolonged Cyclability.

Pushing intercalation-type cathode materials to their theoretical capacity often suffers from fragile Li-deficient frameworks and severe lattice strain, leading to mechanical failure issues within the crystal structure and fast capacity fading. This is particularly pronounced in layered oxide cathodes because the intrinsic nature of their structures is susceptible to structural degradation with excessive Li extraction, which remains unsolved yet despite attempts involving elemental doping and surface coating strategies. Herein, a mechanochemical strengthening strategy is developed through a gradient disordering structure to address these challenges and push the LiCoO2 (LCO) layered cathode approaching the capacity limit (256 mAh g-1, up to 93% of Li utilization). This innovative approach also demonstrates exceptional cyclability and rate capability, as validated in practical Ah-level pouch full cells, surpassing the current performance benchmarks. Comprehensive characterizations with multiscale X-ray, electron diffraction, and imaging techniques unveil that the gradient disordering structure notably diminishes the anisotropic lattice strain and exhibits high fatigue resistance, even under extreme delithiation states and harsh operating voltages. Consequently, this designed LCO cathode impedes the growth and propagation of particle cracks, and mitigates irreversible phase transitions. This work sheds light on promising directions toward next-generation high-energy-density battery materials through structural chemistry design.

Biomarkers associated with pulmonary exacerbations in a randomized trial of nintedanib for radiation pneumonitis.

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is a common side effect of thoracic radiotherapy and often has a long course characterized by acute exacerbations and progression to permanent lung fibrosis. There are no validated biomarkers of prognosis in patients diagnosed with RP. MATERIALS AND METHODS: We analyzed a time course of serum chemokines, cytokines, and other proteins from patients with grade 2+ RP in a randomized clinical trial of a steroid taper plus nintedanib, a multiple tyrosine kinase inhibitor, versus placebo plus a steroid taper for the treatment of RP. Weighted gene correlation network analysis (WGCNA) and univariable zero inflated Poisson models were used to identify groups of correlated analytes and their associations with clinical outcomes. RESULTS: Thirty enrolled patients had biomarker data available, and 17 patients had enough analytes tested for network analysis. WGNCA identified ten analytes, including transforming growth factor beta-1 (TGF-ß1), monocyte chemoattractant protein-1 (MCP-1), and platelet-derived growth factor (PDGF), that in aggregate were correlated with the occurrence of pulmonary exacerbations (p = 0.008), the total number of acute pulmonary exacerbations (p = 0.002), and treatment arm (p = 0.036). By univariable analysis, an increase in rate of change of two components of the RP module were associated with an increased incidence rate of pulmonary exacerbations: interleukin 5 (IL-5, incidence rate ratio (IRR) 1.02, 95% CI 1.01-1.04, p = 0.002), and tumor necrosis factor superfamily 12 (TNFSF12, IRR 1.06, CI 1-1.11, p = 0.036). An increased slope of epidermal growth factor (EGF) was associated with a decreased incidence rate of exacerbations (IRR 0.94, CI 0.89-1, p = 0.036). CONCLUSION: We identified a panel of serum biomarkers that showed association with nintedanib treatment and acute pulmonary exacerbations in patients with RP. A confirmatory study will be needed to validate this panel for use as a prognostic tool in patients with RP.

Methodologic Quality and Pharmacotherapy Recommendations for Patient Blood Management Guidelines for Cardiac Surgery on Cardiopulmonary Bypass.

Patient blood management (PBM) guidelines for patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) have increased during the past decade, and pharmacotherapy plays an important role in PBM. In the face of the undefined consistency in the methodologic quality and pharmacotherapy recommendations across multiple guidelines, this study exclusively evaluated methodologies of the related guideline development process, and compiled medication recommendations of PBM for cardiac surgery patients. PBM guidelines for cardiac surgery under CPB were searched through some mainstream literature and guideline databases from database establishment to May 15, 2023. Nine guidelines meeting inclusion criteria were included in this study. The quality of the guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. "Stakeholder involvement" received the lowest mean score of 49.38% in the AGREE II scoring among the guidelines. PBM for cardiac surgery patients spans the perioperative phase. Drug therapy strategies of PBM for cardiac surgery patients involve anemia therapy, perioperative administration of antithrombotic drugs, intraoperative anticoagulation, and the use of hemostatic drugs. Unlike for adults, there is less evidence about the management of antithrombotic drugs and hemostatic drugs for pediatric cardiac surgery patients. Recombinant activated factor VII (rFVIIa) and desmopressin (DDAVP) are not recommended after pediatric cardiac surgery, whereas prothrombin complex concentrate could be considered in clinical trials. As for the controversies regarding the administration of rFVIIa and DDAVP after adult cardiac surgery by different societies, clinicians should exercise their clinical judgment based on individual patient features.

Associations of glyphosate exposure and serum sex steroid hormones among 6-19-year-old children and adolescents.

Glyphosate, ranked as one of the most widely used herbicides in the world, has raised concerns about its potential disruptive effects on sex hormones. However, limited human evidence was available, especially for children and adolescents. The present study aimed to examine the associations between exposure to glyphosate and sex hormones among participants aged 6-19 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Children and adolescents who had available data on urinary glyphosate, serum sex steroid hormones, including testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG), and covariates were selected. Additionally, the ratio of TT to E2 (TT/E2) and the free androgen index (FAI), which was calculated using TT/SHBG, were also included as sex hormone indicators. Survey regression statistical modeling was used to examine the associations between urinary glyphosate concentration and sex hormone indicators by age and sex group. Among the 964 participants, 83.71% had been exposed to glyphosate (>lower limit of detection). The survey regression revealed a marginally negative association between urinary glyphosate and E2 in the overall population, while this association was more pronounced in adolescents with a significant trend. In further sex-stratified analyses among adolescents, a significant decrease in E2, FAI, and TT (p trend <0.05) was observed in female adolescents for the highest quartile of urinary glyphosate compared to the lowest quartile. However, no similar association was observed among male adolescents. Our findings suggest that exposure to glyphosate at the current level may decrease the levels of sex steroids in adolescents, particularly female adolescents. Considering the cross-sectional study design, further research is needed to confirm our findings.

Efficacy of TNF-α Inhibitors in the Treatment of nr-axSpA: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials.

INTRODUCTION: A growing number of randomized controlled trials (RCTs) have demonstrated the effectiveness of tumor necrosis factor-α (TNF-α) inhibitors in treating non-radiographic axial spondyloarthritis (nr-axSpA). This study aimed to evaluate the efficacy of TNF-α inhibitors in the treatment of nr-axSpA. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were systematically searched for relevant RCTs using specific keywords up to June 2023. The primary outcome was the proportion of patients who achieved Assessment in SpondyloArthritis international Society 40% (ASAS40). Secondary outcomes included ASAS20, Bath Ankylosing Spondylitis Disease Activity Index 50% (BASDAI50), ASAS partial remission, and ASAS5/6. RESULTS: A total of eight RCTs involving 1,376 patients were included. Patients receiving anti-TNF therapy exhibited a higher rate of ASAS40 (pooled RR = 2.36; 95% CI: 1.63-3.42; p < 0.001). In addition, the TNF-α inhibitor group showed higher BASDAI50 rates (pooled RR = 2.06; 95% CI: 1.48-2.89), ASAS20 rates (pooled RR = 1.48; 95% CI: 1.31-1.67), ASAS partial remission rates (pooled RR = 2.33; 95% CI: 1.58-3.43), and ASAS5/6 rates (RR = 3.46; 95% CI: 2.05-5.83) than the placebo group. CONCLUSION: The TNF-α inhibitors were effective in treating nr-axSpA.

Impact of rise and fall phases of shear on platelet activation and aggregation using microfluidics.

Blood flow disorders are often the result of the non-physiological narrowing of blood arteries caused by atherosclerosis and thrombus. The blood then proceeds through rising-peak-decreasing phases as it passes through the narrow area. Although abnormally high shear is known to activate platelets, the shear process that platelets undergo in small arteries is complex. Thus, understanding how each shear phase affects platelet activation can be used to improve antiplatelet therapy and decrease the risk of side effects like bleeding. Blood samples were sheared (68.8 ms,5200 s-1) in vitro by the microfluidic technique, and platelet activation levels (P-selectin and integrin αIIbß3) and von Willebrand factor (vWF) binding to platelets were analyzed by flow cytometry. Post-stenosis platelet aggregation was dynamically detected using microfluidic technology. We studied TXA2, P2Y12-ADP, and integrin αIIbß3-fibrinogen receptor pathways by adding antiplatelet drugs, such as acetylsalicylic acid (ASA, an active ingredient of aspirin that inhibits platelet metabolism), ticagrelor (hinders platelet activation), and tirofiban (blocks integrin αIIbß3 receptor) in vitro, respectively, to determine platelet activation function mediated by transient non-physiological high shear rates. We demonstrated that platelets can be activated under transient pathological high shear rates. The shear rise and fall phases influenced shear-induced platelet activation by regulating the binding of vWF to platelets. The degree of platelet activation and aggregation increased with multiple shear rise and fall phases. ASA did not inhibit shear-mediated platelet activation, but ticagrelor and tirofiban effectively inhibited shear-mediated platelet activation. Our data demonstrated that the shear rise and fall phases play an important role in shear-mediated platelet activation and promote platelet activation and aggregation in a vWF-dependent manner. Blocking integrin αIIbß3 receptor and hindering P2Y12-ADP were beneficial to reducing shear-mediated platelet activation.

The LiaSR Two-Component System Regulates Resistance to Chlorhexidine in Streptococcus mutans.

Chlorhexidine (CHX) is widely considered to be the gold standard for preventing dental caries. However, it is possible to induce resistance to CHX. The LiaSR two-component system has been identified that contributed to CHX resistance in Streptococcus mutans, which is one of the major pathogens in dental caries. However, the underlying mechanisms remain unclear. In this study, an MIC assay and a viability assessment demonstrated that after deleting the liaS and liaR genes, the sensitivity of mutants could increase. The Nile Red efflux assay exhibited that the efflux rates of mutants were significantly decreased. The RT-qPCR results indicated that the LiaSR two-component system-mediating influence on the expression of lmrB in S. mutans contributed to the efflux rate. The hydrophobicity assay and membrane potential assay showed that the mutants had higher levels of hydrophobicity and depolarization, suggesting that their membranes were more easily disturbed. The TEM graphs revealed that the border of the cell membrane was unclear in mutants compared with the wild-type strain, indicating that the cell envelope's stress response may have been inhibited. While the surface charge of mutants showed no significant difference in the wild-type strain according to the result of cytochrome c-based charged determination. This study provides valuable novel insights into the mechanisms of the LiaSR two-component system in the CHX resistance of S. mutans.

Expert consensus on difficulty assessment of endodontic therapy.

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.