Gingipains may be one of the key virulence factors of Porphyromonas gingivalis to impair cognition and enhance blood-brain barrier permeability: An animal study.

AIM: Blood-brain barrier (BBB) disorder is one of the early findings in cognitive impairments. We have recently found that Porphyromonas gingivalis bacteraemia can cause cognitive impairment and increased BBB permeability. This study aimed to find out the possible key virulence factors of P. gingivalis contributing to the pathological process. MATERIALS AND METHODS: C57/BL6 mice were infected with P. gingivalis or gingipains or P. gingivalis lipopolysaccharide (P. gingivalis LPS group) by tail vein injection for 8 weeks. The cognitive behaviour changes in mice, the histopathological changes in the hippocampus and cerebral cortex, the alternations of BBB permeability, and the changes in Mfsd2a and Cav-1 levels were measured. The mechanisms of Ddx3x-induced regulation on Mfsd2a by arginine-specific gingipain A (RgpA) in BMECs were explored. RESULTS: P. gingivalis and gingipains significantly promoted mice cognitive impairment, pathological changes in the hippocampus and cerebral cortex, increased BBB permeability, inhibited Mfsd2a expression and up-regulated Cav-1 expression. After RgpA stimulation, the permeability of the BBB model in vitro increased, and the Ddx3x/Mfsd2a/Cav-1 regulatory axis was activated. CONCLUSIONS: Gingipains may be one of the key virulence factors of P. gingivalis to impair cognition and enhance BBB permeability by the Ddx3x/Mfsd2a/Cav-1 axis.

Nurse-to-patient ratios and readiness for hospital discharge: A moderated mediation model.

AIM: To explore whether and to what extent, nurse-patient assessment differences mediate the association between nurse-to-patient ratios and readiness for hospital discharge, and examine whether nurse-patient characteristics moderate the indirect and/or direct effect of mediation model. DESIGN: A cross-sectional study was carried out from March 2021 to December 2022. METHODS: A total of 523 pairs of gastrointestinal cancer patients with PICC and their nurses were recruited. All the participants were invited to complete the general information questionnaire and the Readiness for Hospital Discharge Scale. Outcome measure was patient-reported readiness for hospital discharge. This study was reported according to the STROBE checklist. RESULTS: The patients reported a low level of readiness for hospital discharge. Nurse-patient assessment differences were positively associated with nurse-to-patient ratios but negatively associated with readiness for hospital discharge. Furthermore, nurse-patient assessment differences fully mediated the effect of nurse-to-patient ratios on readiness for hospital discharge, and age and gender of patients only moderated the indirect path of mediation model.

A 2D-0D-2D Sandwich Heterostructure toward High-Performance Room-Temperature Gas Sensing.

The construction of two-dimensional (2D) van der Waals (vdW) heterostructures over black phosphorus (BP) has been attracting significant attention to better utilize its inherent properties. The sandwich of zero-dimensional (0D) noble metals within BP-based vdW heterostructures can provide efficient catalytic channels, modulating their surface redox potentials and therefore inducing versatile functionalities. Herein, we realize a 2D WS2-Au-BP heterostructure, in which Au nanoparticles are connected between BP and WS2 via ionic bonds. The ultralow conduction band minimum position, the reduced adsorption energies of O2, and the increased dissociation barrier energy of O2- into 2O contribute greatly to improving the long-term stability of BP in the air. The formation of heterostructures can reduce the potential barrier energy in target gas molecules, thus enhancing the absorption energy and charge transfer. Taking the paramagnetic NO2 gas molecules as a representative, a stable response magnitude of 2.11 to 100 ppb NO2 is achieved for 80 days, which is far larger than the initial responses of most BP-based materials. A practical gas sensing system is also developed to demonstrate its real-world implementation. This work provides a promising demonstration of 0D noble metal within 2D BP-based vdW heterostructure for simultaneously improving the long-term stability and room-temperature reversible gas sensing.

Evaluation of tumor microvasculature with 3D ultrasound localization microscopy based on 2D matrix array.

OBJECTIVE: Evaluation of tumor microvascular morphology is of great significance in tumor diagnosis, therapeutic effect prediction, and surgical planning. Recently, two-dimensional ultrasound localization microscopy (2DULM) has demonstrated its superiority in the field of microvascular imaging. However, it suffers from planar dependence and is unintuitive. We propose a novel three-dimensional ultrasound localization microscopy (3DULM) to avoid these limitations. METHODS: We investigated 3DULM based on a 2D array for tumor microvascular imaging. After intravenous injection of contrast agents, all elements of the 2D array transmit and receive signals to ensure a high and stable frame rate. Microbubble signal extraction, filtering, positioning, tracking, and other processing were used to obtain a 3D vascular map, flow velocity, and flow direction. To verify the effectiveness of 3DULM, it was validated on double helix tubes and rabbit VX2 tumors. Cisplatin was used to verify the ability of 3DULM to detect microvascular changes during tumor treatment. RESULTS: In vitro, the sizes measured by 3DULM at 3 mm and 13 mm were 178 µ m and 182 µ m , respectively. In the rabbit tumors, we acquired 9000 volumes to reveal vessels about 30 µ m in diameter, which surpasses the diffraction limit of ultrasound in traditional ultrasound imaging, and the results matched with micro-angiography. In addition, there were significant changes in vascular density and curvature between the treatment and control groups. CONCLUSIONS: The effectiveness of 3DULM was verified in vitro and in vivo. Hence, 3DULM may have potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease. CLINICAL RELEVANCE STATEMENT: 3D ultrasound localization microscopy is highly sensitive to microvascular changes; thus, it has clinical potential for tumor diagnosis and treatment evaluation. KEY POINTS: • 3D ultrasound localization microscopy is demonstrated on double helix tubes and rabbit VX2 tumors. • 3D ultrasound localization microscopy can reveal vessels about 30 µ m in diameter-far smaller than traditional ultrasound. • This form of imaging has potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease.

Safety analysis of antineoplastic drugs for lung cancer: a retrospective analysis based on Shaanxi Province in Western China.

BACKGROUND: China has the highest proportion of lung cancer-related deaths. Drug therapy is the main tool of comprehensive anticancer treatment. However, most studies to date have focused on certain types of targets or immunotherapeutic modalities for drug safety; few studies have addressed the factors that influence ADRs for each type of drug in patients with lung cancer, and even fewer studies have explored the risk factors for certain types of ADRs. Based on it, we comprehensively evaluate the drug safety of patients and provide a clinical reference with a focus on lung cancer. RESEARCH DESIGN AND METHODS: We examined 767 reports of adverse drug reactions (ADRs) in patients with lung cancer and conducted a logistic regression analysis on the risk factors that may cause different types of organ system damage and serious ADRs. RESULTS: The logistic regression identified various independent risk factors for system organ damage, and ADRs involving erythrocyte abnormalities (P < 0.001), respiratory system damage (P < 0.001), and leukocyte and reticuloendothelial system abnormalities (P < 0.001) were more likely to be severe. CONCLUSIONS: Rare adverse reactions and different Clinical medication guidelines for molecular-targeted drugs were identified. These findings had certain practical significance in clinical safe drug use.

Safety analysis of therapeutic drugs for breast cancer patients and construction of a predictive model for serious adverse drug reactions.

OBJECTIVES: To explore the characteristics of the occurrence of antineoplastic drug adverse reactions (ADRs) in breast cancer and to utilize a computerized tool to identify early warning indicators of potentially serious ADRs. METHODS: We conducted descriptive statistical analyses of the demographic features, medication use characteristics, and clinical manifestations of suspected ADRs in ADR-exposed patients using data from the Shaanxi Provincial Adverse Drug Reaction Monitoring Center, China, from 2017 to 2021. Using disproportionality methods (reporting odds ratio, proportional reporting ratio, and comprehensive standard method), the relationship between drugs and ADRs was measured. Finally, a web-based clinical prediction model for serious ADRs based on binary logistic regression was developed to estimate individual event probabilities numerically. RESULTS: We developed a new computer-mineable breast cancer-ADR system. In total, 1119 ADR reports were received between 2017 and 2021, with an increasing trend in the number. Antineoplastic medications of natural sources made up the greatest portion of the drug category (530, 38.10%) while targeted drugs' part increased with time. The medicine with the greatest number of ADR cases was docetaxel. Bone marrow failure was the most reported ADR. The disproportionality methods produced 19 signals of disproportionate reporting, two signals of disproportionate reporting were unknown ADRs. The occurrence of serious ADRs was shown to be substantially correlated with gender, platinum drugs, and blood and lymphatic system disorders. The clinical prediction model for serious ADRs had above-moderate discriminatory power (C-index was 0.775). CONCLUSIONS: The number of ADRs to breast cancer antineoplastic drugs was constantly increasing, with docetaxel ranking first, with the majority of ADRs presenting as bone marrow suppression, nausea, and vomiting. Data mining identified 19 signals of disproportionate reporting.

Deep learning for fast denoising filtering in ultrasound localization microscopy.

Objective.Addition of a denoising filter step in ultrasound localization microscopy (ULM) has been shown to effectively reduce the error localizations of microbubbles (MBs) and achieve resolution improvement for super-resolution ultrasound (SR-US) imaging. However, previous image-denoising methods (e.g. block-matching 3D, BM3D) requires long data processing times, making ULM only able to be processed offline. This work introduces a new way to reduce data processing time through deep learning.Approach.In this study, we propose deep learning (DL) denoising based on contrastive semi-supervised network (CS-Net). The neural network is mainly trained with simulated MBs data to extract MB signals from noise. And the performances of CS-Net denoising are evaluated in bothin vitroflow phantom experiment andin vivoexperiment of New Zealand rabbit tumor.Main results.Forin vitroflow phantom experiment, the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of single microbubble image are 26.91 dB and 4.01 dB, repectively. Forin vivoanimal experiment , the SNR and CNR were 12.29 dB and 6.06 dB. In addition, single microvessel of 24µm and two microvessels separated by 46µm could be clearly displayed. Most importantly,, the CS-Net denoising speeds forin vitroandin vivoexperiments were 0.041 s frame-1and 0.062 s frame-1, respectively.Significance.DL denoising based on CS-Net can improve the resolution of SR-US as well as reducing denoising time, thereby making further contributions to the clinical real-time imaging of ULM.

Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway.

Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer's disease (AD). The blood-brain barrier (BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1 (Cav-1) expression was enhanced after P. gingivalis infection. Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain (RgpA) were detected. Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a (Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.

Use of Failure Mode and Effects Analysis (FMEA) for Risk Analysis of Drug Use in Patients with Lung Cancer.

It is crucial to investigate the risk factors inherent in the medication process for cancer patients since improper antineoplastic drug use frequently has serious consequences. As a result, the Severity, Occurrence, and Detection rate of each potential failure mode in the drug administration process for patients with lung cancer were scored using the Failure Mode and Effect Analysis (FMEA) model in this study. Then, the risk level of each failure mode and the direction of improvement were investigated using the Slacks-based measure data envelopment analysis (SBM-DEA) model. According to the findings, the medicine administration process for lung cancer patients could be classified into five links, with a total of 60 failure modes. The risk of failure modes for patient medication and post-medication monitoring ranked highly, with unauthorized use of traditional Chinese medicine and folk prescription and unauthorized drug addition (incorrect self-medication) ranking first (1/60); doctor prescription was also prone to errors. The study advises actively looking at ways to decrease the occurrence and difficulty of failure mode detection to continually enhance patient safety when using medications.

Endoscopic Ultrasound Localization Microscopy for the Evaluation of the Microvasculature of Gastrointestinal Tract Tumors in Rabbits.

OBJECTIVE: The morphological and hemodynamic characterization of the microvascular network around the gastrointestinal (GI) tract can be of significant clinical value for the early diagnosis and treatment of GI tract cancer. Ultrasound localization microscopy (ULM) imaging has been demonstrated to be capable of resolving the microvascular network. However, the endoscopic application of ULM imaging techniques is still unknown. In this study, an endoscopic ultrasound localization microscopy (e-ULM) imaging technique was developed to evaluate the changes of microvasculature during GI tract tumor growth. METHODS: A customized circular array transducer (center frequency: 6.8 MHz) and the coherent diverging wave compounding method were used to generate B-mode images. Spatiotemporal singular value decomposition processing was used to eliminate the background signals before signal localizations. The centroids of spatially isolated signals were localized and summed to generate the final super-resolution image. RESULTS: The final microvasculature map of a rabbit GI tract tumor reveals that e-ULM can be used to surpass the diffraction limit in traditional endoscopic ultrasound (EUS) imaging. Furthermore, it is observed that data from different stages of tumor growth exhibit significant differences in microvascular pattern and density. CONCLUSION: Our study demonstrated the implementation and application of an in vivo e-ULM imaging technique for the evaluation of the microvasculature of GI tumors. SIGNIFICANCE: The efficient e-ULM imaging technique shows potential for use in the detection of GI tract tumor microcirculation changes and subsequent diagnosis of GI tract cancer.

A Hybrid Assembly with Nickel Poly-Pyridine Polymer on CdS Quantum Dots for Photo-Reducing CO2 into Syngas with Controlled H2 /CO Ratios.

A hybrid photocatalytic assembly with Ni poly-pyridine polymers binding on CdS quantum dots was developed via thiophene immobilization. The fabricated hybrid assembly facilitated efficient charge separation, and each component endowed great synergy. As a result, a high syngas production rate was achieved over 5500 µmol gcat -1 h-1 from photocatalytic CO2 reduction under visible-light irradiation, accompanied by an adjustable H2 /CO ratio ranging from 4 : 1 to 1 : 3. A novel hybrid assembly was described for syngas synthesis with boosted activity and controlled selectivity, which provides a profile to ingeniously understand molecular-level design for photocatalysts.

Assessment of medication adherence, medication safety awareness and medication practice among patients with lung cancer: A multicentre cross-sectional study.

OBJECTIVES: We aimed to explore the current status of medication adherence, safety awareness and practice among patients with lung cancer. METHODS: We conducted a questionnaire-guided cross-sectional study in Xi'an, Yulin, Hanzhong and Weinan in Shaanxi Province, China, from April to June 2021 for a period of 3 months. The study questionnaire was developed according to previous related studies reported in the literature, and includes basic demographic information and patients' medication safety questions. The data were double-entered using EpiData 3.1 software; descriptive statistics, t-test, analysis of variance, the Kruskal-Wallis test and the Mann-Whitney U-test were performed to analyse the data. RESULTS: A total of 567 participants were included, and 409 valid questionnaires were finally completed, with an effective response rate of 72.13%. More than 80% of patients showed good medication adherence; the average adherence score was 22 ± 2.68 of 25. The average score for medication safety awareness was 16.40 ± 4.41, which was significantly lower than that of medication adherence (p < .001). Only 22.74% of patients always checked their medicines before a nurse administered them; 17.60% of patients never checked their medicines. Few patients actively consulted an health care professional to understand safety information before taking a medication. A significant difference existed in safety awareness scores among age groups (p = .039) and geographic regions (p < .001). Patients with three or more comorbidities had the lowest awareness scores (p = .027). CONCLUSION: We found that patients with lung cancer showed better medication adherence, but their awareness about medication safety was poor. Older patients, those with comorbidities and patients in regions with poor medical resources may have worse awareness about safety. Current medication education for patients should not only aim to improve adherence but should also encourage patients to take greater responsibility for their own safety and to actively participate in their medication safety. Greater systematic and individualized medication safety information is needed for older patients, those with more comorbidities and patients in areas with poor medical resources. PATIENT CONTRIBUTION: We conducted a questionnaire-guided cross-sectional study on hospitalized lung cancer patients in Shaanxi Province to explore the patients' practices related to safety medication, including medication adherence and medication safety awareness.

The Effects of Porphyromonas gingivalis on Inflammatory and Immune Responses and Osteogenesis of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are increasingly used in tissue regeneration, not only because of their multilineage differentiation ability, but also because of their immunomodulatory function, which allows them to play a role in the inflammatory milieu, especially in periodontitis. Porphyromonas gingivalis (P. gingivalis) is an important pathogen associated with the progression of periodontitis. Heterogeneous MSC sources show differences in their inflammatory-immune responsiveness and osteogenesis capabilities when exposed to P. gingivalis and its virulence factors. This article reviews the promoted inflammatory and immune responses of periodontal ligament stem cells, which are potential pitfalls in bone regeneration. MSCs from other sources showed contradictory inflammatory and immune reactions in the few studies on this topic. We also summarize the mechanisms involved in the inflammatory, immune responses and osteogenic potential of MSCs exposed to P. gingivalis and its virulence factors to inform an improved utilization of MSCs in regenerative therapies for periodontitis.

1.5-Dimensional Circular Array Transducer for In Vivo Endoscopic Ultrasonography.

OBJECTIVE: Traditional endoscopic ultrasonography (EUS), which uses one-dimensional (1-D) curvilinear or radial/circular transducers, cannot achieve dynamic elevational focusing, and the slice thickness is not sufficient. The purpose of this study was to design and fabricate a 1.5-dimensional (1.5-D) circular array transducer to achieve dynamic elevational focusing in EUS in vivo. METHODS: An 84 × 5 element 1.5-D circular array transducer was successfully developed and characterized in this study. It was fabricated with PZT-5H 1-3 composite that attained a high-electromechanical coupling factor and low-acoustic impedance. The acoustic field distribution was measured with different transmission modes to validate the 1.5-D elevational beam focusing capability. The imaging performance of the 84 × 5 element 1.5-D circular array transducer was evaluated by two wire phantoms, an agar-based cyst phantom, an ex vivo swine pancreas, and an in vivo rhesus macaque rectum based on multifocal ray-line imaging method with five-row elevational beam steering. RESULTS: It was demonstrated that the transducer exhibited a central frequency of 6.47 MHz with an average bandwidth of 50%, a two-way insertion loss of 23 dB, and crosstalk of <-26 dB around the center frequency. CONCLUSION: Dynamic elevational focusing and the enhancement of the slice thickness in EUS were obtained with a 1.5-D circular array transducer. SIGNIFICANCE: This study promotes the development of multirow and two-dimensional array EUS probes for a more precise clinical diagnosis and treatment.

An Shen Ding Zhi Ling Alleviates Symptoms of Attention Deficit Hyperactivity Disorder via Anti-Inflammatory Effects in Spontaneous Hypertensive Rats.

Attention deficit hyperactivity disorder (ADHD) is a childhood-onset chronic neurobehavioral disorder, with multiple genetic and environmental risk factors. Chronic inflammation may be critical for the progression of ADHD. An Shen Ding Zhi Ling (ASDZL) decoction, a traditional Chinese medicine prescription, is clinically used in ADHD treatment. In this study, we investigated the effects and underlying anti-inflammatory mechanisms of ASDZL in young spontaneously hypertensive rats (SHRs), a widely used model of ADHD. SHRs were divided into the SHR model group (vehicle), atomoxetine group (4.56 mg/kg/day) and ASDZL group (21.25 g/kg/day), and orally administered for four weeks. Wistar Kyoto rats were used as controls (vehicle). We found that ASDZL significantly controlled hyperactivity and impulsivity, and improved spatial memory of SHRs in the open field test and Morris water maze test. ASDZL reduced the pro-inflammatory factors interleukin (IL)-1ß, IL-4, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 and increased anti-inflammatory factor IL-10 in SHRs, and decreased the activation of microglia, astrocytes and mast cells in the prefrontal cortex (PFC) and hippocampus. Furthermore, the results indicated that ASDZL inhibited the neuroinflammatory response by protecting the integrity of the blood-brain barrier and suppressing the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways of SHRs. In conclusion, these findings revealed that ASDZL attenuated ADHD symptoms in SHRs by reducing neuroinflammation.