Activates B lymphocytes and enhanced immune response: A promising adjuvant based on PLGA nanoparticle to improve the sensitivity of ZEN monoclonal antibody.

In preparing monoclonal antibodies by hybridoma cell technology, the quality of B lymphocytes used for cell fusion directly affects the sensitivity of monoclonal antibodies. To obtain B-lymphocytes producing high-quality specific antibodies for cell fusion during the immunization phase of the antigen, we prepared a TH2-Cell stimulatory delivery system as a novel adjuvant. Astragalus polysaccharide has a good ability to enhance antigenic immune response, and it was encapsulated in biocompatible materials PLGA as an immunostimulatory factor to form the delivery system (APS-PLGA). The preparation conditions of APSP were optimized using RSM to attain the highest utilization of APS. Immunization against ZEN-BSA antigen using APSP as an adjuvant to obtain B lymphocytes producing ZEN-specific antibodies for cell fusion. As results present, APSP could induce a stronger TH2 immune response through differentiating CD4 T cells and promoting IL-4 and IL-6 cytokines. Moreover, it could slow down the release efficiency of ZEN-BSA and enhance the targeting of ZEN-BSA to lymph nodes in vivo experiments. Ultimately, the sensitivity of mouse serum ZEN-specific antibodies was enhanced upon completion of immunization, indicating a significant upregulation of high-quality B lymphocyte expression. In the preparation of monoclonal antibodies, the proportion of positive wells for the first screening was 60%, and the inhibition rates of the antibodies were all similar (>50%). Then we obtained the ZEN monoclonal antibody with IC50 of 0.049 ng/mL, which was more sensitive than most antibodies prepared under conventional adjuvants. Finally, a TRFIAS strip assay was preliminarily established with a LOD value of 0.246 ng/mL.

[Effect and mechanism of aqueous extract of Strychni Semen on bone destruction in rats with type â ¡ collagen-induced rheumatoid arthritis].

To investigate the mechanism of action of aqueous extract of Strychni Semen(SA) on bone destruction in rats with type Ⅱ collagen-induced arthritis(CIA), the SD rats were randomly divided into normal group, model group, low, medium, and high dose(2.85, 5.70, and 11.40 mg·kg~(-1)) groups of SA, and methotrexate group. Except for the normal group, the CIA model was prepared for the other groups. After the second immunization, different doses of SA were given to the low, medium, and high dose groups of SA once a day, and the methotrexate group was given once every three days. 0.3% sodium hydroxymethylcellulose(CMC-Na) was given once a day to the normal and model groups for 28 d. The clinical score of arthritis was evaluated every three days. Micro computed tomography(Micro-CT) method was used to evaluate the degree of bone destruction. Histopathological changes in the joint tissue and the number of osteoclasts in CIA rats were evaluated by hematoxylin-eosin(HE) staining and tartrate-resistant acid phosphatase(TRAP) staining. The expression of interleukin-1ß(IL-1ß) in the joint tissue of rats was detected by immunohistochemistry. Western blot was used to detect key protein expression in mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathways in the joint tissue of rats. The results showed that different doses of SA were able to improve the red and swollen inflammatory joint and joint deformity in CIA rats to varying degrees, reduce the clinical score, inhibit synovial inflammation, vascular opacification, cartilage erosion, and bone destruction, and reduce the number of TRAP-positive cells in bone tissue. Micro-CT results showed that the SA was able to increase bone mineral density, bone volume fraction, trabecular reduce, and trabecular number and reduce bone surface/bone volume and trabecular separation/spacing. Different doses of SA could down-regulate the protein expression of IL-1ß, p-JNK, p-ERK, p-p38, PI3K, and p-Akt to varying degrees. In conclusion, SA can improve disease severity, attenuate histopathological and imaging changes in joints, and have osteoprotective effects in CIA rats, and its mechanism of action may be related to the inhibition of the overactivation of MAPK and PI3K/Akt signaling pathways.

[Mechanism of Yuxuebi Tablets in treating synovial inflammation in rheumatoid arthritis based on transcriptomics].

This study investigated the mechanism of Yuxuebi Tablets(YXB) in the treatment of synovial inflammation in rheumatoid arthritis(RA) based on transcriptomic analysis. Transcriptome sequencing technology was employed to analyze the gene expression profiles of joint tissues from normal rats, collagen-induced arthritis(CIA) rats(an RA model), and YXB-treated rats. Common diffe-rentially expressed genes(DEGs) were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. RA synovial inflammation-related target genes were retrieved from the OMIM and GeneCards databases. Venny 2.1 software was used to identify the intersection of YXB target genes and RA synovial inflammation-related target genes, and GO and KEGG enrichment analyses were performed on the intersecting target genes. Immunohistochemistry was used to assess the protein expression levels of the inflammatory factors interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) in rat joint tissues. Western blot analysis was employed to measure the expression levels of key proteins in the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway. A total of 2 058 DEGs were identified by intersecting the genes from the normal group vs model group and the model group vs YXB treatment group. A search in OMIM and GeneCards databases yielded 1 102 RA synovial inflammation-related target genes. After intersecting with the DEGs in the YXB treatment group, 204 intersecting target genes were identified, primarily involving biological processes such as immune response, signal transduction, and inflammatory response; cellular components including plasma membrane, extracellular space, and extracellular region; molecular functions like protein binding, identical protein binding, and receptor binding. These target genes were mainly enriched in signaling pathways such as PI3K/Akt, cytokine-cytokine receptor interaction, and Janus kinase/signal transducer and activator of transcription(JAK/STAT). Western blot results showed that YXB at low, medium, and high doses could significantly inhibit the expression levels of key proteins in the PI3K/Akt signaling pathway in rat joint tissues in a dose-dependent manner. Immunohistochemistry further confirmed these findings, showing that YXB not only suppressed the protein expression levels of the inflammatory factors IL-1ß and TNF-α in the joint synovial tissues of CIA rats, but also inhibited p-Akt protein expression. In conclusion, this study used transcriptomic analysis to uncover the key mechanisms of YXB in inhibiting synovial inflammation and alleviating the progression of RA, with a focus on its role in suppressing the PI3K/Akt signaling pathway.

Major influencing factors identification and probabilistic health risk assessment of soil potentially toxic elements pollution in coal and metal mines across China: A systematic review.

Deposition of potentially toxic elements (PTEs) in soils due to different types of mining activities has been an increasingly important concern worldwide. Quantitative differences of soil PTEs contamination and related health risk among typical mines remain unclear. Herein, data from 110 coal mines and 168 metal mines across China were analyzed based on 265 published literatures to evaluate pollution characteristics, spatial distribution, and probabilistic health risks of soil PTEs. The results showed that PTE levels in soil from both mine types significantly exceeded background values. The geoaccumulation index (Igeo) revealed metal-mine soil pollution levels exceeded those of coal mines, with average Igeo values for Cd, Hg, As, Pb, Cu, and Zn being 3.02-15.60 times higher. Spearman correlation and redundancy analysis identified natural and anthropogenic factors affecting soil PTE contamination in both mine types. Mining activities posed a significant carcinogenic risk, with metal-mine soils showing a total carcinogenic risk an order of magnitude higher than in coal-mine soils. This study provides policymakers a quantitative foundation for developing differentiated strategies for sustainable remediation and risk-based management of PTEs in typical mining soils.

[Health Risk Assessment for an Arsenic-contaminated Site Based on Monte Carlo Simulation and Parameters Optimization].

Risk assessment is a critical part of risk management for contaminated sites. However， in the specific management practice of As-contaminated sites， it is difficult to obtain realistic health risks for contaminated sites based on the total amount of pollutants and determined values of the model， thus preventing the control requirements of later remediation to be met. An increasing number of studies have recently been conducting risk assessments by considering bioavailability， modification parameters， and combined probabilistic models. To improve the accuracy of risk assessment results， taking a large As-contaminated site as a case， 432 sampling sites were set up and collected at different depths to analyze the level and distribution characteristics of As pollution， and probabilistic risk assessment was conducted with the modification of model parameters through literature research and Monte Carlo simulation. Then， the impact of traditional methods and probabilistic methods on health risk assessment was explored in comparison. The results indicated that ω（As） in the top soil of the study area ranged from 2.70-97.0 mg·kg-1， with a spatial variation coefficient of 0.61 and weaker spatial continuity. The carcinogenic risk and hazard index obtained by the traditional risk assessment method were 2.12E-4 and 8.36， respectively， which obviously overestimated the actual risk level and were not conductive to the refined management of As-contaminated sites. Combined with modification of model parameters and probabilistic risk assessment， the non-carcinogenic risk for adults and children was found to be at an acceptable level， and the carcinogenic risk was reduced by nearly an order of magnitude compared to that in the conventional method. Considering the relative biological effectiveness （RBA） of As， the 95% quantile of the total carcinogenic risk was 1.24E-5， a reduction of up to 36.41% compared to the uncorrected corresponding risk value of 1.95E-5. The carcinogenic risk of soil As for adults and children in the study area exceeded acceptable risk levels 1E-6， with oral ingestion of soil being the primary route of exposure. In addition， the results of the sensitivity analysis of the parameters showed that As concentration， daily oral ingestion rate of soils， and exposure duration of children had relatively larger effects for health risks. This work will provide a methodological and theoretical basis for achieving accurate risk assessment of As-contaminated sites and provide concepts for refined risk management.

Application of Multidimensional Quality Management Tools in the Management of Medical Adverse Events.

Purpose: This study aims to investigate the impact of multidimensional quality management tools in establishing a medical adverse event management system, with the aim of continuously improving medical quality and safety while ensuring patient well-being. Methods: This study introduces risk management theories, such as the "Gray Rhino Theory", and employs quality management tools like the Plan-Do-Check-Act (PDCA) cycle, Quality Control Circle (QCC), and Root Cause Analysis (RCA), to provide relevant quality management education and training to employees. This approach facilitates the establishment of a medical adverse event management system that encourages reporting and fosters a blame-free reporting culture, while simultaneously implementing quality management across the entire process. The regular utilization of the QCC facilitates ongoing quality improvement. Furthermore, for sentinel events and patient harm incidents with educational values, the study employs the Incident Decision Tree (IDT) to determine appropriate actions. Additionally, the hospital initiates RCA for system-wide improvements, focusing on areas such as management, institutional processes, and environmental aspects. Moreover, an internal medical quality improvement case competition is organized, with outstanding cases being selected to participate in the multidimensional quality management competition organized by the National Quality Management Alliance. Results: The study reveals a significant improvement in employees' awareness of adverse events, the percentage of employees reporting adverse events increased significantly from 39.15% in 2019 to 49.77% in 2022, P=0.002. Furthermore, the adverse event reporting rate has risen significantly from 2.78% (2019) to 5.96% (2022), P=0.002. Additionally, each department has been able to utilize QCC or RCA tools for quality improvement, thereby further reinforcing the development of a patient safety culture. Conclusion: Multidimensional quality management tools play a crucial role in establishing a hospital's adverse event management system, promoting continuous improvement in medical quality, ensuring patient safety, and effectively implementing a culture of patient safety.

The global burden of traumatic amputation in 204 countries and territories.

Background: Traumatic amputation leads to disability and imposes a heavy health burden. This study aims to explore the current status and temporal trends of the global burden of traumatic amputation according to sex, age, amputation site, cause, and reginal level of social development. Methods: The data were extracted from the Global Burden of Diseases (GBD) Study 2019. Prevalence, incidence, years lived with disability (YLDs) and corresponding age-standardized rate were compared. Estimated annual percentage change (EAPC) was applied to reflect trends in age-standardized rates over a specific period. Spearman rank test and curve fitting methods were used to analyze the relationship between disease burden and Socio-Demographic Index (SDI). Results: Globally, the incidence and prevalence number of traumatic amputation increased from 11.37 million and 370.25 million in 1990, to 13.23 million and 552.45 million in 2019, with a raise of 16.4 and 49.2%, respectively. But the age-standardized incidence rate (ASIR) (EAPC = -0.56; 95%CI, -0.72 to -0.41) and age-standardize prevalence rate (ASPR) (EAPC = -0.63; 95%CI, -0.74 to -0.52) declined during this period. The YLDs count also increased by 39.2% globally (from 5.28 million to 7.35 million), while the age-standardize YLDs rate (ASYR) decreased by an average of 1.00% per year (95% CI, -1.10 to -0.90) from 1990 to 2019. The incidence, prevalence, and YLDs rate of traumatic amputation continue to increase with age. Traumatic amputations were most common in the fingers, while unilateral lower limb amputation caused the greatest burden of disability. ASIR and SDI were positively correlated (ρ = 0.442, p < 0.001), while ASYR and SDI were not significantly correlated (ρ = -0.030, p = 0.669), and EAPC in ASYR and SDI were negatively correlated (ρ = -0.275, p < 0.001). Exposure to mechanical forces and falls were the leading causes of traumatic amputation. Conclusion: Despite the declining trends in ASIR, ASPR, and ASYR, the incidence, prevalence, and YLDs counts of traumatic amputation have increased significantly worldwide, especially in the older adults population. With the population aging, targeted health policies are needed to address the increasing global burden of traumatic amputations in the future.

A Dynamic and Pseudo-Homogeneous MBs-icELISA for the Early Detection of Aflatoxin B1 in Food and Feed.

Aflatoxin B1 (AFB1) is one of the most toxic and harmful fungal toxins to humans and animals, and the fundamental way to prevent its entry into humans is to detect its presence in advance. In this paper, the monoclonal antibody mAbA2-2 was obtained via three-step sample amplification and multi-concentration standard detection using a subcloning method based on the limited dilution method with AFB1 as the target. A dynamic and pseucdo-homogeneous magnetic beads enzyme-linked immunosorbent assay (MBs-icELISA) was established using the prepared antibody as the recognition element and immunomagnetic beads as the antigen carrier. The MBs-icELISA showed good linear correlation in the concentration range of 0.004-10 ng/mL with R2 = 0.99396. The limit of detection (LOD) of the MBs-icELISA for AFB1 was 0.0013 ng/mL. This new ELISA strategy significantly shortened AFB1 detection time through improved sensitivity compared to the conventional ELISA method.

Loss of ARHGAP40 expression in basal cell carcinoma via CpG island hypermethylation.

Basal cell carcinoma (BCC) is the most common malignant tumour arising from the basal cells of the epidermis or follicular structures. The aetiology of BCC is a multifactorial combination of genotype, phenotype and environmental factors. The pathogenesis of BCC remains unclear, with diverse and complex signalling pathways involved. ARHGAP40 is a Rho GTPase-activating protein (RhoGAP). Rho GTPases play a crucial role in the formation and progression of numerous cancers. The expression levels and roles of ARHGAP40 in BCC have not been explored. Here, ARHGAP40 expression was detected in a set of formalin-fixed, paraffin-embedded (FFPE) samples of basal cell carcinoma, paracancerous normal skin and benign skin lesions. The epigenetic mechanism that downregulates ARHGAP40 in basal cell carcinoma was investigated. We found that ARHGAP40 is expressed in normal basal cells and most benign skin lesions but lost in most basal cell carcinomas. We detected CpG island hypermethylation at the promoter-associated region of ARHGAP40. Our data suggest that ARHGAP40 is downregulated in BCC due to hypermethylation. ARHGAP40 protein is a potential novel biomarker for distinguishing trichoblastoma from BCC. This report is preliminary, and extensive research into the role of ARHGAP40 in BCC carcinogenesis and its potential as a treatment target is required in the future.

Ezetimibe attenuates functional impairment via inhibition of oxidative stress and inflammation in traumatic spinal cord injury.

Sustained inflammation after a traumatic spinal cord injury (TSCI) triggers oxidative stress and neuronal apoptosis, hindering functional recovery. Ezetimibe (EZE) has been reported to have anti-inflammatory and antioxidative properties in hepatology-related diseases, but its potential role in SCI remains unclear. In this study, we evaluated the therapeutic effect of EZE on inflammatory microglia and in an SCI model and elucidated the underlying mechanism. First, we stimulated the BV2 microglia cell line with LPS, and we also induced moderate spinal cord injuries in adult male C57BL/6 mice. Both the cells and mice were treated with EZE, and we investigated inflammation, oxidative stress, neurologic damage, and motor function in vitro and in vivo, respectively. Our findings demonstrated that EZE administration attenuates inflammation in microglia by regulating the AMPK/Nrf2 axis. Furthermore, EZE treatment reduced inflammation and oxidative stress levels in the injured spinal cord. Additionally, treatment with EZE decreased glial scarring and improved motor function recovery, indicating the protective role of EZE in SCI. EZE was found to have anti-inflammatory and antioxidative effects on SCI, and it modulated the AMPK/Nrf2 pathway in microglia. Moreover, EZE prevented histological destruction of the spinal cord tissue. In conclusion, EZE shows promise as a drug to protect neurologic integrity following post-SCI.

[UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood].

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

Source-oriented probabilistic health risk assessment of soil potentially toxic elements in a typical mining city.

Identifying potential sources of soil potentially toxic elements (PTEs) and developing source-oriented health risk assessments in typical mining cities are key for pollution prevention and risk management. To this end, a case study was conducted to explore the pollution characteristics, potential sources, and human health risks of PTEs in Daye City, China. Indices, including the pollution factor (PF), pollution load index (PLI), and geo-accumulation index (Igeo), were applied to assess PTE pollution. Cd had the highest value among the detected PTEs, and 82.93% of the sampling sites had moderate pollution levels, with the highest mean Igeo value for Cd (2.30). Four potential sources were determined. Cr and Ni originated mainly from natural sources. Zn (91.5%) was exclusively and then Cd (33.1%) was moderately derived from industrial activities. The mixed source of various mineral exploitation smelting, and coal-fired traffic emissions leaded to the accumulation of As, Cd, and Pb. Cu was associated with Cu-related mining and smelting activities. The probabilistic health risk assessment indicated that the non-carcinogenic risks for populations were negligible. Overall, this work provides scientific information for environmental managers to manage soil PTE pollution through the effective management of anthropogenic sources with limited resources and costs.

Production of AFB1 High-Specificity Monoclonal Antibody by Three-Stage Screening Combined with the De-Homologation of Antibodies and the Development of High-Throughput icELISA.

To achieve accurate detection of AFB1 toxin content in agricultural products and avoid false-positive rates in the assays, the specificity of mAbs is critical. We improved the specificity of the prepared monoclonal antibodies by modifying the traditional limiting dilution subcloning method. The traditional finite dilution method was modified with three-stage screening (the trending concentration of standards used in the screening is low-high-low) to achieve high specificity in pre-cell screening and increased the number of subclones to 10 to achieve the de-homologation of antibodies. A modified limiting dilution obtained a highly specific AFB1 monoclonal cell line, ZFG8, with a 50% inhibition concentration (IC50) of 0.3162 ng/mL. Notably, it exhibited the highest specificity compared to anti-AFB1 monoclonal antibodies prepared by other investigators. The maximum cross-reactivity of the mAb with structural analogues for AFB2, AFG1, AFG2, and AFM1 was 0.34%. The results showed that this type of screening improves the monoclonal antibodies' specificity. Based on this ZFG8 monoclonal antibody, an icELISA assay was established with an IC50 of 0.2135 ng/mL for AFB1. The limit of the linear detection range of icELISA is 0.0422-1.29267 ng/mL with reasonable specificity and precision. The recoveries of AFB1 in samples of corn flour and wheat meal ranged from 84 to 107%, with CVs below 9.3%. The recoveries of structural analogues (AFB2, AFM1, AFG1, and AFG2) were less than 10% in both corn flour and wheat meal. The results showed that the prepared AFB1 monoclonal antibody could accurately and specifically recognize AFB1 residues in agricultural products while ignoring the effects of other structural analogues.

Expression and hypermethylation of JAM and EPB41L3 in cervical squamous cell carcinoma: Clinical significance and applications.

This study aimed to explore the expression and hypermethylation of EPB41L3 and JAM3 in cervical squamous cell carcinoma (CSCC) and to investigate their clinical significance. JAM3 and EPB41L3 mRNA expression was analyzed using a public database, and protein expression was detected using immunohistochemistry. The methylation status of JAM3 and EPB41L3 was detected in CSCC tissues and cervical cytological specimens using a quantitative methylation-specific PCR (qMSP). JAM3 and EPB41L3 mRNA were downregulated in CSCC. The JAM3 protein was positively detected in 39.4% of CSCC tissues and frequently expressed in those with lower FIGO stage and no lymph node metastasis. EPB41L3 was expressed in 18.9% of CSCC tissues. The hypermethylation of JAM3 was detected in 52.3% of CSCC tissues and related to higher FIGO stage and lymph node metastasis. EPB41L3 hypermethylation was detected in 72.7% of CSCC tissues and related to older ages and lymph node metastasis. In cervical cytological specimens, no methylation of JAM3 and EPB41L3 was found in normal or inflamed cervical epithelial cells. The methylation of JAM3 was detected in 0%, 8.3%, and 6.3% of ASCUS, LSIL, and HSIL samples, while EPB41L3 was detected in 12.5%, 42.9%, and 71.4%, respectively. The sensitivity of the combination of JAM3 and EPB41L3 methylation detection in ASCUS, LSIL, and HSIL was 8.3%, 15.6%, and 85.7%, respectively. The specificity of the combination of JAM3 and EPB41L3 methylation detection was 100%. Downregulation of JAM3 and EPB41L3 by hypermethylation was detected in CSCC. JAM3 and EPB41L3 hypermethylation are potential biomarkers for cervical cancer screening.

Analysis of medical malpractice litigation following vertebral augmentation therapy in China from 2008 to 2018.

The first case of vertebral augmentation therapy in mainland China was reported in 2000. Since then, it has been widely used in China as a minimally invasive procedure to treat vertebral compression fractures. However, the characteristics of malpractice litigation involving vertebral augmentation therapy remains unclear. This study aims to analyze the characteristics of medical malpractice litigation involving vertebral augmentation therapy in mainland China for the past 10 years. Two online legal databases were queried for court verdicts involving vertebral augmentation therapy from Jan 2009 to Dec 2018 in mainland China. Each case file was then thoroughly reviewed and data pertaining to defendants, plaintiffs, case outcomes, allegations, and verdicts were abstracted, and descriptive analyses were performed. Level of evidence: LEVEL III. A total of 96 cases were enrolled for final analysis. The number of claims increased by five times during the past 10 years. More than two thirds (67.7%, n = 65) of the cases underwent percutaneous vertebroplasty, and 22.9% (n = 22) underwent percutaneous kyphoplasty, the rest (9.4%, n = 9) remained undefined. Paralysis was alleged in 35.4% of cases (n = 34), followed by significant physical injury (34.4%, n = 33). Cement leakage to spinal canal (44.8%, n = 43) is the most commonly cited reason for litigation, followed by incomplete informed consent (42.7%, n = 41), accidental dural puncture (20.8%, n = 20), unsatisfactory clinical outcome (18.8%, n = 18), and misdiagnosis (12.5%, n = 12). Acute pulmonary cement embolism (4.2%, n = 4), wrong-level vertebrae procedure (3.1%, n = 3) and postoperative infection (2.1%, n = 2) were less common causes for concern. Doctors successfully defended themselves only in 8 (8.3%) cases, which resulted in no indemnity payment. The rest 88 (91.7%) cases were closed with a mean verdict payout of 361,580 Yuan (51,654 US dollars). There is a quickly rising trend in the number of medical malpractice litigation involving vertebral augmentation therapy in China. Identifying the most common reasons for litigation and summarizing their characteristics may help decrease litigation rate and improve the patient experience.

Anti-angiogenic effect of YuXueBi tablet in experimental rheumatoid arthritis by suppressing LOX/Ras/Raf-1 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: A Chinese patent medicine derived from a classical traditional Chinese medicine formula, Yu-Xue-Bi tablet (YXB) is widely used in the clinic to treat rheumatoid arthritis (RA). During the progression of RA, angiogenesis plays a central role in fostering the production of inflammatory cells, leading to synovial hyperplasia and bone destruction. However, whether YXB attenuates the angiogenesis during RA progression remains to be defined. AIM OF THE STUDY: We aimed to evaluate the anti-angiogenic activity of YXB and explore its mechanism of action in collagen-induced arthritis (CIA) rats and VEGF-induced HUVECs. MATERIALS AND METHODS: Transcriptional regulatory network analysis and a network pharmacology approach were employed to explore mechanism of YXB in RA angiogenesis. The antiarthritic effect of YXB was evaluated by determining the arthritis incidence, and score, and by micro-CT analysis. The anti-angiogenic effect of YXB in vivo was assessed by histological and immunohistochemical analyses. The anti-angiogenic effect of YXB in vitro was assessed by wound healing, Transwell migration, Transwell invasion, and tube formation assays. Western-blotting and immunohistochemical analysis were employed to explore the molecular mechanisms of YXB. RESULTS: YXB reduced disease severity and ameliorated pathological features in CIA rats. YXB markedly decreased bone destruction and synovial angiogenesis. Consistently, we also demonstrated that YXB effectively suppressed angiogenesis marker CD31 and VEGF expression. In vitro, YXB effectively inhibited HUVEC migration, invasion, and tube formation. Following the identification of transcriptional expression profiles, "YXB putative targets-known RA-related genes-genes associated with the therapeutic effect of YXB" interaction network was constructed and analyzed. After that, the LOX/Ras/Raf-1 signaling axis, which is involved in RA angiogenesis, was identified as one of the candidate mechanisms of YXB against RA. Experimentally, YXB dose-dependently decreased the expression levels of LOX, Ras, and Raf-1, as well as the phosphorylation of MEK and ERK in CIA rats, and these effects were better than the inhibitory effects of methotrexate (MTX), an FDA approved drug used for some autoimmune diseases such as RA. In addition, YXB may function as a potent angiogenesis inhibitor and significantly suppress the VEGF-induced activation of LOX/Ras/Raf-1 signaling in vitro. CONCLUSIONS: We provide evidence that YXB may decrease the disease severity of RA and reduce bone erosion by suppressing angiogenesis via inhibition of LOX/Ras/Raf-1 signaling.

A simple and rapid homogeneous fluorescence polarization immunoassay for rapid identification of gutter cooking oil by detecting capsaicinoids.

In order to address the widespread concerns with food safety such as adulteration and forgery in the edible oil field, this study developed a fluorescence polarization immunoassay (FPIA) based on a monoclonal antibody in a homogeneous solution system for determination of capsaicinoids in gutter cooking oil by using chemically stable capsaicinoids as an adulteration marker. The prepared fluoresceinthiocarbamyl ethylenediamine (EDF) was coupled with capsaicinoid hapten C, and the synthesized tracer was purified by thin-layer chromatography (TLC) and showed good binding to the monoclonal antibody CPC Ab-D8. The effects of concentration of tracer and recognition components, type and pH of buffer and incubation time on the performance of FPIA were studied. The linear range (IC20 to IC80) was 3.97-97.99 ng/mL, and the half maximal inhibitory concentration (IC50) was 19.73 ng/mL, and the limit of detection (LOD) was 1.56 ng/mL. The recovery rates of corn germ oil, soybean oil and peanut blend oil were in the range of 94.7-132.3%. The experimental results showed that the fluorescence polarization detection system could realize the rapid detection of capsaicinoids, and had the potential to realize on-site identification of gutter cooking oil. As a universal monoclonal antibody, CPC Ab-D8 can also specifically identify capsaicin and dihydrocapsaicin, so the proposed method can be used to quickly monitor for the presence of gutter cooking oil in normal cooking oil.