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Abstract Background Brain-heart infusion agar supplemented with 4 µg/mL of vancomycin (BHI-V4) was commonly used for the detection of heterogeneous (hVISA) and vancomycin-intermediate Staphylococcus aureus (VISA). However, its diagnostic value remains unclear. This study aims to compare the diagnostic accuracy of BHI-V4 with population analysis profiling with area under the curve (PAP-AUC) in hVISA/VISA. Methods The protocol of this study was registered in INPLASY (INPLASY2023120069). The PubMed and Cochrane Library databases were searched from inception to October 2023. Review Manager 5.4 was used for data visualization in the quality assessment, and STATA17.0 (MP) was used for statistical analysis. Results In total, eight publications including 2153 strains were incorporated into the meta-analysis. Significant heterogeneity was evident although a threshold effect was not detected across the eight studies. The summary receiver operating characteristic (SROC) was 0.77 (95% confidence interval [CI], 0.74–0.81). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic score and diagnostic odds ratio were 0.59 (95% CI: 0.46–0.71), 0.96 (95%CI: 0.83–0.99), 14.0 (95% CI, 3.4–57.1), 0.43 (95%CI, 0.32–0.57), 3.48(95%CI, 2.12–4.85) and 32.62 (95%CI, 8.31-128.36), respectively. Conclusion Our study showed that BHI-V4 had moderate diagnostic accuracy for diagnosing hVISA/VISA. However, more high-quality studies are needed to assess the clinical utility of BHI-V4.

Immune checkpoint therapy, such as programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) blockade, has achieved remarkable results in treating various tumors. However, most cancer patients show a low response rate to PD-1/PD-L1 blockade, especially those with microsatellite stable/mismatch repair-proficient colorectal cancer subtypes, which indicates an urgent need for new approaches to augment the efficacy of PD-1/PD-L1 blockade. Cholesterol metabolism, which involves generating multifunctional metabolites and essential membrane components, is also instrumental in tumor development. In recent years, inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), a serine proteinase that regulates cholesterol metabolism, has been demonstrated to be a method enhancing the antitumor effect of PD-1/PD-L1 blockade to some extent. Mechanistically, PCSK9 inhibition can maintain the recycling of major histocompatibility protein class I, promote low-density lipoprotein receptor-mediated T-cell receptor recycling and signaling, and modulate the tumor microenvironment (TME) by affecting the infiltration and exclusion of immune cells. These mechanisms increase the quantity and enhance the antineoplastic effect of cytotoxic T lymphocyte, the main functional immune cells involved in anti-PD-1/PD-L1 immunotherapy, in the TME. Therefore, combining PCSK9 inhibition therapy with anti-PD-1/PD-L1 immunotherapy may provide a novel option for improving antitumor effects and may constitute a promising research direction. This review concentrates on the relationship between PCSK9 and cholesterol metabolism, systematically discusses how PCSK9 inhibition potentiates PD-1/PD-L1 blockade for cancer treatment, and highlights the research directions in this field.

Background: Increasing evidence suggests that both the vaginal microbiota and human papillomavirus (HPV) may play a role in the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. However, the relationship between the vaginal microbiome and HPV infection remains poorly understood. The objective of this study was to investigate the association between indicators of the vaginal microbiota and HPV infection. Methods: From January 2020 to June 2022, clinical data were collected from 5099 outpatients at Beijing Friendship Hospital. These patients underwent simultaneous testing for vaginal microecology and HPV type. A statistical analysis was conducted to examine the relationship between indicators of the vaginal microbiota and HPV infection. Results: HPV infections were detected in 12.47% (636/5099) of the subjects. Single, double, triple, quadruple, and quintuple infections accounted for 81.29%, 14.62%, 3.14%, 0.94%, and 0.15% of all infections, respectively. A significant disparity in HPV infection prevalence was observed between the vaginitis group and the general population. However, no variation was found among different vaginitis groups. The data indicated that individuals with clue cells and sialidase were more susceptible to HPV infection. Sialidase was identified as an independent risk factor for HPV infection in a multivariable logistic regression model. The most prevalent HPV subtypes were 16 and 52, representing 2.10% and 2.86%, 3.14% and 2.86%, 1.78% and 2.16% in the normal, bacterial vaginitis, and other groups, respectively. Conclusions: Our findings demonstrate the presence of clue cells and sialidase, which are two diagnostic criteria for bacterial vaginitis, in association with HPV infection. Furthermore, our results suggest that sialidase could potentially serve as a valuable predictor of HPV infection.

In recent years, Immune checkpoint inhibitors have been extensively used in the treatment of a variety of cancers. However, the response rates ranging from 13% to 69% depending on the tumor type and the emergence of immune-related adverse events have posed significant challenges for clinical treatment. As a key environmental factor, gut microbes have a variety of important physiological functions such as regulating intestinal nutrient metabolism, promoting intestinal mucosal renewal, and maintaining intestinal mucosal immune activity. A growing number of studies have revealed that gut microbes further influence the anticancer effects of tumor patients through modulation of the efficacy and toxicity of immune checkpoint inhibitors. Currently, faecal microbiota transplantation (FMT) have been developed relatively mature and suggested as an important regulator in order to enhance the efficacy of treatment. This review is dedicated to exploring the impact of differences in flora composition on the efficacy and toxicity of immune checkpoint inhibitors as well as to summarizing the current progress of FMT.

The crosstalk between the oral microbiome and oral cancer has yet to be characterized. This study recruited 218 patients for clinicopathological data analysis. Multiple types of specimens were collected from 27 patients for 16S rRNA gene sequencing, including 26 saliva, 16 swabs from the surface of tumor tissues, 16 adjacent normal tissues, 22 tumor outer tissue, 22 tumor inner tissues, and 10 lymph nodes. Clinicopathological data showed that the pathogenic bacteria could be frequently detected in the oral cavity of oral cancer patients, which was positively related to diabetes, later T stage of the tumor, and the presence of cervical lymphatic metastasis. Sequencing data revealed that compared with adjacent normal tissues, the microbiome of outer tumor tissues had a greater alpha diversity, with a larger proportion of Fusobacterium, Prevotella, and Porphyromonas, while a smaller proportion of Streptococcus. The space-specific microbiome, comparing outer tumor tissues with inner tumor tissues, suggested minor differences in diversity. However, Fusobacterium, Neisseria, Porphyromonas, and Alloprevotella were more abundant in outer tumor tissues, while Prevotella, Selenomonas, and Parvimonas were enriched in inner tumor tissues. Clinicopathology-specific microbiome analysis found that the diversity was markedly different between negative and positive extranodal extensions, whereas the diversity between different T-stages and N-stages was slightly different. Gemella and Bacillales were enriched in T1/T2-stage patients and the non-lymphatic metastasis group, while Spirochaetae and Flavobacteriia were enriched in the extranodal extension negative group. Taken together, high-throughput DNA sequencing in combination with clinicopathological features facilitated us to characterize special patterns of oral tumor microbiome in different disease developmental stages.

To identify an apoptosis-related gene (ARG) prediction model for oral squamous cell carcinoma (OSCC), we analyzed and validated the data from TCGA and GEO, respectively. Kaplan–Meier survival analysis and ROC curves showed a good prognostic ability of the model both in the internal training set and in the external testing set. Furthermore, we built a nomogram using these ARGs to forecast the survival probability of OSCC patients. Moreover, we evaluated the rate of immune cells infiltrating in the tumor samples and found obvious, different patterns between the high and low risk groups. GO and KEGG analyses demonstrated multiple molecular biological processes and signaling pathways connecting with this prognostic model in OSCC. The expression of these risk genes in clinical specimens was higher in the non-survival patients than in the well-survival patients by immunohistochemical staining analysis. In conclusion, we established a signature made up of six risk apoptosis-related genes to predict the survival rate of OSCC. These genes could also be targets for the treatment of OSCC.

Vancomycin is regarded as the last resort of defense for a wide range of infections due to drug resistance and toxicity. The detection of vancomycin in plasma has always aroused particular concern because the performance of the assay affects the clinical treatment outcome. This article reviews various methods for vancomycin detection in human plasma and analyzes the advantages and disadvantages of each technique. Immunoassay has been the first choice for vancomycin concentration monitoring due to its simplicity and practicality, occasionally interfered with by other substances. Chromatographic methods have mainly been used for scientific research due to operational complexity and the particular requirement of the instrument. However, the advantages of a small amount of sample needed, high sensitivity, and specificity makes chromatography irreplaceable. Other methods are less commonly used in clinical applications because of the operational feasibility, clinical application, contamination, etc. Simplicity, good performance, economy, and environmental friendliness have been points of laboratory methodological concern. Unfortunately, no one method has met all of the elements so far.

It is important to examine the ignition of energetic materials for launch safety. Given that there is a paucity of experimental tests, numerical simulations are important for analysing energetic materials. A computer program based on the finite volume method and viscoelastic statistical crack mechanics model is developed to study the ignition of energetic materials. The trends of temperature and stress of energetic materials subjected to projectile base pressure are studied by numerical examples. The results are compared with those in an extant study, which verified the correctness of the proposed method. Additionally, the relationships between the temperature increase and nonimpact ignition of energetic materials were analysed. The results show that when the temperature at the bottom of the explosive rises to a certain value, it will cause the explosive to ignite. This research has significance to the study of the base gap of explosives, and it provides a reference for launch safety evaluation of energetic materials.

Large steel storage tanks designed with long-span structures, employed for storing oil and fuel, have been widely used in many countries over the past twenty years. Most of these tanks are thin-walled cylindrical shells. Owing to the high risk of gas explosions and the resulting deaths, injuries, and economic losses, more thorough damage analyses of these large structures should be conducted. This study examines the structural response of a simplified steel storage tank under a blast impact, as calculated by the LS-DYNA software package. The numerical results are then compared with a scale-model experiment. On that basis, the simplified storage tank prototype, which has a 15 × 104 m3 capacity, is analyzed using numerical simulation. In this study, we address issues around the variation in structural responses—particularly of the failure mode, resultant displacement, structural energy, and dynamic strain under the impact. In addition, we also discuss the effects of varying the internal liquid level, constraint conditions, and blast intensity.

The Khokhlov–Zabolotskaya–Kuznetsov (KZK) equation has been widely used in the simulation and calculation of nonlinear sound fields. However, the accuracy of KZK equation reduced due to the deflection of the direction of the sound beam when the sound beam is inclined incidence. In this paper, an equivalent sound source model is proposed to make the calculation direction of KZK calculation model consistent with the sound propagation direction after acoustic refraction, so as to improve the accuracy of sound field calculation under the inclined incident conditions. The theoretical research and pool experiment verify the feasibility and effectiveness of the proposed method.

The integrated observation of seabed topography, sediment geomorphology and sub-bottom profile information is very important for seabed remote sensing and mapping. To improve the efficiency of seabed detection and meet the needs of portable development of detection equipment, we developed a portable seabed feature integrated detection sonar (PSIDS) with whcih a single sonar device can simultaneously detect the above three types of seabed information. The underwater transducer is mainly composed of the following three components: a parametric emission array as the sound source, a high frequency receiving linear array for multibeam echo signal collection, and a two-dimensional vector hydrophone for receiving the low-frequency sediment echo signal. Field experiments were conducted to validate the performance of the PSIDS on 11–17 January 2018 in Jiaozhou Bay, China. (1) PSIDS could perform the functions of both multibeam sonar and sub-bottom profiler; (2) The synchronously and integrated measurement of various seabed information was achieved by alternately emitting multibeam echo-sounding and sub-bottom profiling signal using parametric source. The detection results proved the feasibility and practicability of PSIDS to achieve multiple seafloor characteristics. PSIDS provides a new idea for developing integrated seabed detection sonar. In terms of convenience and data fusion, it is a good option to use this equipment for integrated seabed detection.

A stochastic material point method is proposed for stochastic analysis in non-linear dynamics of metals with varying random material properties. The basic random variables are parameters of equation of state and those of constitutive equation. In conjunction with the material point method, the Taylor series expansion is employed to predict first- and second-moment characteristics of structural response. Unlike the traditional grid methods, the stochastic material point method does not require structured mesh; instead, only a scattered cluster of nodes is required in the computational domain. In addition, there is no need for fixed connectivity between nodes. Hence, the stochastic material point method is more suitable than the stochastic method based on grids, when solving dynamics problems of metals involving large deformations and strong nonlinearity. Numerical examples show good agreement between the results of the stochastic material point method and Monte Carlo simulation. This study examines the accuracy and convergence of the stochastic material point method. The stochastic material point method offers a new option when solving stochastic dynamics problems of metals involving large deformation and strong nonlinearity, since the method is convenient and efficient.

Launch safety of explosive charges has become an urgent problem to be solved by all countries in the world as launch situation of ammunition becomes consistently worse. However, the existing numerical models have different defects. This paper formulates an efficient computational model of the combustion of an explosive charge affected by a bottom gap in the launch environment in the context of the material point method. The current temperature is computed accurately from the heat balance equation, and different physical states of the explosive charges are considered through various equations of state. Microcracks in the explosive charges are described with respect to the viscoelastic statistical crack mechanics (Visco–SCRAM) model. The method for calculating the temperature at the bottom of the explosive charge with respect to the bottom gap is described. Based on this combustion model, the temperature history of a Composition B (COM B) explosive charge in the presence of a bottom gap is obtained during the launch process of a 155-mm artillery. The simulation results show that the bottom gap thickness should be no greater than 0.039 cm to ensure the safety of the COM B explosive charge in the launch environment. This conclusion is consistent with previous results and verifies the correctness of the proposed model. Ultimately, this paper derives a mathematical expression for the maximum temperature of the COM B explosive charge with respect to the bottom gap thickness (over the range of 0.00–0.039 cm), and establishes a quantitative evaluation method for the launch safety of explosive charges. The research results provide some guidance for the assessment and detection of explosive charge safety in complex launch environments. [ABSTRACT FROM AUTHOR]

Background: Hashimoto thyroiditis (HT) combined with papillary thyroid cancer (PTC) is more common in clinical practice, maybe posing a serious threat to the health of patients. It is uncertain whether HT is a risk factor or protective factor for PTC. The aim of the study was to retrospectively explore the effect of HT on the biological behavior of PTC. Methods: A total of 200 patients were included in the study. Among them, 100 patients with PTC without HT were in the control group (PTC group), and 100 cases diagnosed as PTC with HT were in the experimental group (HT + PTC group). The following data were counted and analyzed, respectively: (1) the basic clinicopathologic characteristics of patients; (2) postoperative thyroid function indicators; (3) blood biochemical indicators; (4) liver function indicators; and (5) histopathological report. Results: Compared with the PTC group, women were predominant in the PTC + HT group ( P

Hepatocellular carcinoma is one of the common malignant tumors of digestive tract, which seriously threatens the life of patients due to its high incidence rate, strong invasion, metastasis, and prognosis. At present, the main methods for preventing and treating HCC include medication, surgery, and intervention, but patients frequently encounter with specific adverse reactions or side effects. Many Traditional Chinese medicine can improve liver function, reduce liver cancer recurrence and have unique advantages in the treatment of HCC because of their acting mode of multi-target, multi-pathway, multi-component, and multi-level. Sesquiterpenoids, a class of natural products which are widely present in nature and exhibit good anti-tumor activity, and many of them possess good potential for the treatment of HCC. This article reviewed the anti-tumor activities, natural resources, pharmacological mechanism of natural sesquiterpenoids against HCC, providing the theoretical basis for the prevention and treatment of HCC and a comprehensive understanding of their potential for development of new clinical drugs.

BackgroundUterine Corpus Endometrial Carcinoma (UCEC) stands as one of the prevalent malignancies impacting women globally. Given its heterogeneous nature, personalized therapeutic approaches are increasingly significant for optimizing patient outcomes. This study investigated the prognostic potential of cellular senescence genes(CSGs) in UCEC, utilizing machine learning techniques integrated with large-scale genomic data.MethodsA comprehensive analysis was conducted using transcriptomic and clinical data from 579 endometrial cancer patients sourced from the Cancer Genome Atlas (TCGA). A subset of 503 CSGs was assessed through weighted gene co-expression network analysis (WGCNA) alongside machine learning algorithms, including Gaussian Mixture Model (GMM), support vector machine - recursive feature elimination (SVM-RFE), Random Forest, and eXtreme Gradient Boosting (XGBoost), to identify key differentially expressed cellular senescence genes. These genes underwent further analysis to construct a prognostic model.ResultsOur analysis revealed two distinct molecular clusters of UCEC with significant differences in tumor microenvironment and survival outcomes. Utilizing cellular senescence genes, a prognostic model effectively stratified patients into high-risk and low-risk categories. Patients in the high-risk group exhibited compromised overall survival and presented distinct molecular and immune profiles indicative of tumor progression. Crucially, the prognostic model demonstrated robust predictive performance and underwent validation in an independent patient cohort.ConclusionThe study emphasized the significance of cellular senescence genes in UCEC progression and underscored the efficacy of machine learning in developing reliable prognostic models. Our findings suggested that targeting cellular senescence holds promise as a strategy in personalized UCEC treatment, thus warranting further clinical investigation.

Pterocephin A is a natural triterpenoid saponin isolated from Pterocephalus hookeri, a traditional Tibetan medicine with slight toxicity, which can induce liver injury in rats. This study aimed to establish a sensitive and reliable UPLC-MS/MS method for exploring the toxicokinetics and tissue distribution of pterocephin A following single intravenous and intragastric administration. Pterocephin A and prosapogenin 1C (internal standard, IS) were extracted using a simple protein precipitation technique with methanol as the precipitant for plasma samples and methanol/acetonitrile = 1:1 (v/v) for tissue samples. UPLC separation was achieved by gradient elution with 0.3 mL/min and a mobile phase consisting of 5 mM ammonium formate (A) and acetonitrile (B) (0–2 min 30% B; 2–4 min: 30–80% B; 4–5 min: 80–98% B; 5–6.5 min: 98% B; 6.5–7 min: 98–30% B; and 7–8 min: 30% B, v/v) with a column temperature of 35 °C. MS spectrometry adopted negative ion scanning mode, primary MS spectrometry adopted full scan monitoring mode, and secondary MS spectrometry adopted targeted MS2 scan monitoring mode. The assay exhibited a linear dynamic range of 0.02–15 μg/mL for pterocephin A in biological samples, with the low limit of quantification set at 0.02 μg/mL. Non-compartmental toxicokinetic parameters indicated that pterocephin A was well absorbed into the systemic circulation and had a long residual time after intravenous (10 mg/kg) and intragastric (60 mg/kg) administration, as it could still be detected after 72 h. Tissue distribution analysis revealed detectable levels of pterocephin A in various tissues, and a high concentration was maintained in the liver after intravenous (10 mg/kg) administration, with the highest concentration being 610.95 ± 25.73 ng/mL and a specific distribution pattern of liver > lung > kidney > intestine > spleen > testes > heart > stomach. The toxicokinetic process and tissue distribution characteristics of pterocephin A were expounded in this study, which can provide relevant data support for further research and clinical application of pterocephin A with its slight toxicity.

Abstract The aim of the study was to investigated the mechanism of Strychnos nux-vomica L. (Semen Strychni, SS) against papillary carcinoma thyroid (PTC) by combined of network pharmacology and experimental verification. By searching the TCMSP, SEA and SwissTarget Prediction database, the main active ingredients and related targets were obtained. Utilizing Venny 2.1.0 String database and Cytoscape 3.7.2 to screened the intersection target and constructed protein–protein interaction (PPI) network diagram. Using R 4.0.4 software carried out the enrichment analysis of GO and KEGG. HPLC was carried out using LC-20A modular HPLC system to identify the bioactive compound brucine present in SS. Molecular docking was performed using Discovery 2019 software. The inhibition rate was detected by CCK8 method. Western blot was used to detect the expression levels of brucine anti-PTC related pathway proteins. 14 active components were screened out, of which 4 main components showed tight relationship with PTC. SS may play the anti-PTC role by acting on two main pathways (TNF signaling pathway and MAPK signaling pathway) and mediating various biological functions. HPLC analysis revealed that brucine was a suitable marker for standardization of the SS. 4 active components exhibit strong binding energy with core protein. Brucine could significantly reduce the activity of BCPAP cells compared with isobrucine, stigmasterol, (+)-catechin. Brucine may reduce the protein expression levels of IL-6, VEGFA, JUN, TP53, 1L1B, PTGS2, BCL2, CASP3, CASP8, and CASP9 while increase the protein expression levels of BAD, cleaved-CASP3, cleaved-CASP8, and cleaved-CASP9 in BCPAP cells, respectively. The active components of SS against PTC mainly include isobrucine, stigmasterol, (+)-catechin, brucine. Among them, brucine exhibits the strongest anti-PTC activity in BCPAP cells, which may reduce the PTC-related protein expression levels. Therefore, SS may exhibits the anti-PTC activities through multiple targets and pathways.

The shale gas well station plays a critical role in the extraction of shale gas, and its safety status exerts significant influence not only on shale gas production but also on the ecological balance of the surrounding environment. To investigate the response characteristics of the shale gas well station under the impact of tailings dam failure debris flow, a comprehensive analysis was conducted using a combination of physical modeling and numerical simulation. The analysis focused on the dynamic inundation process and the impact siltation law caused by the downstream flow of tailings dam failure debris at the shale gas well station. The depth of inundation and the extent of siltation damage were employed as key parameters for characterization. Experimental findings revealed that the downstream mudflow inundation process could be divided into three distinct stages: rapid increase (0–60 s), steady increase (60–106 s), and slow advance (106–250 s). The pattern of mudflow siltation height variation at the well station exhibited an initial rise, followed by a subsequent decline and eventual stabilization. The highest siltation volumes recorded at measurement points A to D were 4.4, 4, 5.2, and 6 m, respectively. Additionally, by employing computational fluid dynamics, numerical calculations were performed under unprotected conditions, with the error between the calculated conclusions and the test results not exceeding 15%. Furthermore, the blocking effect of 8 and 16 m debris flow blocking dam on the debris flow was thoroughly investigated. The study demonstrated that the check dam with a height of 16 m yielded the most effective blockage, resulting in the highest sediment siltation height of 0.4 m. The research results provide some reference for the prevention and control of debris flow disasters.

Background Prosthetic-joint infection (PJI) is one of the severest complications after arthroplasty. However, antibiotics are not effective in the bacteria in biofilm outside the prosthetic-joint. Antimicrobial peptides have an efficient antimicrobial activity in staphylococcus aureus compared with conventional antibiotics. Methods Bone marrow stem cells (BMSCs) were isolated, cultured and transfected with cathelicidins antimicrobial peptides proline-arginine-rich 39 amino acid peptide (PR-39) lentivirus. The expression of PR-39 gene in BMSCs was detected by RT-PCR, and the antibacterial activity of PR-39 was measured by agar diffusion method. The transfection efficiency was detected by fluorescence microscopy. The infection model of artificial knee joint in rabbits were established. Kirschner wire was used as the knee joint implant to implant the distal femur through the femoral intercondylar fossa of rabbits. 24 rabbits were randomly divided into 2 groups for the above operations: group A was inoculated 0.5 mL into the joint cavity immediately after the incision was sutured 1 × 10 7 Staphylococcus aureus of colony forming unit (CFU), group B was inoculated with Staphylococcus aureus and PR-39. After operation, the wound conditions and histological changes were observed by X-ray and optical microscope respectively, CRP and erythrocyte sedimentation rate were measured by test assay. Results The transfection efficiency of lentivirus vectortransfected BMSCs was 74.09%. The supernatant of lentivirus vector had obvious inhibitory effect on Staphylococcus aureus , and the antibacterial rate was 98.43%. 100% infection observed in group A while few infection observed in group B; serum CRP and ESR at a high level in group A while decreased in group B after operation. There were no significant difference in CRP and ESR between the pLV/PR-39 group and pLV/EGFP group at day 1 and 3 respectively after surgery. However, CRP and ESR in the pLV/PR-39 groupwere significantly lower than the pLV/EGFP group at day 7 and 14 respectively after operation. Conclusions Rabbits planted BMSCs expressing PR-39 were significantly increased resistance to Staphylococcus aureus in PJI than control group thus showing great potential for preventing implant-associated infection. It will provide a potential new therapeutic agent for implant-associated infection.