Controllable concentric electric field line distribution for simultaneous separation of DNA.

An approach for the controllable separation and concentration of nucleic acid using a circular nonuniform electric field was proposed and developed. Using six different lengths of DNA molecules as standard samples, the distribution of the gradient electric field was increased from the outer circular electrode to the inner rod-shaped electrode, contributing to the migration of DNA molecules at a velocity gradient towards the region with the strongest inner electric field. The DNA molecules were arranged in a distribution of concentric circles that aligned with the distribution of concentric equipotential lines. The concentration of DNA multiplied with the alternation of radius. As a result, this platform allowed simultaneous DNA separation, achieving a resolution range of 1.17-3.03 through an extended electrophoresis time, resulting in enhanced concentration factors of 1.08-6.27. Moreover, the manipulation of the relative height of the inner and outer electrodes enabled precise control over the distribution and the deflection degree of electric field lines, leading to accurate control over DNA deflection.

Causal association between obstructive sleep apnea and amyotrophic lateral sclerosis: a Mendelian randomization study.

Background: Obstructive sleep apnea (OSA) had a high prevalence in the population. Whether OSA increases the risk of amyotrophic lateral sclerosis (ALS) is unknown. Our aim was to clarify this issue using two-sample Mendelian randomization (MR) analysis in a large cohort. Methods: Two-sample MR was used to evaluate the potential causality between OSA and ALS by selecting single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method was chosen as the primary method to estimate causal association. Weighted median, weighted mode and simple mode methods were used as sensitivity analyses to ensure the robustness of the results. Results: In MR analysis, IVW mode showed genetic liability to OSA was found to be significantly associated with a higher ALS risk (OR, 1.220; 95% confidence interval, 1.031-1.443; p = 0.021). No evidence of heterogeneity and horizontal pleiotropy were suggested. Conclusion: We found potential evidence for a causal effect of OSA on an increased risk of ALS.

A Case of Clonorchiasis in a Non-endemic Region of China.

Clonorchiasis, an important foodborne parasitic disease, is prevalent in several Asian countries. In China, the three provinces with the highest incidence are Guangdong, Guangxi, and Heilongjiang, with no reported cases in Qingdao for nearly a decade. In this study, a 29-year-old male patient was diagnosed with fatty liver due to abnormal liver function during physical examination and was admitted to the hospital multiple times for examination and treatment within 3 years, but his liver function did not improve. Eventually, clonorchis eggs were found in the stool, confirming the diagnosis of clonorchiasis. The purpose of this report is to enhance the understanding of clonorchiasis among clinicians in no-prevalence areas, to familiarize laboratory technicians with egg identification, to strengthen parasite-knowledge training, and to reduce missed and misdiagnosed cases.

Prognostic relevance of global work index and global constructive work in patients with non-ischemic dilated cardiomyopathy.

Myocardial work (MW) derived from pressure-strain loops is a novel non-invasive tool to assess left ventricular (LV) function, incorporating global longitudinal strain (GLS) by speckle tracking echocardiography and non-invasively assessed blood pressure. Studies on the role of MW in dilated cardiomyopathy (DCM) are still limited. Therefore, the aim of this study was to evaluate the potential value of MW for predicting adverse outcomes in patients with DCM. 116 consecutive patients with DCM who underwent heart catheterization were retrospectively recruited from June 2009 to July 2014. 34 patients (30%) met the composite endpoints for major adverse cardiac events (MACE) of cardiac transplantation, need for implantable cardioverter-defibrillator (ICD) therapy, heart failure hospitalization and all-cause mortality. Patients with DCM were followed up for a mean of 5.1 years (IQR: 2.2-9.1 years). Global work index (GWI) and global constructive work (GCW) were not only independent predictors but also provided incremental predictive values (Integrated discrimination improvement [IDI] > 0) of MACE in multivariate Cox models. Furthermore, Patients with GWI < 788 mm Hg% (HR 5.46, 95%CI 1.66-17.92, p = 0.005) and GCW < 1,238 mm Hg% (HR 4.46, 95%CI 1.53-12.98, p = 0.006) had higher risks of MACE. GWI and GCW assessed by strain imaging echocardiography may have an additional value beyond LV-EF and GLS for predicting adverse outcomes in DCM.

Establishment of a novel efferocytosis potential index predicts prognosis and immunotherapy response in cancers.

The biological function and prognostic value of efferocytosis in cancer remains unclear. In this study, we systematically analysed the expression profiles and genetic variations of 50 efferocytosis-related regulator genes in 33 cancer types. Using data from The Cancer Genome Atlas, we established an efferocytosis potential index (EPI) model to represent the efferocytosis level in each cancer type. The relationship between the EPI and prognosis, immune-related molecules, specific pathways, and drug sensitivity was determined. We found that efferocytosis regulator genes were abnormally expressed in cancer tissue, perhaps owing to copy number variations, gene alterations, and DNA methylation. For the most part, the EPI was higher in tumour vs. normal tissues. In most of the 33 cancer types, it positively correlated with cell death- and immune-related pathway enrichment, the tumour microenvironment, immune infiltration, and drug sensitivity. For specific cancers, a high EPI may be a prognostic risk factor and, in patients treated receiving immune checkpoint therapy, a predictor of poor prognosis. Our study reveals the biological functions of efferocytosis-related regulator genes in distinct cancers and highlights the potential of efferocytosis intervention in cancer therapy.

Distribution and Severity of Cervical Intraepithelial Neoplasia in Women With Different Human Papillomavirus: An Analysis From Liaoning Province of Northeastern China.

OBJECTIVE: Persistent infection with high-risk human papillomavirus (HPV) is a key contributor to cervical intraepithelial neoplasia (CIN), but the relation between high-risk HPV genotypes and the location of CIN lesions remains unclear. The aims of this study were to investigate the most frequent biopsy site of CIN lesions in women with different HPV infection and to analyze the biopsy times, CIN frequency, and the clustering of CIN frequency based on 12-o'clock sites and cervical quadrant locations. MATERIALS AND METHOD: We conducted a retrospective study of HPV detection and genotyping at the virology department of our hospital. Colposcopy exams were performed by specialists according to a standardized protocol, and all visually abnormal areas were further biopsied. Pearson chi-squared tests and cluster analyses were implemented to analyze the data. RESULTS: Among 1,381 women enrolled in this study, 933 cases infected with HPV. HPV16, HPV58, and HPV18 were the most common genotypes. The most frequent biopsy site was the 6 o'clock position. The highest frequency of high-grade CIN findings in single-genotype HPV groups was the 6 o'clock position and that for multiple-genotype HPV group was the 12 o'clock location. All CIN clusters were found in the 6 and 12 o'clock biopsy sites, except in the HPV18 group. Quadrant 2 and 4 were clustered in most groups. CONCLUSIONS: The 6 and 12 o'clock sites in cervical quadrant 2 and 4 should be targeted during cervical biopsy procedures. These findings can provide clinicians with specific recommendations on the optimal site for CIN biopsy when considering the HPV genotype.

Population pharmacokinetics of adebrelimab - Support of alternative flat dose regimen in extensive-stage small-cell lung cancer.

Adebrelimab, a novel anti-PD-L1 antibody, has been approved by the National Medical Products Administration of China as an intravenous infusion for use in combination with carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer in 2023. A two-compartment model with empirical time-varying CL for adebrelimab was established based on data from 263 patients receiving body weight-based doses from two clinical studies. Significant covariate effects of baseline body weight, albumin levels, tumor size, neutrophil counts, and presence of anti-drug antibodies were identified on CL of debrelimab, none of which were clinically significant or warranted dose adjustment. The degree of decrease in CL was higher in patients who responded to treatment with adebrelimab than in non-responders. Adebrelimab exposures (AUC, Ctrough, or Cmax) were not identified as a statistically significant factor related to efficacy or safety endpoint in the exposure-response analysis. Distribution of simulated exposure metrics from the flat dose regimen (1200 mg q3w) was similar to the marketed weight-based dosing regimen (20 mg/kg q3w), supporting the alternative flat dose regimen in the clinic.

DNAJC24 acts directly with PCNA and promotes malignant progression of LUAD by activating phosphorylation of AKT.

Heat shock proteins (HSPs) are a group of highly conserved proteins found in a wide range of organisms. In recent years, members of the HSP family were overexpressed in various tumors and widely involved in oncogenesis, tumor development, and therapeutic resistance. In our previous study, DNAJC24, a member of the DNAJ/HSP40 family of HSPs, was found to be closely associated with the malignant phenotype of hepatocellular carcinoma. However, its relationship with other malignancies needs to be further explored. Herein, we demonstrated that DNAJC24 exhibited upregulated expression in LUAD tissue samples and predicted poor survival in LUAD patients. The upregulation of DNAJC24 expression promoted proliferation and invasion of LUAD cells in A549 and NCI-H1299 cell lines. Further studies revealed that DNAJC24 could regulate the PI3K/AKT signaling pathway by affecting AKT phosphorylation. In addition, a series of experiments such as Co-IP and mass spectrometry confirmed that DNAJC24 could directly interact with PCNA and promoted the malignant phenotypic transformation of LUAD. In conclusion, our results suggested that DNAJC24 played an important role in the progression of LUAD and may serve as a specific prognostic biomarker for LUAD patients. The DNAJC24/PCNA/AKT axis may be a potential target for future individualized and precise treatment of LUAD patients.

Nicotine promotes Staphylococcus aureus-induced osteomyelitis by activating the Nrf2/Slc7a11 signaling axis.

Although smoking is a significant risk factor for osteomyelitis, there is limited experimental evidence that nicotine, a key tobacco constituent, is associated with this condition, leaving its mechanistic implications uncharacterized. This study revealed that nicotine promotes Staphylococcus aureus-induced osteomyelitis by increasing Nrf2 and Slc7a11 expression in vivo and in vitro. Inhibition of Slc7a11 using Erastin augmented bacterial phagocytosis/killing capabilities and fortified antimicrobial responses in an osteomyelitis model. Moreover, untargeted metabolomic analysis demonstrated that Erastin mitigated the effects of nicotine on S. aureus-induced osteomyelitis by altering glutamate/glutathione metabolism. These findings suggest that nicotine aggravates S. aureus-induced osteomyelitis by activating the Nrf2/Slc7a11 signaling pathway and that Slc7a11 inhibition can counteract the detrimental health effects of nicotine.

CCCTC-binding factor suppresses alpha-2-macroglobulin transcription to improve vascular endothelial cell functions in lower extremity arteriosclerosis obliterans.

Vascular endothelial cell functions affect lower extremity arteriosclerosis obliterans (LEASO), while alpha-2-macroglobulin (A2M) and CCCTC-binding factor (CTCF) are closely related to the function of such cells. This paper aims to identify the influences of CTCF on vascular endothelial cells in LEASO by regulating A2M. A rat model of LEASO was established to measure intima-media ratio, blood lipid, and inflammatory factor levels. By constructing LEASO cell models, cell viability and apoptosis were assayed, while autophagy-related proteins, CTCF and A2M levels in femoral artery tissues and HUVECs were determined. The transcriptional regulation of CTCF on A2M was verified. In LEASO rat models, femoral artery lumen was narrowed and endothelial cells were disordered; levels of total cholesterol, IL-1, and TNF-α enhanced, and HDL-C decreased, with strong expression of A2M and low expression of CTCF. The viability of ox-LDL-treated HUVECs was decreased, together with higher apoptosis, lower LC3II/I expression, and higher p62 expression, which were reversed by sh-A2M transfection. Overexpression of CTCF inhibited A2M transcription, promoted the viability and autophagy of HUVECs, and decreased apoptosis. Collectively, CTCF improves the function of vascular endothelial cells in LEASO by inhibiting A2M transcription.

Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.

Entrectinib as first-line vs. second-line therapy in ROS1 fusion-positive non-small cell lung cancer: a cost-effectiveness analysis.

Background: The concept of cost-effectiveness is crucial for the optimal allocation of scarce healthcare resources. However, the cost-effectiveness of entrectinib in ROS1 fusion-positive non-small cell lung cancer (NSCLC) has not been evaluated. We aim to evaluate the cost-effectiveness of entrectinib as a first-line treatment compared to its reservation for second-line therapy or the exclusive use of chemotherapy in ROS1 fusion-positive advanced NSCLC. Methods: A Markov model was created to assess the clinical outcomes and healthcare costs associated with these three treatment approaches. Cost and utility values were obtained from established literature and cost databases. To test model robustness, probabilistic and univariate sensitivity analyses were conducted. Results: In the first-line setting, where entrectinib was administered as the initial therapy, it yielded an extra 0.07 quality-adjusted life years (QALYs) at an incremental cost of $73,453, leading to an incremental cost-effectiveness ratio (ICER) of $1,090,594.30 per QALY compared to chemotherapy. Conversely, in the second-line setting, when entrectinib was used as a second-line therapy following chemotherapy, it provided an extra 0.11 QALYs at an incremental cost of $53,480, resulting in an ICER of $494,290.39 per QALY compared to chemotherapy. Furthermore, the analysis revealed that the cost of entrectinib and utility values of progressed disease were the most influential factors for the ICER. Conclusions: Considering the current pricing of entrectinib, it is not deemed cost-effective as a first-line or second-line therapy for patients with ROS1 fusion-positive advanced NSCLC when compared to chemotherapy. Alternatively, reserving entrectinib exclusively for second-line therapy might strike a balance between healthcare expenditures and patient outcomes.

Tumour-reactive plasma cells in antitumour immunity: current insights and future prospects.

Tumour-reactive plasma cells (TRPCs) have been reported to be positively associated with the long-term survival of patients with various cancers. However, unlike tumour-specific antigen (TSA)-induced T cells which have precise effects against tumours, plasma cells require TSA to obtain specific responses. Therefore, the search for a TSA suitable for B-cell recognition is urgent. In this review, we discuss the functions of tumour-reactive plasma cells. Further, this review also explores the concept of screening for neoantigen-reactive plasma cells, drawing inspiration from T-cell screening methods. While challenges exist, such as epitope prediction and efficient screening, the development of novel techniques may lead to the discovery of highly specific plasma cells for adoptive cell therapy. In conclusion, tumour-reactive plasma cells are emerging as powerful players in cancer immunotherapy. Their ability to produce antibodies against a variety of antigens, especially neoantigens, opens new avenues for personalised treatments. Overcoming challenges in epitope prediction and screening will be crucial in harnessing the full potential of these plasma cells for the benefit of cancer patients.

Research on prediction of coal water medium separation effect based on multi-models.

To improve the separation efficiency of raw coal and ensure clean use, the accurate calculation of the partition coefficients (PCs) in coal water medium sorting is required. Single models have been used to predict the partition coefficient (PC) for decades, but their accuracy remains constrained. This study proposes a multi-model (MM) calculation method based on the Gompertz model (GM), the Logistic model (LM), the Arctangent model (AM), and the Approximate formula (AFM) to improve the accuracy of the predicted coal water medium sorting PCs. Four groups of coal samples and two specific cases were used to verify the accuracy of the MM calculation method. The PCs of the MM method had a minimal Ef (0.91-8.84), a maximal R2 (0.9648-0.9994), a maximal F-value (199.17-11352.31), and the highest significance of all the models. The MM method was found to be the most suitable of all the models for predicting any coal water medium separation process. Further, when calculating the PC for cleaned coal ash, the separation density of MM is closer to the actual separation density than that of either the GM, LM, AM, or AFM models. The MM method, therefore, produces more accurate results compared to a single model. MM is expected to predict the PC based on the required cleaned coal ash, and then regulate the sorting density to improve the production efficiency.

The Laparoscopic Right-lower Quadrant Approach for the Treatment of Right-sided Colon Cancer Offers Advantages Such as Shorter Surgical Time and Less Blood Loss.

Objective: This study aims to compare the therapeutic efficacy of laparoscopic right-lower quadrant and midline approaches for the treatment of right-sided colon cancer and evaluate the analgesic effect of parecoxib sodium. Methods: Sixty patients with right-sided colon cancer admitted to Hospital of Lin 'an District between January 2019 and November 2022 were selected. They were divided into the study group A (n=30) with a right-lower quadrant approach and the study group B (n=30) with a midline approach. All patients received parecoxib sodium. Surgical time, blood loss, postoperative complications, and other relevant indicators were recorded and compared between the two groups. Additionally, a control group of 60 right-sided colon cancer patients who underwent conventional non-exclusive analgesic laparoscopic surgery during the same period was included to compare the analgesic effects between the study and control groups. Results: The surgical time (RR = 0.608, 95%CI 0.51, 1.53, P = .042), blood loss (RR = 0.798, 95%CI 0.52, 1.02, P < .001), time for bowel function recovery (RR = 0.808, 95%CI 0.50, 1.77, P = .007), and length of hospital stay (RR = 0.766, 95%CI 0.56, 1.72, P =.052) were significantly lower in group A than in group B, while the number of lymph node dissections was higher in group A (RR = 0.803, 95%CI 0.62, 1.52, P = .047). The postoperative levels of tumor-specific growth factor (TSGF) (RR = 0.710, 95%CI 0.50, 1.55, P < .001) and carcinoembryonic antigen (CEA) (RR = 0.803, 95%CI 0.62, 1.52, P < .001) were significantly decreased in both groups A and B, with no significant difference between the groups (P > .05). The incidence of complications in group A was significantly lower than in group B (RR = 0.167, 95%CI 0.17, 0.63, P = .044). The VAS scores of the study group at 2/4/6/8 hours postoperatively were significantly lower than those of the control group (RR = 0.702, 95%CI 0.52, 1.62, P < .001). The SF-36 scores of the study group were significantly higher than those of the control group (RR = 0.753, 95%CI 0.56, 1.82, P < .001). Conclusions: The Laparoscopic right-lower quadrant approach for the treatment of right-sided colon cancer offers advantages such as shorter surgical time and less blood loss. It demonstrates significant clinical efficacy and reduces the incidence of postoperative complications. Parecoxib sodium enhances postoperative analgesic effect, effectively alleviating patient pain, promoting recovery, and improving quality of life. It is worth promoting in clinical practice.

Superionic fluoride gate dielectrics with low diffusion barrier for two-dimensional electronics.

Exploration of new dielectrics with a large capacitive coupling is an essential topic in modern electronics when conventional dielectrics suffer from the leakage issue near the breakdown limit. Here, to address this looming challenge, we demonstrate that rare-earth metal fluorides with extremely low ion migration barriers can generally exhibit an excellent capacitive coupling over 20 µF cm-2 (with an equivalent oxide thickness of ~0.15 nm and a large effective dielectric constant near 30) and great compatibility with scalable device manufacturing processes. Such a static dielectric capability of superionic fluorides is exemplified by MoS2 transistors exhibiting high on/off current ratios over 108, ultralow subthreshold swing of 65 mV dec-1 and ultralow leakage current density of ~10-6 A cm-2. Therefore, the fluoride-gated logic inverters can achieve notably higher static voltage gain values (surpassing ~167) compared with a conventional dielectric. Furthermore, the application of fluoride gating enables the demonstration of NAND, NOR, AND and OR logic circuits with low static energy consumption. In particular, the superconductor-insulator transition at the clean-limit Bi2Sr2CaCu2O8+δ can also be realized through fluoride gating. Our findings highlight fluoride dielectrics as a pioneering platform for advanced electronic applications and for tailoring emergent electronic states in condensed matter.

The effect of age on cerebral vasospasm and delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: The association between patient age and cerebral arterial vasospasm (CVS) and delayed cerebral ischemia (DCI) risk following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. This study aims to assess the role of age on aSAH-related complications. METHODS: Single-center retrospective study comprising aSAH patients treated between January 2009 and March 2023. Age was analyzed as continuous and categorical variables (<60yrs vs. ≥60yrs and by decade). Outcomes of interest included radiographic CVS, DCI, cerebral infarction, in-hospital mortality, length-of-stay, ventriculoperitoneal shunt placement, and modified Rankin Scale (mRS) scores at discharge and 3-month follow-up. RESULTS: 925 aSAH patients were included. Most (n=598; 64.6%) were <60yrs old (46±9.1yrs). CVS likelihood was lower in the older cohort (aOR=0.56 [0.38-0.82]). Patients ≥60yrs had higher mortality rates (aOR=2.24 [1.12-4.47]) and worse mRS scores at discharge (aOR=2.66 [1.91-3.72]) and 3-month follow-up (aOR=2.19 [1.44-3.32]). Advanced age did not have a significant effect on DCI or cerebral infarction risk. Higher in-hospital mortality was documented with increasing age (p<0.001). A significant interaction between CVS and age for the outcome of DCI was documented, with a stronger positive effect on poor outcomes (i.e., higher odds of DCI) among patients aged <60 years compared to those aged ≥60. CONCLUSION: There is an inverse relationship between patient age and CVS incidence following aSAH. Nonetheless, patients ≥60yrs had comparable DCI rates, higher in-hospital mortality, and worse functional outcomes than their younger counterparts. Routine screening and reliance on radiographic CVS as primary marker for aSAH-related complications should be reconsidered, particularly in older patients.

Brevilin A Inhibits Prostate Cancer Progression by Decreasing PAX5-Activated SOX4.

Brevilin A possesses inhibitory effects on the development of prostate cancer (PCa); however, the underlying mechanism remains unclear. The present work aims to analyze how Brevilin A regulates PCa cell malignancy. RNA expression of paired box 5 (PAX5) and SRY-box transcription factor 4 (SOX4) was analyzed by quantitative real-time polymerase chain reaction. Protein expression of PAX5, SOX4, and nuclear proliferation marker (Ki67) was detected by western blotting or immunohistochemistry assay. The viability, proliferation, apoptosis, and migratory and invasive abilities of PCa cells were investigated by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays, respectively. The association between PAX5 and SOX4 was identified by dual-luciferase reporter assay and chromatin immunoprecipitation assay. Xenograft mouse model assay was used to reveal the effect of Brevilin A on tumor tumorigenesis in vivo. PAX5 and SOX4 expression were upregulated in PCa tissues and cells relative to normal prostate tissues and human prostate epithelial cells. Brevilin A treatment inhibited PAX5 protein expression in PCa cells. Additionally, Brevilin A inhibited proliferation, migration and invasion and induced apoptosis of PCa cells, whereas these effects were attenuated after PAX5 overexpression. SOX4 was transcriptionally activated by PAX5, and its introduction partially relieved the inhibitory effects of PAX5 knockdown on PCa cell malignancy. Moreover, Brevilin A delayed tumor formation in vivo. Brevilin A inhibited PCa progression by regulating SOX4 expression in a PAX5-dependent manner, providing a promising anti-tumor drug for PCa.