Pollutants-mediated viral hepatitis in different types: assessment of different algorithms and time series models.

The escalating frequency of environmental pollution incidents has raised significant concerns regarding the potential health impacts of pollutant fluctuations. Consequently, a comprehensive study on the role of pollutants in the prevalence of viral hepatitis is indispensable for the advancement of innovative prevention strategies. Monthly incidence rates of viral hepatitis from 2005 to 2020 were sourced from the Chinese Center for Disease Control and Prevention Infectious Disease Surveillance Information System. Pollution data spanning 2014-2020 were obtained from the National Oceanic and Atmospheric Administration (NOAA), encompassing pollutants such as CO, NO2, and O3. Time series analysis models, including seasonal auto-regressive integrated moving average (SARIMA), Holt-Winters model, and Generalized Additive Model (GAM), were employed to explore prediction and synergistic effects related to viral hepatitis. Spearman correlation analysis was utilized to identify pollutants suitable for inclusion in these models. Concurrently, machine learning (ML) algorithms were leveraged to refine the prediction of environmental pollutant levels. Finally, a weighted quantile sum (WQS) regression framework was developed to evaluate the singular and combined impacts of pollutants on viral hepatitis cases across different demographics, age groups, and environmental strata. The incidence of viral hepatitis in Beijing exhibited a declining trend, primarily characterized by HBV and HCV types. In predicting hepatitis prevalence trends, the Holt-Winters additive seasonal model outperformed the SARIMA multiplicative model ((1,1,0) (2,1,0) [12]). In the prediction of environmental pollutants, the SVM model demonstrated superior performance over the GPR model, particularly with Polynomial and Besseldot kernel functions. The combined pollutant risk effect on viral hepatitis was quantified as ßWQS (95% CI) = 0.066 (0.018, 0.114). Among different groups, PM2.5 emerged as the most sensitive risk factor, notably impacting patients with HCV and HEV, as well as individuals aged 35-64. CO predominantly affected HAV patients, showing a risk effect of ßWQS (95% CI) = - 0.0355 (- 0.0695, - 0.0016). Lower levels of PM2.5 and PM10 were associated with heightened risk of viral hepatitis incidence with a lag of five months, whereas elevated levels of PM2.5 (100-120 µg/m3) and CO correlated with increased hepatitis incidence risk with a lag of six months. The Holt-Winters model outperformed the SARIMA model in predicting the incidence of viral hepatitis. Among machine learning algorithms, SVM and GPR models demonstrated superior performance for analyzing pollutant data. Patients infected with HAV and HEV were primarily influenced by PM10 and CO, whereas SO2 and PM2.5 significantly impacted others. Individuals aged 35-64 years appeared particularly susceptible to these pollutants. Mixed pollutant exposures were found to affect the development of viral hepatitis with a notable lag of 5-6 months. These findings underscore the importance of long-term monitoring of pollutants in relation to viral hepatitis incidence.

Profound primary prevention of liver cancer following a natural experiment in China: A 50-year perspective and public health implications.

Liver cancer causes upwards of 1 million cancer deaths annually and is projected to rise by at least 55% over the next 15 years. Two of the major risk factors contributing to liver cancer have been well documented by multiple epidemiologic studies and the hepatitis B virus (HBV) and aflatoxin show a synergy that increases by more than 8-fold the risk of liver cancer relative to HBV alone. Using the population-based cancer registry established by the Qidong Liver Cancer Institute in 1972 and aflatoxin-specific biomarkers, we document that reduction of aflatoxin exposure has likely contributed to a nearly 70% decline in age-standardized liver cancer incidence over the past 30 years despite an unchanging prevalence of HBV infection in cases. A natural experiment of economic reform in the 1980s drove a rapid switch from consumption of heavily contaminated corn to minimally, if any, contaminated rice and subsequent dietary diversity. Aflatoxin consumption appears to accelerate the time to liver cancer diagnosis; lowering exposure to this carcinogen adds years of life before a cancer diagnosis. Thus, in 1990 the median age of diagnosis was 48 years, while increasing to 67 years by 2021. These findings have important translational public health implications since up to 5 billion people worldwide might be routinely exposed to dietary aflatoxin, especially in societies using corn as the staple food. Interventions against aflatoxin are an achievable outcome leading to a reduction in liver cancer incidence and years of delay of its nearly always fatal diagnosis.

Comparison of Autolumo A2000 Plus and Architect i2000 for detection of hepatitis B virus serological markers.

Serological detection of hepatitis B virus markers plays a vital role in the diagnosis, treatment, prognosis, and therapeutic surveillance of hepatitis B. To compare the diagnostic performance of Autolumo A2000Plus and Abbott Architect i2000 systems in the detection of hepatitis B infection markers. A total of 6 HBV seroconversion panels and 743 participants were enrolled in this study, including 383 HBV-infected patients and 360 healthy adults. Clinical diagnostic information, laboratory results, and HBV genotyping were collected to evaluate the diagnostic performance of the A2000Plus and i2000 systems in detecting HBV infection markers. The results showed that the total percent agreement of HBV markers was all >90 % in both detection systems among the six seroconversion panels and 743 serum samples from the population. The χ2 values of the Chi-square test among hepatitis B virus serological markers in both analyzers were between 550.7 and 743.0, p < 0.0001. HBV marker consistency test results show perfect consistency between the two analyzers, with Kappa values ranging from 0.854 to 1.000. For specific samples, including Hepatitis B patients with Genotype C, chronic hepatitis B, hepatitis B-related cirrhosis, and hepatocellular carcinoma, spearman correlation analysis showed HBsAg correlation coefficients ranging from 0.8532 to 0.9745, p < 0.001 in both analyzers. In conclusion, Autolumo A2000Plus diagnostic performance in consistency and correlation is comparable to Abbott Architect i2000 when detecting markers of hepatitis B infection. The Autolumo A2000Plus system can be used as a reliable instrument for HBV marker detection.

The RING-Type E3 Ubiquitin Ligase Gene GhDIRP1 Negatively Regulates Verticillium dahliae Resistance in Cotton (Gossypium hirsutum).

Cotton is one of the world's most important economic crops. Verticillium wilt is a devastating cotton disease caused by Verticillium dahliae, significantly impacting cotton yield and quality. E3 ubiquitin ligases are essential components of the ubiquitin-mediated 26S proteasome system, responsible for recognizing ubiquitinated target proteins and promoting their degradation, which play a crucial regulatory role in plant immune responses. In this study, on the basis of the confirmation of differential expression of GhDIRP1, a RING-type E3 ubiquitin ligase encoding gene, in two cotton varieties resistant (Zhongzhimian 2) or susceptible (Jimian 11) to V. dahliae, we demonstrated that GhDIRP1 is a negative regulator of V. dahliae resistance because silencing GhDIRP1 in cotton and heterogeneously overexpressing the gene in Arabidopsis enhanced and compromised resistance to V. dahliae, respectively. The GhDIRP1-mediated immune response seemed to be realized through multiple physiological pathways, including hormone signaling, reactive oxygen species, and lignin biosynthesis. Based on the sequences of GhDIRP1 isolated from Zhongzhimian 2 and Jimian 11, we found that GhDIRP1 had identical coding but different promoter sequences in the two varieties, with the promoter of Zhongzhimian 2 being more active than that of Jimian 11 because the former drove a stronger expression of GUS and LUC reporter genes. The results link the ubiquitination pathway to multiple physiological pathways acting in the cotton immune response and provide a candidate gene for breeding cotton varieties resistant to V. dahliae.

Causal role of immune cells in thyroid cancer: a bidirectional Mendelian randomization study.

Background: The immune system plays an important role in the development and treatment of thyroid cancer(THCA).However, the correlation between immune cells and THCA has not been systematically studied. Methods: This study used a two-sample Mendelian randomization (MR) study to determine the causal relationship between immune cell characteristics and THCA. Based on a large sample of publicly available genetic data, we explored the causal relationship between 731 immune cell characteristics and THCA risk. The 731 immunophenotypes were divided into 7 groups, including B cell panel(n=190),cDC panel(n=64),Maturation stages of T cell panel(n=79),Monocyte panel(n=43),Myeloid cell panel(n=64),TBNK panel(n=124),and Treg panel(n=167). The sensitivity of the results was analyzed, and heterogeneity and horizontal pleiotropy were excluded. Results: After FDR correction, the effect of immunophenotype on THCA was not statistically significant. It is worth mentioning, however, that there are some unadjusted low P-values phenotypes. The odds ratio (OR) of CD62L on monocyte on THCA risk was estimated to be 0.953 (95% CI=0.930~0.976, P=1.005×10-4),and which was estimated to be 0.975(95% CI=0.961-0.989, P=7.984×10-4) for Resting Treg%CD4 on THCA risk. Furthermore, THCA was associated with a reduced risk of 5 immunophenotype:CD25 on CD39+ CD4 on Treg (OR=0.871, 95% CI=0.812~0.935, P=1.274×10-4), activated Treg AC (OR=0.884, 95% CI=0.820~0.953, P=0.001), activated & resting Treg % CD4 Treg (OR=0.872, 95%CI=0.811~0.937,P=2.109×10-4),CD28- CD25++ CD8br AC(OR=0.867,95% CI=0.809~0.930,P=6.09×10-5),CD28-CD127-CD25++CD8brAC(OR=0.875,95%CI=0.814~0.942,P=3.619×10-4).THCA was associated with an increased risk of Secreting Treg % CD4 Treg (OR=1.143, 95% CI=1.064~1.229, P=2.779×10-4) and CD19 on IgD+ CD24+ (OR=1.118, 95% CI=1.041~1.120, P=0.002). Conclusions: These findings suggest the causal associations between immune cells and THCA by genetic means. Our results may have the potential to provide guidance for future clinical research.

Engineering of a DNA/γPNA Hybrid Nanoreporter for ctDNA Mutation Detection via γPNA Urinalysis.

Detection of circulating tumor DNA (ctDNA) mutations, which are molecular biomarkers present in bodily fluids of cancer patients, can be applied for tumor diagnosis and prognosis monitoring. However, current profiling of ctDNA mutations relies primarily on polymerase chain reaction (PCR) and DNA sequencing and these techniques require preanalytical processing of blood samples, which are time-consuming, expensive, and tedious procedures that increase the risk of sample contamination. To overcome these limitations, here the engineering of a DNA/γPNA (gamma peptide nucleic acid) hybrid nanoreporter is disclosed for ctDNA biosensing via in situ profiling and recording of tumor-specific DNA mutations. The low tolerance of γPNA to single mismatch in base pairing with DNA allows highly selective recognition and recording of ctDNA mutations in peripheral blood. Owing to their remarkable biostability, the detached γPNA strands triggered by mutant ctDNA will be enriched in kidneys and cleared into urine for urinalysis. It is demonstrated that the nanoreporter has high specificity for ctDNA mutation in peripheral blood, and urinalysis of cleared γPNA can provide valuable information for tumor progression and prognosis evaluation. This work demonstrates the potential of the nanoreporter for urinary monitoring of tumor and patient prognosis through in situ biosensing of ctDNA mutations.

Midterm Outcomes of Percutaneous Intramyocardial Septal Radiofrequency Ablation for Hypertrophic Cardiomyopathy: A Single-Center, Observational Study.

BACKGROUND: Percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) has been reported to be safe and effective at midterm follow-up to treat drug-refractory hypertrophic obstructive cardiomyopathy in a single center. However, data from other centers are lacking. This retrospective cohort study aimed to investigate the efficacy and safety of PIMSRA from another independent center. METHODS AND RESULTS: PIMSRA was performed in 76 patients with hypertrophic obstructive cardiomyopathy in our center from April 2020 to June 2023. The primary outcome was the reduction of left ventricular outflow tract gradient after 6 months or more post-PIMSRA. Secondary outcomes were periprocedural major adverse clinical events. Sixty-one patients returned to the hospital for follow-up 6 to 30 (median, 14) months after the procedure. At the last follow-up of the 61 patients, the maximum septal thickness decreased from a median of 23.6 (interquartile range, 20.5-26.4) to 19.1 (interquartile range, 16.0-22.1) mm (P<0.001) and the left ventricular outflow tract peak gradient at rest decreased from a median of 70.0 (interquartile range, 29.1-107.5) to 20.0 (interquartile range, 10.8-48.8) mm Hg (P<0.001). The percentage of patients with symptoms of New York Heart Association functional class III/IV decreased from 51% to 0%. Of all 76 patients, there was no in-hospital or 30-day death, no right or left branch block, and no permanent pacemaker implantation. Six (8%) patients had pericardial effusion, with 1 experiencing cardiac tamponade and ventricular fibrillation, and 1 (1%) patient developed septal branch aneurysm that was treated with coil occlusion. CONCLUSIONS: PIMSRA allows for the reduction in the left ventricular outflow tract gradient and enhances symptomatic improvement, with a limited incidence of adverse events and complications among patients with hypertrophic obstructive cardiomyopathy.

Expert consensus on One Health for establishing an enhanced and integrated surveillance system for key infectious diseases.

China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities.

Brain-Inspired Image Perceptual Quality Assessment based on EEG: A QoE Perspective.

Human-oriented image communication should take the quality of experience (QoE) as an optimization goal, which requires effective image perceptual quality metrics. However, traditional user-based assessment metrics are limited by the deviation caused by human high-level cognitive activities. To tackle this issue, in this paper, we construct a brain response-based image perceptual quality metric and develop a brain-inspired network to assess the image perceptual quality based on it. Our method aims to establish the relationship between image quality changes and underlying brain responses in image compression scenarios using the electroencephalography (EEG) approach. We first establish EEG datasets by collecting the corresponding EEG signals when subjects watch distorted images. Then, we design a measurement model to extract EEG features that reflect human perception to establish a new image perceptual quality metric: EEG perceptual score (EPS). To use this metric in practical scenarios, we embed the brain perception process into a prediction model to generate the EPS directly from the input images. Experimental results show that our proposed measurement model and prediction model can achieve better performance. The proposed brain response-based image perceptual quality metric can measure the human brain's perceptual state more accurately, thus performing a better assessment of image perceptual quality.

A chemically adjustable BMP6-IL6 axis in mesenchymal stem cells drives acute myeloid leukemia cell differentiation.

Chemotherapy alone or in combination with allogeneic stem cell transplantation has been the standard of care for acute myeloid leukemia (AML) for decades. Leukemia relapse with limited treatment options remains the main cause of treatment failure. Therefore, an effective and safe approach to improve treatment outcomes is urgently needed for most AML patients. Mesenchymal stem cells (MSCs) have been reported to efficiently induce apoptosis and shape the fate of acute myeloid leukemia cells. Here, we identified LG190155 as a potent compound that enhances the antileukemia efficiency of MSCs. Pretreatment of MSCs with LG190155 significantly provoked differentiation in both AML patient-derived primary leukemia cells and AML cell lines and reduced the tumor burden in the AML mouse model. Using the quantitative proteomic technique, we discovered a pivotal mechanism that mediates AML cell differentiation, in which autocrine bone morphogenetic protein 6 (BMP6) in MSCs boosted IL-6 secretion and further acted on leukemic cells to trigger differentiation. Furthermore, the activity of the BMP6-IL6 axis was dramatically enhanced by activating vitamin D receptor (VDR) in MSCs. Our data illustrated an effective preactivated approach to reinforcing the antileukemia effect of MSCs, which could serve as an effective therapeutic strategy for AML.

Temperature Effect on the Growth and Development of Habrobracon hebetor Say (Hymenoptera: Braconidae) Reared on Ephestia elutella (Hübner) (Lepidoptera: Pyralidae) Larvae.

Augmentative release of parasitoids has been an important component of integrated insect management for stored product protection. Understanding the effect of different temperatures on the growth and development of parasitoids is in favor of mass rearing of parasitoids. Habrobracon hebetor Say (Hymenoptera: Braconidae) is a highly cosmopolitan, gregarious ecto-parasitoid of a variety of Lepidopterous larvae. Thus, the growth and development of H. hebetor reared on Ephestia elutella (Hübner) (Lepidoptera: Pyralidae) larvae were investigated at 15, 20, 25, 30, and 35 °C. Habrobracon hebetor could complete growth and development, and the developmental duration decreased with increasing temperature at 15, 20, 25, 30, and 35 °C. The development threshold temperatures of H. hebetor eggs, larvae, pupae, and egg-to-adult stages were 13.89, 6.39, 9.24, and 9.29 °C, and the effective accumulated temperatures were 23.33, 46.40, 142.68, and 240.31 °C·d, respectively. The total number of eggs laid by H. hebetor, the hatching rate of H. hebetor eggs, and the percentage of female offspring reached the maximum of 192.39, 83.89%, and 74.04% at 30 °C, respectively. There was no significant difference in pupal survival rate in the temperature range of 15 °C to 35 °C. At 30 °C, the pre-oviposition duration of H. hebetor was the shortest (0.87 d). Therefore, the optimal rearing temperature of H. hebetor was 30 °C. The present results are useful for the large-scale rearing of H. hebetor using E. elutella larvae as hosts and effectively implementing the biological control of stored-product insects.

Paradigm shifts of climate science for climate solutions.

Climate science is an indispensable part of climate solutions, and an era of climate actions necessitates certain paradigm shifts of climate science to better support viable climate actions and solutions. Three paradigm shifts are exemplified, namely (1) transcending the boundaries between physical science basis, adaptation, and mitigation; (2) embracing the synergy between climate science and technical innovations for effective climate solutions; and (3) shifting the paradigm from equilibrium climate dynamics toward non-equilibrium dynamics of climate/Earth systems. Beyond the application-driven and solution-oriented studies, curiosity-driven theoretical research is emphasized in the shift toward non-equilibrium climate/Earth systems-tipping elements, abrupt climate changes, and extremes-which may open avenues for new discoveries not only within climate science but also in mathematics, physics, and complex systems science.

Programming peptide-oligonucleotide nano-assembly for engineering of neoantigen vaccine with potent immunogenicity.

Background: Neoantigen nanovaccine has been recognized as a promising treatment modality for personalized cancer immunotherapy. However, most current nanovaccines are carrier-dependent and the manufacturing process is complicated, resulting in potential safety concerns and suboptimal codelivery of neoantigens and adjuvants to antigen-presenting cells (APCs). Methods: Here we report a facile and general methodology for nanoassembly of peptide and oligonucleotide by programming neoantigen peptide with a short cationic module at N-terminus to prepare nanovaccine. The programmed peptide can co-assemble with CpG oligonucleotide (TLR9 agonist) into monodispersed nanostructures without the introduction of artificial carrier. Results: We demonstrate that the engineered nanovaccine promoted the codelivery of neoantigen peptides and adjuvants to lymph node-residing APCs and instigated potent neoantigen-specific T-cell responses, eliciting neoantigen-specific antitumor immune responses with negligible systemic toxicity. Furthermore, the antitumor T-cell immunity is profoundly potentiated when combined with anti-PD-1 therapy, leading to significant inhibition or even complete regression of established melanoma and MC-38 colon tumors. Conclusions: Collectively, this work demonstrates the feasibility and effectiveness of personalized cancer nanovaccine preparation with high immunogenicity and good biosafety by programming neoantigen peptide for nanoassembly with oligonucleotides without the aid of artificial carrier.

Pyroptosis-related gene signature for predicting gastric cancer prognosis.

Gastric cancer (GC) is a prevalent form of malignancy characterized by significant heterogeneity. The development of a specific prediction model is of utmost importance to improve therapy alternatives. The presence of H. pylori can elicit pyroptosis, a notable carcinogenic process. Furthermore, the administration of chemotherapeutic drugs is often employed as a therapeutic approach to addressing this condition. In the present investigation, it was observed that there were variations in the production of 17 pyroptosis-regulating proteins between stomach tissue with tumor development and GC cells. The predictive relevance of each gene associated with pyroptosis was assessed using the cohort from the cancer genome atlas (TCGA). The least absolute shrinkage and selection operator (LASSO) was utilized to enhance the outcomes of the regression approach. Patients with gastric cancer GC in the cohort from the TCGA were categorized into low-risk or high-risk groups based on their gene expression profiles. Patients with a low risk of gastric cancer had a higher likelihood of survival compared to persons classified as high risk (P<0.0001). A subset of patients diagnosed with GC from a Genes Expression Omnibus (GEO) cohort was stratified according to their overall survival (OS) duration. The statistical analysis revealed a higher significance level (P=0.0063) regarding OS time among low-risk individuals. The study revealed that the GC risk score emerged as a significant independent prognostic factor for OS in patients diagnosed with GC. The results of Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) research revealed that genes associated with a high-risk group had significantly elevated levels of immune system-related activity. Furthermore, it was found that the state of immunity was diminished within this particular group. The relationship between the immune response to cancer and pyroptosis genes is highly interconnected, suggesting that these genes have the potential to serve as prognostic indicators for GC.

Near-full-length genome analysis of two novel HIV second recombinant forms in Hebei, China.

The number of individuals infected with HIV-1 among men who have sex with men (MSM) has risen rapidly in recent years in China, and the subtypes CRF01_AE, CRF07_BC, and B, as well as many novel unique recombinant forms (URFs) are prevalent among them. Co-circulation of strains among MSM populations allows the generation of circulating recombinant forms (CRFs) and URFs. In this study, we identified two new URFs from two HIV-1-positive subjects who were infected through homosexual contact in Hebei, China. Analysis of near-full-length genome sequences, using phylogenetic and recombination analysis showed that the two URFs originated from CRF01_AE, CRF07_BC, and B, and CRF01_AE segments in the backbone of the URFs were derived from cluster 4 of CRF01_AE. The CRF07_BC segments of two URFs were clustered with 07BC_N in a phylogenetic tree. The identification of novel URFs with complex genomic structures shows that it is necessary to strengthen surveillance of HIV-1 variants in MSM populations in this region.

Organ/Cell-Selective Intracellular Delivery of Biologics via N-Acetylated Galactosamine-Functionalized Polydisulfide Conjugates.

Biologics, including proteins and antisense oligonucleotides (ASOs), face significant challenges when it comes to achieving intracellular delivery within specific organs or cells through systemic administrations. In this study, we present a novel approach for delivering proteins and ASOs to liver cells, both in vitro and in vivo, using conjugates that tether N-acetylated galactosamine (GalNAc)-functionalized, cell-penetrating polydisulfides (PDSs). The method involves the thiol-bearing cargo-mediated ring-opening polymerization of GalNAc-functionalized lipoamide monomers through the so-called aggregation-induced polymerization, leading to the formation of site-specific protein/ASO-PDS conjugates with narrow dispersity. The hepatocyte-selective intracellular delivery of the conjugates arises from a combination of factors, including first GalNAc binding with ASGPR receptors on liver cells, leading to cell immobilization, and the subsequent thiol-disulfide exchange occurring on the cell surface, promoting internalization. Our findings emphasize the critical role of the close proximity of the PDS backbone to the cell surface, as it governs the success of thiol-disulfide exchange and, consequently, cell penetration. These conjugates hold tremendous potential in overcoming the various biological barriers encountered during systemic and cell-specific delivery of biomacromolecular cargos, opening up new avenues for the diagnosis and treatment of a range of liver-targeting diseases.

Elucidating hepatocellular carcinoma progression: a novel prognostic miRNA-mRNA network and signature analysis.

There is increasing evidence that miRNAs play an important role in the prognosis of HCC. There is currently a lack of acknowledged models that accurately predict patient prognosis. The aim of this study is to create a miRNA-based model to precisely forecast a patient's prognosis and a miRNA-mRNA network to investigate the function of a targeted mRNA. TCGA miRNA dataset and survival data of HCC patients were downloaded for differential analysis. The outcomes of variance analysis were subjected to univariate and multivariate Cox regression analyses and LASSO analysis. We constructed and visualized prognosis-related models and subsequently used violin plots to probe the function of miRNAs in tumor cells. We predicted the target mRNAs added those to the String database, built PPI protein interaction networks, and screened those mRNA using Cytoscape. The hub mRNA was subjected to GO and KEGG analysis to determine its biological role. Six of them were associated with prognosis: hsa-miR-139-3p, hsa-miR-139-5p, hsa-miR-101-3p, hsa-miR-30d-5p, hsa-miR-5003-3p, and hsa-miR-6844. The prognostic model was highly predictive and consistently performs, with the C index exceeding 0.7 after 1, 3, and 5 years. The model estimated significant differences in the Kaplan-Meier plotter and the model could predict patient prognosis independently of clinical indicators. A relatively stable miRNA prognostic model for HCC patients was constructed, and the model was highly accurate in predicting patients with good stability over 5 years. The miRNA-mRNA network was constructed to explore the function of mRNA.

Visualization of nasal powder distribution using biomimetic human nasal cavity model.

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Comparison of the effect between cefazolin/cefuroxime and broad-spectrum antibiotics in preventing post-operative pulmonary infections for smoking patients receiving video-assisted thoracoscopic lung surgery: a propensity score-matched retrospective cohort study.

BACKGROUND: The selection of prophylactic antibiotics for preventing post-operative pulmonary infections in smoking patients undergoing video-assisted thoracoscopic lung surgery (VATLS) is not clear. METHODS: In this retrospective cohort study, the outcomes of 572 smoking patients undergoing VATLS with prophylactic cefazolin/cefuroxime or other antibiotics were analyzed. Patients were classified as cefazolin/cefuroxime group and the control group. A 1:1 propensity score matching was also performed. RESULTS: The primary outcome of the incidence of post-operative pulmonary infection did not differ significantly between the two groups (23.7% vs 30.5%, RR = 0.777, 95%CI 0.564 ~ 1.070 p = 0.113). Similarly, secondary outcomes including the incidence of post-operative fever, the white blood cell count and neutrophils on the 3rd day after the surgery, and time for blood routine test recovery were all found without significant difference between the two groups. In the multivariate logistic regression model, no association was found between prophylactic use of cefazolin/cefuroxime and post-operative pulmonary infections after controlling other possible confounding factors (OR = 0.685, 95%CI 0.441 ~ 1.065, p = 0.093). CONCLUSIONS: Prophylactic use of cefazolin/cefuroxime was not associated with more adverse clinical outcomes among smoking populations undergoing VATLS when compared with broad-spectrum antibiotics and the two drugs are still feasible for peri-operative prophylactic use for smoking population before the surgery.