The optimal choice for patients underwent minimally invasive pancreaticoduodenectomy: a systematic review and meta-analysis including patient subgroups.

The aim of this meta-analysis was to evaluate the efficacy and safety of robotic pancreaticoduodenectomy (RPD) in improving perioperative aspects and postoperative complications in patients. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library database systems for studies that compared RPD with laparoscopic pancreaticoduodenectomy (LPD). Meta-analysis was performed for 24 relevant outcomes, including perioperative outcomes and postoperative complications. Subsequently, a subgroup analysis based on geographical regions was conducted to investigate the impact of regional differences on the perioperative outcomes of the RPD group and the LPD group. RESULTS: This review found 19 studies with 12,731 individuals (3539 RPD and 9192 LPD). In comparison to LPD, RPD had lower rates of Conversion (OR = 0.58, P < 0.00001), Blood Transfusion (OR = 0.59, P = 0.02), Length of Stay (MD = - 0.54, P = 0.01), postoperative complications [Pneumonia (OR = 0.31, P < 0.0001), and Wound Disruption (OR = 0.26, P = 0.0007)], and more thorough lymph node harvesting (MD = 1.25, P = 0.001). Subgroup analysis showed that Blood Transfusion (I2 = 55%, P = 0.02), Conversion (I2 = 30%, P < 0.00001), Length of Stay (I2 = 71%, P = 0.01), and Lymph Node Harvested (I2 = 87%, P = 0.001) were statistically significant. Interestingly, compared to China, other countries had lower rates of Conversion and more lymph nodes harvested for RPD surgery. CONCLUSION: The benefits of RPD surgery over LPD surgery in terms of therapy and an optimistic short-term prognosis are clearly supported by this study. Moreover, subgroup analysis based on regional differences revealed statistically significant results for Conversion, Length of Stay (days), Number of Lymph Nodes Harvested and the rate of Blood Transfusion, indicating significant variability across regions. This study provides a solid theoretical foundation and basis for the advancement of RPD in clinical practice.

Tertiary lymphoid structures: Associated multiple immune cells and analysis their formation in hepatocellular carcinoma.

The prognostic value of immune cells in tertiary lymphoid structures (TLSs) remains unclear in hepatocellular carcinoma (HCC). Here, 59 of 145 patients had TLSs in training set, 48 of 120 patients had TLSs in testing set. Immunohistochemistry (IHC) were used to label CD3+ T cells, CD20+ B cells, CD8+ T cells, CD208+ dendritic cells, and CD21+ follicular dendritic cells in TLSs. High CD20+, CD208+, and CD8+ cell densities were favorable prognostic factors for overall survival (OS). High CD3+, CD20+, CD208+, and CD8+ cell densities were significantly associated with reduced early recurrence. TLSs were divided into three grades (A, B, and C) based on immune cell density. Patients with grade C or B had significantly improved OS. Patients with grade C had the lowest recurrence rate, followed by those with grade B, while patients with grade A had the highest recurrence rate. The stromal, immune, and ESTIMATE scores derived from the ESTIMATE package were significantly higher and tumor purity was significantly lower in patients with TLSs. Patients with TLSs had significantly higher relative numbers of memory B cells, plasma cells, CD8+ T cells, NK cells, and dendritic cells and lower relative numbers of Treg cells, macrophages, and M2 macrophages according to the CIBERSORT assessment. Bioinformatics analysis and experiments confirmed that KLRK1 and GZMA expression are associated TLSs formation and can predict TLSs existence. Grade B and grade C were favorable prognostic factors for OS and recurrence and could represent immune-active tumors.

Changes of HFRS Incidence Caused by Vaccine Intervention in Yichun City, China, 2005-2013.

BACKGROUND: Since 2009, the Hemorrhagic Fever with Renal Syndrome (HFRS) Targeted Expanded Program on Immunization (EPI) has been carried out in the 16-60 age population in Yichun City of Jiangxi Province. However, the annual reported incidences of HFRS in Yichun City Increased significantly from 2009 to 2013. MATERIAL/METHODS: The information on HFRS reported cases were obtained from the China Information System for Disease Control and Prevention (CISDCP), and demographic data was collected from the Basic Information System. Hantavirus-specific antigen and antibody of rodent specimens were tested by enzyme-linked immunosorbent assay (ELISA) or immune fluorescent assay. RESULTS: The annual HFRS incidences among all age subgroups presented growth tendencies in non-EPI targeted regions and EPI targeted regions, except for the EPI target population. The annual incidences of EPI target population were stable at around 10 per 100,000 population from 2008 to 2013. HFRS annual incidence was significantly related to rat virus index among all age subgroups in non-EPI targeted regions and >60 age subgroup in EPI targeted regions. CONCLUSIONS: HFRS vaccine implement has had a notable effect in HFRS prevention and control.

Analysis of the therapeutic effect of right mid-axillary approach in the surgical treatment of ASD and VSD in children.

BACKGROUND: To compare the therapeutic effects of right vertical infra-axillary thoracotomy (RVIAT) and Standard Median Sternotomy (SMS) in the repair of atrial septal defect (ASD) and ventricular septal defect (VSD), and to evaluate the safety and effectiveness of right subaxillary incision technique in the surgical treatment of common congenital heart disease (CHD) in children. METHODS: Data of children diagnosed with ASD repair or VSD repair at our center from September 2019 to September 2022 were collected. Based on propensity score matching, 214 children (107 in the RVIAT group and 107 in the SMS group) who completed ASD repair surgery and 242 children (121 in the RVIAT group and 121 in the SMS group) who completed VSD repair surgery were selected for the study. The perioperative and follow-up data of the two surgical approaches were compared to evaluate clinical efficacy. RESULTS: There was no statistically significant difference (p > 0.05) between the two surgical approaches in terms of surgical time, aortic occlusion time, total amount of ultrafiltration fluid, ICU stay time, and hospital stay; The intraoperative blood loss and total postoperative drainage fluid in the RVIAT group were lower than those in the SMS group (p < 0.05); The incidence of postoperative thoracic deformities in the SMS group is higher than that in the RVIAT group. CONCLUSION: The safety and effectiveness of the two approaches are similar, but RVIAT has less intraoperative bleeding, less postoperative drainage fluid and tube time, and better concealment and cosmetic effects, which is worthy of further clinical promotion and application.

How the chemical structure of phosphoramides affect the fire retardancy and mechanical properties of polylactide?

Phosphoramides, as a kind of high-efficient fire retardants, have been designed in many structures and endowed exceptional fire retardancy to polylactide (PLA). However, due to ignorance of the structure-property correlation, the effect of phosphoramides' structure on the fire retardancy and mechanical properties of PLA is still unclear. Herein, a series of biobased phosphoramides (phosphoramide (V1), linear polyphosphoramide (V2) and hyperbranched polyphosphamide (V3)) were designed and incorporated into PLA, and the structural effect of phosphoramides on the fire-retardant and mechanical properties of PLA was deeply researched. Among three kinds of phosphoramides, the hyperbranched polyphosphoramide is more effective than the corresponding linear polyphosphoramide and phosphoramide in improving the fire-retardant and anti-dripping properties of PLA, and only linear polyphosphoramide shows a positive effect in the mechanical strength of PLA. This work provides a feasible strategy for creating mechanically robust and fire-retardant polymer composites by molecularly tailoring the structure of fire retardants and uncovering their structure-property relationship.

NeuroQuantify - An image analysis software for detection and quantification of neuron cells and neurite lengths using deep learning.

BACKGROUND: The segmentation of cells and neurites in microscopy images of neuronal networks provides valuable quantitative information about neuron growth and neuronal differentiation, including the number of cells, neurites, neurite length and neurite orientation. This information is essential for assessing the development of neuronal networks in response to extracellular stimuli, which is useful for studying neuronal structures, for example, the study of neurodegenerative diseases and pharmaceuticals. NEW METHOD: We have developed NeuroQuantify, an open-source software that uses deep learning to efficiently and quickly segment cells and neurites in phase contrast microscopy images. RESULTS: NeuroQuantify offers several key features: (i) automatic detection of cells and neurites; (ii) post-processing of the images for the quantitative neurite length measurement based on segmentation of phase contrast microscopy images, and (iii) identification of neurite orientations. COMPARISON WITH EXISTING METHODS: NeuroQuantify overcomes some of the limitations of existing methods in the automatic and accurate analysis of neuronal structures. It has been developed for phase contrast images rather than fluorescence images. In addition to typical functionality of cell counting, NeuroQuantify also detects and counts neurites, measures the neurite lengths, and produces the neurite orientation distribution. CONCLUSIONS: We offer a valuable tool to assess network development rapidly and effectively. The user-friendly NeuroQuantify software can be installed and freely downloaded from GitHub at https://github.com/StanleyZ0528/neural-image-segmentation.

Single nucleotide polymorphisms rs2120131, rs4935047, and rs7095891 in the MBL2 gene show no association with susceptibility to chronic hepatitis B in a Chinese Han population.

Thus far, many studies have evaluated the correlation between MBL2 gene polymorphisms and hepatitis B infection. Tag single nucleotide polymorphisms (SNPs) were used to investigate the relationship between MBL2 gene polymorphisms and susceptibility to chronic hepatitis B virus (HBV) infection by comparing 996 chronic HBV infection cases to 301 acute infection controls. There was no significant correlation between rs2120131, rs4935047, and rs7095891 and chronic HBV infection. This suggested that the new SNPs within MBL2 were not associated with susceptibility to chronic hepatitis B in a Chinese Han population.

Association between tumor necrosis factor-α (TNF-α) promoter -308 G/A and response to TNF-α blockers in rheumatoid arthritis: a meta-analysis.

OBJECTIVES: Tumor necrosis factor (TNF)-α promoter -308G/A polymorphism has been shown to be associated with high TNF-α production and poor response to anti-TNF-α treatment. However, not all patients show a good response to TNF-α antagonists, so this association remains controversial. This study was designed to investigate whether TNF-α promoter -308 G/A polymorphism is associated with responsiveness to anti-TNF therapy in rheumatoid arthritis (RA) patients. The 28-joint count Disease Activity Score (DAS) 28 or the American College of Rheumatology (ACR) improvement criteria 20 were used to measure patient response. METHODS: A meta-analysis was performed. Pooled ORs and 95 % CIs were calculated by both dominant and recessive genetic models. RESULTS: Fifteen studies with a total of 2127 patients were included in this meta-analysis. The results showed that patients with the G allele responded better to the treatment (OR = 1.87, 95 % CI 1.26-2.79). A subanalysis showed similar results. CONCLUSIONS: Based on the results of this meta-analysis, RA patients with the TNF-α promoter -308 G allele respond better to TNF-α antagonist treatment, suggesting that this allele plays a major role in anti-TNF-alpha treatment response.

Association of KIR genotype with susceptibility to HLA-B27-positive ankylosing spondylitis.

OBJECTIVE: Recent studies have explored the role of killer cell immunoglobulin-like receptors (KIRs) in chronic autoimmune diseases. The purpose of this study was to demonstrate whether KIR genes contribute to the pathogenesis of ankylosing spondylitis (AS) in Chinese populations. METHODS: Sixteen KIR genes were genotyped from 60 unrelated patients with AS and 60 HLA-B27-positive matched healthy controls by PCR-SSP. The frequencies of the KIR alleles and genotypes in the AS and control groups were assessed by the χ(2) test. RESULTS: Our results showed that the frequency of the activator receptor KIR3DS1 gene in the AS group was significantly increased compared to the controls (χ(2) = 5.263, P = 0.006, OR = 3.059, 95 % CI = 1.357-6.896). Moreover, the frequency of the KIR3DL1/3DS1 genotype was greater in the AS group than in the control group (P = 0.039, OR = 3.059, 95 % CI = 1.357-6.896). In contrast, the frequency of the no KIR3DL1/no 3DS1 genotype was lower in patients with AS compared with the controls (P = 0.032, OR = 0.110, 95 % CI = 0.013-0.911). CONCLUSION: KIR3DS1, in addition to HLA-B27, may play an important independent role in the pathogenesis of AS in the Chinese population.

A long-term retrospective analysis of the haemorrhagic fever with renal syndrome epidemic from 2005 to 2021 in Jiangxi Province, China.

Jiangxi is one of the provinces in China most seriously affected by the haemorrhagic fever with renal syndrome (HFRS) epidemic. The aim of this paper was to systematically explore the HFRS epidemic in Jiangxi from the perspective of Hantavirus (HV) prevalence in rodents and humans and virus molecular characteristics. Individual information on all HFRS cases in Jiangxi from 2005 to 2021 was extracted from the China Information System for Disease Control and Prevention. All S and M fragment sequences of the Seoul virus and Hantan virus strains uploaded by Jiangxi and its neighbouring provinces and some representative sequences from provinces in China or some countries of Southeast Asia with the highest HV prevalence were retrieved and downloaded from NCBI GenBank. Periodogram and spatial autocorrelation were adopted for temporal periodicity and spatial clustering analysis of the HFRS epidemic. Joinpoint regression was utilized to explore the changing morbidity trend patterns of HFRS. Multiple sequence alignment and amino acid variation analysis were used to explore the homology and variation of strain prevalence in Jiangxi. Based on monthly morbidity time series, the periodogram analysis showed that the prevalence of HFRS had periodicities of 6 months and 12 months. Spatial autocorrelation analysis showed that HFRS distributed in Jiangxi was not random, with a "High-High" clustering area around Gaoan County. HFRS morbidity among the 0 ~ 15-year-old and ~ 61-year-old or older populations in Jiangxi increased significantly during the period of 2008-2015. Generally, HFRS morbidity was significantly positively correlated with the index of rat with virus (IRV) (r = 0.742) in the counties surrounding Gaoan from 2005 to 2019. HTNV strains in Jiangxi were in one independent branch, while the SEOV strains in Jiangxi were relatively more diverse. Both the YW89-15 and GAW30/2021 strains shared approximately 85% nucleotide homology and approximately 97% amino acid homology with their corresponding standard strains and vaccine strains. GAW30/2021 and YW89-15 had some amino acid site variations in nucleoprotein, glycoprotein precursor and RNA-dependent polymerase with their corresponding vaccine strains Z10 (HTNV) and Z37 (SEOV). The HFRS epidemic in Jiangxi has obvious temporal periodicity and spatial clustering, and the significant increase in the non-Immunization Expanded Program (EPI) targeted population (children and elderly) suggests that HFRS vaccination in this population needs to be considered. Although applying the EPI played a certain role in curbing the incidence of HFRS in Jiangxi from the perspective of ecological epidemiology, HTNV and SEOV strains prevalent in Jiangxi have some amino acid site variations compared to their corresponding vaccine strains, suggesting that HV variation needs to be continuously monitored in the future to observe vaccine protective efficiency.

Psychological resilience matters in the relationship between the decline in economic status and adults' depression half a year after the outbreak of the COVID-19 pandemic.

Background/objective: The outbreak of COVID-19 in China since 2019 has had a significant impact on the mental health of people in Hubei Province during the three-year pandemic period. Therefore, studying the prevalence of depression among the population of Hubei Province since the pandemic is of great significance. Methods: Based on opportunity and stress theory, we collected provincial-level data from Hubei (N = 3,285) to examine the impact of declining economic status on depressive symptoms and to investigate the moderating effect of psychological resilience during the period of economic adjustment. Results: We used propensity score matching to estimate the treatment effect of economic status decline on depression severity and confirmed the moderating effect of psychological resilience. We found that the more that an individual's economic status declines, the more severe that his or her depressive symptoms become. Specifically, each unit decrease in economic status is associated with an increase of approximately 0.117 units in depression level. In addition, our results indicated that psychological resilience significantly moderated the relationship between economic decline and depression (-0.184*). Conclusions and implications: Our study confirms the role of economic status in depressive symptoms. Compared with traditional research on the relationship between economic status and mental illness, this paper expands the research regarding the two in the context of a major public health emergency. Furthermore, we suggest ways to improve people's mental health following the pandemic.

Revealing Prognostic and Immunotherapy-Sensitive Characteristics of a Novel Cuproptosis-Related LncRNA Model in Hepatocellular Carcinoma Patients by Genomic Analysis.

Immunotherapy has shown strong anti-tumor activity in a subset of patients. However, many patients do not benefit from the treatment, and there is no effective method to identify sensitive immunotherapy patients. Cuproptosis as a non-apoptotic programmed cell death caused by excess copper, whether it is related to tumor immunity has attracted our attention. In the study, we constructed the prognostic model of 9 cuproptosis-related LncRNAs (crLncRNAs) and assessed its predictive capability, preliminarily explored the potential mechanism causing treatment sensitivity difference between the high-/low-risk group. Our results revealed that the risk score was more effective than traditional clinical features in predicting the survival of HCC patients (AUC = 0.828). The low-risk group had more infiltration of immune cells (B cells, CD8+ T cells, CD4+ T cells), mainly with anti-tumor immune function (p < 0.05). It showed higher sensitivity to immune checkpoint inhibitors (ICIs) treatment (p < 0.001) which may exert the effect through the AL365361.1/hsa-miR-17-5p/NLRP3 axis. In addition, NLRP3 mutation-sensitive drugs (VNLG/124, sunitinib, linifanib) may have better clinical benefits in the high-risk group. All in all, the crLncRNAs model has excellent specificity and sensitivity, which can be used for classifying the therapy-sensitive population and predicting the prognosis of HCC patients.

Peritumor tertiary lymphoid structures are associated with infiltrating neutrophils and inferior prognosis in hepatocellular carcinoma.

BACKGROUND: The positive prediction of prognosis and immunotherapy within tertiary lymphoid structure (TLS) in cancerous tissue has been well demonstrated, including liver cancer. However, the relationship between TLS and prognosis in the peritumoral region of hepatocellular carcinoma (HCC) has received less attention. Few studies on whether TLS, as a typical representative of acquired immune cell groups, is associated with innate immune cells. The aim of this paper was to identify the prognostic role of peritumor TLS in HCC and to simply explore the relationship with neutrophils infiltration. METHODS: This study included cancerous and paracancerous tissue from 170 patients after surgical resection of HCC. TLS was examined and identified by pathological H&E examination, and the impact on prognosis was further classified by determination of total TLS area. Immunohistochemical staining of CD15+ neutrophils was also performed on half of the cases. The obtained results were validated by external public database, as TLS has been widely shown to be tagged with 12 chemokines. RESULTS: In peritumoral tissue, the TLS- group had better overall survival (OS) and disease-free survival (DFS) outcomes compared with the TLS+ group. On the contrary, the intratumor TLS+ group showed better DFS outcomes. When further investigating the relationship between TLS area distribution and DFS, progressively worse prognosis was only found in the peritumor region with increasing TLS density (TLS- vs. TLSL vs. TLSH ). In addition, neutrophil infiltration increased in parallel with TLS density in the peritumoral region, which was not observed in the intratumoral region. CONCLUSIONS: TLS might have a dual prognostic role in different regions of HCC. The abundance of peritumoral TLS is an independent influence of DFS. The inconsistent correlation between neutrophils and corresponding TLS in different regions may indicate different pathways of immune aggregation and may serve as an explanation for the different prognosis of TLS, which needs to be specifically explored.

Epidemiological and clinical characteristics of respiratory syncytial virus and influenza infections in hospitalized children before and during the COVID-19 pandemic in Central China.

Background: Globally, the epidemiology of non-SARS-CoV-2 respiratory viruses like respiratory syncytial virus (RSV) and influenza virus was remarkably influenced by the implementation of non-pharmacological interventions (NPIs) during the COVID-19 pandemic. Our study explored the epidemiological and clinical characteristics of pediatric patients hospitalized with RSV or influenza infection before and during the pandemic after relaxation of NPIs in central China. Methods: This hospital-based prospective case-series study screened pediatric inpatients (age ≤ 14 years) enrolled with acute respiratory infections (ARI) for RSV or influenza infection from 2018 to 2021. The changes in positivity rates of viral detection, epidemiological, and clinical characteristics were analyzed and compared. Results: Median ages of all eligible ARI patients from 2018-2019 were younger than those from 2020-2021, so were ages of cases infected with RSV or influenza (RSV: 4.2 months vs. 7.2 months; influenza: 27.3 months vs. 37.0 months). Where the positivity rate for influenza was considerably decreased in 2020-2021 (1.4%, 27/1964) as compared with 2018-2019 (2.9%, 94/3275, P < 0.05), it was increased for RSV (11.4% [372/3275] vs. 13.3% [262/1964], P < 0.05) in the same period. The number of severe cases for both RSV and influenza infection were also decreased in 2020-2021 compared with 2018-2019. Conclusions: The implemented NPIs have had varied impacts on common respiratory viruses. A more effective prevention strategy for RSV infections in childhood is needed.

Interleukin-23 receptor genetic polymorphisms and ankylosing spondylitis susceptibility: a meta-analysis.

Up to now, many publications have evaluated the correlation between IL-23R polymorphisms and ankylosing spondylitis with conflicting results. We perform this meta-analysis to collect all the relevant studies up to date to further clarify the association of IL-23R polymorphisms with AS. Relevant published data were retrieved through Medline, PubMed, Embase, Web of Science, CNKI, Chinese BioMedical Literature Database on disc, and the statistical analysis was conducted using Stata 11.0. (1) A total of 11 literatures, including 13 population samples, were studied. (2) The allele A frequency of rs11209032 was higher in the AS group than in the controls (A vs. G: OR = 1.173, 95% CI = 1.107-1.243, P < 0.001). (3) The allele A of rs1004819 was higher in the AS group than in the controls in both all-pooled population (A vs. G: OR = 1.147, 95% CI = 1.022-1.287, P = 0.02) and Europe-pooled population (A vs. G: OR = 1.199, 95% CI = 1.007-1.429, P = 0.042). (4) The allele frequency T of rs1343151, G of rs10489629, and A of rs11209026 was lower in the AS group than in the controls. (5) No significant differences were found in allele frequency of rs10889677 polymorphism between cases and controls by random effects model. We concluded that the genetic susceptibility for AS is associated with the IL-23R gene polymorphisms. The protective SNPs include rs1343151, rs10489629, and rs11209026 while rs1004819 and rs11209032 may be the susceptibility SNPs.

Protective effect of tertiary lymphoid structures against hepatocellular carcinoma: New findings from a genetic perspective.

Background: Tertiary lymphoid structures (TLS) have an effect on hepatocellular carcinoma (HCC), but the underlying mechanism remains to be elucidated. Methods: Intratumoral TLS (iTLS) was classified in the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort using pathological sections from the Cancer Digital Slide Archive. Univariate and multivariate Cox regression analyses were performed to validate the effect of iTLS on overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS). The genes differentially expressed between the iTLS-negative and iTLS-positive groups were analyzed in combination with sequencing data. Gene set enrichment analysis (GSEA) was used to explore the signaling pathways affected by these differentially expressed genes. The random forest algorithm was used to identify genes with the highest correlation with the iTLS in the training set. Multivariate logistic regression was used to build a model to predict iTLS in tissue samples. Spearman's correlation was used to analyze the relationship between TLS-associated chemokines and signature genes, and CIBERSORT was used to calculate immune infiltration scores. Copy number variation and its relationship with immune cell infiltration and signature genes were assessed using the gene set cancer analysis (GSCA). The Correlation R package was used for gene ontology (GO), disease ontology (DO), and gene mutation analyses. The GSCA was used for drug sensitivity analysis. LASSO regression was used to build prognostic models, and external data were used to validate the models. Results: There were 218 positive and 146 negative samples for iTLS. iTLS was significantly associated with better RFS and DFS according to Cox regression analysis. Twenty signature genes that were highly associated with iTLS positivity were identified. GO and mutation analyses revealed that the signature genes were associated with immunity. Most signature genes were sensitive to immune checkpoint inhibitors. Risk scores calculated using a characteristic gene-based prognostic model were found to be an independent prognostic factor for OS. Conclusions: The improvement of RFS in HCC by iTLS was not limited to the early period as previously reported. iTLS improved DFS in patients. Characteristic genes are closely related to the formation of iTLS and TLS chemokines in HCC. These genes are closely related to immunity in terms of cellular infiltration, biological functions, and signaling pathways. Most are sensitive to immune checkpoint inhibitors, and their expression levels can affect prognosis.

Development and analysis of a comprehensive diagnostic model for aortic valve calcification using machine learning methods and artificial neural networks.

Background: Although advanced surgical and interventional treatments are available for advanced aortic valve calcification (AVC) with severe clinical symptoms, early diagnosis, and intervention is critical in order to reduce calcification progression and improve patient prognosis. The aim of this study was to develop therapeutic targets for improving outcomes for patients with AVC. Materials and methods: We used the public expression profiles of individuals with AVC (GSE12644 and GSE51472) to identify potential diagnostic markers. First, the R software was used to identify differentially expressed genes (DEGs) and perform functional enrichment analysis. Next, we combined bioinformatics techniques with machine learning methodologies such as random forest algorithms and support vector machines to screen for and identify diagnostic markers of AVC. Subsequently, artificial neural networks were employed to filter and model the diagnostic characteristics for AVC incidence. The diagnostic values were determined using the receiver operating characteristic (ROC) curves. Furthermore, CIBERSORT immune infiltration analysis was used to determine the expression of different immune cells in the AVC. Finally, the CMap database was used to predict candidate small compounds as prospective AVC therapeutics. Results: A total of 78 strong DEGs were identified. The leukocyte migration and pid integrin 1 pathways were highly enriched for AVC-specific DEGs. CXCL16, GPM6A, BEX2, S100A9, and SCARA5 genes were all regarded diagnostic markers for AVC. The model was effectively constructed using a molecular diagnostic score system with significant diagnostic value (AUC = 0.987) and verified using the independent dataset GSE83453 (AUC = 0.986). Immune cell infiltration research revealed that B cell naive, B cell memory, plasma cells, NK cell activated, monocytes, and macrophage M0 may be involved in the development of AVC. Additionally, all diagnostic characteristics may have varying degrees of correlation with immune cells. The most promising small molecule medicines for reversing AVC gene expression are Doxazosin and Terfenadine. Conclusion: It was identified that CXCL16, GPM6A, BEX2, S100A9, and SCARA5 are potentially beneficial for diagnosing and treating AVC. A diagnostic model was constructed based on a molecular prognostic score system using machine learning. The aforementioned immune cell infiltration may have a significant influence on the development and incidence of AVC.

Tertiary Lymphatic Structures in Primary Hepatic Carcinoma: Controversy Cannot Overshadow Hope.

Tertiary lymphoid structures (TLSs) are organized aggregates of immune cells found in the tumor microenvironment. TLS can influence primary hepatic carcinoma (PHC) occurrence and have an active role in cancer. TLS can promote or inhibit the growth of PHC depending on their location, and although available findings are controversial, they suggest that TLS have a protective role in PHC tissues and a non-protective role in paracancerous tissues. In addition, the cellular composition of TLS can also influence the outcome of PHC. As an immunity marker, TLS can act as a marker of immunotherapy to predict its effect and help to identify patients who will respond well to immunotherapy. Modulation of TLS formation through the use of chemokines/cytokines, immunotherapy, or induction of high endothelial vein to interfere with tumor growth has been studied extensively in PHC and other cancers. In addition, new tools such as genetic interventions, cellular crosstalk, preoperative radiotherapy, and advances in materials science have been shown to influence the prognosis of malignant tumors by modulating TLS production. These can also be used to develop PHC treatment.

Bioinformatics and Machine Learning Methods to Identify FN1 as a Novel Biomarker of Aortic Valve Calcification.

Aim: The purpose of this study was to identify potential diagnostic markers for aortic valve calcification (AVC) and to investigate the function of immune cell infiltration in this disease. Methods: The AVC data sets were obtained from the Gene Expression Omnibus. The identification of differentially expressed genes (DEGs) and the performance of functional correlation analysis were carried out using the R software. To explore hub genes related to AVC, a protein-protein interaction network was created. Diagnostic markers for AVC were then screened and verified using the least absolute shrinkage and selection operator, logistic regression, support vector machine-recursive feature elimination algorithms, and hub genes. The infiltration of immune cells into AVC tissues was evaluated using CIBERSORT, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. Finally, the Connectivity Map database was used to forecast the candidate small molecule drugs that might be used as prospective medications to treat AVC. Results: A total of 337 DEGs were screened. The DEGs that were discovered were mostly related with atherosclerosis and arteriosclerotic cardiovascular disease, according to the analyses. Gene sets involved in the chemokine signaling pathway and cytokine-cytokine receptor interaction were differently active in AVC compared with control. As the diagnostic marker for AVC, fibronectin 1 (FN1) (area the curve = 0.958) was discovered. Immune cell infiltration analysis revealed that the AVC process may be mediated by naïve B cells, memory B cells, plasma cells, activated natural killer cells, monocytes, and macrophages M0. Additionally, FN1 expression was associated with memory B cells, M0 macrophages, activated mast cells, resting mast cells, monocytes, and activated natural killer cells. AVC may be reversed with the use of yohimbic acid, the most promising small molecule discovered so far. Conclusion: FN1 can be used as a diagnostic marker for AVC. It has been shown that immune cell infiltration is important in the onset and progression of AVC, which may benefit in the improvement of AVC diagnosis and treatment.

Analysis on the interaction between IL-1F7 gene and environmental factors on patients with ankylosing spondylitis: a case-only study.

To examine the interaction between IL-1F7 gene and environmental factors in patients with ankylosing spondylities (AS). 150 AS Han Chinese patients (all human leukocyte antigen-B27 positive) were genotyped using a panel of single-nucleotide polymorphism markers within IL-1F7 gene (rs3811047) by ligase detection reactions. Polymerase chain reaction with sequence-specific primer was used to determine HLA-B27 subtypes. We analyzed the interaction between IF-1F7 gene and eight environmental factors in AS patients by using a case-only study. The genetic polymorphism and environmental factors were considered as dependent variables in logistic models, and P-values, ORi and 95% confidence intervals were used for estimating the effects of interaction. The different frequency of A/G between drinking group and non-drinking group was significant (ORi 3.163, 95% CI 1.368-7.317, P=0.006). Within the cooking oil group, odds ratio for interaction of G×E between main plants fats and half plants -half animal fats subunits was 4.273 (95% CI 1.590-11.479, P=0.004). Our data show that there was no interaction between IL-1F7 alleles and the other six environmental factors in AS patients (all P>0.05). We observed that there was an interaction between IF-1F7 gene and drinking in AS patients. Thus, drinking may be a risk exposure factor to take combined action with predisposing genes in AS patients. This action may increase the incident risk of AS. Also, main plants fats may be protective factors to AS.