Predicting malignant potential of solitary pulmonary nodules in patients with COVID-19 infection: a comprehensive analysis of CT imaging and tumor markers.

OBJECTIVE: To analyze the value of combining computed tomography (CT) with serum tumor markers in the differential diagnosis of benign and malignant solitary pulmonary nodules (SPNs). METHODS: The case data of 267 patients diagnosed with SPNs in the First Affiliated Hospital of Zhengzhou University from March 2020 to January 2023 were retrospectively analyzed. All individuals diagnosed with coronavirus disease 2019 (COVID-19) were confirmed via respiratory specimen viral nucleic acid testing. The included cases underwent CT, serum tumor marker testing and pathological examination. The diagnostic efficacy and clinical significance of CT, serum tumor marker testing and a combined test in identifying benign and malignant SPNs were analyzed using pathological histological findings as the gold standard. Finally, a nomogram mathematical model was established to predict the malignant probability of SPNs. RESULTS: Of the 267 patients with SPNs, 91 patients were not afflicted with COVID-19, 36 exhibited malignant characteristics, whereas 55 demonstrated benign features. Conversely, within the cohort of 176 COVID-19 patients presenting with SPNs, 62 were identified as having malignant SPNs, and the remaining 114 were diagnosed with benign SPNs. CT scans revealed statistically significant differences between the benign and malignant SPNs groups in terms of CT values (P<0.001), maximum nodule diameter (P<0.001), vascular convergence sign (P<0.001), vacuole sign (P = 0.0007), air bronchogram sign (P = 0.0005), and lobulation sign (P = 0.0005). Malignant SPNs were associated with significantly higher levels of carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) compared to benign SPNs (P < 0.05), while no significant difference was found in carbohydrate antigen 125 (CA125) levels (P = 0.054 for non-COVID-19; P = 0.072 for COVID-19). The sensitivity (95.83%), specificity (95.32%), and accuracy (95.51%) of the comprehensive diagnosis combining serum tumor markers and CT were significantly higher than those of CT alone (70.45%, 79.89%, 76.78%) or serum tumor marker testing alone (56.52%, 73.71%, 67.79%) (P < 0.05). A visual nomogram predictive model for malignant pulmonary nodules was constructed. CONCLUSION: Combining CT with testing for CEA, CA125, and NSE levels offers high diagnostic accuracy and sensitivity, enables precise differentiation between benign and malignant nodules, particularly in the context of COVID-19, thereby reducing the risk of unnecessary surgical interventions.

Angiotensin II depends on hippo/YAP signaling to reprogram angiogenesis and promote liver fibrosis.

Liver fibrosis is a chronic pathological process in which the abnormal proliferation of connective tissue is induced by various pathogenic factors. During the process of fibrosis, excessive angiogenesis is observed. Physiological angiogenesis has the potential to impede the progression of liver fibrosis through augmenting matrix metalloenzyme activity; however, pathological angiogenesis can exacerbate liver fibrosis by promoting collagen accumulation. Therefore, a key scientific research focus in the treatment of liver diseases is to search for the "on-off" mechanism that regulates angiogenesis from normal proliferation to pathological proliferation. In this study, we found that excessive angiogenesis appeared during the initial phase of hepatic fibrosis without mesenchymal characteristics. In addition, angiogenesis accompanied by significant endothelial-to-mesenchymal transition (EndMT) was observed in mice after the intraperitoneal injection of angiotensin II (Ang II). Interestingly, the changes in Yes-associated protein (YAP) activity in endothelial cells (ECs) can affect the regulation of angiogenesis by Ang II. The results of in vitro experiments revealed that the regulatory influence of Ang II on ECs was significantly attenuated upon suppression of YAP activity. Furthermore, the function of Ang II in regulating angiogenesis during fibrosis was investigated in liver-specific transgenic mice. The results revealed that Ang II gene deletion could restrain liver fibrosis and EndMT. Meanwhile, Ang II deletion downregulated the profibrotic YAP signaling pathway in ECs. The small molecule AT1R agonist olmesartan targeting Ang II-YAP signaling could also alleviate liver fibrosis. In conclusion, this study identified Ang II as a pivotal regulator of EndMT during the progression of liver fibrosis and evaluated the therapeutic effect of the Ang II-targeted drug olmesartan on liver fibrosis.

[Advances in Research of the Effects and Mechanisms of Polyethylene Microplastics on Soil Nitrogen Transformation].

In the agricultural lands of China, polyethylene is the main component of microplastics （MPs）, with characteristics such as small size, wide distribution, easy accumulation, and difficult degradation. Therefore, it may have an impact on the elemental cycling process of the soil. On the basis of reviewing the key literatures in the past few years, this study systematically analyzed and summarized the key factors and processes of the polyethylene microplastics （PE-MPs） affecting soil nitrogen transformation. On the one hand, PE-MPs directly affected the activities of microorganisms and key enzymes related to soil nitrogen transformation by enriching microorganisms, selecting colonized microbial populations, and releasing additives. On the other hand, PE-MPs had indirect impacts on the activities of microorganisms and key enzymes related to soil nitrogen transformation by affecting soil physicochemical properties of soil and changing the microenvironment for microbial growth. Moreover, phthalates, an important additive of the MPs, may be the key factor affecting soil nitrogen transformation in the short-term. Finally, we posed key scientific issues that should be further studied in order to provide scientific support for nitrogen nutrition regulation and ecological risk assessment of soils contaminated by PE-MPs.

Global Epidemiologic Trends and Projections to 2030 in Non-Rheumatic Degenerative Mitral Valve Disease from 1990 to 2019: An Analysis of the Global Burden of Disease Study 2019.

Background: No studies have updated the epidemiologic changes in non-rheumatic degenerative mitral valve disease (DMVD) since 2019, thus this study utilized data from the Global Study of Diseases, Injuries, and Risk Factors 2019 (GBD2019) to assess the burden of DMVD in 204 countries and territories over the period 1990-2019, as well as changes in the prevalence, incidence, deaths and changes in disability-adjusted life years (DALYs). Methods: Using the results from the GBD2019, analyzing the incidence, prevalence, deaths, and DALYs rates, as well as their age-standardized rates (ASR). Based on the human development index (HDI), the socio-demographic index (SDI), age, and sex. Results: In 2019, there were 24.229 million (95% uncertainty interval (UI) 23.081-25.419 million) existing cases of DMVD worldwide, with 1.064 million (95% UI 1.010-1.122 million) new cases and 0.034 million (95% UI 0.028-0.043 million) deaths, and 0.883 million (95% UI 0.754-1.092 million) disability-adjusted life years. The incidence, prevalence, deaths, and DALYs of DMVD and their ASR showed significant differences across sex, age groups, regions, and countries from 1990 to 2019. It is projected that by 2030, the incidence of DMVD in females will be 0.72 million with an ASR of 15.59 per 100,000 population, 0.51 million in males with an ASR of 11.75 per 100,000 population, and a total incidence of 1.23 million with an ASR of 14.03 per 100,000 population. Conclusions: DMVD remains a significant public health problem that cannot be ignored, despite a decreasing trend in the ASR of global incidence, prevalence, deaths and DALYs from 1990 to 2019. However, we note an adverse development trend in countries with low socio-demographic indexes and seriously aging societies, and sex inequality is particularly prominent. This indicates the need to reposition current prevention and treatment strategies, with some national health administrations developing corresponding strategies for preventing an increase in DMVD based on local health, education, economic conditions, sex differences, and age differences.

[Anti-inflammatory effect and its mechanism of Saracae Cortex based on zebrafish model and network pharmacology].

This paper aims to explore the anti-inflammatory mechanism of Saracae Cortex by using network pharmacology and molecular docking methods and verify it through the inflammation model of zebrafish. The effective components, potential core targets, and signaling pathways of Saracae Cortex were obtained by using network pharmacology. A lipopolysaccharide(LPS)-induced inflammation model of zebrafish was established to evaluate the anti-inflammatory activity of aqueous extract and 70% ethanol extract of Saracae Cortex with cell apoptosis rate and reactive oxygen species(ROS) production rate as indicators. q PCR was performed to verify the main targets predicted by network pharmacology. The prediction found that there were 121 potential anti-inflammatory targets in Saracae Cortex. Protein-protein interaction(PPI) analysis showed that Saracae Cortex mainly acted on signal transducer and activator of transcription 3(STAT3), vascular endothelial growth factor A( VEGFA), epidermal growth factor( EGF), tumor necrosis factor( TNF),tumor protein p53(TP53), matrix metalloprotein 9(MMP9), c-fos proto-oncogene protein(FOS), estrogen receptor 1(ESR1), cx-c motif chemokine ligand 8(CXCL8), cluster of differentiation 8(CD8), and other targets. Gene Ontology(GO) analysis showed the biological process mainly acted on the inhibition of apoptosis, the positive regulation of gene expression, and the positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that the mitogen-activated protein kinase(MAPK) signaling pathway, PI3K-Akt signaling pathway, and hypoxia-inducible factor 1(HIF-1) signaling pathway may play a key role in anti-inflammation of Saracae Cortex. Molecular docking verified that five key compounds had a strong binding force with their corresponding core target. Zebrafish animal experiments showed that Saracae Cortex could significantly inhibit ROS formation and reduce cell apoptosis in juvenile fish caused by inflammation and inhibit the further enhancement of inflammatory response in tissue. In addition, compared with the blank group, the transcription levels of nuclear factor kappa-B(NF-κB), TP53, FOS, adaptor protein complex-1(AP-1), and mitogen-activated protein kinases P38(P38) were significantly up-regulated in the model group. Compared with the model group, the m RNA expression of NF-κB, TP53, FOS, AP-1, and P38 was significantly down-regulated in zebrafish tissue treated with aqueous extract and 70% ethanol extract of Saracae Cortex. Saracae Cortex plays an anti-inflammatory role through multiple components and targets, and its anti-inflammatory effect may be related to the inhibition of the MAPK signaling pathway.

Exploring the Mechanism of Asiatic Acid against Atherosclerosis Based on Molecular Docking, Molecular Dynamics, and Experimental Verification.

Asiatic acid (AA) is a pentacyclic triterpene derived from the traditional medicine Centella asiatica. It is known for its anti-inflammatory, antioxidant, and lipid-regulating properties. Though previous studies have suggested its potential therapeutic benefits for atherosclerosis, its pharmacological mechanism is unclear. The objective of this study was to investigate the molecular mechanism of AA in the treatment of atherosclerosis. Therefore, network pharmacology was employed to uncover the mechanism by which AA acts as an anti-atherosclerotic agent. Furthermore, molecular docking, molecular dynamics (MD) simulation, and in vitro experiments were performed to elucidate the mechanism of AA's anti-atherosclerotic effects. Molecular docking analysis demonstrated a strong affinity between AA and PPARγ. Further MD simulations demonstrated the favorable stability of AA-PPARγ protein complexes. In vitro experiments demonstrated that AA can dose-dependently inhibit the expression of inflammatory factors induced by lipopolysaccharide (LPS) in RAW264.7 cells. This effect may be mediated through the PPARγ/NF-κB signaling pathway. This research underscores anti-inflammation as a crucial biological process in AA treatments for atherosclerosis, with PPARγ potentially serving as a key target.

Combining metabolomics and network pharmacology to investigate the protective effect of Jiawei Xinglou Chengqi Granules in ischemic stroke.

Jiawei Xinglou Chengqi Granule (JXCG) is an effective herbal medicine for the treatment of ischemic stroke (IS). JXCG has been shown to effectively ameliorate cerebral ischemic symptoms in clinical practice, but the underlying mechanisms are unclear. In this study, we investigated the mechanisms of action of JXCG in the treatment of IS by combining metabolomics with network pharmacology. The chemical composition of JXCG was analyzed using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry (UHPLC-Q-TOF MS) untargeted metabolomics were used to identify differential metabolites within metabolic pathways. Network pharmacology was applied to mine potential targets of JXCG in the treatment of IS. The identified key targets were validated by constructing an integrated network of metabolomics and network pharmacology and by molecular docking using Cytoscape. The effect of JXCG on IS was evaluated in vivo, and the predicted targets and pathways of JXCG in IS therapy were assessed using immunoblotting. Combining metabolomics and network pharmacology, we identified the therapeutic targets of JXCG for IS. Notably, JXCG lessened neuronal damage and reduced cerebral infarct size in rats with IS. Western blot analysis showed that JXCG upregulated PRKCH and downregulated PRKCE and PRKCQ proteins. Our combined network pharmacology and metabolomics findings showed that JXCG may have therapeutic potential in the treatment of IS by targeting multiple factors and pathways.

Size Dependence of Ultrafast Electron Transfer from Didodecyl Dimethylammonium Bromide-Modified CsPbBr3 Nanocrystals to Electron Acceptors.

Charge transfer efficiencies in all-inorganic lead halide perovskite nanocrystals (NCs) are crucial for applications in photovoltaics and photocatalysis. Herein, CsPbBr3 NCs with different sizes are synthesized by varying the ligand contents of didodecyl dimethylammonium bromide at room temperature. Adding benzoquinone (BQ) molecules leads to a decrease in the PL intensities and PL decay times in NCs. The electron transfer (ET) efficiency (ηET) increases with NC size in complexes of CsPbBr3 NCs and BQ molecules (NC-BQ complexes), when the same concentration of BQ is maintained, as investigated by transient photobleaching and photoluminescence spectroscopies. Controlling the same number of attached BQ acceptor molecules per NC induces the same ηET in NC-BQ complexes even though with different NC sizes. Our findings provide new insights into ultrafast charge transfer behaviors in perovskite NCs, which is important for designing efficient light energy conversion devices.

Evaluating nomogram models for predicting survival outcomes in gastric gastrointestinal stromal tumors with SEER database analysis.

Gastrointestinal stromal tumors (GISTs) predominantly develop in the stomach. While nomogram offer tremendous therapeutic promise, there is yet no ideal nomogram comparison customized specifically for handling categorical data and model selection related gastric GISTs. (1) We selected 5463 patients with gastric GISTs from the SEER Research Plus database spanning from 2000 to 2020; (2) We proposed an advanced missing data imputation algorithm specifically designed for categorical variables; (3) We constructed five Cox nomogram models, each employing distinct methods for the selection and modeling of categorical variables, including Cox (Two-Stage), Lasso-Cox, Ridge-Cox, Elastic Net-Cox, and Cox With Lasso; (4) We conducted a comprehensive comparison of both overall survival (OS) and cancer-specific survival (CSS) tasks at six different time points; (5) To ensure robustness, we performed 50 randomized splits for each task, maintaining a 7:3 ratio between the training and test cohorts with no discernible statistical differences. Among the five models, the Cox (Two-Stage) nomogram contains the fewest features. Notably, at Near-term, Mid-term, and Long-term intervals, the Cox (Two-Stage) model attains the highest Area Under the Curve (AUC), top-1 ratio, and top-3 ratio in both OS and CSS tasks. For the prediction of survival in patients with gastric GISTs, the Cox (Two-Stage) nomogram stands as a simple, stable, and accurate predictive model with substantial promise for clinical application. To enhance the clinical utility and accessibility of our findings, we have deployed the nomogram model online, allowing healthcare professionals and researchers worldwide to access and utilize this predictive tool.

Selenobacteria-mediated Se transformation and uptake involving the unique genetic code.

Selenium (Se) is a crucial micronutrient for human health. Plants are the primary source of Se for humans. Selenium in the soil serves as the primary source of Se for plants. The soil contains high total Se content in large areas in Guangxi, China. However, the available Se is low, hindering Se uptake by plants. Microorganisms play a pivotal role in the activation of Se in the soil, thereby enhancing its uptake by plants. In this study, selenobacteria were isolated from Se-rich soils in Guangxi. Then two selenobacteria strains, YLB1-6 and YLB2-1, representing the highest (30,000 µg/mL) and lowest (10,000 µg/mL) Se tolerance levels among the Se-tolerant bacteria, were selected for subsequent analysis. Although the two selenobacteria exhibited distinct effects, they can significantly transform Se species, resulting in a decrease in the soil residual Se (RES-Se) content while concurrently increasing the available Se (AVA-Se) content. Selenobacteria also enhance the transformation of Se valencies, with a significant increase observed in soluble Se6+ (SOL-Se6+). Additionally, selenobacteria can elevate the pH of acidic soil. Selenobacteria also promote the uptake of Se into plants. After treatment with YLB1-6 and YLB2-1, the Se content in the aboveground part of Chinese flowering cabbage increased by 1.96 times and 1.77 times, respectively, while the Se accumulation in the aboveground part of the plant significantly increased by 104.36% and 81.69%, respectively, compared to the control. Further whole-genome sequencing revealed the genetic difference between the two selenobacteria. Additionally, 46 and 38 candidate genes related to selenium utilization were identified from YLB1-6 and YLB2-1, respectively. This work accelerates our understanding of the potential molecular mechanism of Se biofortification by selenobacteria. It also provides microorganisms and gene targets for improving crop varieties or microorganisms to exploit the rich Se source in soil.

Spatially Confined π-Complexation within Pore-Space-Partitioned Metal-Organic Frameworks for Enhanced Light Hydrocarbon Separation and Purification.

Ultramicroporous metal-organic frameworks (MOFs) are demonstrated to be advantageous for the separation and purification of light hydrocarbons such as C2H2, C2H4, and CH4. The introduction of transition metal sites with strong π-complexation affinity into MOFs is more effective than other adsorption sites for the selective adsorption of π-electron-rich unsaturated hydrocarbon gases from their mixtures. However, lower coordination numbers make it challenging to produce robust MOFs directly utilizing metal ions with π-coordination activity, such as Cu+, Ag+, and Pd2+. Herein, a series of novel π-complexing MOFs (SNNU-33s) with a pore size of 4.6 Å are precisely constructed by cleverly introducing symmetrically matched C3-type [Cu(pyz)3] (pyz = pyrazine) coordinated fragments into 1D hexagonal channels of MIL-88 prototype frameworks. Benifit from the spatial confinement combined with π-complex-active Cu+ of [Cu(pyz)3], pore-space-partitioned SNNU-33 MOFs all present excellent C2H2/CH4, C2H4/CH4, and CO2/CH4 separation ability. Notably, the optimized SNNU-33b adsorbent demonstrates top-level IAST selectivity values for C2H2/CH4 (597.4) and C2H4/CH4 (69.8), as well as excellent breakthrough performance. Theoretical calculations further reveal that such benchmark light hydrocarbon separation and purification ability is mainly ascribed to the extra-strong binding affinity between Cu+ and π-electron donor molecules via a spatially confined π-complexation process.

Case report: Urachal perivascular epithelioid cell tumor.

Background: Urachal tumors are rare in clinical practice, among which urachal adenocarcinoma is the most common. In this study, we report a rare case of urachal perivascular epithelioid cell tumor to improve our understanding of the disease. Case presentation: A 26-year-old male patient was hospitalized for lower abdominal pain. The US showed a hypoechoic mass measuring 26mm × 18mm in the superior aspect of the bladder. MRI showed an irregular mass located anterior to the bladder roof, near the midline. The tumor exhibited hypointense on T1WI and heterogeneous hyperintense on T2WI. Additionally, contrast-enhanced T1-weighted imaging revealed obvious ring enhancement of the tumor. The patient underwent surgical resection of the urachal tumor, with subsequent pathological examination revealing a diagnosis of urachal PEComa. Following surgery, the patient underwent regular follow-up assessments, with no evidence of recurrence or metastasis observed after three and a half years. Conclusions: Urachal PEComa is a rare mesenchymal tumor that presents challenges in diagnosis through imaging and clinical symptoms. Definitive diagnosis relies on pathological and immunohistochemical analysis. Due to the rarity of urachal PEComa, prognosis assessment necessitates long-term follow-up and evaluation of more cases.

Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma.

BACKGROUND: Dysregulation of iron metabolism has been shown to have significant implications for cancer development. We aimed to investigate the prognostic and immunological significance of iron metabolism-related genes (IMRGs) in nasopharyngeal carcinoma (NPC). METHODS: Multiple Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were analyzed to identify key IMRGs associated with prognosis. Additionally, the immunological significance of IMRGs was explored. RESULTS: A novel risk model was established using the LASSO regression algorithm, incorporating three genes (TFRC, SLC39A14, and ATP6V0D1).This model categorized patients into low and high-risk groups, and Kaplan-Meier analysis revealed significantly shorter progression-free survival for the high-risk group (P < 0.0001). The prognostic model's accuracy was additionally confirmed by employing time-dependent Receiver Operating Characteristic (ROC) curves and conducting Decision Curve Analysis (DCA). High-risk patients were found to correlate with advanced clinical stages, specific tumor microenvironment subtypes, and distinct morphologies. ESTIMATE analysis demonstrated a significant inverse relationship between increased immune, stromal, and ESTIMATE scores and lowered risk score. Immune analysis indicated a negative correlation between high-risk score and the abundance of most tumor-infiltrating immune cells, including dendritic cells, CD8+ T cells, CD4+ T cells, and B cells. This correlation extended to immune checkpoint genes such as PDCD1, CTLA4, TIGIT, LAG3, and BTLA. The protein expression patterns of selected genes in clinical NPC samples were validated through immunohistochemistry. CONCLUSION: This study presents a prognostic model utilizing IMRGs in NPC, which could assist in assessing patient prognosis and provide insights into new therapeutic targets for NPC.

Light-induced photoluminescence enhancement in chiral CdSe quantum dot films.

Chiral quantum dots (QDs) are promising materials applied in many areas, such as chiral molecular recognition and spin selective filter for charge transport, and can be prepared by facile ligand exchange approaches. However, ligand exchange leads to an increase in surface defects and reduces the efficiencies of radiative recombination and charge transport, which restricts further applications. Here, we investigate the light-induced photoluminescence (PL) enhancement in chiral L- and D-cysteine CdSe QD thin films, providing a strategy to increase the PL. The PL intensity of chiral CdSe QD films can be significantly enhanced over 100 times by continuous UV laser irradiation, indicating a strong passivation of surface defects upon laser irradiation. From the comparative measurements of the PL intensity evolutions in vacuum, dry oxygen, air, and humid nitrogen atmospheres, we conclude that the mechanism of PL enhancement is photo-induced surface passivation with the assistance of water molecules.

A radiomics signature derived from CT imaging to predict MSI status and immunotherapy outcomes in gastric cancer: a multi-cohort study.

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.

Development and validation of a nomogram for Siewert II esophagogastric junction adenocarcinoma: a retrospective analysis.

Background: Due to the complex histological type and anatomical structures, there has been considerable debate on the classification of adenocarcinoma of the esophagogastric junction (AEG), especially Siewert II AEG. Furthermore, neither the American Joint Committee on Cancer (AJCC) 7th tumor-node-metastasis (TNM) [esophageal adenocarcinoma (E) or gastric cancer (G)] nor the AJCC 8th TNM (E or G) accurately predicted the prognosis of patients with Siewert II AEG. Objective: This study aimed to investigate the factors influencing the survival and prognosis of patients with Siewert II AEG and establish a new and better prognostic predictive model. Design: A retrospective study. Methods: Patients with Siewert II AEG, retrieved from the Surveillance, Epidemiology, and End Results (SEER) databases, were assigned to the training set. Patients retrieved from a single tertiary medical center were assigned to the external validation set. Significant variables were selected using univariate and multivariate Cox regression analyses to construct the nomogram. Nomogram models were assessed using the concordance index (C-index), a calibration plot, decision curve analysis (DCA), and external validation. Results: Age, tumor grade, and size, as well as the T, N, and M stages, were included in the nomograms. For the SEER training set, the C-index of the nomogram was 0.683 (0.665-0.701). The C-index of the nomogram for the external validation set was 0.690 (0.653-0.727). The calibration curve showed good agreement between the nomogram estimations and actual observations in both the training and external validation sets. The DCA showed that the nomogram was clinically useful. Conclusion: The new predictive model showed significant accuracy in predicting the prognosis of Siewert II AEG.

Combining metabolomics and network pharmacology to investigate the protective effect of Jiawei Xinglou Chengqi Granules in ischemic stroke

Jiawei Xinglou Chengqi Granule (JXCG) is an effective herbal medicine for the treatment of ischemic stroke (IS). JXCG has been shown to effectively ameliorate cerebral ischemic symptoms in clinical practice, but the underlying mechanisms are unclear. In this study, we investigated the mechanisms of action of JXCG in the treatment of IS by combining metabolomics with network pharmacology. The chemical composition of JXCG was analyzed using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry (UHPLC-Q-TOF MS) untargeted metabolomics were used to identify differential metabolites within metabolic pathways. Network pharmacology was applied to mine potential targets of JXCG in the treatment of IS. The identified key targets were validated by constructing an integrated network of metabolomics and network pharmacology and by molecular docking using Cytoscape. The effect of JXCG on IS was evaluated in vivo, and the predicted targets and pathways of JXCG in IS therapy were assessed using immunoblotting. Combining metabolomics and network pharmacology, we identified the therapeutic targets of JXCG for IS. Notably, JXCG lessened neuronal damage and reduced cerebral infarct size in rats with IS. Western blot analysis showed that JXCG upregulated PRKCH and downregulated PRKCE and PRKCQ proteins. Our combined network pharmacology and metabolomics findings showed that JXCG may have therapeutic potential in the treatment of IS by targeting multiple factors and pathways.

Paired Box 5 (PAX5) Gene Has Diagnostic and Prognostic Potential in Nasopharyngeal Carcinoma.

Purpose: Paired Box 5 (PAX5) is a transcription factor that is widely associated with carcinogenesis. PAX5 can maintain Epstein-Barr virus (EBV) latency in B cells, while a close association exists between EBV infection and nasopharyngeal carcinoma (NPC). However, there are very few reports on the correlation between PAX5 and NPC development. The aim of this study was to investigate the role of PAX5 in NPC. Patients and Methods: The clinical value and prognostic significance of PAX5 in NPC and the association with PAX5 expression and immune cell infiltration were analyzed by multiple GEO datasets. In vivo and in vitro experiments including real-time PCR, Western blot, CCK-8 assay, and methylation sequencing were used to validate the results of bioinformatics analysis. Results: The expression of PAX5 was significantly reduced in NPC tissues, with the low expression being correlated with advanced clinical stage, low tumor mutation burden and immune activation, high relative expression of EBV, poor survival for NPC patients. PAX5 exhibited excellent diagnostic performance and had potential as a predictive factor for response to the immune checkpoint inhibitors therapy. Enrichment analysis suggested that the low expression of PAX5 was associated with the dysregulation of Hippo and Wnt signaling pathways. The promoter of PAX5 gene was hypermethylated in NPC tissues. Furthermore, the in vitro and in vivo experiments revealed that NPC tissue and cell lines had low mRNA expression levels of PAX5, the PAX5 promoter was hypermethylated in NPC cell lines, and PAX5 overexpression inhibited NPC cell proliferation and tumor growth in nude mice. Conclusion: PAX5 may be a tumor suppressor and serve as a novel potential diagnostic and prognostic marker for NPC.

Zhilong Huoxue Tongyu capsule alleviates myocardial fibrosis by improving endothelial cell dysfunction.

Background and aim: Zhilong Huoxue Tongyu (ZL) capsule is a classical traditional Chinese medicine (TCM) with satisfactory curative effects. Endothelial cell (EC) dysfunction plays an important role during myocardial fibrosis (MF). But the therapeutic effect of ZL capsule on EC dysfunction remains unknown in the development of MF. This study aims to investigate the effect of ZL capsule on EC dysfunction during MF in vivo. Experimental procedure: The model of MF is established in vivo by injecting isoproterenol for 14 days, simultaneously, we examined the therapeutic effect of ZL capsule on MF in vivo. An integrative approach combining biomarker examination, echocardiography and myocardial fibrosis condition using Hematoxylin-eosin staining, Masson staining, and Sirius red staining were performed to assess the efficacy of ZL capsule against MF. Subsequently, comprehensive immunofluorescence staining was performed to evaluate the therapeutic effect of ZL capsule on EC dysfunction. Results and conclusion: Prior to experiments, analysis of the published single-cell sequencing data was performed and it was discovered that EC dysfunction plays an important role. Further pharmacological results showed that ZL capsule could alleviate fibrosis injury and collagen fiber deposition. The mechanism investigation results showed that the endothelial-to-mesenchymal transition (EndMT) and MHC class-II (MHC-II) expression in EC were improved. In addition, ZL capsule can attenuate the inflammatory response during MF by intervening the activation of CD4+T cell mediated by EC. For the first time, we provided evidence that ZL capsule could improve MF by alleviating EC dysfunction via the regulation of EndMT and expression of MHC-II. Taxonomy classification by evise: Myocardial fibrosis, Chinese Herbal Medicine, Traditional Medicine, Endothelium, dysfunction, Endothelial-to-mesenchymal transition.