Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

Due to its synergistic effects and reduced side effects, combination therapy has become an important strategy for treating complex diseases. In traditional Chinese medicine (TCM), the "monarch, minister, assistant, envoy" compatibilities theory provides a systematic framework for drug compatibility and has guided the formation of a large number of classic formulas. However, due to the complex compositions and diverse mechanisms of action of TCM, it is difficult to comprehensively reveal its potential synergistic patterns using traditional methods. Synergistic prediction based on molecular compatibility theory provides new ideas for identifying combinations of active compounds in TCM. Compared to resource-intensive traditional experimental methods, artificial intelligence possesses the ability to mine synergistic patterns from multi-omics and structural data, providing an efficient means for modeling and optimizing TCM combinations. This paper systematically reviews the application progress of AI in the synergistic prediction of TCM active compounds and explores the challenges and prospects of its application in modeling combination relationships, thereby contributing to the modernization of TCM theory and methodological innovation.
Artificial Intelligence ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Drug Synergism

Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it's imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI^- towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
Schwann Cells/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Cancer-Associated Fibroblasts/metabolism* ; Animals ; Carcinoma, Squamous Cell/metabolism* ; Neoplasm Invasiveness/pathology* ; Male ; Female ; Mice ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Cell Line, Tumor ; Leukemia Inhibitory Factor/metabolism* ; Middle Aged

Objective: To investigate the mechanism of electroacupuncture (EA) for treating depression and to explore the role of brevican in the medial prefrontal cortex (mPFC) in modulating stress susceptibility and the antidepressant effects of EA in rats. Methods: Twenty-four Sprague–Dawley (SD) rats were equally divided into three groups: green fluorescent protein (GFP) + control, GFP + chronic unpredicted mild stress (CUMS), and short-hairpin RNA targeting on brevican (shBcan) + CUMS. Another 24 SD rats were equally divided into CUMS + GFP, CUMS + GFP + EA, and CUMS + shBcan + EA groups. Behavioral tests were conducted to assess depression-like behavior. Western blot analysis was used to evaluate the expression of brevican, aggrecan, GLuA1, and PSD95 in mPFC subregions. Results: Behavioral parameter evaluation show that rats in the shBcan + CUMS group exhibited a significantly reduced sucrose preference (P = .0002) and increased immobility time (P = .0011) compared to those in rats in the GFP + CUMS group. Western blotting showed that brevican expression was significantly downregulated in the PrL of the shBcan + CUMS group compared with that in the GFP + CUMS group (P = .0192). Furthermore, compared to the CUMS + GFP + EA group, the CUMS + shBcan + EA group exhibited a significantly decreased sucrose preference (P = .0334), increased immobility time (P = .0465), and increased latency to food (P = .0261). In the CUMS + shBcan + EA group, the EA-induced brevican and PSD95 overexpression was reversed, compared with that in the CUMS + GFP + EA group (P = .0454 and P = .0198, respectively). Conclusion EA exerts its antidepressant effects through the modulation of brevican expression in rats. Our findings highlight the important role for brevican in stress susceptibility, which could be a potential target for treating depression.

Chronic Disease ; Heart Failure ; therapy ; Heart Rate ; Humans

Cardiovascular Diseases ; epidemiology ; China ; epidemiology ; Humans

Objective To investigate the roles of transforming growth factor(TGF)-β1 gene polymorphisms in severe acute respiratory syndrome-coronavirus(SARS-CoV)infection and the interstitial lung fibrosis after recovered.Methods Sixty-five recovered SARS patients,37 health care workers and 66 healthy controls were enrolled in this case-case study.The association between genetic polymorphisms of TG F-β1 and suscept ibility to SARS or interstitial lung changes after SARS reco,vered was carried out.Polymerase chain reaction-sequencing based typing(PCR-SBT)method was used to determine the polymorphisms of TGF-β1 gene at locus+869 and+915.Data were analyzed using t test and chi square test.Results There was no significant association of TGF+β1 gene polymorphisms at locus+869 and+915 in recovered SARS patients,health care workers and heahhy controls.And gene linkage of this two loci was not related with SARS-CoV susceptibility.Furthermore,no association between interstitial lung changes in recovered SARS palients and TGF-β1 gene polymorphisms or genetic linkage of this two loci.Conclusions It may not be related between TGFβ1 gene polymorphisms at locus+869 and+915 and SARS-CoV susceptibility.And interstitial lung changes in recovered SARS patients may not be influenced by TGF-β1 gene polymorphisms.

Objective To analyse the cause of constipation and evaluate the diagnostic value of colonic transit test and defecography for constipation diagnosis. Methods 110 cases with constipation were studied with colonic transit test and defecography. Results Abnormal colonic transit in 79 cases and defecography in 53 cases, overpassing the integrated analysis for the result of colonic transit test and defecography, the 40 cases were colonic inertia and 53 cases were function outlet obstruction. Conclusion The associated application of colonic transit test and defecography could be more accurate to differentiate constipations which are colonic inertia or function outlet obstruction and more specific the pathogeny of function outlet obstruction, to offer reliable foundation for the clinical cure.

AIM: To explore the expression of nuclear factor-?B(NF-?B) in asthmatic guinea pigs, and the effect of erigeron breviscapus, a protein kinase C(PKC) inhibitor, on the expression of nuclear factor-?B(NF-?B). METHODS: 48 guinea pigs were randomly divided into 6 groups ( n= 8). Airway resistance and eosinophilic inflammation of airway wall were examined, the expression of NF-?B in the lung tissue was detected by immunohistochemical staining. RESULTS: The expression of NF-?B was mainly found in airway epithelium, all the asthmatic animals showed significantly higher optical densities than that of the normal control group( P