Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.

ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Tetrodotoxin（TTX）is a potent neurotoxin known for its specific sodium channel blocking effects, widely used in biomedical research. While TTX has been identified in various marine organisms, its true origin remains unclear, and the specific biosynthetic pathways are yet to be elucidated. The reported sources of TTX and the progress in research on TTX biosynthesis were summarized, with a focus on potential microbial sources of TTX, which could provide scientific reference for the production and biosynthesis studies of TTX.

Neurological diseases have high morbidity and disability rates， posing a severe threat to human health. Cli nical manifestations include motor， sensory， cognitive and conscious disorders. Chaihu jia longgu muli decoction is derived from Treatise on Febrile Diseases ， with the effects of harmonizing Shaoyang， activating Yang and clearing heat， and tranquilizing the mind. This paper systematically reviews the research progress in clinical application and mechanism of Chaihu jia longgu muli decoction in the field of neurological diseases. It has been found that the decoction shows favorable efficacy in various neurological diseases such as insomnia， depression， epilepsy， vertigo， migraine and vascular dementia. The specific mechanisms are related to regulating neurotransmitter levels， repairing neuronal function， alleviating neuroinflammation， improving mitochondrial dysfunction and regulating intestinal flora. In the future， standardized prospective follow-up cohorts should be established， and core outcome indicators should be clearly defined to strengthen the evidence base. Furthermore， multidisciplinary research should be leveraged to expand the therapeutic value of Chaihu jia longgu muli decoction in the management of neurological diseases.

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.

Moyamoya disease (MMD) is widely recognized as an important cause of ischemic stroke and hemorrhagic stroke. Cerebral revascularization is the standard treatment for preventing stroke recurrence in patients with MMD. However, cerebral hyperperfusion syndrome (CHS) is one of the main complications of cerebral revascularization in patients with MMD. This article reviews the predictive factors for postoperative CHS in patients with MMD undergoing cerebral revascularization.

Objective To investigate the mechanism by which angiopoietin-like protein 8(ANGPTL8)regulates vascular smooth muscle cell(VSMCs)apoptosis.Methods An in vitro abdominal aortic aneurysm cell model was established by stimulating human VSMCs(HUSMCs)with angiotensin Ⅱ(AngⅡ).Stable ANGPTL8 knockdown and over-expression VSMC cell strains were generated using lentiviral transfection.TUNEL staining was used to de-tect apoptosis.Western blot analysis was performed to measure the protein expression of ANGPTL8,caspase9,caspase3,Bcl-2,Bax,p53,and PUMA,while RT-qPCR was used to assess mRNA expression of ANGPTL8,Bcl-2 and Bax.Results AngⅡ significantly induced ANGPTL8 expression in HVSMCs in a time-and dose-de-pendent manner(P＜0.05).ANGPTL8 knockdown significantly reduced the expression of apoptosis-related proteins caspase9,caspase3,and Bax,while increased the expression of the anti-apoptotic protein Bcl-2(P＜0.05).Con-versely,ANGPTL8 over-expression markedly induced HVSMCs apoptosis,which was significantly suppressed by treatment with the p53 pathway inhibitor pifithrin-α(PFT-α).Conclusions ANGPTL8 may promote VSMC apop-tosis by activation of p53 signaling pathway.

Objective To investigate the relationships of the mRNA expression levels of mitochon-drial ribosomal large subunit protein 13(MRPL13),BCL2-associated protein A1(BCL2A1)and TP53 apoptosis-inducing protein 1(TP53AIP1)in the serum of breast cancer patients with their chemotherapy efficacy as well as immune function.Methods A total of 148 triple-negative breast cancer patients undergoing chemotherapy were selected as the study subjects.Based on chemotherapy efficacy,they were divided into responsive group(97 cases)and non-responsive group(51 cases).Sixty healthy individuals undergoing physical examinations during the same period were selected as the control group.The mRNA expression levels of MRPL13,BCL2A1 and TP53AIP1 in the serum of patients were detected.The concentrations of immunoglobulin M(IgM),immunoglobulin G(IgG)and im-munoglobulin A(IgA)in the serum of patients were measured,and the proportions of CD4+and CD8+cells in whole blood were determined.The mRNA expression levels of MRPL13,BCL2A1 and TP53AIP1 were compared between the breast cancer group and the control group.The mRNA ex-pression levels of MRPL13,BCL2A1 and TP53AIP1 were compared between the responsive and non-responsive groups.The differences in immune function indicators before and after chemotherapy be-tween the responsive and non-responsive groups,were compared.The correlations of the mRNA ex-pression levels of MRPL13,BCL2A1 and TP53AIP1 with immune indicators were analyzed.Factors influencing chemotherapy efficacy were screened.Results The mRNA expression levels of MRPL13 and BCL2A1 in the breast cancer group were higher than those in the control group,while the mRNA expression level of TP53AIP1 was lower,with statistically significant differences(P＜0.05).In the responsive group,the mRNA expression levels of MRPL13 and BCL2A1 were lower than those in the non-responsive group,while the mRNA expression level of TP53AIP1 was higher,with statistically significant differences(P＜0.05).After chemotherapy,the IgM concentration in the responsive group was higher than that in the non-responsive group,with a statistically significant difference(P＜0.05).The proportion of CD8+cells in the responsive group was lower than that in the non-responsive group,with a statistically significant difference(P＜0.05).The mRNA expres-sion level of MRPL13 was positively correlated with IgM,IgG and CD8+(r=0.672,0.716,0.824,P＜0.05).The mRNA expression level of BCL2A1 was positively correlated with IgA and CD4+(r=0.654,0.862,P＜0.05).The mRNA expression level of TP53AIP1 was negatively cor-related with CD4+and CD8+(r=-0.846,-0.792,P＜0.05).High expressions of MRPL13 and BCL2A1 were independent risk factors for chemotherapy efficacy in breast cancer patients(P＜0.05),while high expression of TP53AIP1 was protective factor(P＜0.05).Conclusion The mRNA expression levels of MRPL13,BCL2A1 and TP53AIP1 in the serum of triple-negative breast cancer patients undergoing chemotherapy are correlated with the levels of IgM,IgG and IgA,the proportions of CD4+and CD8+T cells,and chemotherapy efficacy.High expression of MRPL13 and BCL2A1 are independent risk factors for poor chemotherapy efficacy,while high expression of TP53AIP1 is a protective factor.

Objective:To explore the movement patterns and factors influencing lung tumors tracked using the M6 cyberknife stereotactic radiotherapy(SRT)system and to provide a reference for the implementation of precise stereotactic radiotherapy for lung tumors.Method:A retrospective analysis was conducted on 29 patients with lung tumors who were treated using x-sight lung tracking technology and the M6 cyberknife SRT system at Tianjin Medical University Cancer Institute&Hospital,from January 2022 to August 2024.The tumor location and volume,irradiation dose,isodose line,and number of divisions were recorded.Lung tumor location and SPSS 26.0 software were used to analyze the movement amplitude of tumors in the left and right(LFT/RGT,LR)directions,the anterior-posterior(ANT/POS,AP)direction,and the superior-inferior(SUP/INF,SI)direction.The results are expressed as the mean±standard deviation((x)±s)mm,and a t-test was used for inter-group comparisons.Multiple linear regression was used to analyze the effects of factors such as age,gender,tumor location(upper and lower lungs),and tumor volume on the amplitudes of the lung tumor movements.Result:The average motion amplitudes in the LR direc-tions,AP direction,and SI direction of the tumor target areas were(3.5±1.8)mm,(5.3±1.7)mm,and(7.3±5.4)mm for the upper lung,based on 19 cases,and(3.1±1.6)mm,(4.5±2.2)mm,and(12.2±4.4)mm for the lower lung,based on 10 cases,respectively.There was a statistic-ally significant difference(P=0.015 3)in the amplitude of movements between the lower and upper lung tumors in the SI direction.The lung tumor movement amplitude in the SI direction was influenced by tumor location(P=0.035),and the movement amplitudes in the LR direc-tions and the AP direction were not related to factors such as gender,age,tumor location,and tumor volume.Conclusions:The lung tumor movement amplitudes for the different locations varied depending on the respiratory movement shown by the patient.In the SI direction,the movement amplitude of the lower lung tumors was greater than that of upper lung tumors,and this was due to tumor location effects.The movement amplitudes of the lower and upper lung tumors were similar in the LR directions and AP directions.Furthermore,movement amplitude was not affected by gender,age,tumor location,and tumor volume.

Objective:To establish criteria for diagnosing lymph node metastasis (LNM) in newly diagnosed papillary thyroid cancer (PTC) patients based on 18F-FDG PET/MR and evaluate its diagnostic efficiency. Methods:The data of 14 patients with PTC (all females, age (38.8±13.5) years) who underwent 18F-FDG PET/MR and ultrasound sequentially 2 weeks before surgery at the First Affiliated Hospital of the Air Force Medical University from May 2021 to August 2023 were retrospectively analyzed. Visual and semi-quantitative assessments were performed on all patients step by step (Ⅱ-Ⅵ area) and neck by neck (left, right, and central area). The dimensions of all suspected lymph nodes were measured on T 2 weighted imaging (WI)-MRI and SUV max was measured on PET. Taking postoperative pathology as the reference standard, the independent risk factors for predicting LNM were determined by multivariate logistic regression analysis, and the diagnostic efficiency of each model was evaluated by ROC curve analysis. Results:A total of 21 macroscopic regions of lymph nodes(15 were malignant, 6 were benign) and 178 lymph nodes (120 were malignant, 58 were benign) were cleared by surgery. Multivariate logistic regression analysis showed that SUV max (odds ratio ( OR)=1.865, 95% CI: 1.323-2.630, P<0.001) and short diameter on MRI (SD-MRI) ( OR=1.752, 95% CI: 1.189-2.580, P=0.005) were independent predictors of LNM. The cut-off value of SD-MRI in predicting LNM was 5.7mm (AUC=0.812, Youden index (YI)=0.463). For the SD-MRI cut-off values ≥5.7 or <5.7mm, the corresponding SUV max cut-off values were 1.6 and 1.8, respectively. When " dual threshold" quantitative criteria (SD-MRI≥5.7mm + SUV max≥1.6 or SD-MRI<5.7mm + SUV max≥1.8) was used as the diagnostic criteria of 18F-FDG PET/MR, the AUC and YI could be improved to 0.909 and 0.818. Based on the regional level analysis, sensitivity, specificity, and accuracy of LNM diagnosis by ultrasound, MRI, and 18F-FDG PET/MR " dual threshold" criteria were 11/15 vs 12/15 vs 13/15, 5/6 vs 3/6 vs 5/6, 76.2%(16/21) vs 71.4%(15/21) vs 85.7%(18/21), respectively. Conclusion:Compared with the ultrasound and MRI, the 18F-FDG PET/MR " dual threshold" criteria exhibits higher sensitivity and accuracy in determining the scope of LNM clearance for PTC patients.