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.

Objective To investigate the effects of serum insulin-like growth factor 2(IGF2),leucine-rich repeat and fibronectin type Ⅲ domain containing 5(LRFN5)levels on neurological rehabilitation in patients with ischemic stroke(IS).Methods A total of 103 patients with IS who were treated in Shiyan Taihe Hospi-tal from October 2022 to March 2024 were selected as the study group.According to the modified Rankin scale(mRS)score,they were divided into 46 cases in the poor rehabilitation group and 57 cases in the good rehabili-tation group.Another 61 healthy individuals who underwent physical examinations in the hospital during the same period were selected as the control group.The levels of serum IGF2 and LRFN5 were detected by en-zyme-linked immunosorbent assay.Pearson and Spearman correlation analyses were used to analyze the corre-lations between the levels of serum IGF2 and LRFN5 in the poor rehabilitation group and the related indica-tors of neurological function.Logistic regression was used to analyze the influencing factors of poor neurologi-cal rehabilitation in patients with IS,and the receiver operating characteristic curve was plotted to analyze the diagnostic value of serum IGF2 and LRFN5 levels for poor neurological rehabilitation in patients with IS.Re-sults The serum IGF2 level in the study group was significantly lower than that in the control group,and the LRFN5 level was significantly higher than that in the control group.The difference was statistically significant(P<0.05).The scores of the National Institutes of Health Stroke Scale(NIHSS)at admission,the 90-day mRS score,the maximum diameter of the cerebral infarction lesion and the LRFN5 level in the poor rehabilita-tion group were significantly higher than those in the good rehabilitation group,and the IGF2 level was signifi-cantly lower than that in the good rehabilitation group.The differences were statistically significant(P<0.05).The level of serum IGF2 was negatively correlated with the NIHSS score at admission,the 90-day mRS score and the maximum diameter of cerebral infarction lesions.The level of LRFN5 was positively correlated with the NIHSS score at admission,the 90-day mRS score and the maximum diameter of cerebral infarction lesions.The level of IGF2 was negatively correlated with the level of LRFN5(P<0.05).The results of Logis-tic regression analysis showed that the 90-day mRS score and LRFN5 level were risk factors for poor neuro-logical function rehabilitation in patients with IS,and the IGF2 level was a protective factor for poor neurologi-cal function rehabilitation in patients with IS(P<0.05).The area under the curve(AUC)of the combined diagnosis of serum IGF2 and LRFN5 was 0.943(95%CI:0.902-0.984),which was significantly higher than AUC of the diagnosis by a single indicator(Zcombined with the two-IGF2=2.039,P=0.041;Zcombined with the two-LRFN5=2.139,P=0.032).Conclusion The IS patients have a significant reduction in serum IGF2 level and a signifi-cant increase in serum LRFN5 level,which are closely related to their neurological function recovery.The combination of IGF2 and LRFN5 has a certain diagnostic value for neurological function recovery in IS pa-tients.

Objective:To explore the mechanism of Danxing Zhishuang Prescription in the treatment of Parkinson's disease (PD) by combining network pharmacology with animal models.Methods:TCMSP, BATMAN database, Genecards, and OMIM databases were retrieved to obtain the active components and action targets of Danxing Zhishuang Prescription. Venny 2.1.0 was used to intersect drug targets and PD related genes, and a protein interaction network of the intersection targets was constructed using the STRING 12.0 platform. Topology analysis was performed using Cytoscape 3.10.0 software to identify the key targets of Danxing Zhishuang Prescription on PD; GO functional and KEGG pathway enrichment analysis was performed on key targets using the WeChat platform, and molecular docking was validated through AutoDockTools 1.5.7. Using a random number table method, mice were divided into a blank control group, a model group, and a Danxing Zhishuang Prescription group, with 20 mice in each group; except for the blank group, all other groups of mice were orally administered fisetin to prepare PD models; Danxing Zhishuang Prescription group was orally administered with concentrated Danxing Zhishuang Prescription at a dosage of 10.5 g/kg, while the blank group and model group were orally administered with 0.2 ml of physiological saline for 21 days; Western blot was used to detect the expressions of Akt1, Bcl-2, Bax, and α-Syn proteins.Results:359 intersection targets, 69 core targets, and 185 active components were obtained the treatment of PD with Danxing Zhishuang Prescription. The main active components included quercetin, kaempferol, phenylalanine, etc., and the key targets were AKT1, TP53, TNF, ESR1, etc. KEGG analysis revealed several key signaling pathways, such as AGE-RAGE, PI3K-Akt, fluid shear stress and atherosclerosis signaling pathways. The validation experiment results showed that compared with the model group, the expression of Bcl-2 protein was up-regulated ( P<0.01), and the expressions of Bax, Akt1, and α-Syn proteins were down-regulated in the Danxing Zhishuang Prescription group ( P<0.01). Conclusions:Danxing Zhishuang Prescription has the advantages of multi target and multi pathway treatment for PD. Its mechanism may be related to down-regulating the expressions of Bax, Akt1, and α-Syn proteins, improving brain blood supply, regulating neurotransmitter balance, inhibiting oxidative stress response, and promoting nerve regeneration.

BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.

Objective: To conduct a scoping review on the types, construction methods and predictive performance of health literacy prediction models based on machine learning methods, so as to provide the reference for the improvement and application of such models. Methods: Publications on health literacy prediction models conducted using machine learning methods were retrieved from CNKI, Wanfang Data, VIP, PubMed and Web of Science from inception to May 1, 2024. The quality of literature was assessed using the Prediction Model Risk of Bias ASsessment Tool. Basic characteristics, modeling methods, data sources, missing value handling, predictors and predictive performance were reviewed. Results: A total of 524 publications were retrieved, and 22 publications between 2007 and 2024 were finally enrolled. Totally 48 health literacy prediction models were involved, and 25 had a high risk of bias (52.08%), with major issues focusing on missing value handling, predictor selection and model evaluation methods. Modeling methods included regression models, tree-based machine learning methods, support vector machines and neural network models. Predictors primarily encompassed factors at four aspects: individual, interpersonal, organizational and society/policy aspects, with age, educational level, economic status, health status and internet use appearing frequently. Internal validation was conducted in 14 publications, and external validation was conducted in 4 publications. Forty-two models reported the areas under the receiver operating characteristic curve, which ranged from 0.52 to 0.983, indicating good discrimination. Conclusion Health literacy prediction models based on machine learning methods perform well, but have deficiencies in risk of bias, data processing and validation.

OBJECTIVES: To explore potential keywords, research clusters, collaborative pattern, and research trends in the field of medical technology management (MTM) through bibliometric analysis, providing insights for researchers, policy makers, and hospital administrators. METHODS: A retrieval formula was applied to the title, abstract, and keywords in the Web of Science (WoS) Core Collection, along with system-recommended terms, to identify articles on MTM. A total of 181 articles published between 1974 and 2022 were retained for quantitative analysis. The global trend of research output; total citations, average citations, and H-index; and bibliographic coupling, co-authorship, and keyword co-occurrence were analyzed using VOSviewer. RESULTS: The number of articles on MTM has been steadily increasing year by year. The focus of research has shifted from addressing basic medical needs to prioritizing emergency response and medical information security. The United States, Italy, and the United Kingdom emerged as the main contributors, with the United States leading in both volume of publications (60 articles) and academic impact (H-index = 21). Authors from the United Kingdom and the United States led the way in cross-border cooperation. The top five institutions, ranked by total link strength among cross-institutional authors, were primarily located in Canada and Spain. CONCLUSIONS The field of MTM has experienced stable growth over the past three decades (1993-2022). The shift of research focus has prompted a heightened emphasis on protecting patient privacy and ensuring the security of medical data. Future research should emphasize interdisciplinary and professional collaboration, as well as international cooperation and open sharing of knowledge.
Bibliometrics ; Humans ; Biomedical Technology

Objective: To investigate the prevalence of human T-lymphotropic virus (HTLV) infection among blood donors in Hunan Province from 2022 to 2024. Methods: A total of 1 830 342 blood donors from 14 prefecture-level blood centers in Hunan Province over the past three years were screened for anti-HTLV-Ⅰ/Ⅱ using enzyme-linked immunosorbent assay (ELISA). Initially reactive samples were further tested with Line Immunoassay (LIA )/MP-Western blot and RT-PCR nucleic acid test for confirmation. Blood donors confirmed positive for HTLV were tracked and followed up. Results: From 2022 to 2024, the initial ELISA reactive rate for anti-HTLV-I/II among blood donors in Hunan Province was 1.36 per 10 000 (249/1 830 342). The confirmed positive rate was 0.20 per 10 000 (37/1 830 342), accounting for 14.86% of the initially reactive donors. The follow-up success rate for confirmed HTLV-positive blood donors was only 18.92%, while that for HTLV-indeterminate donors was 54.17%. Conclusion: The confirmed HTLV infection rates in Yueyang, Loudi, Shaoyang, Yiyang, and Zhuzhou cities were higher than the provincial (0.20 per 10 000). Chenzhou, Yongzhou, Zhangjiajie, and Xiangxi were identified as low prevalence areas, with an infection rate of 0. The overall follow-up success rate was low, indicating significant difficulties and bottlenecks in follow-up work. The comprehensive screening for HTLV and follow-up studies in Hunan provide valuable data to further improve blood safety testing strategies and risk warning mechanisms.

Objective To investigate the value of ¹⁸F-FDG PET/CT metabolic parameters in the prognostic assessment of nasopharyngeal cancer patients. Methods The clinical data and PET/CT metabolic parameters of 185 nasopharyngeal cancer patients were retrospectively analyzed. The collected parameters were SUV_max, MTV, TLG, total metabolic tumor volume (TMTV) and whole-body total lesion glycolysis (WTLG). The ROC curve was used to determine the optimal cut-off values of PET/CT metabolic parameters. Univariate and multivariate Cox regression models were used to screen the independent prognostic factors. Kaplan–Meier curves were used to analyze the survival differences. Results The results of univariate Cox regression analysis showed that age, pathologic type, WTLG, TMTV, MTV, and TLG were closely associated with OS and PFS; and SUV_max was associated with PFS (P<0.05). Multivariate Cox regression analysis results showed that age, TMTV, and WTLG were the independent prognostic factors for OS and PFS (P<0.05). The combination of WTLG with T/N staging (AUC=0.781 and 0.781) and TMTV with T/N staging (AUC=0.800 and 0.790) yielded greater predictive accuracy than that of WTLG and TMTV alone (AUC=0.724 and 0.719) or T/N staging (AUC=0.593 and 0.575). Conclusion TMTV and WTLG are important prognostic predictors of nasopharyngeal carcinoma. TLG and MTV of primary lesions are prognostic factors for patients’ PFS and OS. SUV_max has limited prognostic value. Systemic metabolic indexes (TMTV and WTLG), when combined with T/N staging, can optimize prognostic stratification.

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 explore the protective effects and underlying mechanisms of H ₂S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells. METHODS: Cell viability was evaluated using CCK-8 assay. Apoptosis was measured using flow cytometry. Reagent kits were used to detect carbonyl stress markers malondialdehyde, 4-hydroxynonenal, thiobarbituric acid reactive substances, and protein carbonylation. Aldehyde-protein adduct formation and alcohol dehydrogenase, aldehyde dehydrogenase 2, aldo-keto reductase, nuclear factor E2-related factor 2 (Nrf2), and cystathionine β-synthase (CBS) expression were determined using western blotting or real-time PCR. Sulforaphane (SFP) was used to activate Nrf2. RNA interference was used to inhibit CBS expression. RESULTS: GYY4137 (an H ₂S donor) pretreatment significantly reversed the uranium-induced increase in carbonyl stress markers and aldehyde-protein adducts. GYY4137 effectively restored the uranium-decreased Nrf2 expression, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2, accompanied by a reversal of the uranium-decreased expression of CBS and aldehyde-metabolizing enzymes. The application of CBS siRNA efficiently abrogated the SFP-enhanced effects on the expression of CBS, Nrf2 activation, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2 and concomitantly reversed the SFP-enhanced effects of the uranium-induced mRNA expression of aldehyde-metabolizing enzymes. Simultaneously, CBS siRNA reversed the SFP-mediated alleviation of the uranium-induced increase in reactive aldehyde levels, apoptosis rates, and uranium-induced cell viability. CONCLUSION H ₂S induces Nrf2 activation and nuclear translocation, which modulates the expression of aldehyde-metabolizing enzymes and the CBS/H ₂S axis. Simultaneously, the Nrf2-controlled CBS/H ₂S axis may at least partially promote Nrf2 activation and nuclear translocation. These events form a cycle-regulating mode through which H ₂S attenuates the carbonyl stress-mediated NRK-52E cytotoxicity triggered by uranium.
NF-E2-Related Factor 2/genetics* ; Animals ; Hydrogen Sulfide/pharmacology* ; Rats ; Signal Transduction/drug effects* ; Lipid Peroxidation/drug effects* ; Cell Line ; Uranium/toxicity* ; Antioxidant Response Elements ; Kidney/metabolism* ; Oxidative Stress/drug effects* ; Cell Survival/drug effects* ; Apoptosis/drug effects*