The spine is the most common site of skeletal metastasis in lung cancer, which frequently leads to severe complications such as pathological fracture and neurological compromise and is associated with poor prognosis. The development and progression of spinal metastasis from lung cancer are linked to the unique local microenvironment and tumor microenvironment (TME) of the vertebral column. During metastatic evolution, the dense vascular network of the spine and a plethora of signaling molecules, together with the complex cellular constituents and their intricate interactions within the TME, all cooperate to facilitate the tumor invasion and colonization of the vertebral compartment. Mechanistic studies delineating the role of the TME in spinal metastasis from lung cancer have markedly expanded, fostering the emergence of innovative therapeutic strategies—including nanomedicines, sono-photodynamic therapy, gene therapy, and combination regimens. These strategies demonstrate remarkably potential for clinical translation and offer new directions for the precision management of spinal metastasis from lung cancer.

Purpose To investigate the functional connectivity(FC)pattern between the bilateral lower limb sensorimotor cortex(LSM)and the whole brain in type 2 diabetic peripheral neuropathy(DPN).Materials and Methods A total of 44 DPN patients and 43 healthy controls admitted to Shaanxi Provincial People's Hospital from February 2021 to December 2022 were enrolled prospectively and underwent neuropsychological assessment and resting-state fMRI scans.Using bilateral LSM as the regions of interest,the differences of bilateral LSM and whole brain FC between DPN patients and healthy controls were compared.FC in different brain areas were extracted and correlated with clinical/neuropsychological scores.Results Compared with healthy controls,DPN patients had reduced FC of the LSM with the right cerebellar lobule Ⅵ,the right lateral occipitotemporal cortex,the bilateral rostral prefrontal cortex and the bilateral anterior cingulate gyrus.The FC between LSM and right cerebellar Ⅵ in DPN patients were significantly negatively correlated with fasting blood glucose(r=-0.490,P=0.001).The FC between LSM and bilateral anterior cingulate gyrus in DPN patients were significantly positively correlated with Montreal cognitive assessment scores(r=0.479,P=0.001).Conclusion Abnormal FC between LSM and multiple brain regions,suggesting that DPN may have extensive effects on brain regions that maintain motion and motor control function in type 2 diabetes mellitus patients.

Objective:To analyze the efficacy and prognosis of surgical patients with traumatic epidural hematoma straddling the transverse sinus (TEHSTS).Methods:Clinical data of 4 360 patients with epidural hematoma admitted to the First Affiliated Hospital of Henan University of Science and Technology from January 2010 to April 2024 were collected. Among them, 109 cases (2.5%) were diagnosed with TEHSTS. Based on the rapid progression criteria for posterior fossa epidural hematoma [sudden deterioration of Glasgow Coma Scale (GCS) score within hours (a decrease of ≥1 point in the best motor response and/or a decrease of ≥2 points in GCS score), and progressive enlargement of TEHSTS on repeat CT scan], the timing and method of surgery were determined. Two surgical approaches were compared: combined supratentorial and infratentorial craniotomy (craniotomy group) and modified supratentorial burr-hole drainage (burr-hole group). Clinical data, surgical timing, surgical outcomes, and prognosis were compared between the two groups.Results:There were 57 cases (52.3%) in the craniotomy group and 52 cases (47.7%) in the modified burr-hole group. The proportion of patients presenting with vomiting upon admission was higher in the craniotomy group than in the burr-hole group [77.2%(44/57) vs 59.6%(31/52), P=0.048], and the proportion of patients with linear occipital fractures on CT was also higher in the craniotomy group [91.2%(52/57) vs 75.0%(39/52), P=0.023]. No significant differences were observed in other admission symptoms or CT findings between the two groups (all P>0.05). The GCS score upon admission was significantly lower in the craniotomy group [(11.0±1.0)points] than in the modified burr-hole group [(13.0±1.0)points] ( P<0.05). Four cases in the burr-hole group developed delayed hematomas, including two cases of bilateral delayed epidural hematomas. The preoperative GCS score in the craniotomy group [(9.0±0.5)points] was significantly lower than upon admission [(11.0±1.0)points] ( P<0.05), and the surgical timing was (6.5±1.5)hours after injury. The preoperative GCS score in the burr-hole group [(11.5±0.5)points] was also significantly lower than upon admission [(13.0±1.0)points] ( P<0.05), with surgical timing at (19.5±5.5)hours after injury. Preoperative CT scans showed no significant difference in hematoma volume between the burr-hole group [(35.5±7.5)ml] and the craniotomy group [(36.5±9.5)ml] ( P>0.05). The preoperative GCS score was significantly lower in the craniotomy group than in the burr-hole group ( P<0.05). The GCS scores at 24 hours postoperatively were significantly improved compared to preoperative scores in both groups (all P<0.05). The burr-hole group had significantly shorter operative time, less intraoperative blood loss, shorter intensive care unit (ICU) stay, and shorter hospital stay than the craniotomy group (all P<0.01). The incidence of postoperative pulmonary infection was lower in the burr-hole group than in the craniotomy group ( P<0.05). At 3-month follow-up, the rate of good recovery [Glasgow Outcome Scale (GOS) score≥4 points] was significantly higher in the burr-hole group (98.1%) than in the craniotomy group (93.0%) ( P<0.01). Conclusions:TEHSTS should be managed with different surgical approaches based on admission symptoms, GCS score, and the speed of disease progression. The modified burr-hole drainage procedure is convenient, safe, and associated with better prognosis.

Parkinson's disease (PD), a major neurodegenerative disease faced by an aging society worldwide, has not yet been fully elucidated in terms of its pathogenesis. Currently, clinical treatment mainly relies on symptom management and can only be relieved by medication. In recent years, many studies have shown that polysaccharides have potential in treatment of neurodegenerative diseases. Polysaccharides play a role in PD in ways such as anti-oxidative stress response, improvement of mitochondrial dysfunction, inhibition of neuroinflammation, anti-neurotoxicity, and activation of autophagy. This study discusses the mechanism of polysaccharides in PD, aiming to provide new ideas for PD prevention and treatment and new drug development in the future.

Objective:This study identifies independent predictive indicators to distinguish autoimmune gastritis from Helicobacter pylori ( H. pylori)-induced atrophic gastritis and validates their diagnostic performance to compare laboratory indicators of autoimmune gastritis and H. pylori-induced atrophic gastritis. Methods:A retrospective comparison of laboratory examination indicators was conducted for chronic atrophic gastritis patients with involvement of the gastric fundus and corpus, who were followed up at the Department of Gastroenterology, Xijing Hospital, from January 2014 to September 2024. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cutoff points and corresponding diagnostic thresholds. In addition, multivariate logistic regression analysis was conducted to identify independent predictive indicators for autoimmune gastritis, with further assessment in a validation cohort.Results:A total of 139 patients with autoimmune gastritis and 209 patients with H. pylori-induced atrophic gastritis were included. Pepsinogen (PG) Ⅰ levels and the PG Ⅰ/PG Ⅱ ratio in patients with autoimmune gastritis were significantly lower than in those with H. pylori-induced atrophic gastritis [11.0 (4.8, 22.5) vs. 41.8 (32.2, 59.9) μg/L, U=722.00, P<0.001; 1.24 (0.75, 3.54) vs. 5.76 (4.31, 7.12), U=817.00, P<0.001], while gastrin levels were significantly higher [375 (84, 738) vs. 49 (35, 81) ng/L, U=378.00, P<0.001]. PG Ⅰ was identified as an independent predictive variable, with an area under the ROC curve of 0.847 (95% CI 0.791-0.904), sensitivity of 77.6%, specificity of 91.8%, positive predictive value of 80.5%, and negative predictive value of 90.5%. Conclusions:Significant differences in laboratory indicators were observed between autoimmune gastritis and H. pylori-induced atrophic gastritis in chronic atrophic gastritis involving gastric fundus and corpus. Besides, PG Ⅰ demonstrated good diagnostic performance in identifying autoimmune gastritis and can effectively differentiate between different types of atrophic gastritis.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

OBJECTIVES: To analyze the trends of disease burden of lip and oral cancers in East Asia from 1990 to 2021 and its future projections. METHODS: We used the Global Burden of Disease 2021 database to conduct a comprehensive analysis of disease burden data from China (including Taiwan Province of China), Japan, Republic of Korea, Democratic People's Republic of Korea and Mongolia. The data were stratified by age, gender and major risk factors, and a Bayesian age-period-cohort model was employed to predict the future trends. RESULTS: From 1990 to 2021, the burden of lip and oral cancers in East Asian countries exhibited a steady increase. Taiwan Province of China experienced the most significant increases in incidence, prevalence, mortality, and disability-adjusted life years (DALYs), while Mongolia saw a decline in both mortality and DALYs. In 2021, Taiwan Province of China reported the highest rates of lip and oral cancer incidence (27.50 per 100 000), prevalence (137.92 per 100 000), mortality (9.59 per 100 000), and DALYs (292.07 person-years per 100 000), particularly among male and elderly populations. Tobacco use and alcohol consumption significantly exacerbated the disease burden in Taiwan Province of China and Japan. Future projections indicate that the incidence and prevalence of lip and oral cancer in China (excluding Taiwan Province of China) will continue to rise, while their mortality rates are expected to decline in most regions, except for Taiwan Province of China and Democratic People's Republic of Korea. CONCLUSIONS By the year 2035, the disease burden of lip and oral cancers in East Asia is expected to continue to increase, especially in Taiwan Province of China. To address this challenge, it is essential to implement effective measures to control major risk factors, promote early screening, and ensure equitable distribution of healthcare resources.
Humans ; Mouth Neoplasms/epidemiology* ; Incidence ; Lip Neoplasms/epidemiology* ; Asia, Eastern/epidemiology* ; Male ; Disability-Adjusted Life Years ; Prevalence ; Female ; Forecasting ; Risk Factors ; Cost of Illness ; Middle Aged ; Global Burden of Disease ; Aged ; Bayes Theorem

Cancer is a serious global health problem and a major cause of human death. Conventional cancer treatments often run the risk of impairing vital organ functions. Anticancer peptides (ACPs) are considered to be one of the most promising therapeutic agents against common human cancers due to their small sizes, high specificity, and low toxicity. Since ACP recognition is highly limited to the laboratory, expensive, and time-consuming, we proposed pLM4ACP, a model for predicting ACPs based on machine learning and protein language models. In this model, the protein language model ProtT5 was used to extract the features of ACPs, and the extracted features were input into the support vector machine (SVM) classification algorithm for optimization and performance evaluation. The model showcased significantly higher accuracy than other methods, with the overall accuracy of 0.763, F1-score of 0.767, Matthews correlation coefficient of 0.527, and area under the curve of 0.827 on the independent test set. This study constructs an efficient anticancer peptide prediction model based on protein language models, further advancing the application of artificial intelligence in the biomedical field and promoting the development of precision medicine and computational biology.
Machine Learning ; Antineoplastic Agents/chemistry* ; Humans ; Peptides/chemistry* ; Support Vector Machine ; Algorithms ; Computational Biology/methods* ; Neoplasms/drug therapy*

BACKGROUND:Human umbilical cord mesenchymal stem cell-derived exosomes were found to be effective in promoting neural repair in spinal cord injury.OBJECTIVE:To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells are able to attenuate neuroinflammation and promote recovery of motor function by promoting polarization of microglia toward the M2 type.METHODS:Totally 48 SD rats were randomly divided into a sham operation group,a model group,and an exosome group(n=16 per group).A rat spinal cord injury model was established using the modified Allen method.The exosome group was injected with 20 μL of human umbilical cord mesenchymal stem cell-derived exosomes intrathecally via neuroendoscopy 24 hours after injury.At 3,7,14,and 21 days after modeling,the recovery of the motor function of the hind limbs of the rats was assessed by BBB scoring method combined with Rivlin's slant plate test.The damage of spinal cord tissues was detected by using hematoxylin-eosin staining and Nissl staining.The expression levels of brain-derived neurotrophic factor and vascular endothelial growth factor A proteins were detected by western blot assay.The expression proportion of M1-type markers(inducible nitric oxide synthase)and M2 markers(arginase-1)in the spinal cord tissues was detected by immunofluorescence method.qRT-PCR and western blot assay were used to detect the expression levels of inducible nitric oxide synthase and arginase-1 in spinal cord tissues.ELISA was utilized to detect the levels of pro-inflammatory factors(tumor necrosis factor α,interleukin 1β,and interleukin 6)and anti-inflammatory factors(interleukin 10)levels in spinal cord tissues.RESULTS AND CONCLUSION:(1)At 3,7,and 14 days postoperatively,the BBB scores of the exosome group were better than those of the model group(P＜0.05).The angles of the Rivlin slanting plate experiments of the exosome group were significantly higher than those of the model group at 7 and 14 days postoperatively(P＜0.05).The results of hematoxylin-eosin staining and Nissl staining indicated that the spinal cord tissues and nerve injuries of the exosome group were reduced in comparison with those of the model group,and the levels of brain-derived neurotrophic factor and vascular endothelial growth factor A in spinal cord tissues of the exosome group were higher than those in the model group at 7 days postoperatively(P＜0.05).(2)Immunofluorescence experiments showed that the number of inducible nitric oxide synthase-positive microglial cells in the lesion area of the exosome group was significantly reduced and the level of Arg1-positive microglial cells increased in the lesion area of the exosome group compared with the model group at 7 days postoperatively(P＜0.05).qRT-PCR and western blot assay also confirmed the results of immunofluorescence experiments.(3)The secretion of pro-inflammatory factors tumor necrosis factor α,interleukin 1β,and interleukin 6 in spinal cord tissues of the exosome group was reduced compared with the model group(P＜0.05),whereas the secretion of the inflammation-suppressing factor interleukin 10 was increased compared with the model group(P＜0.05).These findings conclude that human umbilical cord mesenchymal stem cell-derived exosomes could promote the polarization of microglial cells from the M1 to the M2 type and decrease the release of pro-inflammatory factors,thereby reducing the secondary damage of neuroinflammation in spinal cord injury.

OBJECTIVE To explore the potential mechanisms of forkhead box protein A1(FOXA1)in benzo[a]pyrene(BaP)-induced carcinogenesis by investigating the effect of FOXA1 by knockout on microRNA(miRNA)expression profiles in BaP malignant transformed cells THBEc1 and establishing regulatory networks between FOXA1,miRNA and their target genes.METHODS FOXA1 knockout THBEc1 cells THBEc1-ΔFOXA1-c34 and control cells THBEc1-ctrl were used as study models.Western blotting was employed to determine FOXA1 protein expression levels.Next-generation sequencing(NGS)tech-nology was used to identify differentially expressed miRNAs between THBEc1-ΔFOXA1-c34 and THBEc1-ctrl cells,with subsequent validation by RT-qPCR.Five databases(ENCORI,miRDB,mirDIP,miRWalk and TargetScan 8.0)were used in conjunction with NGS results of mRNA between THBEc1-ΔFOXA1-c34 and THBEc1-ctrl to predict different expressed genes(DEGs)regulated by the identified differentially expressed miRNAs.GO and KEGG enrichment analyses were conducted on the DEGs using the DAVID database.Interaction network analysis of the proteins encoded by the DEGs was performed using STRING 12.0 and Cytoscape 3.10.2 software.RESULTS No FOXA1 expression was detected in THBEc1-ΔFOXA1-c34 cells.A differential analysis of miRNA expressions revealed 33 miRNAs with a fold change of＞2 or＜0.5 and a false discovery rate of＜0.05 between THBEc1-ΔFOXA1-c34 and THBEc1-ctrl cells,13 of which were down-regulated and 20 were up-regulated in THBEc1-ΔFOXA1-c34 cells.A regulatory network was formed by 11 down-regulated miRNAs and 32 up-regulated mRNAs,while a second network included 16 up-regulated miRNAs and 56 down-regulated mRNAs.The 27 differentially expressed miRNAs participated in various biological processes through the regulation of 88 DEGs,primarily associated with cell growth,proliferation,migration,apoptosis,angiogenesis,epithe-lial-mesenchymal transition,and signal transduction(TGF-β,Hippo,NF-kappa B and MAPK pathways).CONCLUSION The miRNA expression profile in BaP-malignant transformed THBEc1 cells is altered following FOXA1 knockout that may disrupt TGF-β and MAPK signaling pathways by changing miRNA expression levels,thereby inhibiting cell proliferation and migration.