Objective:To screen the interacting protein of ubiquitin-conjugating enzyme E2S(UBE2S)and construct the hepatocellular carcinoma(HCC)based on UBE2S interacting protein prognosis model(UIPM),and to discuss the value of UIPM in assessing the prognosis of the HCC patients.Methods:Co-immunoprecipitation(Co-IP)was used to screen the protein complexes binding to Flag-UBE2S.After validation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting methods;liquid chromatography-mass spectrometer(LC-MS)was used to identify the UBE2S interacting proteins;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted on these proteins;the prognosis-related proteins from The Cancer Genome Atlas(TCGA)were cross-referenced with UBE2S interacting proteins by survival package of R software;the key proteins were extracted through LASSO regression analysis to build the UIPM;the prognostic model risk scoring formula was established.The HCC patients in TCGA were divided into high risk group and low risk group based on median value of the risk scores.The predictive accuracy of UIPM was evaluated by receiver operating characteristic curve(ROC),and the predictive accuracy was further validated by International Cancer Genome Consortium(ICGC)Database;univariate regression analysis and multivariate Cox regression analysis were used to detect whether the UIPM risk score was an independent prognostic factor for HCC.Furthermore,the nomogram model was built.Results:A total of 97 UBE2S interacting proteins were identified through Co-IP combined with LC-MS analysis.The GO functional enrichment analysis and KEGG signaling pathway enrichment analysis results showed that the interacting proteins were closely associated with cysteine-type endopeptidase activity,oxidative stress,and cell death.The TCGA revealed 5 163 HCC prognosis-related proteins;after intersecting with UBE2S interacting proteins,40 prognosis-related interacting proteins were found.Seven key proteins were determined through LASSO regression analysis,including UBE2S,heat shock protein family A member 8(HSPA8),heterogeneous nuclear ribonucleoprotein H1(HNRNPH1),chaperonin containing TCP1 subunit 3(CCT3),eukaryotic translation initiation factor 2 subunit 1(EIF2S1),receptor for activated C kinase 1(RACK1),and actin related protein 2/3 complex subunit 4(ARPC4),and the UIPM was constructed.There was significant difference in survival rate of the patients between high risk group and low risk group(P<0.05).The ROC curve analysis results showed the area under ROC curve(AUC)values of UIPM for predicting 1-year,2-year,and 3-year survival risk scores of the HCC patients were all greater than 0.7,indicating the model had high predictive accuracy.This was also confirmed by ICGC Database data.The univariate and multivariate Cox regression analysis results showed that the UIPM risk score was an independent prognostic risk factor for the HCC patients(P<0.05).The nomogram results showed good consistency between predicted survival rate and actual survival rate of the patient.Conclusion:A total of 97 interacting proteins that interact with UBE2S may promote the occurence and devolopment of HCC through oxidative stress and dysregulation of ferroptosis pathways.The UIPM risk score is an independent risk factor for the prognosis of HCC and can be used to predict the outcomes of the patients.UBE2S,HSPA8,HNRNPH1,CCT3,EIF2S1,RACK1,and ARPC4 could be regarded as the new biomarkers and therapeutic targets for HCC.

Objective To clarify the anti-inflammatory quality markers(Q-markers)of Salvia plebeia and determine their contents,so as to provide a reference for the quality control of Salvia plebeia.Methods The main components of Salvia plebeia were characterized by high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS).According to the fragmentation information of the secondary mass spectrometry and the literature data,the analysis and identification were carried out.Further,the active components with high oral bioavailability(OB)and in line with the five principles of drug-like(DL)were screened from the identified chemical components through the SwissADME platform.The SwissTargetPrediction database was used to find and predict the component targets of Salvia plebeia.Disease targets were screened through online Mendelian Inheritance in Man(OMIM),GeneCards database,etc.String11.5 database and Cytoscape3.7.2 software were used to construct the PPI network and screen core targets.Gene Ontology(GO)annotation and KEGG pathway enrichment analysis were performed using DAVID6.8,and the enriched pathways were verified by experiments to clarify their mechanism of action.Reverse traceability was used to analyze the potential pharmacodynamic material basis of key pathways,experimental verification was carried out,and high-performance liquid chromatography(HPLC)content determination method was established.Results 36 main components were identified,including flavonoids and terpenoids.Further screening of 190 active ingredients and disease intersection targets;through network topology screening,18 core targets were obtained;enrichment analysis showed that the primary pathways involved in the anti-inflammatory effect of Salvia plebeia include:NF-κB signaling pathway,PI3K-Akt signaling pathway and TNF signaling pathway.Four related components including homoplantaginin,hispidulin,luteolin and isorhamnetin were obtained by reverse traceability of the NF-κB signaling pathway.Molecular docking demonstrated excellent docking activities of the 4 components to PTGS2 with the binding energies of-9.5,-9.7,-9.4,and-9.4 kcal·mol-1,respectively.According to the measurability of quality markers,it was determined that homoplantaginin and hispidulin could be used as anti-inflammatory quality markers of Salvia plebeia.Western Blot results showed that homoplantaginin and hispidulin could significantly reduce the expression of COX-2 and NF-κB p-p65(P<0.05,P<0.01).Conclusion The anti-inflammatory quality markers of Salvia plebeia are homoplantaginin and hispidulin,which can exert anti-inflammatory effects through the NF-κB pathway.

Objective To identify epidemiological characteristics and pathogen distribution of hand,foot,and mouth disease(HFMD)in Hebei Children's Hospital in order to support prevention and treatment of HFMD.Methods A total of 1 698 cases throat swab samples from children diagnosed as HFMD from 2016 to 2023 were collected.Real-time PCR was used to detect the specific classification of HFMD.Statistical analysis was performed according to the year,season,age,and sex and enterovirus type of HFMD in the children.Results From 2016 to 2023,the ratio of male to female patients among the 1 698 children admitted to Hebei Children's Hospital was 1.72∶1.Among them,the highest incidence rate in summer was 778 cases,accounting for 45.8%of all cases,followed by autumn,with a total of 614 cases,accounting for 36.2%of cases.The highest incidence was recorded in age group of 1-3 years,with a total of 1 032 cases(60.8%).The lowest incidence was 38 cases in age group＞6 years old(2.2%);There were 988 cases of HFM(58.2%)caused by different strains of enterovirus undefined(EVU)except enterovirus 71(EV71)and coxsackievirus A16(CA16).Conclusions HFMD found in Hebei Children's Hospital from 2016 to 2023 are mainly caused by enteroviruses except EV 71 and coxsackievirus A16.High morbid-ity is found in children aged 1-3 years,and summer and autumn are the main epidemic seasons.This result may facilitate and support decision making and strategy development in disease prevention and control as well as to strengthen public health resources.

Neutrophils originate from the bone marrow,differentiating from hematopoietic stem cells,and are the most prevalent polymorphonuclear leukocytes in the blood,accounting for approximately 70%of the total white blood cells in adult peripheral blood.Neutrophils are recognized as one of the relatively short-lived cells in the body,with a normal half-life of just a few hours in the peripheral blood,which rely on continuous replenishment from the bone marrow to maintain the number.As short-lived effectors of the innate immune system,neutrophils participate in various inflammatory and immune processes,and constitute the first line of defense against infection,playing a crucial role in the activation and regulation of both innate and adaptive immunity.Neutrophils were once considered as key effectors of inflammation and infection.Because of their short lifespan and non-proliferative nature,the role of neutrophils in cancer was overlooked.Their role in cancer has been increasingly recognized in recent years.However,more and more studies demonstrate that neutrophils play a much more significant role in cancer than previously thought.Breast cancer is one of the common malignant tumors in women,and its morbidity and mortality are in the forefront of female malignant tumors.The incidence of breast cancer is rising globally,posing a severe threat to the physical and mental health of women worldwide.Recent studies confirm that tumor-associated neutrophils(TANs)have become a critical component of the tumor microenvironment(TME)and play a significant role in the development,progression and metastasis of breast cancer.TANs are formed via the interaction of various tumor-derived cytokines which stimulate and recruit neutrophils to accumulate in the TME.The strong plasticity and diversity of neutrophils endow TANs with dual potential to both promote and inhibit tumors.TANs advance breast cancer progression by promoting tumor growth and metastasis,supporting tumor angiogenesis,immune suppression,and generating neutrophil extracellular traps(NETs).Conversely,TANs mediate antitumor responses through direct tumor cell killing and contributing to the formation of antitumor immune network.Research on TANs-related breast cancer therapies,particularly in triple-negative breast cancer(TNBC),has become a research hotspot.This review summarized recent advances in the origin,formation,classification and function of TANs in breast cancer,as well as a detailed discussion of their clinical relevance.We further combined recent clinical studies to systematically summarize the treatment strategies targeting TANs in breast cancer,with the aim of providing new insights into the functional mechanisms of TANs and the treatment of breast cancer.

Purpose: Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes. Materials and Methods: CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group. Results: A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003). Conclusion Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

Objective : To investigate the effect of CD147 on reducing hydrogen peroxide - induced oxidative stress injury in prostate cancer LNCaP cells. Methods : The lentiviral system was used to establish a CD147 ⁃silencing prostate cancer cell model (LNCaP/shCD147 cells) and a negative control cell (LNCaP/Scramble cell) , and RT⁃qPCR was performed for verification. By detecting the activity of reactive oxygen species ( ROS) , superoxide dismutase (SOD) , glutathione peroxidase ( GSH⁃PX) and malondialdehyde ( MDA) in LNCaP/shCD147 and LNCaP/Scramble cells to verify the changes of oxidative stress and antioxidant enzymes in prostate cancer cells after silencing CD147 ; hydrogen peroxide( H2 O2 ) was added to the cells and the cell growth was detected by CCK⁃8 ; Western blot was used to detect the expression changes of nuclear factor E2 related factors (Nrf2) and heme oxygenase⁃1 (HO⁃1) to verify the relationship between the oxidative stress that occurs in prostate cancer cells after silencing CD147 and the PI3K/AKT signaling pathway. Results : Successfully constructed a CD147⁃silencing prostate cancer cell model. Compared with LNCaP/Scramble cells , the expression of CD147 in mRNA was reduced (P <0. 01) . The results of oxidative stress showed that the content of ROS and MDA in cells increased after silencing CD147 (ROS , P < 0. 01 ; MDA , P < 0. 05) , while the activities of SOD and GSH⁃PX decreased(P < 0. 01) , indicating that after silencing CD147 , LNCaP/shCD147 cells undergo oxidative stress. In addition , with the increase of H2O2 concentration , the survival rate of LNCaP/shCD147 group cells decreased (P < 0. 01) . After inhibiting the PI3K/AKT signaling pathway , the expressions of Nrf2 and HO⁃1 in the LNCaP/shCD147 group were reduced (P < 0. 01) , indicating that CD147 inhibits the oxidative stress injury of prostate cancer cells through the PI3K/AKT pathway. Conclusion CD147 can reduce the oxidative stress damage of PCa cells , and its inhibitory mechanism may be related to the PI3K/AKT signaling pathway.

The protection of language function is one of the major challenges of brain surgery. Over the past century, neurosurgeons have attempted to seek the optimal strategy for the preoperative and intraoperative identification of language-related brain regions. Neurosurgeons have investigated the neural mechanism of language, developed neurolinguistics theory, and provided unique evidence to further understand the neural basis of language functions by using intraoperative cortical and subcortical electrical stimulation. With the emergence of modern neuroscience techniques and dramatic advances in language models over the last 25 years, novel language mapping methods have been applied in the neurosurgical practice to help neurosurgeons protect the brain and reduce morbidity. The rapid advancements in brain-computer interface have provided the perfect platform for the combination of neurosurgery and neurolinguistics. In this review, the history of neurolinguistics models, advancements in modern technology, role of neurosurgery in language mapping, and modern language mapping methods (including noninvasive neuroimaging techniques and invasive cortical electroencephalogram) are presented.
Brain Mapping ; Brain Neoplasms ; Humans ; Language ; Neurosurgery ; Neurosurgical Procedures

Objective:To analyze the changes in T lymphocyte subsets, B lymphocytes and NK cells in children with active tuberculosis (TB) and their clinical significance.Methods:T lymphocyte subsets, B lymphocytes and NK cells in peripheral blood samples of 106 patients with acute TB (TB group) and 106 healthy children (healthy control group) were detected by flow cytometry and compared between different groups.Results:The percentages of CD3 + T, CD4 + T and NK cells as well as the CD4 +/CD8 + T cell ratio were significantly lower in the TB group than in the healthy control group ( Z=-3.783, P=0.000; Z=-5.401, P=0.000; Z=-3.434, P=0.001; Z=-2.014, P=0.044). The percentages of double negative T (DNT) and B cells in the TB group were significantly higher than those in the healthy control group ( Z=2.765, P=0.006; Z=6.880, P=0.000). No significant difference in the percentage of CD8 + T or double positive T (DPT) cells was observed between the two groups ( P>0.05). The expression of peripheral lymphocyte subsets varied in TB children of different age groups (0-<3, 3-<6, 6-<10 and 10-<16 years old). There were significant differences in CD3 + T, DNT and B cells among the four age groups ( H=10.081, P=0.018; H=14.583, P=0.002; H=8.498, P=0.037). The percentage of CD4 + T cells was significantly lower in children with extrapulmonary TB than in those with pulmonary TB ( Z=-3.068, P=0.002). No statistically significant difference in other lymphocyte subsets was found between children with extrapulmonary and pulmonary TB ( P>0.05). Conclusions:Tuberculosis could lead to immune dysfunction in children. Dynamic monitoring of the changes in peripheral lymphocyte subsets in children with TB could be conducive to better assessment of immune status and providing personalized treatment.

42 cases with gastroesophageal varices were prospectively included. The groups were treated with endoscopic band ligation or combined with tissue adhesive. The results showed that the left gastric vein internal diameter, average blood flow velocity and blood flow volume after the treatment of band ligation combined with tissue adhesive were significantly lower than that of the treatment of band ligation alone, and the differences were statistically significant ( P < 0.05). Spleen and portal vein internal diameter, blood flow and average velocity, the liver and spleen size, shear wave velocity and liver function grade of the two groups after treatment did not change significantly ( P > 0.05). The effective rate of band ligation combined with tissue adhesive in the treatment of esophageal and gastric varices (66.67%, 52.38%) were higher than that of band ligation alone (42.85%, 23.81%) ( P > 0.05), and the re-bleeding rate of the latter was higher (9.52% and 19.05%, P > 0.05). Hence, it is suggested that the combined therapy is safe and more effective, and has no apparent effect on liver function and portal hypertension.

Objective:To construct and validate a prediction model combined machine learning with imaging omics characteristics in differentiating anaplastic glioma from glioblastoma.Methods:Imaging data of 241 patients with anaplastic glioma or glioblastoma, confirmed by pathology in our hospital from August 2005 to August 2012, were retrospectively collected. These patients were divided into a training group ( n=140) and a verification group ( n=101) according to random number table method. MRIcron software was used to delineate tumor boundaries of patients from the training group on preoperative T1 enhanced MR imaging. The regions of interest (ROIs) were outlined on preoperative T1 enhanced MR imaging, and the radiomic features were extracted from ROIs by Matlab software. Least absolute shrinkage and selection operator (LASSO) regression model was used to screen the features, and then, the selected features were used to construct the prediction model by support vector machine (SVM) classifier. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of the model. Results:In these 241 patients, 101 were with anaplastic glioma and 140 were with glioblastoma confirmed by pathology. In the training group and validation group, there was statistical difference in age between patients with anaplastic glioma and glioblastoma ( P<0.05); there was no significant difference in gender distribution, tumor location, and percentages of tumor necrosis or edema between patients with anaplastic glioma and glioblastoma ( P>0.05). Totally, 431 radiomic features were extracted; 11 radiomic features were screened by LASSO regression model and the prediction model was established. The AUC of ROC curve was 0.942 and 0.875, respectively, in the training group and validation group. Conclusion:The prediction model combined machine learning and imaging omics characteristics can effectively discriminate anaplastic glioma from glioblastoma.