This paper aims to explore the effect of electrical stimulation of triboelectric nanogenerators (TENGs) on the osteogenic and other biological behaviors of mouse embryonic osteoblast precursor cells (MC3T3-E1 cells) on titanium surfaces. First, an origami-type TENG was fabricated, and its electrical output performance was tested. The optimal current of the generator and the feasibility of the experiment were verified by the CCK-8 assay and scratch assay. At the optimal current, the osteogenic conditions of the cells in each group were determined by quantitative analysis of the total protein content, alkaline phosphatase (ALP) activity, and alizarin red staining (ARS) on the titanium surface. Finally, the adhesion and spreading of cells on the titanium surface after electrical stimulation were observed. The results showed that the TENG had good electrical output performance, with an open-circuit voltage of 65 V and a short-circuit current of 42 μA. Compared with the rest of the current, a current strength of 30 μA significantly improved cell proliferation and migration, osteogenesis, and adhesion and spreading capabilities. The above results confirm the safety and operability of TENG in biomedical applications, laying the foundation for future TENG applications in reducing the time of bone integration around titanium implants after surgery.
Titanium/chemistry* ; Osteogenesis ; Animals ; Mice ; Osteoblasts/cytology* ; Electric Stimulation/instrumentation* ; Cell Adhesion ; Cell Proliferation ; Surface Properties ; Cell Differentiation ; Nanotechnology

Objective To investigate the expression levels of serum high-mobility group box 1(HMGB1),soluble CD163(sCD163),and prostaglandin E2(PGE2)in patients with hepatitis B virus-related chronic-on-acute liver failure(HBV-ACLF),and to evaluate the value of the three indicators used alone or in combination in predicting prognosis.Methods A total of 76 patients with HBV-ACLF who were hospitalized in Department of Infectious Diseases,The First Affiliated Hospital of Xinxiang Medical University,from July 1,2022 to September 30,2023 were enrolled,and according to the 28-day prognosis,they were divided into survival group with 48 patients and death group with 28 patients.General data were collected,Model for End-Stage Liver Disease(MELD)score was calculated,and ELISA was used to measure the serum levels of HMGB1,sCD163,and PGE2.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.The Spearman rank correlation test was used to analyze the correlation of HMGB1,sCD163,and PGE2 with MELD score;the receiver operating characteristic(ROC)curve was used to analyze the value of HMGB1,sCD163,and PGE2 used alone or in combination in predicting the prognosis of HBV-ACLF patients.Results There were significant differences between the two groups in total bilirubin,white blood cell count,the percentage of neutrophils,procalcitonin,serum amyloid A,interleukin-6,serum sodium,and serum creatinine(all P＜0.05).Compared with the survival group,the death group had significantly higher serum levels of HMGB1(Z=-2.997,P=0.003)and sCD163(Z=-2.972,P=0.003),a significantly higher MELD score(t=-6.997,P＜0.001),and a significantly lower serum level of PGE2(Z=-4.909,P＜0.001).The Spearman rank correlation test showed that HMGB1 and sCD163 were positively correlated with MELD score(r=0.431 and 0.319,both P＜0.05),while PGE2 was negatively correlated with MELD score(r=-0.412,P＜0.05).The ROC curve analysis showed that HMGB1,sCD163,and PGE2 used alone had an area under the ROC curve(AUC)of 0.717,0.716,and 0.856,respectively,while the combination of the three indicators had the highest predictive value,with an AUC of 0.930,a sensitivity of 0.778,and a specificity of 0.920.Conclusion Serum HMGB1,sCD163,and PGE2 used alone or in combination have a good reference value in predicting the prognosis of HBV-ACLF patients,and the combination of the three indicators has the highest predictive value,which holds promise for further observation and research.

In order to understand the prevalence of Akabane disease(AKAD)in Guizhou Province and the molecular characteristics of the isolates,the whole-genome sequence of a strain of Akabane virus(AKAV)from a bovine AKAD-positive sample was determined and analyzed.The genotype and genetic variation of the strain were also explored.Based on the conserved S sequence,a fluores-cence quantitative PCR(qPCR)detection method was established and applied for the investigation of AKAV infection status in four large-scale beef cattle farms of Guizhou.Results showed that the S,M and L fragments of the bovine strain were highly homologous to the Tianjin strain(TJ2016/China/2016)and the Australian strain(JaLAB39/Australia/1959),where they were in the same evolutionary branch and belonged to genotype Ⅱ.Sensitivity assay found that the lowest detection limit was 2.5 X 101 copies/μL.Specificity assay showed the established method detected only AKAV with no amplification on bovine bluetongue virus(BLUV),Pasteurella multocida(PM),bovine infectious rhinotracheitis virus(IBRV)and bovine Mycoplasma bovis.The variation coefficients of inter-and intra batches in the repeatability test were both lower than 2.26％.These findings illus-trated that the established qPCR method had high sensitivity,good specificity and repeatability.A total of 298 serum samples from 4 large-scale beef cattle farms in Qianxi City and Huangping County of Guizhou Province were collected and tested for AKAV by the method.Out of 298 sam-ples,25 positive samples(25/298)were detected as positive with a positive rate of 8.39％.In sum-mary,this work provided the reference data for a deep understanding of the molecular prevalence of AKAV in Guizhou Province and laid foundation for the prevention and control of AKAD.

Objective To propose strategies for developing clinical predictive models,aiming to assist researchers in conducting standardized clinical prediction model studies.Methods Literature review was conducted to summarize the operational steps and content for developing clinical predictive models.Then,a methodological framework was summarized and refined through expert consultation.Results The 11-step methodological framework for developing clinical predictive models was obtained by synthesizing the experience of 456 clinical predictive modeling studies and expert consultation,and the details were analyzed and elaborated.Conclusions This study presents methodological strategies and recommendations for the development of clinical predictive models,intended to serve as a guide for researchers.

BACKGROUND:The pedicle navigation template has many advantages,but there are still some problems.For example,poor soft tissue dissection leads to poor adhesion of the pedicle navigation template,resulting in screw path deviation;careful dissection of soft tissue to fit the pedicle navigation template leads to prolonged surgery time and increased bleeding;the design of the pedicle navigation template cannot predict the vertebral rotation and the impact of body position changes,resulting in the poor fitting. OBJECTIVE:To explore the utility of a new 5-point positioning point-contact pedicle navigation template in the case of scoliosis and complex pedicle. METHODS:A total of 20 patients with scoliosis and complicated pedicle admitted to the Department of Spinal Surgery,Guizhou Hospital,Beijing Jishuitan Hospital from February 2020 to February 2023 were selected for scoliosis orthopedics.During the operation,the 5-point positioning point-contact pedicle navigation template was used to guide the screws.According to the inclusion and exclusion criteria,34 cases were matched as the empirical nail placement group,and conventional barehanded nail placement was performed.The time of placement,the amount of bleeding,the number of fluoroscopies,the number of manual diversions,the level and accuracy of pedicle screws,the complications of placement,and the rate of correction of main curvature were compared between the two groups. RESULTS AND CONCLUSION:(1)There were no significant differences in sex,age,coronal Cobb's angle of the main curvature,bending Cobb's angle of the main curvature,pedicle variation,apex rotation,fusion segment,number of screws,level of screws,accuracy of screws,and rate of correction of main curvature between the navigation template group and the empirical nail placement group(P>0.05).(2)Compared with the empirical nail placement group,the navigation template group had more advantages in time of placement(P=0.034),amount of bleeding(P=0.036),number of fluoroscopies(P=0.000)and number of manual diversions(P=0.021).(3)There were 0 cases of screw-related complications in both groups.(4)In conclusion,the 5-point positioning point-contact 3D printing pedicle navigation template has a claw-like structure.It can firmly adapt to various deformities of the lamina articular process,avoid drift,and accurately place the screws.It has a point-like contact lamina structure to avoid extensive and complete dissection of the posterior structure,and reduce bleeding,operation time,and trauma.Pre-designed screw entry points and directions can reduce the number of fluoroscopy and operation time.Segmental design can avoid discomfort due to changes in anesthesia position.The operation is simple and the accuracy of screw placement is high.

ObjectiveTo explore the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements of macroangiopathy in patients with type 2 diabetes mellitus （T2DM） and the key elements of occurrence， development and progression of disease. MethodsA multicenter cross-sectional study was conducted to enroll 445 T2DM patients from five hospitals， and according to the presence or absence of macroangiopathy， the patients were divided into a T2DM group （120 cases） and a diabetic macroangiopathy （DM） group （325 cases）. Patients in DM group were divided into grade Ⅰ， Ⅱ， Ⅲ and Ⅳ according to the peripheral vascular color Doppler ultrasound results and the vascular anomalies classification standard. The general data including gender， age， duration of T2DM and body mass index （BMI） were collected， and the data of four examinations were obtained for syndrome differentiation. According to the diagnostic criteria of TCM syndrome elements， the patients can be divided into 9 patterns including qi deficiency， blood deficiency， yin deficiency， yang deficiency， qi stagnation， blood stasis， excess heat， and excess cold. The general data and distribution of TCM syndrome elements were compared between the two groups. The distribution of TCM syndrome elements in different vascular anomalies grades in the DM group was analyzed. Logistic regression analysis was used to explore the influence of various TCM syndrome elements on the occurrence of macroangiopathy in T2DM. ResultsThere was no significant difference in gender and BMI between groups （P＞0.05）. The age and duration of diabetes in the DM group were older and longer than those in the T2DM group （P＜0.01）. With the increase of age and prolonged course of disease， the severity of diabetic macroangiopathy increases gradually （P＜0.05 or P＜0.01）. There was no significant difference in BMI and course of disease among the different TCM syndrome elements （P＞0.05）. The average age of patients with blood stasis syndrome was the oldest （P＜0.05）. There was significant difference in gender distribution between the excess heat syndrome and yin deficiency syndrome （P＜0.05）. A total of 240 TCM syndrome elements were extracted from the T2DM group， while 731 TCM syndrome elements extracted from the DM group. The top two high-frequency syndrome elements in the two groups were qi deficiency and yin deficiency， with a frequency of larger than 50%. The distribution of phlegm-damp syndrome and blood-stasis syndrome were significantly higher in the DM group than in the T2DM group （P＜0.01）. There were significant differences in the distribution of qi deficiency syndrome， yin deficiency syndrome， phlegm-damp syndrome， blood stasis syndrome， and excess heat syndrome among different grades of vascular anomalies （P＜0.01）； qi deficiency and yin deficiency were both high-frequency TCM syndrome elements in patients at grades 0 to Ⅲ； phlegm-damp syndrome increased in frequency with the progression of the disease from grades 0 to Ⅳ， and the frequency of blood stasis syndrome showed an overall upward trend. The frequency of phlegm-dampness syndrome increased from grades 0 to Ⅳ with the progression of the disease， and the frequency of blood stasis syndrome showed an overall upward trend. Logistic regression analysis showed that phlegm-damp syndrome and blood stasis syndrome were important TCM syndrome elements related to the vascular anomalies degree of macrovascular disease in T2DM （P＜0.05 or P＜0.01）. ConclusionQi deficiency and yin deficiency are the basic TCM syndrome elements throughout the whole process of T2DM and diabetic macrovascular disease. Phlegm-damp and blood stasis are related to the degree of vascular anomalies in diabetic macrovascular disease and are the key TCM syndrome elements in the progression of macroangiopathy in T2DM.

Itaconate is a pivotal intermediate metabolite in the tricarboxylic acid (TCA) cycle of immune cells. It is produced by decarboxylation of cis-aconitic acid under the catalysis of aconitate decarboxylase 1 (ACOD1), which is encoded by the immune response gene 1 (IRG1). Itaconate has become a focal point of research on immunometabolism. Studies have demonstrated that itaconate plays a crucial role in diseases by regulating inflammation, remodeling cell metabolism, and participating in epigenetic regulation. This paper reviewed the research progress in itaconnate from its chemical structure, regulatory effects on different diseases, and mechanisms, proposes the future research directions, aiming to provide a theoretical basis for the development of itaconate-related drugs.
Humans ; Succinates/metabolism* ; Carboxy-Lyases/genetics* ; Inflammation/metabolism* ; Citric Acid Cycle ; Animals ; Epigenesis, Genetic ; Neoplasms/immunology*

Objective To investigate the changes of macrophage polarization during acute rejection (AR) after intestinal transplantation. Methods Six Brown Norway (BN) rats and 24 Lewis rats were divided into the sham operation group (6 Lewis rats), syngeneic transplantation group (Lewis→Lewis, 6 donors and 6 recipients) and allogeneic transplantation group (BN→Lewis, 6 donors and 6 recipients). At postoperative 7 d, the intestinal graft tissues in all groups were collected for hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Pathological manifestations and cell apoptosis were observed. The expression levels of serum cytokines related to M1 and M2 macrophage polarization were determined by enzyme-linked immunosorbent assay (ELISA). Surface markers of M1 and M2 macrophages of intestinal graft tissues in each group were co-localized and counted by immunofluorescence staining. Results HE staining and TUNEL assay showed that the intestinal epithelial morphology and structure were normal and no evident apoptotic bodies were found in the sham operation and syngeneic transplantation groups. At 7 d after transplantation, the epithelial villi structure of intestinal graft tissues was severely damaged, the number of crypts was decreased, the number of apoptotic bodies was increased, and inflammatory cells infiltrated into the whole intestinal wall, manifested with moderate to severe AR in the allogeneic transplantation group. ELISA revealed that the expression levels of serum cytokines related to M1 macrophage polarization, such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-12, of the recipient rats in the allogeneic transplantation group were higher than those in the sham operation and syngeneic transplantation groups. The expression levels of serum cytokines related to M2 macrophage polarization, such as IL-10 and transforming growth factor (TGF)-β, in the syngeneic transplantation group were higher compared with those in the sham operation and allogeneic transplantation group, and the differences were statistically significant (all P<0.05). Immunofluorescence staining showed that the number of M1 macrophages in the allogeneic transplantation group was higher than those in the sham operation and syngeneic transplantation groups, and the number of M2 macrophages in the syngeneic transplantation group was higher than those in the sham operation and allogeneic transplantation groups, and the differences were statistically significant (all P<0.05). Conclusions Among the allografts with AR after intestinal transplantation, a large number of macrophages, mainly M1 macrophages secreting a large number of pro-inflammatory cytokines, infiltrate into the whole intestinal wall. Regulating the direction of macrophage polarization is a potential treatment for AR after intestinal transplantation.

Background::Heterogeneity of tumor cells and the tumor microenvironment (TME) is significantly associated with clinical outcomes and treatment responses in patients with urothelial carcinoma (UC). Comprehensive profiling of the cellular diversity and interactions between malignant cells and TME may clarify the mechanisms underlying UC progression and guide the development of novel therapies. This study aimed to extend our understanding of intra-tumoral heterogeneity and the immunosuppressive TME in UC and provide basic support for the development of novel UC therapies.Methods::Seven patients with UC were included who underwent curative surgery at our hospital between July 2020 and October 2020. We performed single-cell RNA sequencing (scRNA-seq) analysis in seven tumors with six matched adjacent normal tissues and integrated the results with two public scRNA-seq datasets. The functional properties and intercellular interactions between single cells were characterized, and the results were validated using multiplex immunofluorescence staining, flow cytometry, and bulk transcriptomic datasets. All statistical analyses were performed using the R package with two-sided tests. Wilcoxon-rank test, log-rank test, one-way analysis of variance test, and Pearson correlation analysis were used properly.Results::Unsupervised t-distributed stochastic neighbor embedding clustering analysis identified ten main cellular subclusters in urothelial tissues. Of them, seven urothelial subtypes were noted, and malignant urothelial cells were characterized with enhanced cellular proliferation and reduced immunogenicity. CD8 + T cell subclusters exhibited enhanced cellular cytotoxicity activities along with increased exhaustion signature in UC tissues, and the recruitment of CD4 + T regulatory cells was also increased in tumor tissues. Regarding myeloid cells, coordinated reprogramming of infiltrated neutrophils, M2-type polarized macrophages, and LAMP3 + dendritic cells contribute to immunosuppressive TME in UC tissues. Tumor tissues demonstrated enhanced angiogenesis mediated by KDR + endothelial cells and RGS5 +/ACTA2 + pericytes. Through deconvolution analysis, we identified multiple cellular subtypes may influence the programmed death-ligand 1 (PD-L1) immunotherapy response in patients with UC. Conclusion::Our scRNA-seq analysis clarified intra-tumoral heterogeneity and delineated the pro-tumoral and immunosuppressive microenvironment in UC tissues, which may provide novel therapeutic targets.

Arrhythmia is a significant cardiovascular disease that poses a threat to human health, and its primary diagnosis relies on electrocardiogram (ECG). Implementing computer technology to achieve automatic classification of arrhythmia can effectively avoid human error, improve diagnostic efficiency, and reduce costs. However, most automatic arrhythmia classification algorithms focus on one-dimensional temporal signals, which lack robustness. Therefore, this study proposed an arrhythmia image classification method based on Gramian angular summation field (GASF) and an improved Inception-ResNet-v2 network. Firstly, the data was preprocessed using variational mode decomposition, and data augmentation was performed using a deep convolutional generative adversarial network. Then, GASF was used to transform one-dimensional ECG signals into two-dimensional images, and an improved Inception-ResNet-v2 network was utilized to implement the five arrhythmia classifications recommended by the AAMI (N, V, S, F, and Q). The experimental results on the MIT-BIH Arrhythmia Database showed that the proposed method achieved an overall classification accuracy of 99.52% and 95.48% under the intra-patient and inter-patient paradigms, respectively. The arrhythmia classification performance of the improved Inception-ResNet-v2 network in this study outperforms other methods, providing a new approach for deep learning-based automatic arrhythmia classification.
Humans ; Arrhythmias, Cardiac/diagnostic imaging* ; Cardiovascular Diseases ; Algorithms ; Databases, Factual ; Electrocardiography