This study aims to explore the mechanism of Buyang Huanwu Decoction(BHD) in promoting angiogenesis after oxygen-glucose deprivation/reoxygenation(OGD/R) of mouse brain microvascular endothelial cell line(brain-derived Endothelial cells.3, bEnd.3) based on the caveolin-1(Cav1)/Yes-associated protein 1(YAP1)/hypoxia-inducible factor-1α(HIF-1α) signaling pathway. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze the blood components of BHD. The cell counting kit-8(CCK-8) method was used to detect the optimal intervention concentration of drug-containing serum of BHD after OGD/R injury of bEnd.3. The lentiviral transfection method was used to construct a Cav1 silent stable strain, and Western blot and polymerase chain reaction(PCR) methods were used to verify the silencing efficiency. The control bEnd.3 cells were divided into a normal group(sh-NC control group), an OGD/R model + blank serum group(sh-NC OGD/R group), and an OGD/R model + drug-containing serum group(sh-NC BHD group). Cav1 silent cells were divided into an OGD/R model + blank serum group(sh-Cav1 OGD/R group) and an OGD/R model + drug-containing serum group(sh-Cav1 BHD group). The cell survival rate was detected by the CCK-8 method. The cell migration ability was detected by a cell migration assay. The lumen formation ability was detected by an angiogenesis assay. The apoptosis rate was detected by flow cytometry, and the expression of YAP1/HIF-1α signaling pathway-related proteins in each group was detected by Western blot. Finally, co-immunoprecipitation was used to verify the interaction between YAP1 and HIF-1α. The results showed astragaloside Ⅳ, formononetin, ferulic acid, and albiflorin in BHD can all enter the blood. The drug-containing serum of BHD at a mass fraction of 10% may be the optimal intervention concentration for OGD/R-induced injury of bEnd.3 cells. Compared with the sh-NC control group, the sh-NC OGD/R group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, significantly increased cell apoptotic rate, significantly lowered phosphorylation level of YAP1 at S127 site, and significantly elevated nuclear displacement level of YAP1 and protein expression of HIF-1α, vascular endothelial growth factor(VEGF), and vascular endothelial growth factor receptor 2(VEGFR2). Compared with the same type of OGD/R group, the sh-NC BHD group and sh-Cav1 BHD group had significantly increased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly decreased cell apoptotic rate, a further decreased phosphorylation level of YAP1 at S127 site, and significantly increased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC OGD/R group, the sh-Cav1 OGD/R group exhibited significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC BHD group, the sh-Cav1 BHD group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at the S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. YAP1 protein was present in the protein complex precipitated by the HIF-1α antibody, and HIF-1α protein was also present in the protein complex precipitated by the YAP1 antibody. The results confirmed that the drug-containing serum of BHD can increase the activity of YAP1/HIF-1α pathway in bEnd.3 cells damaged by OGD/R through Cav1 and promote angiogenesis in vitro.
Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Signal Transduction/drug effects* ; Glucose/metabolism* ; Caveolin 1/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; YAP-Signaling Proteins ; Oxygen/metabolism* ; Endothelial Cells/metabolism* ; Cell Line ; Adaptor Proteins, Signal Transducing/genetics* ; Neovascularization, Physiologic/drug effects* ; Cell Hypoxia/drug effects* ; Angiogenesis

The objective of this study is to map the global scientific competitive landscape in the field of artificial intelligence (AI) medical devices using scientific data. A bibliometric analysis was conducted using the Web of Science Core Collection to examine global research trends in AI-based medical devices. As of the end of 2023, a total of 55 147 relevant publications were identified worldwide, with 76.6% published between 2018 and 2024. Research in this field has primarily focused on AI-assisted medical image and physiological signal analysis. At the national level, China (17 991 publications) and the United States (14 032 publications) lead in output. China has shown a rapid increase in publication volume, with its 2023 output exceeding twice that of the U.S.; however, the U.S. maintains a higher average citation per paper (China: 16.29; U.S.: 35.99). At the institutional level, seven Chinese institutions and three U.S. institutions rank among the global top ten in terms of publication volume. At the researcher level, prominent contributors include Acharya U Rajendra, Rueckert Daniel and Tian Jie, who have extensively explored AI-assisted medical imaging. Some researchers have specialized in specific imaging applications, such as Yang Xiaofeng (AI-assisted precision radiotherapy for tumors) and Shen Dinggang (brain imaging analysis). Others, including Gao Xiaorong and Ming Dong, focus on AI-assisted physiological signal analysis. The results confirm the rapid global development of AI in the medical device field, with "AI + imaging" emerging as the most mature direction. China and the U.S. maintain absolute leadership in this area-China slightly leads in publication volume, while the U.S., having started earlier, demonstrates higher research quality. Both countries host a large number of active research teams in this domain.
Artificial Intelligence ; Bibliometrics ; Humans ; China ; Equipment and Supplies ; United States ; Biomedical Research

Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC₅₀) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL^-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G₀/G₁ phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe²⁺, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
Animals ; Humans ; Mice ; Antineoplastic Agents, Phytogenic ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cyclin D1/genetics* ; Cyclin-Dependent Kinase 4/genetics* ; DNA Damage/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Ferroptosis/drug effects* ; G1 Phase Cell Cycle Checkpoints/drug effects* ; Heme Oxygenase-1/genetics* ; Mice, Inbred BALB C ; Mice, Nude ; Plant Extracts/pharmacology* ; Stomach Neoplasms/physiopathology* ; Thymelaeaceae/chemistry* ; Up-Regulation/drug effects*

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, defined by several phases, ranging from benign fat accumulation to non-alcoholic steatohepatitis (NASH), which can lead to liver cancer and cirrhosis. Although NAFLD is a disease of disordered metabolism, it also involves several immune cell-mediated inflammatory processes, either promoting and/or suppressing hepatocyte inflammation through the secretion of pro-inflammatory and/or anti-inflammatory factors to influence the NAFLD process. However, the underlying disease mechanism and the role of immune cells in NAFLD are still under investigation, leaving many open-ended questions. In this review, we presented the recent concepts about the interplay of immune cells in the onset and pathogenesis of NAFLD. We also highlighted the specific non-immune cells exhibiting immunological properties of therapeutic significance in NAFLD. We hope that this review will help guide the development of future NAFLD therapeutics.

Tumor is one of the major diseases that endanger people’s health. At present, the treatments used for tumor include surgery, chemotherapy, radiotherapy and so on. Nonetheless, the traditional treatments have some disadvantages, such as insufficient treatment effect, liable to cause multidrug resistance, toxicity and side effect. Further research and exploration of tumor treatment schemes are still necessary. As the energy converter of cells, mitochondria are currently considered to be one of the most important targets for the design of new drugs for tumor, cardiovascular and neurological diseases. Nano-drug delivery carriers have the characteristics of being easily modified with active targeting groups, and it can achieve accurate targeted drug delivery to cells and organelles. This paper reviews the application of mitochondrial targeted nanoparticles in tumor diagnosis and treatment from the aspects of inhibiting tumor cell proliferation, promoting tumor cell apoptosis, inhibiting tumor recurrence and metastasis, and inducing cell autophagy.

Objective To explore the application effect of the Mini-CEX evaluation model based on the OBE concept in the clinical Practice teaching of neurology.Methods We Selected 100 students who will Practice in the Department of Neurology from 2022 to 2023 as the research objects,and divided them into the experimental group(n=50)and the control group(n=50).Under the guidance of the OBE concept,the experimental group was guided by learning outcomes,refined the teaching objectives,and applied the Mini-CEX evaluation mode for evaluation and feedback.In contrast,the control group adopted the traditional teaching mode.Combined with the observation data,we analyzed and compared the data of various indicators of the two groups of students at the beginning and end of the internship.Results At the end of the internship,the scores of clinical consultation,Physical examination,humanistic medicine,clinical diagnosis,health consultation,organizational effect,and overall evaluation of the experimental group were significantly improved and were higher than those of the control group.After the Practice,in terms of skill test scores,the experimental group scored higher than the control group,the difference was statistically significant(P<0.05),and the experimental group also scored higher in satisfaction evaluation than the control group.Conclusion The Mini-CEX evaluation teaching model based on the concept of OBE is applied to the clinical practice teaching of the neurology department,which can enhance the training effect of students'clinical practice skills.

Objective To observe the change in the prevalence of post-traumatic stress disorder(PTSD)1 year after trauma exposure and analyze the risk factors of PTSD 1 year after trauma exposure.Methods Convenience sampling was conducted at the initial outbreak of the coronavirus disease 2019 epidemic and 1 year later,respectively.Participants participated in the anonymous online survey.The survey consisted of 2 self-completed questionnaires:1 collected personal information(gender,age,education level,occupation)and subjective sleep quality;the other is the PTSD checklist(PCL-5)from the Diagnostic and Statistical Manual of Mental Disorders,5th edition.Valid questionnaires of 2 091 and 2 092 were respectively retrieved at the initial stage of trauma exposure and 1 year later.Results The prevalence of PTSD at the initial stage of trauma exposure was 5.3％(111/2 091)and 1 year after trauma exposure was 19.1％(399/2 092).Multiple linear regression analysis showed that age(P＜0.01),gender(P＜0.01),and subjective sleep quality(P＜0.01)were risk factors related to PTSD.Conclusions One year after trauma exposure,the prevalence of PTSD increases.Psychological intervention measures should be given at the early stage of trauma exposure,and special attention should be paid to young individuals,women,and those with sleep disorders.

OBJECTIVE To observe the clinical efficacy and effect on serum thymic stromal lymphopoietin(TSLP)levels of pa-tients with advanced liver cancer of qi deficiency and toxic stasis type by Jiawei Yupingfeng San.METHODS Using random double blind method,120 patients with advanced liver cancer of qi deficiency and toxic stasis type were randomly divided into 3 groups:Jiawei Yupingfeng San group,Yupingfeng San group,and placebo group,each consisting of 40 cases.All patients in the 3 groups were given conventional treatment such as radiotherapy,chemotherapy,interventional or targeted therapy;Jiawei Yupingfeng San group was given Jiawei Yupingfeng San granules,Yupingfeng San group was given Yupingfeng San granules,and placebo group was given placebo.The course of treatment was 2 months.The changes of Karnofsky functional status score(KPS score),TCM syndrome score,tumor size and serum TSLP level in the 3 groups were observed before and after treatment,and the correlation between the changes of tumor size and TSLP was analyzed.RESULTS After treatment,the KPS scores of Yupingfeng San group and Jiawei Yupingfeng San group were sig-nificantly increased(P<0.05,P<0.01),TCM syndrome score were decreased(P<0.01),tumor growth(P<0.05,P<0.01)was de-layed,and serum TSLP levels(P<0.05,P<0.01)were decreased.Furthermore,there was a slight positive correlation between chan-ges in tumor size and changes in TSLP(P<0.05).In terms of improving tumor size,the curative effect of Jiawei Yupingfeng San group was better than that of Yupingfeng San group(P<0.05).During the treatment period,no obvious adverse reactions were observed in the 3 groups of patients.CONCLUSION Combined with conventional treatment,Jiawei Yupingfeng San can significantly delay tumor growth in patients with advanced liver cancer of qi deficiency and toxic stasis type and improve patients'TCM syndromes and their qual-ity of survival.The therapeutic mechanism is related to reducing the expression of serum TSLP and improving the immune status of pa-tients,thereby delaying the growth of tumors.

Background and purpose:Breast cancer is a major global public health problem.Bone is the most common site of distant metastasis of breast cancer,accounting for about 70%of all metastatic cases.Bone metastasis of breast cancer can cause a series of complications,including severe pain,pathological fracture,hypercalcemia,spinal cord compression,etc.,which bring great inconvenience to patients'physical activities and affect their quality of life.Metastatic recurrence is the leading cause of death in breast cancer patients.Therefore,there is an urgent need to build a diagnostic model of bone metastasis in breast cancer to identify patients with a high risk of bone metastasis.The aim of this study was to develop a predictive model based on machine learning to predict the probability of breast cancer developing bone metastasis.Methods:Data of breast cancer patients diagnosed between 2010 and 2015 were extracted from The Surveillance,Epidemiology,and End Results(SEER)database.The variables were screened by least absolute shrinkage and selection operator(LASSO)regression,univariate and multivariate logistic regression analysis,and statistically significant risk factors were included to build a prediction model.In this study,nine machine learning algorithms,including decision tree,elastic network,K-nearest neighbor,lightweight gradient elevator,logistic regression,neural network,random forest,support vector machine and limit gradient lifting,were used to adjust the model hyperparameters through random search and 5x cross-validation to build a breast cancer bone metastasis prediction model.The area under the receiver operating characteristic(ROC)curve,calibration curve and decision curve were used to evaluate the model,the optimal model was obtained,and the importance of variables was analyzed based on the optimal model.Finally,a network calculator for predicting the risk of bone metastasis of breast cancer was established using the optimal model.Results:The study included 10 106 patients with breast cancer,7 073 patients in the training set,and 3 033 patients in the validation set.We found that 4 494(63.5%)patients in the training set and 1 927(63.5%)patients in the validation set developed bone metastases,respectively.Race,pathologic grade,estrogen receptor(ER)status,progesterone receptor(PR)status,human epidermal growth factor receptor 2(HER2)status,N stage,lung metastasis,radiotherapy,chemotherapy and surgery were independent predictors of bone metastasis.The training set and verification set were used to verify the model,and the limit gradient lifting algorithm was superior to other machine learning algorithms by integrating the evaluation indexes such as the area under the ROC curve,calibration curve and decision curve.Finally,we used limit gradient algorithm to build network calculator for prediction of breast cancer bone metastases(https://bcbm.shinyapps.io/DynNomapp/).Conclusion:This study developed a predictive model based on machine learning to predict the probability of bone metastases in breast cancer patients,hoping to help clinicians make more rational treatment decisions.

Objective To explore characteristics of co-infection of Chlamydia pneumoniae(Cpn)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and identify their effect on SARS-CoV-2-induced inflammatory response.Methods Patients with coronavirus disease 2019(COVID-19)who received treatment in a hospital in Chenzhou City from December 20,2022 to February 20,2023 were selected.According to the severity of COVID-19,severe and critical cases were classified as the severe symptom group,while mild and moderate cases were classified as the mild symptom group.Meanwhile,according to the age of patients(≥18 years old as adults,＜18 years old as juveniles),they were divided into the adult severe symptom group,adult mild symptom group,juvenile severe symptom group,and juvenile mild symptom group.Propensity score was adopted to match age,gender,and under-lying diseases of patients in severe symptom and mild symptom group in a 1∶1 ratio.Bronchoalveolar lavage fluid(BALF),throat swabs,and serum specimens of patients were collected.Cpn IgG/IgM antibody was detected by enzyme-linked immunosorbent assay(ELISA),levels of 12 common cytokines(including interleukin-8[IL-8])in BALF were detected by flow cytometry,differences among groups were compared.Results A total of 102 patients were included,with 61 severe and critical(severe symptom)patients,as well as 41 mild and moderate(mild symp-tom)patients.There were 71 patients aged ≥18 years and 31 juvenile patients aged＜18 years.There were 39 pa-tients in the adult severe symptom group and 32 in the adult mild symptom group,and 30 pairs were successfully matched through propensity score analysis.There were 22 patients in the juvenile severe symptom group and 9 in the juvenile mild symptom group,and 8 pairs were successfully matched through propensity score analysis.Among COVID-19 patients,the positive rates of Cpn IgG and IgM were 36.27％(n=37)and 8.82％(n=9),respective-ly,with 1 case positive for both Cpn IgG and IgM.The level of interferon(IFN)-α in serum specimens from adult patients with severe symptom combined with positive Cpn IgG was higher than that of IgG negative patients(P=0.037).There was no statistically significant difference in the levels of other cytokines in BALF and serum speci-mens between the two groups of patients(all P＞0.05).The levels of IL-8 and IL-17 in serum specimens of patients with positive Cpn IgG in the adult mild symptom group were both higher than those in Cpn IgG negative patients(both P＜0.05).The levels of IL-8 in both BALF and serum specimens from Cpn IgM positivity patients in the ju-venile mild symptom group were higher than those from patients with negative Cpn IgM(both P＜0.05).Logistic regression analysis results showed that Cpn IgG and IgM positivity were not risk factors for the development of se-vere COVID-19.Conclusion Combined Cpn infection is not a risk factor for the development of severe symptom in COVID-19 patients,and Cpn infection has limited impact on the secretion of inflammatory factors caused by SARS-CoV-2.