The αPD-L1 antibody-based immune checkpoint blockade therapy is still limited by the poor clinical response rate as it is mainly utilized to block surface PD-L1 on tumor cells while ignoring abundant PD-L1 exosomes secreted in the environment, causing tumor immune evasion. Here, we proposed an exosome biogenesis inhibition strategy to suppress tumor exosomes secretion from the source, reducing the inhibitory effect on T cells and enhancing chemo-immunotherapy efficacy. We developed sulfafurazole homodimers (SAS) with disulfide linkages, effectively releasing the drug in response to glutathione (GSH) and inhibiting 4T1 tumor-derived exosomes secretion. Subsequently, gemcitabine (Gem) was encapsulated to induce immunogenic cell death (ICD). Consequently, Gem@SAS inhibited the secretion of tumor exosomes by more than 70%, increased proliferation and granzyme B secretion ability of T cells by more than 2 times, and showed superior efficacy in breast cancer treatment as well as lung metastasis of breast cancer.

Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective To investigate the feasibility and clinical experience of kidney transplantation from donors with Marfan syndrome (MFS). Methods Clinical data of 2 recipients undergoing kidney transplantation from the same MFS patient were retrospectively analyzed and literature review of 2 cases was conducted. Characteristics and clinical diagnosis and treatment of kidney transplantation from MFS patients were summarized. Results The Remuzzi scores of the left and right donor kidneys of the MFS patient during time-zero biopsy were 1 and 2. No significant difference was observed in the renal arteriole wall compared with other donors of brain death and cardiac death. Two recipients who received kidney transplantation from the MFS patient suffered from postoperative delayed graft function. After short-term hemodialysis, the graft function of the recipients received the left and right kidney began to gradually recover at postoperative 10 d and 20 d. After discharge, serum creatinine level of the recipient received the left kidney was ranged from 80 to 90 μmol/L, whereas that of the recipient received the right kidney kept declining, and the lowest serum creatinine level was 232 μmol/L before the submission date (at postoperative 43 d). Through literature review, two cases successfully undergoing kidney transplantation from the same MFS donor were reported. Both two recipients experienced delayed graft function, and then renal function was restored to normal. Until the publication date, 1 recipient has survived for 6 years, and the other recipient died of de novo cerebrovascular disease at postoperative 2 years. Conclusions MFS patients may serve as an acceptable source of kidney donors. However, the willingness and general conditions of the recipients should be carefully evaluated before kidney transplantation. Intraoperatively, potential risk of tear of renal arterial media should be properly treated. Extensive attention should be paid to the incidence of postoperative complications.

Objectives:To analyze the consistency of evaluating left ventricular hemodynamics (HDF) based on single plane and multi plane cine sequences of magnetic resonance mitral valve orifice.Methods:A prospective study was conducted on 48 healthy adults, and two methods were used to measure the mitral valve diameter and calculate HDF parameters. The first method was to measure the diameter of the mitral valve opening in the left ventricular three chamber cine sequence; The second method is to measure the mitral valve diameter using cine sequences of two chamber, three chamber, and four chamber hearts, and then take the average value. Paired t-tests were used to compare the differences in HDF measured by two methods, and Pearson correlation coefficient ( r), intra group correlation coefficient ( ICC), and Bland-Altman analysis were used to test the consistency and reproducibility of the two methods. Results:The root mean square (RMS) of longitudinal HDF calculated using single plane and multi plane mitral valve diameters were [(17.28±4.41)% vs (17.21±4.61)%] ( P=0.379) for the entire cardiac cycle, [(21.45±5.54)% vs (21.49±5.68)%] ( P=0.646) for systolic phase, and [(12.78±4.10)% vs (12.54±4.24)%] ( P=0.106) for diastolic phase, respectively. The difference in the calculation results of HDF parameters related to ventricular function was not statistically significant (all P>0.05), and there was good consistency ( r=0.924-0.996, ICC=0.924-0.995). The two HDF parameters related to atrial function were sensitive to the measurement method of mitral valve orifice diameter [RMS of longitudinal HDF during active atrial emptying: (3.26±1.51)% vs (3.32±1.55)%, P=0.006; longitudinal HDF pulse during active atrial emptying: (-2.60±1.28)% vs (-2.76±1.30)%, P<0.001]. Conclusions:The ventricular function related HDF parameters obtained from the analysis of mitral valve orifice diameter using single plane and multi plane methods have good consistency, and can be evaluated using relatively simple single plane methods for left ventricular HDF.

Objective To investigate the current status,obstacles,and specific needs associated with the application of transradial access(TRA)in peripheral interventions in Chinese hospitals,with the aim of promoting the broader adoption of TRA in interventional procedures.Methods The Committee of Interventional Oncology of China Anti-Cancer Association conducted a cross-sectional questionnaire survey to investigate and analyze the nationwide situation of TRA in peripheral interventional surgeries in 2022.Results Personnel from 60 hospitals participated in the questionnaire.The results showed that the number of peripheral interventionals performed using TRA was significantly lower than that performed using transfemoral access(TFA),with considerable variability among hospitals.The primary obstacles to the adoption of TRA were the lack of suitable catheters and the difficulty of radial artery puncture.Approximately 86.67％of the institutions expressed a high expectation for the innovation of new TRA-specific devices,particularly catheters,microcatheters,and guidewires.60.00％of medical institutions indicated a strong desire for systematic training and participation in multi-center clinical trials.Conclusions TRA peripheral intervention is feasible in many hospitals in China,however,systematic training and further promotion of TRA are essential.The innovation of new TRA-specific devices and TRA in peripheral intervention is urgent.

Stroke often causes severe motor, sensory, and daily living function impairments, especially the recovery of distal limb extensor motor function is the most difficult. With the widespread application of Contralateral Control Functional Electrical Stimulation (CCFES) in stroke rehabilitation and continuous improvement of integrated wearable devices in recent years, it has been found that CCFES and combination therapy have good therapeutic effects in improving wrist extension and ankle dorsiflexion function in stroke patients. CCFES can improve both distal and proximal upper limb function, when applied to lower limbs, attention should be paid to the reverse coordination mechanism. Early intervention, sufficient treatment courses, and multiple combination CCFES treatment plans can accelerate the improvement of stroke patients' function.

ObjectiveTo visualize the research trends of verbal and nonverbal cognitive functions in patients with post-stroke aphasia (PSA). MethodsPapers about verbal and nonverbal cognitive functions after stroke were extracted from Web of Science Core Collection from establishment to August, 2022, and a bibliometric analysis was conducted on the distribution of articles published by year, author, journal, institution, and country. Author cooperation, author co-citation, journal co-citation, country/institution cooperation, dynamic evolution, keyword hotspots, and trends were visually analyzed by using VOSviewer software. ResultsA total of 1 630 publications were identified for final analysis. The first article related to the topic was retrieved in 2004. After that, the number of published papers showed an increasing trend year by year, with some fluctuations after 2019. Matthew A. Lambon Ralph and Elizabeth Jefferies were the authors who produced the most, were cited the most, and were the most influential. Neuropsychologia was a highly productive and well-cited publication. The University of Manchester in the United Kingdom and Johns Hopkins University in the United States were the nations/institutions with high yield and high centrality. Although China had a high yield and was in the top five, the centrality was insufficient. The dynamic emergence of keywords revealed that the research had gone through the following stages: evaluating the mechanism of language and nonverbal cognitive function impairment based on neuroimage, exploring the role of nonverbal cognitive dysfunction in pathology and recovery mechanisms of patients with PSA, examining the therapeutic mechanism of non-invasive brain stimulation and electronic tele-rehabilitation equipment, and revealing not only the frontal and temporal areas but also brain network supporting nonverbal cognition. ConclusionIn recent years, some achievements have been made in the researches on verbal and nonverbal cognitive function, particularly in the studies of the neuroimaging-based mechanisms of common damage and the intervention effects of synergistic therapy. In the future, academic cooperation between different regions and different teams needs to be strengthened. Further exploration should be focused on refining the cognitive neuropsychology and exploring new technologies to improve the therapeutic effect of PSA.

Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors. Although degradation of fiber is a promising strategy, its application was still bottlenecked by the side effects of causing metastasis, resulting in the failure of immunotherapy. Here, we developed an antimetastatic polymer (HPA) for the delivery of chemo-drug and antifibrotic siPAI-1 to form the nano-permeator. Nano-permeator shrank after protonation and deeply penetrated into the tumor core to down-regulate the expression of PAI-1 for antifibrosis, and further promoted the sustained infiltration and activation of T cells for killing tumor cells. Moreover, metastasis after fiber elimination was prevented by multivalent CXCR4 antagonistic HPA to reduce the attraction of CXCL12 secreted by distant organs. The administration of stroma-alleviated immunotherapy increased the infiltration of CD8⁺ T cells to 52.5% in tumor tissues, inhibiting nearly 90% metastasis by HPA in distant organs. The nano-permeator reveals the mechanism and correlation between antifibrosis and antimetastasis and was believed to be the optimizing immunotherapy for solid fibrotic tumors.

ObjectiveTo investigate the abnormal changes of gray matter structure covariant network in post-stroke aphasia (PSA) patients. MethodsFrom June, 2019 to March, 2022, 15 PSA patients (patient group) from Dongzhimen Hospital, Beijing University of Chinese Medicine and Beijing Bo'ai Hospital were recruited, as well as 15 healthy subjects (control group). Their brain structure magnetic resonance imaging data were collected. The brain covariant network was constructed based on gray matter volume correlation, and graph theory analysis method was used to evaluate the global and node network level topology properties of structural covariant network. The differences of gray matter covariant network properties between patients and controls were compared. ResultsThere was no significant difference in the global network level topology properties between two groups (P > 0.05). At the nodal level, compared with the control group, the betweenness decreased in the right middle frontal gyrus, right posterior cingulate gyrus, right amygdala, left middle occipital gyrus, and increased in the right inferior frontal gyrus and the right suboccipital gyrus of the insula operculum (P < 0.05); the node degree decreased in the left superior frontal gyrus, left anterior cingulate and paracingulate gyrus, left hippocampus and left amygdala, while it increased in the right inferior frontal gyrus, left supplementary motor area, right superior occipital gyrus, right inferior occipital gyrus, and right lentiform pallidus (P < 0.05); the node efficiency decreased in the left anterior cingulate and paracingulate gyrus, left hippocampus, left amygdala, left temporal pole: superior temporal gyrus, and increased in the inferior frontal gyrus of right insula, left supplementary motor area and right suboccipital gyrus (P < 0.05). ConclusionThe abnormal reduction of node network properties in some brain regions in the left hemisphere of PSA patients may be a characteristic structural covariation pattern, and there may be some compensation in the right hemisphere of the structural network in some brain regions.