ObjectiveTo explore the process and guidelines for ethical review in decentralized drug clinical trials， promote clinical trial progress， and ensure drug development progress. MethodsThe key points of the ethical review were summarized by studying the relevant laws and regulations on decentralized drug clinical trials， analyzing the advantages and challenges of decentralized drug clinical trials， and combining the experience of the ethics committee of the institution in reviewing decentralized drug clinical trials. ResultsRelevant laws and regulations were the basis for the ethical review， and the ethics committee should adopt appropriate review methods based on regulations and hospital ethical standard operating procedures. The ethics committee should focus on the feasibility， applicability， and rationality， the adequacy of informed consent， the protection of rights and interests and privacy of subjects， as well as the qualification and standard operating procedures of electronic platforms for conducting decentralized drug clinical trials. ConclusionDecentralized drug clinical trials are in their early stages and urgently require guidance from relevant laws and regulations. Ethical review is also constantly being refined through exploration. It is necessary to supervise the implementation of responsibilities by all parties， pay attention to the rights and interests of subjects， and gradually promote the implementation of decentralized drug clinical trials.

ObjectiveGliomas in the motor functional area can damage the corticospinal tract (CST), leading to motor dysfunction. Currently, there is a lack of unified methods for evaluating the extent of CST damage, especially in patients with high surgical risk where the minimum distance from the lesion to the CST is less than 10 mm. This study aims to further clarify the classification method and clinical significance of CST morphological changes in these patients. MethodsThis retrospective study analyzed 109 high-risk functional area glioma patients who underwent neurosurgical treatment with preoperative diffusion tensor imaging (DTI) imaging and intraoperative neurostimulation guidance between 2014 and 2024. All patients had a lesion-to-tract distance (LTD) of less than 10 mm between the CST and the lesion. Preoperative DTI evaluation of CST involvement-induced morphological changes were reviewed. Patients were divided into 3 groups: 17 cases (15.6%) with symmetric CST morphology compared to the healthy side (CST symmetry), 48 cases (44.0%) with significant CST morphology changes compared to the healthy side (CST deformation), and 44 cases (40.4%) with CST overlap with the tumor (CST overlap). Then we classified patients according to preoperative assessment of tumor-induced morphological changes, and analyze postoperative motor function for each category. ResultsPostoperative pathology showed a significantly higher proportion of high-grade gliomas (HGG) in the CST overlap group compared to the other two groups (P=0.001). Logistic regression analysis showed that CST overlap was a predictor of HGG (P=0.000). The rate of total tumor resection in the CST deformation group and overlap group was lower than in the CST symmetric group (P=0.008). There was a total of 41 postoperative hemiplegic patients, with 4 cases (23.5%) in the CST symmetric group, 11 cases (22.9%) in the CST deformation group, and 26 cases (59.1%) in the CST overlap group. CST overlap with the tumor predicted postoperative hemiplegia (P=0.016). Two-way ANOVA analysis of the affected/healthy side and CST morphology groups showed significant main effects of CST grouping and healthy-affected side (P=0.017 and P=0.010), with no significant interaction (P=0.31). The fractional anisotropy (FA) value in the CST overlap group and the affected side was lower. A decrease in the FA value on the affected side predicted postoperative hemiplegia (sensitivity 69.2%, specificity 71.9%). ConclusionWe have established a method to predict postoperative hemiplegia in high-risk motor functional area glioma patients based on preoperative CST morphological changes. CST overlap leads to a decrease in CST FA values. This method can be used for precise patient management and aid in accurate preoperative surgical planning.

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

OBJECTIVES: To explore the association between GPSM2 expression level and gastric cancer progression and analyze the functional pathways and action mechanism of GPSM2. METHODS: We analyzed GPSM2 expression levels in gastric cancer tumors based on data from the GEPIA database and the clinical data of 109 patients. Public databases enrichment analysis were used to assess the impact of GPSM2 expression level on survival outcomes and the functional pathways and action mechanism of GPSM2. We further observed the effects of GPSM2 knockdown and overexpression on proliferation, migration and apoptosis of MGC803 cells using CCK-8 assay, colony formation assay, flow cytometry and immunoblotting and on the growth of MGC803 cell xenografts in nude mice. RESULTS: Bioinformatic analysis and immunohistochemical staining of the clinical specimens both revealed high GPSM2 expressions in gastric cancer (P<0.01). A high GPSM2 expression was significantly correlated with T3-4 stages, N2-3 stages, a carcinoembryonic antigen (CEA) level ≥5 μg/L, and a carbohydrate antigen (CA) 19-9 level ≥37 kU/L (P<0.05). Cox regression analysis identified high GPSM2 expression as an independent risk factor affecting 5-year survival of the patients (P<0.05). Gene ontology (GO) analysis suggested that GPSM2 was involved in cell cycle regulation. In MGC803 cells, GPSM2 overexpression significantly promoted cell proliferation and G1/S transition and xenograft growth in nude mice. KEGG pathway enrichment analysis indicated that GPSM2 executed its biological functions by regulating the p53 signaling pathway, which was confirmed by the results of immunoblotting experiments showing suppression of p53 signaling pathway activity in GPSM2-over expressing MGC803 cells. CONCLUSIONS GPSM2 is highly expressed in gastric cancer to affect patient prognosis by promoting tumor cell proliferation and G1/S transition possibly via inhibiting the p53 pathway.
Stomach Neoplasms/metabolism* ; Humans ; Cell Proliferation ; Prognosis ; Animals ; Mice, Nude ; Cell Line, Tumor ; Mice ; Apoptosis ; Tumor Suppressor Protein p53/metabolism* ; Cell Movement

Due to their good properties of elastic modulus, degradability and ability to promote bone repair, magnesium alloys have become a research hotspot in research of orthopedic implants. Nevertheless, most of the biomedical magnesium alloys currently available fail to meet the requirements in orthopedics because of their rapid degradation after implantation. Rare earth-magnesium alloys possess excellent corrosion resistance and are expected to become important materials as clinical orthopedic implants. This review summarizes the recent progress in studies of the physiological functions of rare earth elements, the effects of supplementation of rare earth elements on biomechanical properties and the in vitro and in vivo biocompatibility of magnesium alloys, and their contribution to tendon-bone healing, addressing also the current clinical orthopedic applications of different rare earth-magnesium alloys, challenges, and future strategies for improving these alloys.
Alloys/chemistry* ; Magnesium/chemistry* ; Metals, Rare Earth/chemistry* ; Humans ; Biocompatible Materials ; Prostheses and Implants

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Gallbladder cancer with delayed diagnoses, as a malignant tumor diagnosed intraoperatively or postoperatively incidentally in benign gallbladder diseases, radical surgical treatment is its core treatment, and the necessity of re-operation, timing of surgery, choice of surgical procedure, definition of resection extent, and preoperative neoadjuvant therapy still remain controversial. Re-operation for gallbladder cancer with delayed diagnoses needs to balance tumor radicalization, postoperative risk, and survival benefit, and combining neoadjuvant therapy to facilitate radical treatment, and develop individualized protocols. The multidisciplinary team should integrate innovative technologies and multi-center prospective studies to promote the development of precise treatment strategies for gallbladder cancer with delayed diagnoses and optimize the survival of patients.

Non-small cell lung cancer(NSCLC)is a highly lethal malignant tumor that poses a serious threat to human health.Traditional methods for tumor diagnosis and treatment have many limitations.However,circulating tumor DNA(ctDNA)detection,a kind of liquid biopsy technology,has gained widespread attention in the field of NSCLC personalized therapy and monitoring due to its non-invasive,convenient,and comprehensive sensitivity.This article will review the latest research progress of ctDNA detection in the clinical diagnosis and treatment of NSCLC in recent years,including its applications in early screening,disease diagnosis,tumor mutation monitoring,treatment efficacy evaluation,and prognosis assessment.

Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and adolescents. Methods A cross-sectional study was conducted including 3,079 Chinese children and adolescents,aged 6 to 17 years,from Jiangsu,China.Anthropometric indices,such as,children's body mass index(BMI),BMI z-scores,waist circumference,and waist-to-height ratio were utilized.Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B12 levels with anthropometric indices and odds of obesity. Results We observed that serum vitamin B12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity[odds ratio(OR)= 0.68;95%confidence interval(CI)= 0.59,0.78]and abdominal obesity(OR = 0.68;95%CI = 0.60,0.77).When compared to participants with both serum vitamin levels in the two middle quartiles,those with both serum folate and vitamin B12 levels in the highest quartile were less prone to general(OR = 0.31,95%CI = 0.19,0.50)or abdominal obesity(OR = 0.46,95%CI = 0.31,0.67).Conversely,participants with vitamin B12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity(OR = 2.06,95%CI = 1.09,3.91). Conclusion Higher serum vitamin B12 concentrations,but not serum folate concentrations,were associated with lower odds of childhood obesity.Children and adolescents with high levels of vitamin B12 and folate were less likely to be obese.