ObjectiveTo clarify the expression of TRIM28 in non-M3 acute myeloid leukemia （AML） and its correlation with clinical indicators and prognosis， and to further explore the effect of TRIM28 expression levels on the proliferation and apoptosis of AML cells using small interfering RNA. MethodsThe GSE34577 dataset was analyzed using R software to compare TRIM28 expression between healthy controls and non-M3 acute myeloid leukemia （AML） patients. Clinical samples from non-M3 AML patients were collected， with TRIM28 expression levels measured using real-time quantitative PCR （qPCR）. The analysis focused on correlations between TRIM28 expression and various clinical indicators， treatment efficacy， and patient prognosis. Furthermore， small interfering RNA （siRNA） technology was employed to downregulate TRIM28 expression in human primary AML cells （HL60 cell line）. The effects on cell proliferation and apoptosis were then assessed through CCK-8 assays and flow cytometry， respectively. ResultsThe results showed that TRIM28 was up-regulated in non-M3 AML of both online database GSE34577 and clinical samples （P<0.000 1）， TRIM28 expression of new diagnosis group and relapsed refractory group was higher than iron deficiency anemia group （P<0.01）， and there was no significance between different French-American-British classification systems subtype. TRIM28 expression was higher in non-M3 AML patients with a poor genetic prognosis stratified as moderate than in the good prognosis group， and TRIM28 expression was associated with NPM1 combined with the FLT3-ITD mutation， positively correlated with age， bone marrow blast， peripheral blood blast and white blood cell， negatively correlated with hemoglobin. In addition， interference TRIM28 greatly inhibited cell proliferation and promoted cell apoptosis. ConclusionThis study reveals that TRIM28 is highly expressed in non-M3 AML and associated with prognosis， and plays a key role in the proliferation and apoptosis of AML cells， suggesting that TRIM28 may serve as a novel therapeutic target for non-M3 AML.

[Objective] To establish a new scoring system to predict the perioperative outcomes (operation time, intraoperative blood loss, and trifecta achievement) in patients undergoing robot-assisted partial nephrectomy (RAPN) by integrating the RENAL and Mayo adhesive probability (MAP) scores. [Methods] Clinical data of 178 patients with renal cell carcinoma who underwent RAPN performed by the same surgeon in our hospital during Jan.2015 and Jan.2022 were retrospectively analyzed.The RENAL and MAP scores of all patients were calculated.Linear regression and logistic regression were used to evaluate the associations between the components of the RENAL and MAP scores (a total of 6 variables) and perioperative outcomes.The factors with significant associations were then included into logistic regression analysis to identify independent predictors for constructing an assessment system for perioperative outcomes, and the receiver operating characteristic (ROC) curve was plotted to calculate the area under the curve (AUC) to predict its efficacy. [Results] Multivariate linear regression analysis showed that tumor size (β=6.14, 95%CI: 1.93—10.34, P=0.004), exophytic rate (β=10.60, 95%CI: 3.44—17.76, P=0.004), and perinephric fat thickness (β=16.48, 95%CI: 8.52—24.45, P<0.001) were significantly associated with operation time.Tumor size (β=10.55 95%CI: 5.60—15.49, P<0.001) was associated with both intraoperative blood loss and trifecta achievement (OR=1.73, 95%CI: 1.26—2.36, P=0.001). Multivariate logistic regression analysis of these 3 factors identified tumor size (OR=9.07, 95% CI: 1.18—69.45, P=0.03) and perinephric fat thickness (OR=2.28, 95%CI: 1.86—6.04, P=0.01) as independent predictors of perioperative outcomes.Based on these findings, the tumor size and perinephric fat thickness (RP) scoring was constructed, which demonstrated better predictive ability than RENAL score or MAP score alone (RP vs.RENAL vs.MAP: 0.766 vs.0.548 vs.0.684). [Conclusion] The RP score includes fewer variables than the RENAL and MAP scores but outperforms them.

BACKGROUND:The imbalance between bone resorption and bone formation in microgravity environments leads to significant bone loss in astronauts.Current research indicates that bone loss under microgravity conditions is the result of the combined effects of various cells,tissues,and systems. OBJECTIVE:To review different biological effects of microgravity on various cells,tissues,or systems,and summarize the mechanisms by which microgravity leads to the development of osteoporosis. METHODS:Databases such as PubMed,Web of Science,and the Cochrane Database were searched for relevant literature from 2000 to 2023.The inclusion criteria were all articles related to tissue engineering studies and basic research on osteoporosis caused by microgravity.Ultimately,85 articles were included for review. RESULTS AND CONCLUSION:(1)In microgravity environment,bone marrow mesenchymal stem cells tend to differentiate more into adipocytes rather than osteoblasts,and hematopoietic stem cells in this environment are more inclined to differentiate into osteoclasts,reducing differentiation into the erythroid lineage.At the same time,microgravity inhibits the proliferation and differentiation of osteoblasts,promotes apoptosis of osteoblasts,alters cell morphology,and reduces the mineralization capacity of osteoblasts.Microgravity significantly increases the number and activity of osteoclasts.Microgravity also hinders the differentiation of osteoblasts into osteocytes and promotes the apoptosis of osteocytes.(2)In a microgravity environment,the body experiences changes such as skeletal muscle atrophy,microvascular remodeling,bone microcirculation disorders,and endocrine disruption.These changes lead to mechanical unloading in the bone microenvironment,insufficient blood perfusion,and calcium cycle disorders,which significantly impact the development of osteoporosis.(3)At present,the mechanism by which microgravity causes osteoporosis is relatively complex.A deeper study of these physiological mechanisms is crucial to ensuring the health of astronauts during long-term space missions,and provides a theoretical basis for the prevention and treatment of osteoporosis.

As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an ¹⁸F-labeled PET tracer (QTFT) that targets the P2Y₁₂, a receptor highly expressed on anti-inflammatory microglia. [¹⁸F]QTFT exhibited high binding affinity to the P2Y₁₂ (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [¹⁸F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y₁₂ antagonist. Furthermore, [¹⁸F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y₁₂ in anti-inflammatory microglia. In a pilot clinical study, [¹⁸F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [¹⁸F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y₁₂ overexpressed in anti-inflammatory microglia.

Objective:To develop an evaluation index system for the quality management process of investigator-initiated trials(IITs) in ophthalmology, providing a scientific tool and reference for improving clinical research quality and standardized management.Methods:Key quality management elements of ophthalmology IITs were identified through a literature review and experts interviews. A three-round Delphi consultation was conducted with experts from 16 provinces and municipalities in China who specialize in ophthalmic clinical research management. The importance of each index was scored, and weighting calculations were performed. Based on ranking and feasibility, a validated quality index system for ophthalmology IITs was established.Results:A three-tier index system was developed, comprising three first-level indicators (structure, process, and outcome), 15 secondary indicators, and 44 tertiary indicators. The expert authority coefficient was 0.87, and the response rates for the three Delphi rounds were 100%, 92.58%, and 100%, respectively. Among the first-level indicators, the highest weight was assigned to ″Structure″ (0.443 2). The top three secondary indicators were ″Data analysis report″ (0.098 3), ″Study protocol execution and data archiving″ (0.096 0), and ″Research team″ (0.094 1). At the tertiary level, the highest-ranked indicators were ″Data cleaning, verification, and database locking″ (0.049 2), ″Archiving and preservation of research data″ (0.048 8), and ″Execution of statistical analysis as planned″ (0.048 4).Conclusions:The ophthalmology IIT process quality evaluation index system developed in this study is scientifically grounded and will provides a valuable reference for standardizing quality management and further empirical research in ophthalmology IITs.

Objective:To apply artificial intelligence（AI）in classifying ovarian tumors on ultrasound images，and compare the diagnostic results of several sonographers with varying seniority levels.Methods:A total of 645 patients diagnosed with adnexal masses via gynecological ultrasound examination at Qilu Hospital of Shandong University from January 2021 to December 2024 were enrolled. Three deep learning architectures，i.e.，Alexnet，Densenet121，and Resnet50 were developed and used to internally test the classification effectiveness of ovarian tumors，while the optimal model was selected for external testing. Two junior sonographers and two senior sonographers were recruited to independently diagnose ovarian tumors in the external test dataset. Subsequently，the benign and malignant results of the model's predictions were disclosed to each sonographer，and their revised diagnoses on the same external test data in combination with the best AI model were recorded.Results:The optimal model achieved an accuracy of 0.941，sensitivity of 0.936，and specificity of 0.944 on the internal test dataset，and maintained robust performance on the external test dataset with accuracy of 0.891，sensitivity of 0.880，and specificity of 0.907. Compared to junior sonographers，the optimal model demonstrated significantly higher sensitivity in discriminating benign from malignant ovarian tumors（0.880 vs. 0.723，0.602；all P<0.05）. No statistically significant difference was observed in diagnostic accuracy between the optimal model and senior sonographer 1（ P=0.05）. With assistance from the optimal model，junior sonographers achieved significant improvements in both sensitivity and specificity（sensitivity：0.723 vs. 0.843，0.602 vs. 0.819；specificity：0.778 vs. 0.833，0.685 vs. 0.741；all P<0.05）. Conclusions:The optimal model achieves comparable performance to that of senior sonographers in ovarian tumor classification. With model assistance，the diagnostic performance of junior sonographers is significantly improved.

Functional cure (i.e., clinical cure) of chronic hepatitis B (CHB) is a core research objective in the field of hepatology. With the revision of the Expert opinions on the technical guiding Principles for clinical trials of drugs in the treatment of chronic hepatitis B virus infection, this article concisely reviews the evolving concept of functional cure for hepatitis B, research progress on the dynamic trajectories and threshold of key serological markers (such as HBsAg/anti-HBs), strategies for safety evaluation of treatment discontinuation, and the importance of building a collaborative innovation ecosystem involving scientific research, industry, healthcare, policy, and societal forces. Through multidimensional technological breakthroughs and interdisciplinary collaboration, the functional cure rate of chronic hepatitis B infection is expected to improve significantly over the next 5-10 years, laying the foundation for achieving the World Health Organization (WHO)'s goal of eliminating viral hepatitis as a public health threat by 2030.

Objective:To analyze the results of next generation sequencing (NGS) gene testing in liquid-based cytological specimens of lung adenocarcinoma cavity and evaluate the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment.Methods:Liquid based cytological specimens of 222 cases of lung adenocarcinoma with cavity effusion and 201 cases of metastatic lymph node biopsy were collected. Specimens were obtained from the Cytology Laboratory of the Cancer Hospital of the Chinese Academy of Medical Sciences. The collection period was from January 2018 to December 2022. The results of NGS gene detection were compared. The clinical efficacy of 91 patients treated with EGFR-TKI was evaluated, and the survival curve was analyzed by Kaplan-Meier and other statistical methods.Results:The mutation rates of cancer-related genes detected by NGS were 82.0% (182/222) vs 79.1% (159/201), ( P=0.455) in liquid-based cytological specimens and histological specimens of metastatic lymph node biopsy, respectively. However, the mutation rate of EGFR T790M was significantly higher in cavity effusion than in lymph node biopsy specimens [12.2%(27/222)＞3.5%(7/201), P=0.001]. The results of gene mutation were identical in 10 of the 13 cases with cavity effusion and metastatic lymph node biopsy, and the agreement rate of EGFR was 84.6%(11/13). In 3 inconsistent cases, EGFR mutations were detected in 2 cavity effusion cases that were not detected by lymph node biopsy. Results of genetic analysis of fluid-based cytological samples of 91 patients with cavity effusion were evaluated after drug treatment with EGFR-TKI. The mean progression-free survival (PFS) of the patients was 11.4 months (95% CI: 9.9-12.9). The mean PFS of patients harboring EGFR mutation was 12.3 months (95% CI: 10.8-13.9), and the mean PFS of EGFR wild type was 4.1 months (95% CI: 2.1-6.2). Conclusions:The results of NGS gene detection in liquid-based cytological specimens of lung adenocarcinoma patients with cavity effusion show that the PFS time is similar to that of histological specimens after clinical treatment with EGFR-TKI, which proves the reliability of NGS gene detection results in liquid cytological specimens. NGS gene testing appears higher sensitivity in cavity liquid-based samples than in metastatic lymph node samples.

Objective:To analyze the distribution characteristics of sports facilities in China using geographic information system (ArcGIS) and to investigate their association with mortality risk among residents.Methods:This prospective cohort study included 97 912 community residents from the Chinese Family Database (CFD) between 2013 and 2017. After excluding participants lost to follow-up and those with incomplete data, 53 937 individuals were retained for the analysis. The distribution characteristics of sports facilities in China was mapped using ArcGIS, and the death events were recorded via structured interviews and questionnaires. The Poisson regression was used to assess the association between the distribution characteristics of sports facilities near participants′ residences and their mortality risk.Results:In 2013, a total of 79 714 sports facilities were identified across 262 districts (counties) in China, with large-scale sports facilities accounting for the highest proportion (87.09%). The median number of sports facilities within the residential buffer zone was 17 (4, 30), and the median distance from the residence to the nearest sports facility was 453.2 (341.5, 1 863.5) m. Among the 53 937 community residents analyzed in this study, there were 27 761 males and 26 176 females, 1 326 deaths (2.5%) occurred during the follow-up. Poisson regression revealed that a higher number of sports facilities in the buffer zone (≥21 vs 0-2) was associated with lower mortality risk ( RR=0.74, 95% CI: 0.64-0.85; P0.05). Subgroup analyses showed that being≥60 years old ( RR=0.82, 95% CI: 0.70-0.95), males ( RR=0.78, 95% CI: 0.64-0.95), females ( RR=0.79, 95% CI: 0.64-0.97), having a junior high school education or less ( RR=0.84, 95% CI: 0.71-0.99), and having a urban residence ( RR=0.77, 95% CI: 0.66-0.90) were all negatively associated with residents′ mortality risk (all P0.05). After adjusting for age, greater distance to the nearest sports facility ( RR=1.41, 95% CI: 1.08-1.83) and failing to meet the"10-minute fitness circle"criterion ( RR=1.25, 95% CI: 1.02-1.53) were associated with higher mortality risk among males (both P0.05). After adjusting for age and gender, urban residents with a greater distance to the nearest sports facility ( RR=1.29, 95% CI: 1.04-1.60) or not meeting the 10-minute fitness circle ( RR=1.18, 95% CI: 1.00-1.38) showed a significantly higher mortality risk (both P0.05). Conclusions:The ArcGIS analysis revealed that the distribution of sports facilities in China is characterized by a high proportion of large-scale facilities. Lower facility density within residential buffer zone and greater distance to the nearest facility increase mortality risk among adults.

OBJECTIVE: To investigate the short-and med-term clinical efficacy of unicompartmental knee arthroplasty(UKA)for the treatment of medial knee osteoarthritis (OA) in elderly patients with anterior cruciate ligament deficiency(ACLD). METHODS: A retrospective analysis was conducted on 31 patients aged over 75 years old with primary medial knee OA and ACLD who underwent UKA between January 2018 and December 2022. The cohort included 12 males and 19 females, aged from 75 to 91 years with an average age of (79.56±4.54) years, with 13 left knee, 16 right knee, and 2 bilateral knees. Clinical outcomes were assessed preoperatively and at final follow-up using the visual analogue scale (VAS), Hospital for Special Surgery(HSS) score, range of motion (ROM), hip-knee-ankle angle (HKA), and tibial component posterior slope angle (TCPSA). Complications such as infection, prosthesis wear, prosthesis loosening, and dislocation were also recorded. RESULTS: All 31 patients were followed up from 12 to 63 months with an average of (28.34±10.56) months. The average postoperative TCPSA was (4.83±1.31)° ranged from 2.5° to 6.8°. At the final follow-up, there was significant improvement in VAS (3.24±0.53) vs. (6.59±0.69), HSS score (85.19±4.45) vs. (64.38±5.94), ROM (118.83±5.38)° vs. (98.85±4.08)°, and HKA (176.83±5.16)° vs. (169.57±6.28)° compared to preoperative values (P<0.05). No cases of infection, prosthesis loosening, or dislocation were reported. CONCLUSION UKA provides favorable short-and mid-term outcomes for elderly patients with medial knee OA and ACLD . However, long-term clinical efficacy needs further investigation through extended follow-up.
Humans ; Male ; Female ; Arthroplasty, Replacement, Knee/methods* ; Aged ; Osteoarthritis, Knee/physiopathology* ; Retrospective Studies ; Aged, 80 and over ; Range of Motion, Articular ; Anterior Cruciate Ligament Injuries/surgery*