Objective To explore the prognostic factors for patients with descending duodenum gastrointestinal stromal tumors (GIST), analyze the impact of different surgical approaches on prognosis, and develop a predictive model for surgical approach selection. Methods This single-center retrospective cohort study included patients with primary descending duodenum GIST treated in Zhongshan Hospital, Fudan University from January 2010 to January 2015, with follow-up until August 2025. The primary outcomes were incidence of postoperative complications, disease-free survival (DFS) rate, and overall survival (OS) rate. Cox regression and logistic regression were used to identify factors influencing prognosis and surgical approach selection, respectively. A nomogram model for selecting the surgical approach was constructed. Results A total of 78 patients with descending duodenum GIST were included, with age of (56.14±11.76) years. The 1-, 5-, and 10-year OS rates were 100%, 98.7%, and 85.7%, respectively, and the corresponding DFS rates were 100%, 90.9%, and 82.3%. Intraoperative blood loss, postoperative gastroparesis, mucosal ulceration, maximum tumor diameter, and Ki-67-positive cell ratio were independent risk factors for DFS, while maximum tumor diameter and mitotic figure were independent risk factors for OS (P＜0.05). The 10-year DFS rate was higher in the local resection group than in the pancreaticoduodenectomy group (89.45% vs 74.24%; HR＝0.300, P＝0.013), but there was no statistical difference in OS between the two groups. The incidence of postoperative complications in the pancreaticoduodenectomy group was higher than that in the local resection group (P＜0.001). Maximum tumor diameter and distance from tumor to the duodenal papilla were independent factors influencing surgical approach selection. The nomogram model based on these two indices demonstrated good discrimination and accuracy upon internal validation. Conclusions The long-term prognosis of patients with descending duodenal GIST is favorable, and surgical treatment achieves satisfactory outcomes. The nomogram model developed in this study can effectively guide individualized surgical approach selection and provide a reference for clinical decision-making.

Background: and Purpose Accurately predicting long-term functional outcomes of basilar artery occlusion (BAO) remains challenging. We compared the predictive performance of the baseline, 24-hour, and 72-hour National Institutes of Health Stroke Scale (NIHSS) scores for 90-day BAO functional outcomes using the Acute Basilar Artery Occlusion: Endovascular Thrombectomy versus Standard Medical Treatment (ATTENTION) trial data. We identified the optimal assessment time point, determined treatment-specific NIHSS cutoff values, and explored the role of early neurological function in treatment effects. Methods: This retrospective post hoc analysis included 324 patients with acute BAO with baseline NIHSS scores ≥10 and complete NIHSS assessments at each time point. The primary outcome was a favorable 90-day functional outcome (modified Rankin Scale score, 0–3). Receiver operating characteristic curve analysis was used to assess the predictive ability of NIHSS scores. The optimal 72-hour NIHSS predictive cutoff values were determined for the endovascular treatment (EVT) and best medical management (BMM) subgroups. Results: The 72-hour NIHSS score showed the highest predictive accuracy for the primary outcome (area under the receiver operating characteristic curve [AUC]: 0.954), outperforming the 24-hour (AUC: 0.903) and baseline (AUC: 0.688) scores; its optimal predictive cut-off value was ≤11 in the EVT group (sensitivity: 85.6%, specificity: 92.9%, positive predictive value [PPV]: 91.8%, negative predictive value [NPV]: 87.4%) and ≤9 in the BMM group (sensitivity: 84.6%, specificity: 95.1%, PPV: 84.6%, NPV: 95.1%). Conclusions The 72-hour NIHSS score outperformed the baseline and 24-hour scores in predicting 90-day functional outcomes and mediating the effects of EVT. Treatment-specific 72-hour NIHSS cut-off values may guide early risk stratification and prognostic assessments.

ObjectiveTo generate cynomolgus and rhesus monkey models carrying the Booroola fecundity (FecB) variant of bone morphogenetic protein receptor type 1B (BMPR1B) gene (designated BMPR1B^FecB) using adenine base edit technology and to explore genetic improvement strategies for enhancing the reproductive performance of laboratory macaques. MethodsFour single-guide RNAs (sgRNAs) were designed to target the BMPR1B c.746A>G locus in cynomolgus and rhesus monkeys. The sgRNAs were combined with the ABE8e-SpRY base editor, and the resulting editing complexes were microinjected into zygotes of both macaque species. Following in vitro culture of the injected embryos, nested PCR amplification was performed to detect the base-editing efficiency at the target site to screen for highly efficient sgRNAs. Subsequently, normally developing gene-edited embryos were transferred into the oviducts of surrogates. Seven days after birth, ear skin or peripheral blood samples were collected from the newborn monkeys for genotyping and mosaicism analysis, and the growth, development, and health status of the gene-edited monkeys were monitored. ResultsAmong the four candidate sgRNAs, sgRNA4 was identified as achieving 100% editing efficiency at the c.746A>G site. A total of 17 live monkey offspring were obtained via embryo transfer, including 8 cynomolgus monkeys and 9 rhesus monkeys. Genotyping results showed that all 8 newborn cynomolgus monkeys carried the c.746A>G point mutation, with an editing efficiency of 100% (8/8), of which 37.50% (3/8) were mosaics. Among the 9 newborn rhesus monkeys, 8 individuals carried the c.746A>G mutation, with an editing efficiency of 88.89% (8/9), of which 75.00% (6/8) were mosaics. ConclusionThe ABE8e-SpRY base-editing system enables precise editing at the c.746A>G (p.Q249R) locus of the BMPR1B gene in both cynomolgus and rhesus monkey embryos, resulting in the successful establishment of laboratory monkey models carrying the BMPR1B^FecB variant. These models provide a valuable foundation for future studies of the regulatory role of the BMPR1B^FecB variant in reproductive performance at the non‑human primate level, as well as for exploring genetic improvement strategies to enhance reproductive performance in laboratory monkeys.

OBJECTIVE To identify the active components of Desmodium styracifolium （Osb.） Merr. extract （DME） against cholestatic liver injury （CLI）， and to verify its target and molecular mechanism， so as to provide scientific evidence for the clinical application of D.styracifolium （Osb.） Merr. and the development of new hepatoprotective agents.METHODS High-performance liquid chromatography was applied to establish fingerprints of 19 batches of DME， followed by similarity evaluation and identification of common peaks. An in vitro CLI model was constructed by lithocholic acid （LCA）-induced injury in HepG2 cells to evaluate the in vitro protective effect of DME against CLI. Spearman correlation analysis， grey relational analysis and partial least-squares regression analysis were adopted to investigate the spectrum-effect relationship of DME against CLI and preliminarily screen the core active components. Molecular docking and surface plasmon resonance technology were used to predict and verify the binding capacity between core active components and farnesoid X receptor （FXR）. qRT-PCR， Western blot and immunofluorescence staining tests were performed to validate the influences of core active components on the expression of molecules related to FXR/bile salt export pump （BSEP） pathway in CLI model cells.RESULTS A total of 12 common peaks were calibrated in the fingerprints of 19 batches of DME， and the similarity values were all above 0.990. Four common peaks were identified， namely peak 6 （schaftoside）， peak 7 （isoorientin）， peak 11 （isoschaftoside） and peak 12 （isovitexin）. DME at 80 μg/mL exerted the optimal protective effect on CLI-model cells， and the cell viability reached （75.66±4.60）% after 24 h of treatment. Spectrum-effect analysis revealed that schaftoside possessed the strongest correlation with the anti-CLI activity of DME and served as the core active component. Target prediction and validation results showed that the binding energy between schaftoside and FXR was －8.1 kcal/mol， and the equilibrium dissociation constant was 27.3 μmol/L. Mechanistic experiments demonstrated that 100 μmol/L schaftoside significantly elevated the expression levels of FXR and BSEP， and mRNA of their encoded genes Nr1h4 ， Abcb11 in CLI-model cells （ P ＜0.05）.CONCLUSIONS Schaftoside may be the core active component of DME against CLI， and its mechanism may be related to the activation of FXR/BSEP pathway.

Objective To propose a lung artery segmentation method that integrates shape and position prior knowledge, aiming to solve the issues of inaccurate segmentation caused by the high similarity and small size differences between the lung arteries and surrounding tissues in CT images. Methods Based on the three-dimensional U-Net network architecture and relying on the PARSE 2022 database image data, shape and position prior knowledge was introduced to design feature extraction and fusion strategies to enhance the ability of lung artery segmentation. The data of the patients were divided into three groups: a training set, a validation set, and a test set. The performance metrics for evaluating the model included Dice Similarity Coefficient (DSC), sensitivity, accuracy, and Hausdorff distance (HD95). Results The study included lung artery imaging data from 203 patients, including 100 patients in the training set, 30 patients in the validation set, and 73 patients in the test set. Through the backbone network, a rough segmentation of the lung arteries was performed to obtain a complete vascular structure; the branch network integrating shape and position information was used to extract features of small pulmonary arteries, reducing interference from the pulmonary artery trunk and left and right pulmonary arteries. Experimental results showed that the segmentation model based on shape and position prior knowledge had a higher DSC (82.81%±3.20% vs. 80.47%±3.17% vs. 80.36%±3.43%), sensitivity (85.30%±8.04% vs. 80.95%±6.89% vs. 82.82%±7.29%), and accuracy (81.63%±7.53% vs. 81.19%±8.35% vs. 79.36%±8.98%) compared to traditional three-dimensional U-Net and V-Net methods. HD95 could reach (9.52±4.29) mm, which was 6.05 mm shorter than traditional methods, showing excellent performance in segmentation boundaries. Conclusion The lung artery segmentation method based on shape and position prior knowledge can achieve precise segmentation of lung artery vessels and has potential application value in tasks such as bronchoscopy or percutaneous puncture surgery navigation.

Objective:To analyze the clinical characteristics, treatment, response to treatment, prognosis, and the importance of early recognition and treatment of pediatric systemic lupus erythematosus (SLE) complicated with thrombotic microangiopathy (TMA).Methods:A retrospective summary of the clinical data of 5 children diagnosed with SLE complicated by TMA at Beijing Children′s Hospital, Capital Medical University, from November 2024 to January 2025.Results:Among the 5 children (1 boy and 4 girls, male-to-female ratio of 1∶4), the age of onset ranged from 11 years and 9 months to 14 years and 9 months. All cases had acute onset, rapid disease progression, severe illness, and involvement of multiple organs and systems. The disease activity of SLE was moderately to severely active when TMA was diagnosed. During the course of TMA, all 5 children exhibited varying degrees of hemolytic anemia, thrombocytopenia, renal dysfunction, and proteinuria. Elevated sC5b-9 levels were observed in all 5 children, with 3 showing severely reduced ADAMTS13 activity and 2 with elevated ADAMTS13 inhibitors. Two children had elevated sC5b-9, severely reduced ADAMTS13 activity, and elevated ADAMTS13 inhibitors simultaneously. Four children had newly diagnosed SLE with TMA and achieved stable condition within 2-3 weeks after aggressive treatment, including methylprednisolone pulse therapy, immunosuppressive agents, biologics, plasma infusion, plasma exchange, or dialysis. One child, who had been diagnosed with SLE for 8 years and had irregular oral medication for half a year, suddenly developed TMA with refractory hemolytic anemia and severe thrombocytopenia. This child responded poorly to methylprednisolone pulse therapy, cyclosporine, and eculizumab but showed improvement with plasma exchange. However, the condition was prone to relapse when the interval between plasma exchanges was prolonged. The child eventually responded well to low-dose rituximab and was discharged after 6 weeks of combined treatment. Four children were diagnosed with TMA within 1 week of admission and achieved stable condition after 3 months of follow-up, with no anemia or thrombocytopenia, negative proteinuria, normal complement C3 and C4 levels, and an SLE disease activity score of 0. One child, who had been treated with high-dose glucocorticoid, multiple immunosuppressive agents, and biologics at another hospital, was transferred and diagnosed with TMA 2 weeks after admission. The condition gradually stabilized after treatment with methylprednisolone pulse therapy, immunosuppressive agents, biologics, and plasma exchange. However, at 3-month follow-up, the child still had alopecia and proteinuria, with an SLE disease activity score of 6, indicating mild disease activity.Conclusion:For children with moderate to severe active SLE, especially those with acute onset, rapid disease progression, and prominent manifestations of anemia, thrombocytopenia, renal dysfunction, and poor response to high-dose methylprednisolone pulse therapy, the risk of TMA should be vigilantly monitored. Early diagnosis and aggressive treatment are crucial.

Alzheimer's disease(AD)is the most common neurodegenerative disease in the elderly,and its main pathological manifestations include senile plaques formed by β-amyloid deposition and neuronal fibrillar nodules formed by hyperphosphorylation of tau proteins.Lysosome is an important organelle in eukaryotic cells,containing a variety of hydrolytic enzymes that can break down proteins and other biomolecules.It is closely related to intracellular transport and autophagy,and is important for maintaining cellular homeostasis.This review summarizes the interaction between lysosomal dysfunction and the development and progression of AD and the potential therapeutic mechanisms in treating AD by regulating and restoring the functions of lysosomes.Lysosomal dysfunction can lead to neurodegenerative diseases such as AD.Modulation of lysosomal function is a promising treatment strategy for AD.It is expected that more drugs and therapeutic regimens based on this mechanism can be used in the clinical treatment for AD patients in the future.

Purpose To investigate the changes in quadriceps femoris microcirculatory perfusion level after low-load blood flow restriction training and its relationship with muscle strength.Materials and Methods Twenty-five healthy subjects were prospectively recruited in the First Affiliated Hospital of Kunming Medical University from September to November 2022.A 200 mmHg pressure cuff was applied at the root of the left thigh for blood flow restriction,and the subjects completed regular knee extension training within 4 weeks.Before the first training session and within 24 hours after the last training session,all subjects underwent scanning with the 3.0T MRI intravoxel incoherent motion sequence and the multi-echo steady-state acquisition three-dimentional imaging sequence.After image post-processing,the quadriceps femoris cross-sectional area,perfusion fraction and pseudo-diffusion coefficient were obtained,and the peak torque was measured using an isokinetic dynamometer.The MRI and muscle strength test parameters before and after training were compared,and correlation analyses were performed between the change of peak torque and the change of perfusion fraction,cross-sectional area,and pseudo-diffusion coefficient respectively.Results After low-load blood flow restriction training,the cross-sectional area of the left quadriceps femoris in subjects increased(t=-4.515,P<0.05).Among its components,the cross-sectional area of the left rectus femoris,vastus intermedius and vastus lateralis all increased(t=-3.302,-2.877,-3.207,all P<0.05).The perfusion fraction value of the left quadriceps femoris increased(t=-5.447,P<0.05);the perfusion fraction values of the left rectus femoris,vastus intermedius,vastus lateralis and vastus medialis all increased(t=-5.723,-4.621,-3.767,-4.682,all P<0.05);the muscle strength of the left quadriceps femoris increased(t=-3.983,P<0.05).There was a highly positive correlation between change of perfusion fraction and peak torque of the left quadriceps femoris in subjects(r=0.708,P<0.05).Conclusion After low-load blood flow restriction training,the changes in quadriceps femoris muscle microperfusion quantified by intravoxel incoherent motion are related to muscle strength,which is helpful for formulating rehabilitation training strategies for young patients.

This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.

Objectives:To evaluate the impact of hemoglobin concentration on 5-year cardiovascular mortality in patients with hypertrophic obstructive cardiomyopathy(HOCM).Methods:This study retrospectively analyzed 325 non-surgically treated HOCM patients hospitalized at Fuwai Hospital from October 2009 to December 2014.Baseline information was compared between patients with or without cardiac death.The impact of hemoglobin concentration on 5-year cardiovascular mortality in HOCM patients was analyzed.Results:The median follow-up time was(43.55±19.70)months.During the follow-up period,a total of 29 patients(8.9%)experienced cardiac death.Univariate Cox regression analysis demonstrated that hemoglobin concentration was significantly associated with 5-year cardiac mortality in HOCM patients(P<0.001).After adjusting for potential cardiovascular risk factors in multivariate Cox regression analysis,hemoglobin concentration(P=0.011)remained negatively associated with 5-year cardiac mortality in HOCM patient.HOCM patients with decreased hemoglobin level faced a 3.118-fold increase in 5-year cardiac mortality(HR=4.118,95%CI:1.114-14.822,P=0.030).Kaplan-Meier survival analysis showed that HOCM patients with decreased hemoglobin levels had a significantly higher risk of 5-year cardiac mortality(log-rank test,χ2=24.38,P<0.001).Conclusions:Lower hemoglobin concentration is an independent risk factor for 5-year cardiac mortality in patients with HOCM.Compared to patients with normal hemoglobin levels,HOCM patients with decreased hemoglobin level face a 3-fold increase in 5-year cardiac mortality.