Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

OBJECTIVES: To study the clinical effect of the L-shape technique combined with concentrated growth factor on the horizontal bone defects of maxillary anterior teeth. METHODS: Twenty-five implants from 25 patients who underwent single maxillary anterior tooth implantation with simultaneous bone grafting were selected as the study subjects. Based on the bone grafting techniques, the patients were divided into a test group (L-shaped technique with guided bone regeneration combined with concentrated growth factor, 11 cases) and a control group (traditional guided bone regeneration combined with concentrated growth factor, 14 cases). The early discomfort and wound healing conditions in the two groups at two weeks after surgery were compared. The horizontal bone thickness, vertical bone thickness, and grayscale values in the augmentation area were measured immediately postsurgery and six months after surgery. Implant stability, hard tissue resorption within six months, and grayscale values were compared between the two groups. RESULTS: Differences in early discomfort, wound healing, implant stability, and grayscale values between the two groups were not statistically significant (P>0.05). Vertical bone thickness in the test group was significantly better than that in the control group at six months after surgery (P<0.05). The variation in horizontal bone thickness in the test group was significantly higher than that in the control group (P<0.05). CONCLUSIONS The application of the L-shape technique with concentrated growth factor for horizontal bone defects in the anterior maxillary area yielded satisfactory short-term results in terms of bone augmentation, early discomfort, wound healing, and implant stability at six months after surgery.
Humans ; Maxilla/diagnostic imaging* ; Intercellular Signaling Peptides and Proteins/therapeutic use* ; Wound Healing ; Bone Transplantation/methods* ; Dental Implantation, Endosseous/methods* ; Bone Regeneration ; Male ; Female ; Adult ; Dental Implants, Single-Tooth ; Middle Aged

Glioma is the most common primary malignant tumor of the central nervous system in adults. Despite the standard treatment of surgery combined with radiotherapy and chemotherapy, the prognosis for high-grade glioma patients remains poor, highlighting the urgent need to further explore its pathogenesis and develop new therapeutic strategies. This article reviews the research progress in the field of glioma in China in 2024, covering tumorigenesis mechanisms, tumor immune microenvironment composition, advances in imaging techniques and novel imaging agents, improvements in surgical approaches, mechanisms of radio- and chemoresistance, and explorations of new therapeutic modalities. These studies provide a solid theoretical foundation for advancing clinical diagnosis and treatment of gliomas and may offer new opportunities to improve patient outcomes.

Objective:To investigate the influencing factors for sarcopenia in hospitalized patients,to construct a risk prediction model for sarcopenia in elderly hospitalized patients,and to provide a quantitative tool for early screening and intervention of sarcopenia based on the integration of multi-dimensional indicators.Methods:A retrospective analysis was performed for the data of 2105 elderly patients who were hospitalized in The First Affiliated Hospital of Chongqing Medical University from March 2016 to June 2023.The least absolute shrinkage and selection operator analysis was used for the screening of variables,and the logistic regression analysis was used to investigate the influencing factors for sarcopenia.A predictive model was constructed,and internal and external validation was performed.The Shapley additive explanations model was used to analyze feature contributions,and a nomogram model was constructed to visualize and interpret the results.Results:The 1259 patients from March 2016 to December 2020 were randomly divided into a training set with 882 patients and an internal test set with 377 patients at a ratio of 7∶3,and the 846 patients from January 2021 to June 2023 were established as the external validation set.A total of 489 cases of sarcopenia(55.44%)were detected in the training set.The logistic regression analysis based on the training set showed that asthenia,dependence on Activity of Daily Living,malnutrition,and in-creasing age were risk factors for sarcopenia(odds ratio[OR]>1,P<0.05),and male sex,normal body mass index,and overweight were protective factors against sarcopenia(OR<1,P<0.05).The model had an AUC of 0.876(95%CI=0.854-0.899)in the training set,0.883(95%CI=0.849-0.918)in the internal test set,and 0.750(95%CI=0.717-0.783)in the external validation set,suggesting that the model had good performance.The decision curve analysis showed that the nomogram model had a good clinical value.Conclu-sion:The predictive model for sarcopenia has good performance and holds promise for clinical application.

ObjectiveTo explore the regulatory effect and mechanism of Danggui Shaoyaosan combined with Yinchenhaotang on lipid metabolism in the mouse model of type 2 diabetes mellitus （T2DM） complicated with metabolic dysfunction-associated steatotic liver disease （MASLD） based on network pharmacology and animal experiments. MethodsTwenty-four MKR transgenic diabetic mice were randomly allocated into 4 groups： Model， low-dose （12.6 g·kg^-1） Chinese medicine （concentrated decoction of Danggui Shaoyaosan combined with Yinchenhaotang）， high-dose （25.2 g·kg^-1） Chinese medicine， and Western medicine （metformin， 0.065 g·kg^-1）. Six FVB mice were used as the normal group. All groups were treated for 6 consecutive weeks. The mice in the drug treatment groups were administrated with corresponding agents by gavage， and those in the normal group and model group received the same volume of distilled water. Fasting blood glucose， body weight， liver weight， glucose tolerance， liver function indicators， blood lipid levels， and pathological changes in the liver were evaluated for each group. Network pharmacology was employed to analyze the targets and pathways of Danggui Shaoyaosan combined with Yinchenhaotang in the treatment of T2DM complicated with MASLD. Molecular biological techniques were used to verify the enriched key targets. ResultsCompared with the model group， each treatment group showed reduced fasting blood glucose， body weight， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， and liver weight （P<0.01）. The high-dose Chinese medicine group was superior to the low-dose group in reducing low-density lipoprotein （LDL）， increasing high-density lipoprotein （HDL）， and recovering glucose tolerance （AUC） and ALT （P<0.05）， with the effect similar to that of the Western medicine group. Morphologically， Chinese medicine groups showed reduced lipid accumulation and alleviated pathological damage in the liver tissue， with the high-dose group demonstrating more significant changes. Network pharmacology results showed that Danggui Shaoyaosan combined with Yinchenhaotang may exert therapeutic effects through multiple targets such as fatty acid synthase （FAS）， acetyl-CoA carboxylase （ACC）， B-cell lymphoma-2 （Bcl-2）， MYC oncogene （MYC）， and interleukin-1β （IL-1β）. Western blot showed that compared with the model group， the treatment groups demonstrated down-regulated protein levels of FAS and ACC （P<0.01） and up-regulated protein levels of peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and UCP1 （P<0.01）. Compared with the low-dose Chinese medicine group， the high-dose Chinese medicine group exhibited down-regulated protein levels of FAS and ACC and up-regulated protein levels of PGC-1α and UCP1 （P<0.05）. ConclusionDanggui Shaoyaosan combined with Yinchenhaotang has the effect of ameliorating T2DM complicated with MASLD and can improve the liver lipid metabolism by up-regulating the protein levels of Fas and ACC and down-regulating the protein levels of PGC-1α and UCP1.

Rapid developments in biotechnology have led researchers to seek new method to improve the efficiency and accuracy of biomedical research and drug development,promoting interdisciplinary integration.Recent advancements in artificial intelligence(AI)technologies have brought unprecedented opportunities to this field.The integration of various AI models allows researchers to better utilize multi-omics data,identify disease phenotypes,interpret animal behavior,assess treatment effects,improve experimental designs,reduce the use of experimental animals,enhance animal facility management,and improve animal welfare.This article reviews the advancements in AI biomedical research over the past decade and discusses its contributions to disease phenotype identification,the selection and design of experimental animal models,animal behavior analysis,and animal facility management.It also points out the challenges related to data standardization,AI model selection and interpretability,the extrapolation process from AI models to animal experiments and clinical practice,as well as ethical considerations in using AI in sensitive areas involving human genetics and personalized medicine.This review aims to help researchers and practitioners in relevant fields understand the current state and opportunities of AI development,thus providing support for its broader application.

Objective To investigate the effects of microRNA-34a(miR-34a-5p)on the progression of chronic lymphocytic leukemia(CLL)through the Wnt/β-catenin signaling pathway.Methods Human chronic B-cell leukemia MEC-1 cells were selected for experimentation.MEC cells were divided into two groups,group one:the p53 agonist group and the control group;group two:the control group,the miR-34a-5p mimic group and its corresponding negative control,the miR-34a-5p inhibitor group and its corresponding negative control,as well as the miR-34a-5p inhibitor+Wnt inhibitor XAV-939 group.The expression levels of miR-34a-5p in each group were measured using real-time fluorescence quantitative PCR(qPCR).Cell proliferation was assessed by CCK-8 assay,while cell migration ability was evaluated using Transwell migration assay.Dual-luciferase reporter assay was employed to validate the targeting relationships between p53 and miR-34a-5p,as well as between miR-34a-5p and Wnt1.Western blot analysis was used to detect the protein expressions of β-catenin and Cyclin D1,which were key components of the Wnt/β-catenin signaling pathway.Results In MEC-1 cells:① compared with the control group,there was a increased miR-34a-5p expression and inhibited cell proliferation in the p53 agonist group(P＜0.05).Dual-luciferase reporter assay confirmed a negative regulatory correlation between miR-34a-5p and p53.② the miR-34a-5p mimic group showed significantly upregulated miR-34a-5p expression compared to the control group,leading to suppressed cell proliferation,reduced migration capability and decreased protein expressions of β-catenin and Cyclin D1(P＜0.05).Conversely,the miR-34a-5p inhibitor group demonstrated significantly downregulated miR-34a-5p expression,resulting in enhanced cell proliferation,increased migratory capacity and upregulated protein levels of β-catenin and Cyclin D1 compared to those of the control group(P＜0.05).③ A targeting relationship was observed between miR-34a-5p and Wnt1.④ Compared with the miR-34a-5p inhibitor group,the XAV-939 group exhibited significantly upregulated miR-34a-5p expression,markedly decreased numbers of migrated cells and substantially reduced protein expression levels of β-catenin and Cyclin D1(P＜0.05).Conclusion miR-34a plays the role of a tumor suppressor gene in CLL.Overexpression of miR-34a can inhibit the Wnt/β-catenin signaling pathway,reduce the proliferation activity and migration ability of cells,and promote cell apoptosis.

BACKGROUND:Condylar prosthesis replacement,as one of the surgical methods for the treatment of temporomandibular joint diseases,not only needs to restore the morphology and function,but also needs to ensure long-term stable application.OBJECTIVE:To design finite element analysis of a customized Gyroid condylar prosthesis.METHODS:Gyroid structure specimens with different wall thicknesses(250,350,450,550,650,and 750 μm)were designed by software.Finite element simulation compression experiments were carried out to test the elastic modulus of the specimens.The Gyroid structure wall thickness range that matches the elastic modulus of mandibular cancellous bone and whose pore size meets the osteogenesis conditions was screened out.This range was subdivided and Gyroid structure specimens were made using 3D printing technology.Mechanical compression experiments were carried out on a universal testing machine.The Gyroid structure wall thickness that meets the mechanical properties of mandibular bone,has an easier osteogenesis and a smaller strength was screened out by elastic modulus and compressive strength,and subsequent experiments were carried out.A three-dimensional model of a customized Gyroid condylar prosthesis was designed,and the finite element analysis of the blade jaw position and cusp interdigitation position of the model under natural occlusion was simulated.RESULTS AND CONCLUSION:(1)Finite element analysis results showed that with the increase of wall thickness,the elastic modulus of Gyroid structure specimens increased.The elastic modulus of Gyroid structure specimens with wall thickness of 350,450,550,650,and 750 μm matched the elastic modulus of mandibular cancellous bone.Since the subsequent experiments needed to be subdivided into groups and the pore size of the 550,650,and 750 μm wall thickness group(pore size 800-1 000 μm)was within the osteogenesis range.Gyroid structure specimens with wall thickness of 550,600,650,700,and 750μm were selected for mechanical compression experiments on a universal testing machine.(2)The results of mechanical compression experiments showed that with the increase of wall thickness,the elastic modulus and compressive strength of Gyroid structure specimens increased.The elastic modulus of Gyroid structure specimens with wall thickness of 550,600,and 650 μm was within the elastic modulus of the mandibular cancellous bone.Finally,the wall thickness of 650 μm and the pore size of 900 μm were selected to construct the three-dimensional model of the mandibular customized Gyroid condylar prosthesis.(3)The results of finite element analysis of three-dimensional model of the mandibular customized Gyroid condylar prosthesis showed that the stress of the articular disc in the edge-to-edge occlusion was mainly concentrated on the lower surface of the anterior middle band,and the stress of the articular disc in the interposition of tooth tips was mainly concentrated on the lateral surface of the lower surface.The maximum displacement and the maximum equivalent stress of the left and right articular discs in the edge-to-edge occlusion and the interposition of tooth tips were similar.The maximum displacement was 0.031,0.030,0.028,and 0.018 mm,and the maximum equivalent stress was 2.87,2.30,2.73,and 1.71 MPa,respectively.(4)The results showed that the Gyroid structure with a wall thickness of 650 μm was consistent with the mechanical properties of the mandible,which reduced the strength of the titanium alloy and reduced the damage of the articular disc caused by the customized Gyroid condylar prosthesis.

Objective:To compare the efficacy and safety of flow diverter (FD) implantation versus stent-assisted coil embolization (SACE) in unruptured saccular aneurysms located at distal segments of the Willis circle.Methods:A retrospective study was performed; 119 patients with unruptured saccular aneurysms located at distal segments of the Willis circle who received FD implantation or SACE in Department of Neurosurgery, Guangdong Provincial People's Hospital, Southern Medical University and Department of Cerebrovascular Surgery, Neurosurgery Center, Southern Medical University from January 2018 to May 2025 were selected. According to different surgical methods, they were divided into a FD group ( n=60) and a SACE group ( n=59). These patients were subjected to propensity score matching (PSM) using 1:1 nearest neighbor matching method to eliminate confounding factors such as gender, age, aneurysm location, and aneurysm diameter (maximum diameter); and then, differences in neurological functional prognosis (good prognosis: modified Rankin scale scores of 0-2), complete aneurysm occlusion rate (O'Kelly-Marotta grade D or Raymond occlusion classification class I), and overall (perioperative and follow-up) complications were compared between the two groups. Results:After PSM, there were 43 patients in both FD group and SACE group. No significant difference was found in clinical and imaging follow-ups (12[6, 19] months vs. 10[6, 15] months, 10[5, 19] months vs. 9[2, 15] months) between the FD group and SACE group ( P>0.05). At the last imaging follow-up, the complete aneurysm occlusion rate in the FD group (65.1%[28/43]) was significantly lower than that in the SACE group (76.7%[33/43], P<0.05). At the last clinical follow-up, no significant difference was noted in good prognosis rate (95.3%[41/43] vs. 97.7%[42/43]) and overall complication rate (30.2%[13/43] vs. 18.6%[8/43]) between the FD group and SACE group ( P>0.05). Conclusion:Both FD implantation and SACE are safe and effective for unruptured saccular aneurysms located at distal segments of the Willis circle; the complete aneurysm occlusion rate within 1 year of FD implantation is relatively low.

Objective:To explore the value of three-dimensional automatic right ventricular quantitive analysis（3D Auto RVQ）technology in predicting the improvement of left ventricular ejection fraction（LVEF）in patients with heart failure with reduced ejection fraction（HFrEF）.Methods:A retrospective analysis was conducted on 89 HFrEF patients admitted to the Cardiology Department of Central China Fuwai Hospital of Zhengzhou University from April 2022 to June 2024. All patients received medication treatment and were further divided into heart failure with improved ejection fraction（HFimpEF）group and non HFimpEF group based on changes detected by echocardiography in LVEF after treatment. The clinical data，biological indicators，and medication treatment status of patients were collected，routine echocardiographic parameters and right ventricular strain parameters were measured，3D right ventricular ejection fraction（3D-RVEF），3D right ventricular stroke volume index（3D-RVSVI），3D right ventricular end-diastolic volume index（3D-RVEDVI），3D right ventricular end-systolic volume index（3D-RVESVI），3D tricuspid annular plane systolic excursion（3D-TAPSE），and 3D right ventricular fractional area change（3D-RVFAC）were measured using 3D Auto RVQ technology. The differences of the above parameters between the two groups were compared. The ROC curve was used to analyze the predictive efficiency of right ventricular parameters for HFimpEF，and the area under ROC curve（AUC）was calculated and compared. Logistic regression models were used to analyze the predictive value of right ventricular parameters for HFimpEF.Results:Compared with the non HFimpEF group，the HFimpEF group had a younger age，shorter heart failure course，a smaller proportion of males，New York Heart Association（NYHA）functional class ≥Ⅲ，and patients with concomitant coronary heart disease. The baseline LVEF，absolute value of two dimensional right ventricular global longitudinal strain（2D-RVGLS），3D-RVEF，3D-TAPSE，and 3D-RVSVI were higher in the HFimpEF group（all P<0.05）. ROC curve analysis showed that the AUC of 3D-RVEF for predicting HFimpEF was 0.858，and the predictive efficiency was higher than other right ventricular parameters. According to the Yoden index，the optimal cutoff value for predicting HFimpEF based on 3D-RVEF was 36.2%，with a corresponding sensitivity of 84.0% and specificity of 75.0%. After adjusting for clinical and other echocardiographic parameters，the logistic regression model showed that 3D-RVEF was an independent predictor of HFimpEF（ OR=1.435，95% CI=1.145-1.800， P<0.05）. Conclusions:The 3D-RVEF evaluated by 3D Auto RVQ technology has high predictive value for HFimpEF，which can provide a reference for clinical treatment，thereby improving the prognosis of HFrEF patients.