ObjectiveTo reveal the molecular mechanism by which the traditional Chinese medicine compound prescription Qiangjing tablets regulate the aging of the testicular tissue and Leydig cells in rats through the cyclin-dependent kinase 4 （CDK4）-early 2 factor （E2F） signaling pathway. MethodsFor the cell experiment， 2-month-old SPF-grade SD male rats were selected and randomly assigned into a blank control group （administrated with an equal volume of 0.9% sodium chloride injection） and a Qiangjing tablets group （20 rats in each group） according to body weight. The Leydig cell model of aging was established by treatment of TM3 cells with 100 μmol·L^-1 H₂O₂， and the modeling performance was evaluated based on the levels of p16 and p21 determined by Western blot. The antioxidant NAC （1 mmol·L^-1） was used as the positive control for eliminating reactive oxygen species （ROS）. Cells were intervened with Qiangjing tablets-containing serum at low （2.5%）， medium （5%）， and high （10%） concentrations. The testosterone level in the cell supernatant was determined by enzyme-linked immunosorbent assay （ELISA）， and the protein levels of CDK4， E2F1， and E2F2 were analyzed by Western blot. In the animal experiment， 19-month-old naturally aging rats were used as the model group， and 2-month-old rats as the young control group. The positive control group was subcutaneously injected with 5.21 mg·kg^-1·d^-1 testosterone propionate. Qiangjing tablets were administered by gavage at low， medium， and high doses of 0.72， 1.44， 2.88 g·kg^-1·d^-1， respectively. The general conditions of rats were observed， and the protein levels of CDK4， E2F1， and E2F2 in the testicular tissue were determined by Western blot. ResultsIn the cell experiment， compared with the blank control group， the model group showed upregulated expression of CDK4 and E2F1 （P<0.05） and slightly downregulated expression of E2F2. Compared with that in the model group， the expression of CDK4 was upregulated in the NAC group and the low-dose Qiangjing tablets group （P<0.05）， slightly upregulated in the medium-dose Qiangjing tablets group， and downregulated in the high-dose Qiangjing tablets group （P<0.05）. The NAC group showed downregulated expression of E2F1 （P<0.05） and E2F2， and the low-， medium-， and high-dose Qiangjing tablets groups showed downregulated expression of both E2F1 and E2F2 （P<0.05）. Compared with that in the NAC group， the expression of CDK4 was upregulated in the low-dose Qiangjing tablets group and downregulated in the medium-dose and high dose （P<0.05） groups. The expression of E2F1 was down-regulated in all the three dose groups， with statistically significance in the high dose group （P<0.05）， and that of E2F2 were downregulated in all the three dose groups （P<0.05）. In the animal experiment， compared with the young control group， the model group exhibited downregulated expression of CDK4 （P<0.05） and slightly upregulated expression of E2F1 and E2F2. Compared with that in the model group， the expression of CDK4 decreased in the testosterone propionate group and the low-dose Qiangjing tablets group （P<0.05） but increased in the medium-dose （P<0.05） and high-dose groups. In addition， the expression of E2F1 decreased （P<0.05）， and that of E2F2 was slightly elevated. Compared with that in the NAC group， CDK4 expression was elevated in the Qiangjing tablets groups， with statistical significance in the medium- and high-dose groups （P<0.05）. Similarly， the E2F1 expression was also upregulated in the Qiangjing tablets groups， with statistical significance in the medium-dose group （P<0.05）. The expression of E2F2 was downregulated in all the Qiangjing tablets groups. ConclusionQiangjing tablets delay the aging process of Leydig cells and testicular tissue by up-regulating the expression of CDK4 and lowering the levels of E2F1 and E2F2.

Lung cancer is the cancer with the highest incidence of morbidity and mortality in the world, and the number of lung cancer cases in China is also increasing year by year, which seriously threatens the life and health of human beings. Circulating tumor cells (CTCs) refer to the tumor cell that falls off from primary tumor tissue or metastatic focus into the peripheral blood, which is the key to tumor metastasis. Currently, there are various methods for CTCs testing, each with its own advantages and disadvantages. In recent years, there have been numerous studies on the application of CTCs in lung cancer around the world. Further exploration of the progress of clinical application of CTCs in lung cancer can provide a new basis for the role of CTCs in early diagnosis, efficacy assessment and prognostic monitoring of lung cancer.

Calvarial stem cells are essential for maintaining the health and function of the craniofacial complex and the central nervous system.Under physiological conditions,these stem cells primarily reside within specialized microenvironments known as stem cell niches,located in the bone marrow,periosteum,and sutures of cranial bones.The heterogeneous cellular populations within the microenvironment dynamically regulate the quantity and function of stem cells.Due to their distinct spatial distribution,these stem cells exhibit unique functional characteristics and play crucial roles in the development and progression of various diseases,as well as in relevant therapeutic applications.Herein,we summarize the latest research advances concerning various types of calvarial stem cells,elaborating on their respective functions,microenvironmental regulation,and therapeutic potential,thereby providing new perspectives for both basic research and clinical applications in this field.

Objective To explore the influencing factors of physical activity behavior change in lung cancer patients and provide a basis for developing targeted intervention programs.Methods A descriptive qualitative research method was employed.Using purposive sampling,18 lung cancer pa-tients and 10 healthcare professionals were selected for semi-structured interviews from October to De-cember 2023.The health action process approach(HAPA)theory was used as the framework,and directed content analysis was applied to analyze the data.Results The barriers to physical activity behavior change in lung cancer patients were distilled into six themes:insufficient risk perception,negative outcome expectations,self-doubt and behavior avoidance tendencies,challenges in persist-ence and risk of interruption,lack of behavioral intention and demand,and absence of action and coping plans.The facilitating factors were divided into six themes:perception of the potential hazards of insufficient physical activity,perception of the health benefits of physical activity,cultivation and development of self-efficacy,stimulation of motivation for activity,formulation of differentiated activity plans,and formulation of adaptive coping plans.Conclusion Physical activity behavior in lung cancer patients is influenced by multiple factors.Targeted intervention strategies can be developed based on the HAPA theory to promote physical activity behavior change and improve physical activity levels.

Objective : To analyze the differential expression profile of miRNAs in amniotic fluid exosomes of fetu- ses with Down syndrome (DS) and provide insights for identifying novel biomarkers for the prenatal diagnosis of DS . Methods : Amniotic fluid samples were collected from fetuses with DS and chromosomally normal fetuses . Exo- somes were isolated from the amniotic fluid and subjected to high-throughput sequencing. Differentially expressed miRNAs were identified , and target genes were predicted using TargetScan and miRanda. Target genes located on chromosome 21 were selected , and their biological functions and associated diseases were analyzed using Gene- Cards , HGNC , NCBI Gene , UniProtKB/Swiss-Prot , Ensembl , and OMIM databases . GO and KEGG enrichment analyses were performed to investigate the biological functions of the enriched genes . Results : A total of 59 differ- entially expressed miRNAs were identified , including 31 upregulated and 28 downregulated miRNAs . Based on a fold change > 2 and P < 0. 05 , 10 upregulated and 9 downregulated miRNAs with the highest expression levels were selected . Key miRNAs included hsa-let-7b-5p , hsa-let-7c-5p , hsa-let-7b-3p _ 1ss22CT , and hsa-miR-199b-5p , with BACH1 and IFNAR1 identified as their shared target genes . GO analysis revealed that the enriched target genes were primarily involved in protein binding , metal ion binding , transferase activity , DNA binding , transcriptional regulation by RNA polymerase Ⅱ , and nucleotide binding. KEGG pathway analysis indicated that the target genes were mainly associated with metabolic pathways , cancer-related pathways , the PI3K-Akt signaling pathway , and the Rap1 signaling pathway . Conclusion Differential expression of miRNAs in amniotic fluid exosomes was ob- served between DS fetuses and those with normal karyotypes . Combined analysis with placental miRNAs revealed hsa-miR-199b-5p as a common differentially expressed miRNA in both DS amniotic fluid and placenta. It is hypoth- esized that BACH1 and IFNAR1 , shared target genes of hsa-miR-199b-5p , hsa-let-7b-5p , hsa-let-7c-5p , and hsa- let-7b-3p_1ss22CT , may play a role in the pathogenesis of DS .

ObjectiveTo investigate the potential targets and mechanisms of Draconis Sanguis (DS), a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl (D. Sanguis, Xue Jie), in the treatment of myocardial infarction (MI).MethodsWe explored the potential mechanisms of DS in the treatment of MI using network pharmacology, bioinformatic techniques, and transcriptomic analysis, followed by validation through in vivo and in vitro experiments.ResultsNetwork pharmacology and bioinformatic analyses identified five genes (Fpr1, Glul, Mme, Mmp9, and Pla2g7) as potential targets for MI treatment. Moreover, DS significantly ameliorated cardiac function, inflammatory responses, and MI-induced myocardial fibrosis in vivo. Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI. Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene. Furthermore, DS reduced the expression of Pla2g7 (P = .0009), NLRP3 (P = .003), interleukin-18 (P .001), and interleukin-1β (P = .004) mRNAs in vivo.ConclusionsThe results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response. This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.

Thoracic aortic aneurysm(TAA)significantly endangers the lives of individuals with Marfan syndrome(MFS),yet the intricacies of their biomechanical origins remain elusive.Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA,with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin(mTOR)signaling cascade.We un-covered that activation of the mTOR complex 1(mTORC1)within smooth muscle cells,instigated by the oscillatory wall shear stress(OSS)that stems from disturbed flow(DF),is a catalyst for TAA progression.This revelation was corroborated through both an MFS mouse model(Fbn1+/C1039G)and clinical MFS specimens.Crucially,our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS.Therapeutic administration of rapamycin suppresses mTORC1 activity,leading to the attenuation of aberrant SMC behavior,reduced inflammatory infiltration,and restoration of extracellular matrix integrity—collectively decelerating TAA advancement in our mouse model.These insights posit the mTORC1 axis as a strategic target for intervention,offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.

Objective:To compare the differences in repair of rabbit bone defects between allogeneic platelet rich plasma (PRP) gel and autologous PRP gel.Methods:Thirty-six healthy New Zealand white rabbits were selected and randomly divided into an autologous group, an allogeneic group, and a control group ( n=12). A model of bilateral forelimb bone defects was established in each group. The autologous group was repaired with self-made deproteinized bone scaffold materials + autologous bone marrow mesenchymal stem cells (BMSCs) + autologous PRP gel, the allogeneic group with self-made deproteinized bone scaffold materials + autologous BMSCs + allogeneic PRP gel, and the control group with only self-made deproteinized bone scaffold materials + autologous BMSCs. At postoperative 1, 2, and 3 months, 4 animals were euthanized in each group, respectively, for gross observation, X-ray examination, Micro-CT examination, biomechanical testing and histological analysis (HE staining for tissue morphology) to compare the differences in repair of bone defects. Results:The formation of trabecular bone, cortical reconstruction, and medullary recanalization occurred earlier in the autologous and allogeneic groups than in the control group. Micro-CT analysis at postoperative 2 months showed that bone mineral density [(281.51±33.69) mg/mL and (266.13±37.13) mg/mL], bone volume fraction (23.52%±2.81% and 21.91%±1.94%), and trabecular number [(1.68±0.29) mm -1 and (1.63±0.22) mm -1] in the autologous and allogeneic groups were significantly higher than those in the control group [(197.47±18.61) mg/mL, 16.54%±3.06%, and (1.06±0.11) mm -1] ( P<0.05). No significant differences were found among the 3 groups in trabecular thickness [(0.33±0.09) mm, (0.42±0.16) mm, and (0.28±0.13) mm] or in the maximum compressive load ( P>0.05). HE staining revealed a significantly greater number and earlier formation of chondrocytes and osteoblasts in the autologous and allogeneic groups than in the control group. Conclusion:Since allogeneic PRP exhibits similar efficacy in promoting new bone formation compared with autologous PRP in a rabbit bone defect model, it may serve as a viable substitute for autologous PRP.

Objective:To compare the preliminary efficacy and adverse events of chemoradiotherapy (CRT) with or without immunotherapy in bladder preservation therapy for localized muscle-invasive bladder cancer (MIBC) confined to the pelvis.Methods:Clinical data of 60 patients with MIBC who received CRT with or without immunotherapy for bladder preservation at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to June 2024 were retrospectively analyzed. Patients were divided into CRT plus immunotherapy group and CRT-alone group. Survival outcomes, bladder function preservation, recurrence and metastasis, as well as early and late radiation toxicities were evaluated. The Mann-Whitney U test was used for between-group comparisons. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method, and survival rates were compared by the log-rank test. Results:In the CRT plus immunotherapy group ( n=23), the median follow-up was 20 months. The median OS and median PFS were not reached. The 2-year OS, PFS, LRFS, and DMFS rates were 95.7%, 70.7%, 70.7%, and 92.9%, respectively, and 22 patients (96%) preserved normal bladder function. Patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 had significantly higher 1-year PFS rate than those with CPS <1 (100% vs. 66.7%, P=0.004). In the CRT-alone group ( n=37), the median follow-up was 37 months, with median OS and PFS of 68 and 19 months, respectively. The 2-year OS, PFS, LRFS, and DMFS rates were 92.0%, 41.1%, 60.9% and 81.5%, respectively, and 33 patients (89%) preserved normal bladder function. Compared with the CRT-alone group, the CRT plus immunotherapy group showed a significant improvement in PFS ( χ2=4.38, P=0.036), while no significant differences were observed in OS, LRFS, or DMFS (all P>0.05). The incidence of acute hematologic toxicity in the CRT plus immunotherapy group and CRT-alone group were 52% (12/23), 27% (10/37) respectively, and late genitourinary toxicity was 22% (5/23), 8% (3/37), respectively, with no significant differences in overall acute or late toxicities (all P>0.05). Conclusions:For localized MIBC, bladder preservation with CRT combined with immunotherapy significantly improves PFS compared with CRT alone, while maintaining comparable safety. The PD-L1 status may serve as a favorable predictor for immunotherapy efficacy.

Objective To explore the clinical value of subcutaneous tunneling in the management of chronic subdural hematoma.Methods A retrospective analysis was conducted on 279 cases of unilateral chronic subdural hematoma treated at the Neurosurgery Department of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2019.The patients were randomly assigned to subcutaneous tunnel group(n=164)and control group(n=115)through double-blind randomization.In the subcutaneous tunnel group,the intraoperative drainage tube was extracted through a subcutaneous tunnel,while in the control group,the drainage tube was removed directly from the incision.We analyzed the hematoma clearance rate,complications,and hematoma recurrence rate after 6 months.Results There was no statistical significance in age,sex,comorbidities,hematoma side or hematoma volume between the two groups(P＞0.05).Subcutaneous tunnel group and control group did not significantly differ in operation time[(27.68±4.1)min vs.(27.50±4.02)min],hospital stay[(7.39±1.04)d vs.(7.42±1.04)d],tube removal time[(24.30±4.82)h vs.25.37±5.02)h],or other clinical features(all P＞0.05).The clearance rate of hematoma was significantly higher in subcutaneous tunnel group than in control group(97.6％vs.95.7％,Z=-3.897,P＜0.001).There were 6 cases(3.7％)of hematoma recurrence in the subcutaneous tunnel group and 11 cases(9.6％)in the control group.The subcutaneous tunnel group had significantly lower recurrence of hematoma than the control group(x2=4.122,P=0.042).Conclusion Subcutaneous tunneling for drainage in the treatment of chronic subdural hematoma can increase the hematoma clearance rate and reduce the rates of complications and recurrence.This technique is simple and worthy of broad clinical application.