To explore the inhibitory effect of ginkgolide B (GB) on MH7A human fibroblast-like synoviocytes (FLS) and its potential mechanism. Firstly, 20 μg/L tumor necrosis factor-α (TNF-α) was pretreated with MH7A to establish a cell model of arthritis. After incubation of MH7A cells with various concentrations of GB, CCK-8 assay, Transwell assay, and flow cytometry (FCM) were separately used to detect cell viability, cell invasion, and cell apoptosis rate and cell cycle; Real-time quantitative PCR and Western blot assay were performed to detect the apoptosis- and cycle-related gene transcriptions and protein expressions, respectively. The results showed that compared with the control group, GB dose- and time-dependently suppressed cell viability to a greater extent; GB significantly reduced cell invasive ability and increased cell apoptosis rate and proportion of G0/G1 phase in MH7A cells, along with increased transcription levels of Bcl-2-associated X protein (Bax) and p21 mRNA and decreased transcription levels of Bcl-2, myeloid cell leukemia 1(Mcl-1), protein kinase B (PKB; AKT), IP3K, Cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA; GB remarkably increased expression levels of Bax, p21, and cleaved-Caspase 3 protein and decreased expression levels of Bcl-2, Mcl-1, p-AKT, p-PI3K, Cyclin D1, and CDK4 protein, with decreased ratios of p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax. In conclusion, GB blocks the G1-to-S cell cycle transition, suppresses cell viability and cell invasion and induces cell apoptosis of MH7A human RA-FLS via suppressing the PI3K/AKT signaling pathway.

Diabetic retinopathy is a common blinding complication in diabetic patients. Compared with conventional fundus color photography, fundus fluorescein angiography can dynamically display retinal vessel permeability changes, offering unique advantages in detecting early small lesions such as microaneurysms. However, existing intelligent diagnostic research on diabetic retinopathy images primarily focuses on fundus color photography, with relatively insufficient research on complex lesion recognition in fluorescein angiography images. This study proposed an adaptive multi-label classification model (D-LAM) to improve the recognition accuracy of small lesions by constructing a category-adaptive mapping module, a label-specific decoding module, and an innovative loss function. Experimental results on a self-built dataset demonstrated that the model achieved a mean average precision of 96.27%, a category F1-score of 91.21%, and an overall F1-score of 94.58%, with particularly outstanding performance in recognizing small lesions such as microaneurysms (AP = 1.00), significantly outperforming existing methods. The research provides reliable technical support for clinical diagnosis of diabetic retinopathy based on fluorescein angiography.
Diabetic Retinopathy/diagnostic imaging* ; Humans ; Fluorescein Angiography ; Microaneurysm/diagnostic imaging* ; Retinal Vessels ; Algorithms

OBJECTIVE: To investigate the feasibility and effectiveness of the novel bone hook combined with finger-guided technique in the treatment of irreducible intertrochanteric femoral fractures in elderly. METHODS: Between January 2021 and August 2023, 23 elderly patients with irreducible intertrochanteric femoral fractures were treated with the novel bone hook combined with finger-guided technique. There were 10 males and 13 females; the age ranged from 68 to 93 years (mean, 76.2 years). The time from injury to operation ranged from 36 to 76 hours (mean, 51.2 hours). According to the classification standard proposed by TONG Dake et alin 2021, there were 10 cases of typeⅠA, 1 case of typeⅠB, 6 cases of type ⅡA, 4 cases of type ⅡB, and 2 cases of type ⅡC. The operation time, intraoperative blood loss, intraoperative fluoroscopy frequences, and quality of fracture reduction were recorded. The fracture healing time and occurrence of postoperative complications were observed during follow-up. At last follow-up, the Harris scoring system was used to evaluate the hip joint function. RESULTS: The operation time was 42-95 minutes (mean, 52.1 minutes). The intraoperative blood loss was 40-420 mL (mean, 126.5 mL). Intraoperative fluoroscopy was performed 14-34 times (mean, 20.7 times). According to the criteria proposed by Chang et al, the quality of fracture reduction was rated as good in 20 cases and acceptable in 3 cases. All patients were followed up 6-20 months (mean, 10.2 months). X-ray film showed that all fractures healed with the healing time of 3.0-5.5 months (mean, 4.0 months). At last follow-up, the Harris score of the hip joint ranged from 82 to 97 points (mean, 90.4 points). Among them, 14 cases were rated as excellent and 9 cases as good. No complication such as coxa vara, cutting of the cephalomedullary nail, nail withdrawal, or nail breakage occurred during follow-up. CONCLUSION The treatment of elderly patients with irreducible intertrochanteric femoral fractures by using the novel bone hook combined with finger-guided technique can achieve high-quality fracture reduction and fixation, and has a good effectiveness.
Humans ; Male ; Female ; Aged ; Aged, 80 and over ; Hip Fractures/diagnostic imaging* ; Fracture Fixation, Internal/instrumentation* ; Fracture Healing ; Treatment Outcome ; Operative Time ; Fracture Fixation, Intramedullary/instrumentation* ; Bone Nails ; Postoperative Complications/epidemiology* ; Feasibility Studies ; Fingers

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 uncovered 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.

Surgery is the preferred treatment for resectable esophageal cancer, but in locally advanced esophageal cancer, the effect of surgery alone is not ideal, so surgery-based comprehensive treatment is the best option. Neoadjuvant therapy has become a standard treatment in the treatment of locally advanced resectable esophageal cancer. Neoadjuvant therapy includes neoadjuvant chemotherapy, radiochemotherapy, immunotherapy, targeted therapy, etc. With the significant efficacy and acceptable toxicity of immunotherapy in the first-line and second-line treatment of advanced esophageal cancer, neoadjuvant immunotherapy has become a research hotspot of locally advanced resectable esophageal cancer. This article reviews the latest research progress and some limitations of neoadjuvant immunotherapy in locally advanced resectable esophageal cancer.

Currently，there are still obstacles for patients’ right of self-determination in medical decision-making. By sorting out its historical origins，this paper found that the reasons for the current situation mainly include the influence of familial culture and medical paternalism，as well as the constraints of the behavioral capacity system and the guardianship systems. In this context，this paper criticized the view that “the key to enjoying decision-making power is rationality”，and called for a return to the concept of patient autonomy，so as to achieve a balance between agency decision-making power of others and the special intervention rights of doctors. The legal system for resolving conflicts can be constructed by replacing behavioral capacity with medical decision-making ability，requiring the evaluation of medical decision-making ability based on actual conditions，establishing a pre-medical instruction system，and clarifying the boundaries of medical special intervention rights.

Objective　To explore the effect of Mp1p on host macrophages through transcriptomics combined with metabolomics. Methods Firstly, a THP-1 macrophage strain (THP-1-Mp1p+) stably expressing Mp1p was constructed using lentivirus. Secondly, using high-throughput RNA sequencing (RNA Seq) technology, the expression level of intracellular mRNA was detected in transcriptomics analysis to determine differentially expressed genes; In metabolomics analysis, metabolite identification was performed through database comparison, and pathway analysis was performed on differential metabolites to reveal potential mechanisms of action. Finally, the results of metabolomics and transcriptomics were combined for analysis, and differential metabolites and genes were analyzed to further elucidate the mechanism of action of Mp1p on macrophages. Results Transcriptome analysis showed that, compared with the negative control group, the THP-1-Mp1p+ group had a total of 1 180 differentially expressed genes (DEGs), with 345 upregulated genes and 835 downregulated genes. GO enrichment analysis of DEGs showed that there were 135 differentially expressed genes, including 105 in biological processes (BP), 28 in cellular components (CC), and 2 in molecular functions (MF). The KEGG analysis results showed that the effect of Mp1p on THP-1 macrophages was highly correlated with the TNF pathway. The metabolomic analysis found that both the blank control group and the THP-1-Mp1p+ macrophage group achieved good separation between QC samples in both positive and negative ion modes. The threshold for significant differential metabolites was set at: VIP≥1 and T-test P<0.05, resulting in the identification of 488 differential metabolites, with 230 in the positive ion mode and 258 in the negative ion mode. Pathway enrichment analysis of the identified metabolites pointed to significant enrichment in metabolic pathways. The combined analysis confirmed that the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and NF-kappaB signaling pathway were important metabolic pathways involved. Conclusions The virulence factor Mp1p may affect host macrophages by modulating the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and NF-kappaB signaling pathway. The findings contribute to a better understanding of the mechanisms of action of Mp1p and may offer potential directions for the selection of relevant diagnostic and therapeutic targets in the future.

Objective: To evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa (Schenk) Wight (C. tubulosa, Rou Cong Rong), focusing on central and exercise-induced fatigue in mice. This study investigated the pharmacological effects of the total oligosaccharides, polysaccharides, and phenylethanoid glycosides (CPhGs) extracted from C. tubulosa. Methods: Models of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue. The mice were treated with different extracts of C. tubulosa, and their effects were assessed using behavioral tests to measure exercise capacity, learning, and memory function. Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels, liver and muscle glycogen storage, and various fatigue-related biomarkers. Results: This study found that treatment with C. tubulosa extract improved exercise capacity, learning, and memory in mice. Total oligosaccharides from C. tubulosa enhanced adrenocorticotropic hormone, cholinesterase, and thyroid-stimulating hormone levels, reduced cortisol levels in central fatigue models, and ameliorated biochemical markers of exercise-induced fatigue, including lowering lactic acid, blood urea nitrogen, and malondialdehyde levels. Among the tested extracts, the total oligosaccharides showed the most comprehensive anti-fatigue effects. Conclusion The anti-fatigue effects of C. tubulosa, particularly those of its total oligosaccharides, are pronounced in both central and exercise-induced fatigue. These effects are mediated by the regulation of neurotransmitter levels, enhancement of glycogen storage, and improvement of antioxidant enzyme activity, suggesting potential therapeutic benefits in fatigue-related conditions.

Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.

Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.