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.

Objective To analyze the effect of modified sitting Baduanjin based on the theory of"moving to generate Yang"in promoting the recovery of patients after lung cancer surgery.Methods A total of 92 patients with lung cancer who were admitted to Haian Traditional Chinese Medicine Hospital between January 2022 and December 2024 were enrolled in this prospective study.The patients were assigned to control group(n=46,conventional nursing)or observation group(n=46,conventional nursing and modified sitting Baduanjin based on the theory of"moving to generate Yang")using random number table method.After one month of intervention,the incidence of complications was recorded.Chinese version of Anderson Symptom Assessment Scale(MDASI-C)and Perioperative Lung Symptom Scale(PSA-Lung)were used to assess the severity of symptoms.Pulmonary function indexes(forced expiratory volume in first second[FEV1],FEV1/FVC[forced vital capacity]),diaphragm thickness(DTei),peripheral blood indexes(interleukin[IL]-6,IL-8,vascular endothelial growth factor[VEGF],Apelin levels),quality of life(assessed by SF-36 questionnaire and Lung Cancer Therapeutic Function Assessment Scale[FACT-L])and metabolomic changes before and after intervention were analyzed.Results After intervention,MDASI-C score,PSA-Lung score,IL-6,IL-8,VEGF,and Apelin levels were decreased in both groups,while SF-36 score,FACT-L score,FVC,and FEV1/FVC were increased;the changes of these indexes were greater in the observation group as compared with the control group(P<0.05).There was no significant difference in the DTei between the two groups(P>0.05).Liquid Chromatogram-mass spectrometry showed that after intervention,α-glucose,creatinine and alanine increased,while alanine/glutamine,glycerol,threonine,isoleucine,low density lipoprotein,3-hydroxybutyric acid,very low density lipoprotein,and cholesterol decreased in both groups;the changes of these indexes were greater than those in the control group(P<0.05).The total incidence of adverse reactions in observation group was lower than that in control group(8.70%vs.26.09%,P<0.05).Conclusion The modified sitting Baduanjin based on the theory of"moving to generate Yang"can promote the alleviation of symptoms in patients with lung cancer after surgery,reduce the levels of IL-6,IL-8,VEGF and Apelin in peripheral blood,enhance metabolomics and lung function,improve quality of life,and is associated with a lower incidence of adverse reactions.

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.

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.

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.

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 study the clinical value of serum microRNA-34a (miR-34a) and aryl hydrocarbon receptor nuclear transcript-like protein 1 (BMAL1) in cervical cancer and their relationship with high-risk human papillomavirus (HR-HPV) infection.Methods:The clinical data of 76 patients with cervical cancer and 50 patients with benign cervical diseases in the Affiliated Hospital of Jining Medical University from January to December 2022 were retrospectively analyzed. The expression levels of serum miR-34a and BMAL1 were detected by real-time fluorescence quantitative polymerase chain reaction, and HR-HPV infection was detected by flow fluorescent hybridization. The patients were followed up until December 2023, and the death and poor prognosis (death, tumor recurrence and progression and severe complications at 1-year of follow-up) were recorded. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of miR-34a, BMAL1 and related indexes in evaluating the poor prognosis in patients with cervical cancer at 1-year. Multivariate Cox regression analysis was used to analyze the independent risk factors for death in patients with cervical cancer. The Kaplan-Meier survival curve was used to analyze the relationship between miR-34a, BMAL1 expression and survival period, and the log-rank test was used for comparison.Results:The expression level of serum miR-34a in patients with cervical cancer was significantly lower than that in patients with benign cervical lesions (0.46 ± 0.08 vs. 0.67 ± 0.11), the expression level of serum BMAL1 was significantly higher than that in patients with benign cervical lesions (0.58 ± 0.07 vs. 0.41 ± 0.07), and there were statistical differences ( t= 12.40 and 13.34, P<0.01). The expression levels of serum miR-34a and BMAL1 in patients with cervical cancer were associated with tumor differentiation, myometrial invasion depth, lymph node metastasis, distant metastasis and International Federation of Gynecology and Obstetrics (FIGO) stage, and there were statistical differences ( P<0.05 or<0.01); they were not associated with age, menopause and pathological type, and there were no statistical differences ( P>0.05). In patients with cervical cancer, the expression level of miR-34a in patients with HR-HPV positive infection (60 cases) was significantly lower than that in patients with HR-HPV negative infection (16 cases): 0.41 ± 0.07 vs. 0.49 ± 0.08, the expression level of BMAL1 was significantly higher than that in patients with HR-HPV negative infection: 0.65 ± 0.09 vs. 0.53 ± 0.06, and there were statistical differences ( t = 3.68 and 4.24, P<0.05 or<0.01). In patients with benign cervical diseases, there were no statistical differences in the expression levels of miR-34a and BMAL1 between patients with HR-HPV positive infection (7 cases) and patients with HR-HPV negative infection (43 cases) ( P>0.05). ROC curve analysis result showed that miR-34a combined with BMAL1 had the highest sensitivity (90.4%), specificity (89.9%) and area under curve (0.911) in assessing the 1-year poor prognosis in patients with cervical cancer ( P<0.01), and the optimal cutoff values of miR-34a and BMAL1 expression level were ≤0.39 and ≥0.64. Multivariate Cox regression analysis result showed that poor differentiation, myometrial invasion depth ≥1/2, lymph node metastasis, distant metastasis, FIGO stage Ⅲ+Ⅳ, miR-34a expression level ≤0.46 and BMAL1 expression level ≥0.58 were independent risk factors for death in patients with cervical cancer ( OR = 1.857, 2.125, 2.337, 2.751, 2.457, 3.885 and 3.666; 95% CI 0.845 to 5.788, 0.726 to 5.924, 0.709 to 5.631, 0.693 to 5.727, 0.801 to 5.936, 1.244 to 6.423 and 1.031 to 5.612; P<0.01). Kaplan-Meier survival curve analysis result showed that the median survival time in cervical cancer patients with miR-34a expression level ≤0.39 and BMAL1 expression level ≥0.64 (21 cases) was significantly lower than that in the other cervical cancer patients (miR-34a expression level>0.39 or BMAL1 expression level<0.64, 55 cases): (26.4 ± 4.2) months vs. (34.2 ± 5.6) months, log-rank χ2 = 17.12, P<0.05. Conclusions:The expression level of serum miR-34a in patients with cervical cancer is significantly reduced and the expression level of BMAL1 is significantly increased, which is related to the condition, prognosis and HR-HPV infection. It can be used as a marker for the assessment of the condition and prognosis of cervical cancer. The combined detection of the two can significantly improve the sensitivity and specificity in predicting poor prognosis of cervical cancer.