[Objective] To explore the relationship between neutrophil activation under cardiopulmonary bypass (CPB) and the incidence of cardiac surgery-associated acute kidney injury (CS-AKI). [Methods] This prospective cohort study enrolled adult patients who scheduled for cardiac surgery under CPB at West China Hospital between May 1, 2022 and March 31, 2023. The primary outcome was acute kidney injury (AKI). Blood samples (5 mL) were obtained from the central vein before surgery, at rewarming, at the end of CPB, and 24 hours after surgery. Neutrophils were labeled with CD11b, CD54 and other markers. To assess the effect of neutrophils activation on AKI, propensity score matching (PSM) was employed to equilibrate covariates between the groups. [Results] A total of 120 patients included into the study, and 17 (14.2%) developed AKI. Both CD11b⁺ and CD54⁺ neutrophils significantly increased during the rewarming phase and the increases were kept until 24 hours after surgery. During rewarming, the numbers of CD11b⁺ neutrophils were significantly higher in AKI compared to non-AKI (4.71×10⁹/L vs 3.31×10⁹/L, Z=-2.14, P<0.05). Similarly, the CD54⁺ neutrophils counts were also significantly higher in AKI than in non-AKI before surgery (2.75×10⁹/L vs 1.79×10⁹/L, Z=-2.99, P<0.05), during rewarming (3.12×10⁹/L vs 1.62×10⁹/L, Z=-4.34, P<0.05), and at the end of CPB (4.28×10⁹/L vs 2.14×10⁹/L, Z=-3.91, P<0.05). An analysis of 32 matched patients (16 in each group) revealed that CD11b⁺ and CD54⁺ neutrophil levels of AKI were 1.74 folds (4.83×10⁹/L vs 2.77×10⁹/L, Z=-2.72, P<0.05) and 2.34 folds (3.32×10⁹/L vs 1.42×10⁹/L, Z=-4.12, P<0.05), respectively, of non-AKI at rewarming phase. [Conclusion] Neutrophils are activated during CPB, and they can be identified by CD11b/CD54 markers. The activated neutrophils of AKI patients are approximately 2 folds of non-AKI during the rewarming phase, with disparity reached peak between groups during rewarming. These findings suggest the removal of 50% of activated neutrophils during the rewarming phase may be effective to reduce the risk of AKI.

To analyze the disease burden, temporal trends, and attributable risk factors of early-onset female breast cancer (EOBC) in China and globally from 1990 to 2021.

The identification and optimization of mutations in nanobodies are crucial for enhancing their therapeutic potential in disease prevention and control. However, this process is often complex and time-consuming, which limit its widespread application in practice. In this study, we developed a workflow, named Evolutionary-Nanobody (EvoNB), to predict key mutation sites of nanobodies by combining protein language models (PLMs) and molecular dynamic (MD) simulations. By fine-tuning the ESM2 model on a large-scale nanobody dataset, the ability of EvoNB to capture specific sequence features of nanobodies was significantly enhanced. The fine-tuned EvoNB model demonstrated higher predictive accuracy in the conserved framework and highly variable complementarity-determining regions of nanobodies. Additionally, we selected four widely representative nanobody-antigen complexes to verify the predicted effects of mutations. MD simulations analyzed the energy changes caused by these mutations to predict their impact on binding affinity to the targets. The results showed that multiple mutations screened by EvoNB significantly enhanced the binding affinity between nanobody and its target, further validating the potential of this workflow for designing and optimizing nanobody mutations. Additionally, sequence-based predictions are generally less dependent on structural absence, allowing them to be more easily integrated with tools for structural predictions, such as AlphaFold 3. Through mutation prediction and systematic analysis of key sites, we can quickly predict the most promising variants for experimental validation without relying on traditional evolutionary or selection processes. The EvoNB workflow provides an effective tool for the rapid optimization of nanobodies and facilitates the application of PLMs in the biomedical field.

OBJECTIVE: To explore clinical efficacy of bone cement filling combined with lower extremity arterial balloon dilation in treating Wagner grade Ⅳ diabetic foot (DF). METHODS: From January to October 2024, 9 Wagner grade Ⅳ DF patients with lower extremity vascular occlusion were admitted, including 7 males and 2 females, aged from 51 to 87 years old;5 patients on the left side and 4 patients on the right side. All patients were underwent stageⅠdebridement of the affected foot and bone cement filling, and treated with lower extremity arterial balloon dilation after operation, they were. After the formation of the induced membrane, stageⅡwound repair was performed. The wound healing time and condition were observed. Ankle-brachial index (ABI) was used to evaluate the lower extremity vascular perfusion before operation and 3 months after operation, respectively. RESULTS: The wounds of all 9 patients healed completely, and the healing time ranged from 45 to 65 days. All patients were followed up for at least 6 months without recurrence. The skin of the affected foot wound healed with keratinization, and there was mild scar hyperplasia locally (1 patient had necrosis of the adjacent toe after stageⅠsurgery and was debridement and toe amputation again). The narrowed or occluded blood vessels of the lower extremities were all recanalized. ABI recovered from 0.3 to 0.5 before operation to 1.0 to 1.1 at 3 months after operation. CONCLUSION Bone cement filling combined with lower extremity arterial balloon dilation for the treatment of grade Wagner Ⅳ DF is conducive to promoting healing of the affected foot, effectively preventing secondary ulceration of the affected foot, and clinical therapeutic effect is satisfactory.
Humans ; Male ; Female ; Middle Aged ; Diabetic Foot/surgery* ; Aged ; Bone Cements/therapeutic use* ; Aged, 80 and over ; Lower Extremity/blood supply*

Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

Post-stroke aphasia(PSA)is one of the common complications of stroke,which seriously affects the compliance of rehabilitation training and daily life of patients.Repetitive transcranial magnetic stimulation(rTMS)is a common method for the treatment of PSA in recent years,which can accurately regulate the speech center,and stimulate or inhibit the corresponding targets,to achieve the purpose of neural function remodeling.This article analyzes and summarizes the research on the application of rTMS in PSA at home and abroad,as well as related evaluation indicators,to provide the theoretical basis for the scientific application of rTMS in PSA in the future.

Lung transplantation is an important means to treat end-stage lung disease and improve the survival rate and quality of life of patients. However, many postoperative complications seriously affect the prognosis of recipients. Accurate identification of key prognostic factors and construction of individualized and accurate prediction models are of great significance for postoperative prognosis evaluation, treatment strategy formulation and clinical decision-making. In recent years, the clinical prediction model of lung transplantation has gradually changed from traditional statistical methods to machine learning-driven. Compared with traditional models such as Cox regression and Logistic regression, machine learning models such as random forest, support vector machine and artificial neural network have certain advantages in postoperative survival rate prediction, early warning of complications and pulmonary function evaluation. However, their application is also affected by insufficient sample size and poor interpretability of models. Under the condition of small samples, the traditional model still has important value in prediction accuracy. The appropriate prediction model should be selected according to the clinical status of lung transplantation in China, considering the factors such as sample size, variable complexity and model interpretability. In the future, a multi-center, large-sample lung transplantation database should be constructed to further optimize and tap the potential of machine learning algorithms to improve the robustness and clinical applicability of the model.

Objective:To investigate the efficacy and safety of metallic stent implantation for the treatment of central airway malacia following lung transplantation.Methods:Clinical data of 14 recipients who underwent metallic stent implantation for central airway malacia after lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 2023 to June 2024 were retrospectively analyzed. Clinical symptoms, modified Medical Research Council (mMRC) dyspnea scale scores, Karnofsky Performance Status (KPS) scores, and pulmonary function were evaluated before and 2 weeks after stent implantation. The incidence of post-implantation complications was recorded during follow-up.Results:Among the 14 recipients, 13 were male and 1 was female, with a mean age of (57.29±10.93) years (range: 27-71 years). All patients successfully underwent metallic stent placement in a single attempt, with no serious intraoperative complications. Clinical symptoms such as dyspnea improved significantly after stent implantation. Compared with pre-treatment values, mMRC scores decreased [3.00 (2.00, 4.00) vs 1.00 (1.00, 2.00), P<0.001], KPS scores increased [30.00 (10.00, 32.50) vs 80.00 (60.00, 90.00), P=0.001], and forced expiratory volume in one second (FEV 1) improved [(1.25±0.42) L vs (1.74±0.38) L, P=0.006]. Postoperative complications included granulation tissue formation (7 cases), epithelialization within the stent (3 cases), and mucus plugging (4 cases). As of the last follow-up in September 2024, eight patients had their stents successfully removed, and one patient had died due to cytomegalovirus infection. Conclusions:Metallic stent implantation can significantly relieve clinical symptoms of central airway malacia after lung transplantation, improve quality of life, and shows a favorable safety profile.

Objective To explore the influence of hsa_circ_0004535 on type 2 diabetes(T2DM)combined with metabolic-associated fatty liver disease(MAFLD)model mice.Methods Forty-eight healthy SPF grade Balb/c mice were selected for modeling and divided into the following groups(n=6 per group):Control group:normal feed;T2DM group:diabetes model induced by high-glucose and high-fat diet;T2DM combined MAFLD group:non-alcoholic fatty liver high-glucose and high-fat diet-induced diabetes combined with fatty liver model;T2DM combined MAFLD+hsa_circ_NC group:after 4 weeks of modeling,10 nmol hsa_circ_NC injected into the tail vein;T2DM combined MAFLD+hsa_circ_0004535 group:after 4 weeks of modeling,10 nmol circ_0004535 injected into the tail vein;T2DM combined MAFLD+miRNA_NC group:after 4 weeks of modeling,10 nmol miRNA blank control injected into the tail vein;T2DM combined MAFLD+miR-1827 agomir group:after 4 weeks of modeling,10 nmol miR-1827 agomir injected into the tail vein;and T2DM combined MAFLD+miR-1827 antagomir group:after 4 weeks of modeling,10 nmol miR-1827 antagomir injected into the tail vein.Mouse body weight was measured after the interventions and recorded weekly.Glucose and insulin tolerance tests were performed,blood lipids and liver function were measured,the liver and insulin resistance indexes were calculated,and pathological tests(hematoxylin/eosin(HE),oil red O,and Masson staining,immunohistochemistry,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL))were performed to measure the degree of hepatic inflammation,fat deposition,and fibrosis.Results(1)Body weight,liver weight,liver index,insulin resistance index,and biochemical indexes were all significantly lower in the hsa_circ_0004535 injection group compared with the hsa_circ_NC injection group and the T2DM combined MAFLD group(both P＜0.05).(2)Steatosis vacuoles were reduced and smaller and inflammatory cell infiltration was reduced in the T2DM combined MAFLD+circ_0004535 group,as shown by HE and oil red staining.(3)TUNEL-positive cells were significantly reduced in the T2DM combined MAFLD+hsa_circ_0004535 group(P＜0.05).(4)Collagen fiber deposition was significantly reduced in the T2DM combined MAFLD+hsa_circ_0004535 group,as shown by Masson staining(P＜0.05).Conclusions The expression of hsa_circ_0004535 and miRNA-1827 play important roles in regulating lipid metabolism,insulin sensitivity,inflammatory pathways,hepatocyte apoptosis,and hepatic fibrosis-related pathways in an animal model of T2DM combined with MAFLD.

Objective The effects of stachydrine(STA)on the proliferation,apoptosis and radiosensitivity of acute myeloid leukemia(AML)cells by regulating the transcription factor forkhead box protein O3(FOXO3)-forkhead box protein M1(FOXM1)signaling axis.Methods Human AML cells(HL-60)were treated with STA at a concentration of 50～1 600 μmol/L,and the activity of HL-60 cells was detected using the cell counting kit-8(CCK-8)method to screen for the optimal drug concentration;HL-60 cells were separated into Control group,low,medium,and high concentration STA groups(STA-L group,STA-M group,STA-H group),STA+lentivirus transfection control group(STA-H+LV-NC group),and high-concentration STA+FOXO3 overexpression lentiviral group(STA-H+LV-FOXO3 group).5-ethyny1-2'-deoxyuridine(Edu)was applied to detect HL-60 cell proliferation;flow cytometry(FCM)was applied to detect cell apoptosis;cell cloning experiments were applied to detect the radiotherapy sensitivity of cells;Western blot was applied to detect the expression of cell proliferation antigen markers(Ki67),Cyclin D1,Caspase-3,B-cell lymphoma2 assaciated X protein(Bax),FOXO3,and FOXM1 proteins.Results STA concentrations of 100,200 and 400 μmol/L were selected for subsequent experiments.Compared with the control group,the positive rate of Ki67,Cyclin D1,Edu,FOXO3 and FOXM1 expression levels in the STA-L,STA-M,and STA-H groups decreased sequentially(tSTA-L=2.169～5.879,tSTA-M=3.089～11.284,tSTA-H=4.572～11.502),Caspase-3 and Bax expression levels,the apoptosis rate,increased sequentially(tSTA-L=9.171,10.082,20.144;tSTA-M=5.435,7.530,7.450;tSTA-H=4.138,4.159,5.956)and the differences were statistically significant(all P<0.05),respectively.Compared with the STA-H+LV-NC group,the positive rate of Edu and the expression levels of Ki67,Cyclin D1,FOXO3 and FOXM1 were obviously increased in the STA-H+LV-FOXO3 group(t=10.055～16.267),Caspase-3 and Bax expression levels,the apoptosis rate were obviously reduced(t=5.736,5.433,8.933),and the differences were statistically significant(all P<0.05),respectively.The colony formation rate of HL-60 cells in the radiotherapy group and STA+radiotherapy group decreased with the increase of radiotherapy dose,and the differences were statistically significant(F=78.630,137.843,all P<0.05),and the colony formation rate of HL-60 cells in the STA+radiotherapy group was lower than that in the radiotherapy group at the same dose(t=1.480～11.301,all P<0.05).Conclusion Stachydrine inhibits AML cell proliferation,induces apoptosis,and enhances radiotherapy sensitivity by inhibiting the FOXO3-FOXM1 signaling axis.