Objective:To explore the microbiological and disease distribution characteristics of multidrug-resistant bacteria in patients hospitalized in a critical care rehabilitation ward, and to analyze the risk factors leading to multidrug-resistant bacterial infections.Methods:Microbiology screening data describing 679 patients admitted to a critical care rehabilitation ward were retrospectively analyzed to divide the subjects into a multidrug-resistant group (positive for multidrug-resistant bacterial infections, n=166) and a non-multidrug-resistant group (negative for multidrug-resistant bacterial infections, n=513). The risk factors were then analyzed using logistic regression. Results:Among 369 strains of multidrug-resistant bacteria observed, 329 were gram-negative bacteria (89.2%), mainly Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. They were distributed in sputum (56.9%) and mid-epidemic urine (28.2%) specimens. Patients whose primary disease was hemorrhagic or ischemic cerebrovascular disease accounted for 40.96% and 23.49% of the multidrug-resistant bacterial infections, respectively. Logistic regression analysis showed that albumin level, dependence on mechanical ventilation, central venous cannulation, or an indwelling urinary catheter or cystostomy tube were significant independent predictors of such infections.Conclusion:The multidrug-resistant bacterial infections of patients admitted to the critically ill rehabilitation unit are mainly caused by gram-negative bacteria. Their occurrence is closely related to low albumin levels and mechanical ventilation, as well as to bearing an indwelling central venous catheter, a urinary catheter or a cystostomy catheter.

[Objective]To investigate the effect and mechanism of Shuxuetong and its main component hirudin on the apoptosis of cerebellar granule neurons(CGNs)in Sprague-Dawley(SD)rats.[Methods]CGNs incubated in vitro for 7 days were divided into survival control group or 25 K group(cultured in medium containing 25 mmol/L KCL)and apopto-sis group or 5 K group(cultured in medium containing 5 mmol/L KCL).CGNs were separately treated with proportionally diluted and different concentrations of Shuxuetong(1/50,1/40,1/30,1/20 and 1/10)and the corresponding different con-centrations of hirudin(2,2.5,3.34,5 and 10 U/mL).Hoechst staining was performed to analyze the apoptosis.Western blot was used to detect the expression levels of Cleaved Caspase-3,Bim and VEGF.[Results]Hoechst staining showed that 5 K group had a higher apoptosis rate than 25 K group.In 25 K group,there was no significant change in the apoptosis rate between neurons treated with different concentrations of Shuxuetong and hirudin,but significant changes was found in 5 K group and the higher the concentration,the lower the apoptosis rate.Western blot results revealed that,compared with control neurons in 5 K group,Shuxuetong injection and hirudin treatments resulted in a decrease of Cleaved Caspase-3 and Bim expression,but an increase of VEGF protein.[Conclusions]Shuxuetong and its main component hirudin inhibits the apoptosis of CGNs through suppressing proapoptotic BH3-only protein Bim.

Objective:To investigate the clinical characteristics and prognostic factors of extracranial malignant rhabdoid tumors (eMRTs) in children.Methods:In this retrospective case series study, a retrospective analysis was conducted on clinical data of 21 eMRT patients admitted to Children′s Hospital of Nanjing Medical University from April 2018 to January 2023 and followed up until October 30, 2023.Patients were grouped according to their gender, age, tumor origin site, clinical staging, initial lactate dehydrogenase (LDH) level, extent of tumor resection, chemotherapy regimen, and radiotherapy.The Kaplan-Meier method was used to calculate the 2-year progression-free survival rate (PFS) and overall survival rate (OS) of the patients, and the Cox regression model was used to analyze the prognostic factors.Results:Among the 21 patients with eMRTs, there were 7 males and 14 females, with the age of onset of 24 (3-138) months.Immunohistochemistry showed that all tumor tissues of the patients did not secrete integrase interactor 1 (INI-1).Among them, 13 cases originated from the kidney, and 8 cases originated from extrarenal non-central sites.At the time of diagnosis, there were 4 cases in clinical stages Ⅰ-Ⅱ, 17 cases in stage Ⅲ-Ⅳ.Thirteen patients underwent complete tumor resection surgery, 7 underwent partial resection, and 1 only underwent biopsy.Among the 13 cases of renal rhabdoid tumors, 8 cases were treated with the AVDC (Epirubicin, Vincristine, Actinomycin D, Cyclophosphamide)/ICE (Ifosfamide, Carboplatin, Etoposide) regimen, and 5 cases were treated with the protocol for nephroblastoma; among the 8 cases of extrarenal non-central rhabdoid tumors, 5 cases were treated with the AVDC/ICE regimen, and 3 cases were treated with the commonly used protocol for soft tissue sarcoma.Thirteen patients received radiotherapy.One patient received consolidation therapy with autologous stem cell transplantation following chemotherapy and radiotherapy.As of October 2023, there were 14 survivors and 7 deaths.The overall 2-year PFS and OS were 56%(95% CI: 35.7%-88.5%) and 62%(95% CI: 43.2%-89.4%), respectively.Among the patients who received the AVDC/ICE alternating chemotherapy regimen, the 2-year PFS and OS were 73%(95% CI: 47.0%-100.0%) and 79% (95% CI: 56.4%-100.0%), respectively.Univariate Cox regression analysis showed that complete tumor resection, the AVDC/ICE alternating chemotherapy, and radiotherapy were associated with a better prognosis in children (all P≤0.05).Multivariate Cox regression analysis showed that whether to receive radiotherapy was an independent risk factor affecting the overall survival in children. Conclusions:eMRTs are more common in infants and young children, with high malignancy and invasiveness.There is currently no standard treatment.Complete tumor resection combined with the AVDC/ICE alternating chemotherapy and radiotherapy may improve the prognosis of children with eMRTs.

Glioblastoma(GBM)stands as one of the most aggressive brain tumors,and its pharmacological therapy is severely limited due to the presence of the blood-brain barrier(BBB).Nose-to-brain drug delivery has emerged as a promising approach for directly targeting the central nervous system(CNS)by circumventing the BBB.The nasal cavity is anatomically partitioned into the vestibular,olfactory,and respiratory regions.Nanomedicines can efficiently transport to the CNS through the olfactory pathway of the olfactory region and the trigeminal nerve pathway of the respiratory region.In recent years,nanodelivery platforms in nasal administration for treating GBM have garnered widespread attention,primarily involving polymers,liposomes,inorganic metal nanoparticles,and so on.The advancement of these technologies presents novel avenues and selections for overcoming the BBB,enhancing drug delivery efficacy,and improving the prognosis of GBM patients.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Cell cycle plays a crucial role in cell development. Cell cycle progression is mainly regulated by cyclin dependent kinase (CDK), cyclin and endogenous CDK inhibitor (CKI). Among these, CDK is the main cell cycle regulator, binding to cyclin to form the cyclin-CDK complex, which phosphorylates hundreds of substrates and regulates interphase and mitotic progression. Abnormal activity of various cell cycle proteins can cause uncontrolled proliferation of cancer cells, which leads to cancer development. Therefore, understanding the changes in CDK activity, cyclin-CDK assembly and the role of CDK inhibitors will help to understand the underlying regulatory processes in cell cycle progression, as well as provide a basis for the treatment of cancer and disease and the development of CDK inhibitor-based therapeutic agents. This review focuses on the key events of CDK activation or inactivation, and summarizes the regulatory processes of cyclin-CDK at specific times and locations, as well as the progress of research on relevant CDK inhibitor therapeutics in cancer and disease. The review concludes with a brief description of the current challenges of the cell cycle process, with the aim to provide scientific references and new ideas for further research on cell cycle process.
Cyclin-Dependent Kinases/metabolism* ; Cyclins/metabolism* ; Protein Serine-Threonine Kinases ; Cell Cycle Proteins/metabolism* ; Cell Cycle/physiology* ; Cyclin-Dependent Kinase 2

Based on the teaching concept of constructivism, this study aims to promote independent inquiry-based learning and clinical thinking among students and establish the guiding ideology of "full participation, process control, in-depth discussion, and expansion of thinking". A blending learning model was adopted with offline inquiry-based group learning and in-class defense and comment, as well as online teacher-student interaction and supervision to promote learning. Case-problem-based learning (CPBL) of pathophysiology was carried out among the medical students in the class of 2017, and process management was strengthened to effectively manage the two key links of data retrieval and group discussion. The analysis of 176 teaching evaluations collected at the end of the semester show that in terms of the overall evaluation of CPBL teaching, 162 students (92.05%) had high evaluation on teaching objectives, organization, cases, and personal gains and held a very or relatively favorable attitude. There were more negative feedbacks on "appropriate time allocation"; 21 students (11.93%) held a relatively or very disapproving attitude, and 149 students (84.66%) "felt very tired". In terms of teaching effect evaluation, 150 students (85.23%) strongly or relatively agreed that CPBL teaching may help to understand professional knowledge, stimulate learning enthusiasm and initiative, improve problem solving ability, emphasize clinical practice to cultivate clinical thinking, supervise and promote learning, and enhance team cooperation and teacher-student communication. In terms of the evaluation of teachers, 167 students (94.89%) thought that teachers were rigorous, responsible, and enthusiastic in teaching, attached importance to process management, and did well in effective guidance and thinking inspiration (strongly or relatively agree). The above results suggest that the CPBL teaching reform of pathophysiology based on process management can effectively promote in-depth inquiry-based independent learning and the cultivation of clinical thinking and improve teaching effectiveness, but further improvement is needed for teaching arrangement and time allocation.

We report a case of a 44-year-old female patient with acute liver failure and hepatic encephalopathy. The patient received artificial liver treatment and underwent allogeneic orthotopic liver transplantation at 14 days after admission. Laboratory examination reported a small number of green cytoplasmic inclusions in neutrophils on the peripheral blood smear at 68 days after admission. The patient eventually died of liver failure at 71 days after admission. Green inclusions are bright green or blue-green inclusions presented in the cytoplasm of neutrophils in Wright-Giemsa stained peripheral blood smears, and is associated with liver failure and high short-term mortality.

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
Mice ; Animals ; Diabetes Mellitus, Experimental/metabolism* ; Axons/physiology* ; Diabetic Neuropathies ; Sensory Receptor Cells/metabolism* ; Neuralgia/metabolism*

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder that damages patients' memory and cognitive abilities. Therefore, the diagnosis of AD holds significant importance. The interactions between regions of interest (ROIs) in the brain often involve multiple areas collaborating in a nonlinear manner. Leveraging these nonlinear higher-order interaction features to their fullest potential contributes to enhancing the accuracy of AD diagnosis. To address this, a framework combining nonlinear higher-order feature extraction and three-dimensional (3D) hypergraph neural networks is proposed for computer-assisted diagnosis of AD. First, a support vector machine regression model based on the radial basis function kernel was trained on ROI data to obtain a base estimator. Then, a recursive feature elimination algorithm based on the base estimator was applied to extract nonlinear higher-order features from functional magnetic resonance imaging (fMRI) data. These features were subsequently constructed into a hypergraph, leveraging the complex interactions captured in the data. Finally, a four-dimensional (4D) spatiotemporal hypergraph convolutional neural network model was constructed based on the fMRI data for classification. Experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database demonstrated that the proposed framework outperformed the Hyper Graph Convolutional Network (HyperGCN) framework by 8% and traditional two-dimensional (2D) linear feature extraction methods by 12% in the AD/normal control (NC) classification task. In conclusion, this framework demonstrates an improvement in AD classification compared to mainstream deep learning methods, providing valuable evidence for computer-assisted diagnosis of AD.
Humans ; Alzheimer Disease/diagnostic imaging* ; Neural Networks, Computer ; Magnetic Resonance Imaging/methods* ; Neuroimaging/methods* ; Diagnosis, Computer-Assisted ; Brain ; Cognitive Dysfunction