ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

Objective: To investigate the efficacy of implantable neuromuscular electrical stimulation system on stress urinary incontinence (SUI) model in female rats. Methods: A total of 21 female infertile SD rats were randomly divided into the control，sham stimulation，and stimulation groups，with 7 rats in each group.All rats received vaginal dilation (VD) to simulate postpartum SUI.One week after VD，the control group was given normal feeding，stimulators were implanted in the pelvic floor muscles of the sham stimulation and stimulation groups.The sham stimulation group received normal feeding for 2 weeks，and the stimulation group received pelvic floor electrical stimulation (PFES) for 2 consecutive weeks.The leak point pressure (LPP) of each rat was measured with cystometry before VD (baseline value)，1 week after VD，and 2 weeks after PFES. Results: In the control group and sham stimulation group，LPP increased after 2 weeks of treatment compared with that after 1 week of VD，but it still did not return to the baseline level (P<0.001).In the stimulation group，after 2 consecutive weeks of PFES，LPP increased significantly compared with that 1 week after VD，and returned to the baseline value (P>0.05).There was no significant difference in the LPP baseline values and levels after 1 week of VD among the 3 groups (P>0.05).The LPP in the stimulation group after 2 weeks of PFES was significantly higher than that in the sham stimulation group and stimulation group (P<0.001). Conclusion: The implantable neuromuscular electrical stimulation system is effective in short-term intervention of SUI in female rats，the further studies are needed to confirm the long-term efficacy and safety of the system，the optimal stimulation sites，optimal stimulation parameters，and potential mechanisms of action.

OBJECTIVE: To review the application and progress of unilateral biportal endoscopy (UBE) technology in the treatment of cervical degenerative diseases, and to provide reference for clinical treatment decisions. METHODS: The literature related to UBE technology in the treatment of cervical spondylotic radiculopathy (CSR) and cervical spondylotic myelopathy (CSM) at home and abroad was extensively reviewed, and the surgical methods, indications, effectiveness, and safety were analyzed and summarized. RESULTS: UBE technology is effective in the treatment of CSR and CSM, and has the advantages of good surgical field, reducing the injury of the posterior structure of the cervical spine, and protecting the facet joint process, but in general, the indications are relatively narrow, limited to single-segment or adjacent double-segment lesions, and the requirements for the operator are relatively high, and the learning curve is long. CONCLUSION UBE technology can be applied to the treatment of CSR and CSM, but it needs to be carried out by experienced UBE surgeons for specific cases.
Humans ; Cervical Vertebrae/surgery* ; Endoscopy/methods* ; Radiculopathy/surgery* ; Spondylosis/surgery* ; Decompression, Surgical/methods* ; Spinal Cord Diseases/surgery* ; Treatment Outcome

Cancer is the result of evolving crosstalk between neoplastic cell and its immune microenvironment. In recent years, immune therapeutics targeting T lymphocytes, such as immune checkpoint blockade (ICB) and CAR-T, have made significant progress in cancer treatment and validated targeting immune cells as a promising approach to fight human cancers. However, responsiveness to the current immune therapeutic agents is limited to only a small proportion of solid cancer patients. As major components of most solid tumors, myeloid cells played critical roles in regulating the initiation and sustentation of adaptive immunity, thus determining tumor progression as well as therapeutic responses. In this review, we discuss emerging data on the diverse functions of myeloid cells in tumor progression through their direct effects or interactions with other immune cells. We explain how different metabolic reprogramming impacts the characteristics and functions of tumor myeloid cells, and discuss recent progress in revealing different mechanisms-chemotaxis, proliferation, survival, and alternative sources-involved in the infiltration and accumulation of myeloid cells within tumors. Further understanding of the function and regulation of myeloid cells is important for the development of novel strategies for therapeutic exploitation in cancer.
Humans ; Tumor Microenvironment/immunology* ; Myeloid Cells/immunology* ; Neoplasms/therapy* ; Animals

The pathogenesis of aplastic anemia(AA)is complex and associated with hematopoietic stem cell defect,abnormal bone marrow microenvironment,immune dysfunction,and somatic mutation,in which the immune mechanism plays an important role.This article reviews the pathogenesis of AA from the following aspects:regulatory T cell reduction,hematopoietic stem cell reduction caused by factor-related apoptosis/factor-related apoptosis ligand signaling pathway,aberrant target gene expression induced by inflammatory factor-stimulated microRNAs,and regulatory T cell dysfunction,so as to provide ideas and methods for clinical practice.

Objective To investigate the signal abnormality of conus medullaris in patients with overactive bladder(OAB)and un-deractive bladder(UAB)by MRI diffusion tensor imaging(DTI). Methods From May,2021 to April,2023,23 patients with lower urinary tract dysfunction without trauma and supraspi-nal lesions were enrolled(case group).All patients underwent imaging urodynamics and pelvic floor electromy-ography.Based on the bladder contraction during the filling phase of urodynamics,the patients were divided into UAB group and OAB group.Eight healthy subjects were included as the control group.All participants under-went T10 to L5 spinal segment MRI scans and DTI scans.The position of conus medullaris was determined by comparing the DTI sequences with the MRI scans.The fractional anisotropy(FA),apparent diffusion coefficient(ADC),and relative anisotropy(RA)of the conus medullaris intermediate segment were compared. Results Twelve cases were in UAB group,and eleven in OAB goup.Abnormalities were found in the pelvic floor elec-tromyography in the case group.There was significant difference in sacral reflex arc nerve conduction testing be-tween UAB and OAB groups(P = 0.036).Compared with the control group,ADC increased(t = 2.185,P = 0.037)in the case group;FA decreased(t = 3.439,P = 0.005)and ADC increased(t = 4.582,P<0.001)in UAB group. Conclusion DTI is helpful to find the potential lesion of spinal cord in patients with lower urinary tract dysfunction.FA and ADC are valuable indicators for the diagnosis of conus medullaris injury.

Objective To investigate the influence of type 2 diabetes mellitus(T2DM)on cognitive function and the effective connectivity with in the default mode network(DMN)in the brain.Methods A total of 93 hospitalized patients diagnosed with T2DM were enrolled in this study as T2DM group from The First Affiliated Hospital of Guangzhou University of Chinese Medicine during September 2021 to December 2022.Simultaneously,108 healthy individuals were recruited from the community as normal control(NC)group.The cognitive functions were evaluated in the two groups.A random dynamic causal modeling approach was employed to analyze the effective connectivity within DMN in both groups.Additionally,Pearson correlation analysis was performed to examine the association between differential connectivity,clinical indicators,and cognitive scores in both groups.Results In comparison to the NC group,T2DM individuals exhibited statistically significant reductions in scores in the auditory verbal learning test(AVLT)for immediate recall and the digit symbol substitution test(DSST)(P＜0.05).Additionally,they displayed a notable decrease in effective connectivity from the left lateral parietal cortex(LLPC)to the posterior cingulate cortex(PCC),as well as from the LLPC to the right lateral parietal cortex(RLPC)within the DMN(P＜0.05).Pearson correlation analysis unveiled a negative association between HbA1c levels and the strength of effective connectivity from LLPC to PCC.Conversely,a positive correlation was observed between AVLT(immediate)scores and the strength of effective connectivity from LLPC to PCC and LLPC to RLPC.Additionally,DSST scores displayed a positive correlation with the strength of effective connectivity from LLPC to PCC(P＜0.05).Conclusion Patients with T2DM display compromised effective connectivity from LLPC to PCC and LLPC to RLPC within the DMN network,and this alteration may associated with cognitive impairment.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Cerebral organoids are three-dimensional nerve cultures induced by embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)that mimic the structure and function of human brain.With the continuous optimization of cerebral organoid culture technology and the combination with emerging technologies such as organ transplantation,gene editing and organoids-on-chip,complex brain tissue structures such as functional vascular structures and neural circuits have been produced,which provides new methods and ideas for studying human brain development and diseases.This article reviews the latest advances in brain organoid technology,describes its application in neurological diseases and advances in stroke modeling and transplantation treatment.

Post-stroke cognitive impairment(PSCI)is mainly manifested as learning and memory disorders.Highly enriched RNA m6A methylation modification in mammalian brain is involved in glial cell-mediated neuroinflammation.Given that neuroinflammation is the main mechanism for neural damage and spatial and memory impairment of PSCI,it is speculated that RNA m6A methylation modification can regulate the inflammatory response of glial cells after stroke to improve PSCI.This review summarizes and analyzes the role of RNA m6A methylation modification in the development of PSCI and analyzes its detailed mechanism of regulating glial cell-mediated inflammation,which will provide reference for researchers in this field.