Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

Clathrin-mediated endocytosis (CME) is a critical process by which cells internalize macromolecular substances and initiate vesicle trafficking, serving as the foundation for many cellular activities. Central to this process are clathrin-coated structures (CCSs), which consist of clathrin-coated pits (CCPs) and clathrin plaques. While clathrin-coated pits are well-established in the study of endocytosis, clathrin plaques represent a more recently discovered but equally important component of this system. These plaques are large, flat, and extended clathrin-coated assemblies found on the cytoplasmic membrane. They are distinct from the more typical clathrin-coated pits in terms of their morphology, larger surface area, and longer lifespan. Recent research has revealed that clathrin plaques play roles that go far beyond endocytosis, contributing to diverse cellular processes such as cellular adhesion, mechanosensing, migration, and pathogen invasion. Unlike traditional clathrin-coated pits, which are transient and dynamic structures involved primarily in the internalization of molecules, clathrin plaques are more stable and extensive, often persisting for extended periods. Their extended lifespan suggests that they serve functions beyond the typical endocytic role, making them integral to various cellular processes. For instance, clathrin plaques are involved in the regulation of intercellular adhesion, allowing cells to better adhere to one another or to the extracellular matrix, which is crucial for tissue formation and maintenance. Furthermore, clathrin plaques act as mechanosensitive hubs, enabling the cell to sense and respond to mechanical stress, a feature that is essential for processes like migration, tissue remodeling, and even cancer progression. Recent discoveries have also highlighted the role of clathrin plaques in cellular signaling. These plaques can serve as scaffolds for signaling molecules, orchestrating the activation of various pathways that govern cellular behavior. For example, the recruitment of actin-binding proteins such as F-actin and vinculin to clathrin plaques can influence cytoskeletal dynamics, helping cells adapt to mechanical changes in their environment. This recruitment also plays a pivotal role in regulating cellular migration, which is crucial for developmental processes. Additionally, clathrin plaques influence receptor-mediated signal transduction by acting as platforms for the assembly of signaling complexes, thereby affecting processes such as growth factor signaling and cellular responses to extracellular stimuli. Despite the growing body of evidence that supports the involvement of clathrin plaques in a wide array of cellular functions, much remains unknown about the precise molecular mechanisms that govern their formation, maintenance, and turnover. For example, the factors that regulate the recruitment of clathrin and other coat proteins to form plaques, as well as the signaling molecules that coordinate plaque dynamics, remain areas of active research. Furthermore, the complex interplay between clathrin plaques and other cellular systems, such as the actin cytoskeleton and integrin-based adhesion complexes, needs further exploration. Studies have shown that clathrin plaques can respond to mechanical forces, with recent findings indicating that they act as mechanosensitive structures that help the cell adapt to changing mechanical environments. This ability underscores the multifunctional nature of clathrin plaques, which, in addition to their role in endocytosis, are involved in cellular processes such as mechanotransduction and adhesion signaling. In summary, clathrin plaques represent a dynamic and versatile component of clathrin-mediated endocytosis. They play an integral role not only in the internalization of macromolecular cargo but also in regulating cellular adhesion, migration, and signal transduction. While much has been learned about their structural and functional properties, significant questions remain regarding the molecular mechanisms that regulate their formation and their broader role in cellular physiology. This review highlights the evolving understanding of clathrin plaques, emphasizing their importance in both endocytosis and a wide range of other cellular functions. Future research is needed to fully elucidate the mechanisms by which clathrin plaques contribute to cellular processes and to better understand their implications for diseases, including cancer and tissue remodeling. Ultimately, clathrin plaques are emerging as crucial hubs that integrate mechanical, biochemical, and signaling inputs, providing new insights into cellular function and the regulation of complex cellular behaviors.

OBJECTIVES: To investigate the characteristics and clinical significance of anorectal manometry measurements in children with tethered cord syndrome (TCS) before and after surgery. METHODS: A retrospective study was conducted on 44 children with TCS treated at the Children's Hospital of Zhejiang University School of Medicine from January 2022 to September 2023. These patients were divided into effective subgroup (n=34) and non-effective subgroup (n=10) based on postoperative symptom improvement. Additionally, 34 children with functional constipation were selected as a control group. Baseline data and manometry measurements were compared between the preoperative TCS group and the control group, as well as between the non-effective and effective subgroups. RESULTS: The TCS group had lower short contraction time and defecation relaxation rate compared to the control group (P<0.05), while defecation residual pressure and maximum rectal tolerable threshold were higher than the control group (P<0.05). The length of the anal canal in the high-pressure zone in the effective subgroup was greater postoperatively than preoperatively (P<0.05), and the initial rectal sensation threshold decreased postoperatively (P<0.05). The non-effective subgroup had lower preoperative maximum rectal expulsion pressure compared to the effective subgroup (P<0.05). Postoperative rectal anal inhibition reflex values in the effective subgroup were higher than those in the non-effective subgroup (P<0.05). CONCLUSIONS There are some differences in anorectal dynamics between children with TCS and those with functional constipation. Maximum rectal expulsion pressure may be a key predictor of surgical outcomes. Surgery can alter certain defecation functions in some children.
Humans ; Male ; Anal Canal/physiopathology* ; Female ; Rectum/physiopathology* ; Child ; Child, Preschool ; Retrospective Studies ; Manometry ; Neural Tube Defects/physiopathology* ; Infant ; Defecation ; Adolescent ; Constipation/physiopathology* ; Clinical Relevance

OBJECTIVE: To investigate the predictive value of endothelial activation and stress index (EASIX) for the prognosis of patients with mantle cell lymphoma (MCL). METHODS: A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023, had therapeutic indications and received standard treatment. RESULTS: A total of 66 patients were included and divided into high EASIX group and low EASIX group, according to a cutoff value of 0.97 determined by the receiver operating characteristic (ROC) curve. Multivariate Cox regression analysis showed that prealbumin <0.2 g/L, high EASIX, and ECOG PS score ≥2 were independent risk factors influencing overall survival (OS) in MCL patients. The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months, and the median progression-free survival was 8.8 and 26.0 months, respectively. The proportions of patients with ECOG PS score ≥2 and prealbumin <0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group. CONCLUSION At the time of initial diagnosis, EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL. Furthermore, patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.
Humans ; Lymphoma, Mantle-Cell/pathology* ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; ROC Curve

OBJECTIVE: To investigate the predictive role of the modified Endothelial Activation and Stress Index (mEASIX) in the efficacy of chimeric antigen receptor T-cell (CAR-T) therapy and cytokine release syndrome (CRS). METHODS: The clinical data of 70 relapsed and refractory (R/R) B-cell tumor patients who were treated with CAR-T therapy from September 1, 2018 to February 28, 2023 in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University, were retrospectively analyzed. The value of log-2 mEASIX before conditioning (-7 d) was calculated, and the patients were divided into a low-mEASIX group (42 patients) and a high-mEASIX group (28 patients) based on the cut-off value of 5.443 determined by the receiver operating characteristic (ROC) curve. Eventually, the predictive role of mEASIX before conditioning on the efficacy of CAR-T cell therapy and CRS was analyzed. RESULTS: The high-mEASIX group exhibited significantly worse median overall survival (OS) and median progression-free survival (PFS) in comparison to the low mEASIX group (OS: 3.2 months vs not reached, P < 0.01; PFS: 1.3 months vs 6.0 months, P =0.009). The incidence of grade ≥2 CRS in the high-mEASIX group was substantially higher than that in the low-mEASIX group (57.1% vs 19.0%, P =0.007). The degree of remission after CAR-T therapy (P =0.001), whether CRS occurs or not (P =0.041), the lactate dehydrogenase (LDH) level before conditioning (P =0.046), and the mEASIX score before conditioning (P =0.047) were independent influencing factors for the OS of patients receiving CAR-T cell therapy. CONCLUSION The mEASIX score before conditioning can predict OS and the incidence of grade ≥2 CRS in patients with relapsed and refractory B-cell tumors who receive CAR-T cell therapy.
Cytokine Release Syndrome/therapy* ; Immunotherapy, Adoptive/methods* ; Humans ; Lymphoma, B-Cell/therapy* ; Retrospective Studies ; Hematology ; China ; Receptors, Chimeric Antigen/blood* ; Predictive Value of Tests

OBJECTIVE: To investigate the effect of non-chemotherapy strategy of retinoic acid (ATRA) combined with arsenic trioxide (ATO) on the survival of patients with acute promyelocytic leukemia (APL). METHODS: The data of APL patients with complete information diagnosed in the hematology department of our hospital from June 2009 to November 2024 were retrospective analyzed. All patients in the non-CHT group received ATRA-ATO induction, consolidation and maintenance therapy. Patients in the CHT group received ATRA-ATO+chemotherapy induction therapy, followed by 3 cycles of ATRA-ATO+CHT consolidation therapy and 6-10 cycles of ATRA-ATO maintenance therapy. The primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival (OS), remission rate, differentiation syndrome (DS) and safety. RESULTS: There were 182 patients with APL and 15 patients with early death (ED), accounting for 8.24%, which was related to age and risk stratification. There was no significant difference in remission rate between the non-CHT group and the CHT group (P =0.486). As of February 2025, the median follow-up time of patients was 39.5 months. The EFS of the non-CHT group was significantly better than that of the CHT group (P =0.038). There was no significant difference in OS between the two groups (P =0.442). Subgroup analysis showed that EFS in the non-CHT was longer in standard-risk patients (P =0.012). There was no significant difference in EFS (P =0.585) and OS (P =0.473) between the CHT and non-CHT groups in high-risk patients. The incidence of mild DS was 23.6% in the non-CHT group and 23.1% in the CHT group, respectively, with no statistically significant difference(P =0.937). Compared with CHT group, the incidence of serious adverse events was lower in the non-CHT group. CONCLUSION The non-chemotherapy regimen of ATRA combined with ATO is a feasible method to cure APL patients.
Humans ; Leukemia, Promyelocytic, Acute/drug therapy* ; Arsenic Trioxide/therapeutic use* ; Tretinoin/administration & dosage* ; Retrospective Studies ; Female ; Treatment Outcome ; Male ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Middle Aged ; Remission Induction

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

The dynamin superfamily protein (DSP) encompasses a group of large GTPases that are involved in various membrane remodeling processes within the cell. These proteins are characterized by their ability to hydrolyze GTP, which provides the energy necessary for their function in membrane fission, fusion, and tubulation activities. Dynamin superfamily proteins play critical roles in cellular processes such as endocytosis, organelle division, and vesicle trafficking. It is typically classified into classical dynamins and dynamin-related proteins (Drp), which have distinct roles and structural features. Understanding these proteins is crucial for comprehending their functions in cellular processes, particularly in membrane dynamics and organelle maintenance. Classical dynamins are primarily involved in clathrin-mediated endocytosis (CME), a process crucial for the internalization of receptors and other membrane components from the cell surface into the cell. These proteins are best known for their role in pinching off vesicles from the plasma membrane. Structually, classical dynamins are composed of a GTPase domain, a middle domain, a pleckstrin homology (PH) domain that binds phosphoinositides, a GTPase effector domain (GED), and a proline-rich domain (PRD) that interacts with SH3 domain-containing proteins. Functionally, the classical dynamins wrap around the neck of budding vesicles, using GTP hydrolysis to constrict and eventually acting as a “membrane scissor” to cut the vesicle from the membrane. In mammals, there are three major isoforms: dynamin 1 (predominantly expressed in neurons), dynamin 2 (ubiquitously expressed), and dynamin 3 (expressed in testes, lungs, and neurons). Recent studies have also revealed some non-classical functions of classical dynamins, such as regulating the initiation and stabilization of clathrin-coated pits (CCPs) at the early stages of CME, influencing the formation of the actin cytoskeleton and cell division. Drps share structural similarities with classical dynamins but are involved in a variety of different cellular processes, primarily related to the maintenance and remodeling of organelles, and can be mainly categorized into “mediating membrane fission”, “mediating membrane fusion” and “non-membrane-dependent functions”. Proteins like Drp1 are crucial for mitochondrial division, while others like Fis1, Mfn1, and Mfn2 are involved in mitochondrial and peroxisomal fission and fusion processes, which are essential for the maintenance of mitochondrial and peroxisomal integrity and affect energy production and apoptosis. Proteins like the Mx protein family exhibit antiviral properties by interfering with viral replication or assembly, which is critical for the innate immune response to viral infections. Some other proteins are involved in the formation of tubular structures from membranes, which is crucial for the maintenance of organelle morphology, particularly in the endoplasmic reticulum and Golgi apparatus. Studies on dynamin superfamily proteins have been extensive and have significantly advanced our understanding of cellular biology, disease mechanisms, and therapeutic potential. These studies encompass a broad range of disciplines, including molecular biology, biochemistry, cell biology, genetics, and pharmacology. By comprehensively summarizing and organizing the structural features and functions of various members of the dynamin superfamily protein, this review not only deepens the understanding of its molecular mechanisms, but also provides valuable insights for clinical drug research related to human diseases, potentially driving further advancements in the field.