Sleep is an instinctive behavior alternating awakening state, sleep entails many active processes occurring at the cellular, circuit and organismal levels. The function of sleep is to restore cellular energy, enhance immunity, promote growth and development, consolidate learning and memory to ensure normal life activities. However, with the increasing of social pressure involved in work and life, the incidence of sleep disorders (SD) is increasing year by year. In the short term, sleep disorders lead to impaired memory and attention; in the longer term, it produces neurological dysfunction or even death. There are many ways to directly or indirectly contribute to sleep disorder and keep the hormones, including pharmacological alternative treatments, light therapy and stimulus control therapy. Exercise is also an effective and healthy therapeutic strategy for improving sleep. The intensities, time periods, and different types of exercise have different health benefits for sleep, which can be found through indicators such as sleep quality, sleep efficiency and total sleep time. So it is more and more important to analyze the mechanism and find effective regulation targets during sleep disorder through exercise. Dopamine (DA) is an important neurotransmitter in the nervous system, which not only participates in action initiation, movement regulation and emotion regulation, but also plays a key role in the steady-state remodeling of sleep-awakening state transition. Appreciable evidence shows that sleep disorder on humans and rodents evokes anomalies in the dopaminergic signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Experiments have shown that DA in different neural pathways plays different regulatory roles in sleep behavior, we found that increasing evidence from rodent studies revealed a role for ventral tegmental area DA neurons in regulating sleep-wake patterns. DA signal transduction and neurotransmitter release patterns have complex interactions with behavioral regulation. In addition, experiments have shown that exercise causes changes in DA homeostasis in the brain, which may regulate sleep through different mechanisms, including cAMP response element binding protein signal transduction, changes in the circadian rhythm of biological clock genes, and interactions with endogenous substances such as adenosine, which affect neuronal structure and play a neuroprotective role. This review aims to introduce the regulatory effects of exercise on sleep disorder, especially the regulatory mechanism of DA in this process. The analysis of intracerebral DA signals also requires support from neurophysiological and chemical techniques. Our laboratory has established and developed an in vivo brain neurochemical analysis platform, which provides support for future research on the regulation of sleep-wake cycles by movement. We hope it can provide theoretical reference for the formulation of exercise prescription for clinical sleep disorder and give some advice to the combined intervention of drugs and exercise.

OBJECTIVE To prepare hyaluronic acid （HA）-modified emodin （EMD）-contained multi-walled carbon nanotubes （MWCNTs） drug delivery system （HA-MWCNTs-EMD） and explore its in vitro inhibitory effect on breast cancer cells. METHODS EMD was loaded onto MWCNTs to prepare a drug delivery system MWCNTs-EMD； subsequently， the system was further modified with HA to obtain the drug delivery system HA-MWCNTs-EMD. The two drug delivery systems mentioned above were characterized. With free EMD as the reference， the drug release in vitro of the above two drug delivery systems was investigated； the uptake of EMD by two breast cancer cells （MCF-7， MDA-MB-231 cells） was detected. The impacts of the above two drug delivery systems on the expression of surface glycoprotein differentiation group 44 （CD44）， activity， apoptosis and lactate dehydrogenase （LDH） release of two breast cancer cells were detected. RESULTS The encapsulation efficiencies of MWCNTs-EMD and HA-MWCNTs-EMD were both （63.52±2.74）%， with drug loading rates of （25.01±1.83）% and （12.13± 1.96）%， particle sizes of （865.95±2.16） and （351.86±1.68） nm， polydispersity indexes of 0.54±0.02 and 0.23±0.01， and Zeta potentials of （23.87±0.14） and （－42.79±0.39） mV， respectively. The 2， 4， 6， 8， 10， 12 and 24-hour cumulative release rates of EMD in MWCNTs-EMD and HA-MWCNTs-EMD were significantly lower than those in free EMD， while the cumulative release rate of HA-MWCNTs-EMD was significantly higher than that of MWCNTs-EMD （P＜0.05）； the EMD uptakes of MWCNTs-EMD and HA-MWCNTs-EMD by the two types of breast cancer cells were significantly higher than their uptake of free EMD （P＜0.05）. Compared with the free EMD group， the MWCNTs-EMD and MWCNTs-EMD groups showed significantly higher apoptosis rate and LDH release， significantly lower surface CD44 expression （except for the MWCNTs-EMD group） and cell viability in both cell types， and the effect of HA-MWCNTs-EMD was more pronounced （P＜0.05）. CONCLUSIONS A novel drug delivery system HA-MWCNTs- EMD loaded with EMD is developed successfully； the drug delivery system has a certain slow-release effect， which can significantly reduce the activity of breast cancer cells， promote their apoptosis and increase the release of LDH， and the above anti- breast cancer effect is significantly stronger than that of free EMD and MWCNTs-EMD.

This study developed a core outcome set(COS) for traditional Chinese medicine(TCM) interventions in diabetic peripheral neuropathy(DPN), standardizing evaluation metrics for TCM efficacy and providing a new framework for DPN treatment and management. A systematic search was conducted across databases, including CNKI, Wanfang, and PubMed, targeting clinical trial literature published between January 1, 2013, and January 1, 2023. The search focused on extracting outcome indicators and measurement tools used in TCM treatments for DPN. Retrospective data collection was performed from January 2018 to June 2023, involving 200 DPN patients hospitalized at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine. Additionally, semi-structured interviews were conducted with inpatients, outpatients, their families, and nursing staff to further refine and enhance the list of outcome indicators. After two rounds of Delphi questionnaire survey and consensus meeting, a consensus was reached. The study initially retrieved 3 421 publications, of which 170 met the inclusion criteria after review. These publications, combined with retrospective analysis and semi-structured interviews, supplemented the list of indicators. After two rounds of Delphi surveys, experts agreed on 24 indicators and 6 measurement tools. The final COS determined by expert consensus meeting included 5 domains and 13 outcome indicators: neurological function signs, quality of life, TCM syndrome score, nerve conduction velocity, current perception threshold test, fasting blood glucose, 2 h postprandial blood glucose, glycated hemoglobin, complete blood count, urinalysis, liver function test, kidney function test, and electrocardiogram.
Humans ; Diabetic Neuropathies/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Male ; Female

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

Objective： Varicocele (VC) induces male infertility by mediating changes in the testicular microenvironment, in which testicular hypoxia and high-pressure are important pathological conditions. This study aims to compare the mouse spermatogenesis (GC-2spd) cells and Sertoli (TM4) cells of mouse testis after hypoxic modeling and hypoxic and high-pressure combined modeling, and to explore the feasibility of establishing a hypoxic and high-pressure combined cell model. Methods： On the basis of cell hypoxia induced by CoCl2, the complex model of testicular cell hypoxia and high pressure was constructed by changing the osmotic pressure of GC-2 and TM4 cell medium with a high concentration of NaCl solution. After selecting the intervention concentration of CoCl2 by MTT test and detecting the expression level of HIF-1α for the determination of the optimal osmotic pressure conditions of the cell model, the cells were divided into normal group, hypoxia model group and composite model group. And the levels of OS, programmed cell death, inflammatory factors, and the expression levels of pyroptosis-related proteins were compared between the normal group and the groups with different modeling methods. Results： The optimal intervention concentration of CoCl2 in GC-2 and TM4 cells was 150 and 250μmol/L, respectively, and the expression of HIF-1α was the highest in both cells under osmotic pressure of 500 mOsmol/kg (P<0.05). Compared with the normal group, the SOD levels of GC-2 and TM4 cells decreased (all P<0.05), CAT level decreased (all P<0.05), and MDA level increased (all P<0.01), and the OS level of GC-2 and TM4 cells was more obvious than that of the hypoxia model group (all P<0.05). Compared with the normal group, apoptosis occurred in GC-2 and TM4 cells after composite modeling (all P<0.05). Compared with the normal group, the mRNA expressions of IL-1β, IL-18, TNF-α and COX-2 in GC-2 and TM4 cells significantly increased (P<0.01) and higher than those in hypoxia model group (P<0.05) and induced pyroptosis (P<0.01). The expression level of GSDMD increased (P<0.05). Conclusion： The cell model with hypoxia and high pressure combined modeling can not only induce oxidative stress and apoptosis of cells better than that with hypoxia alone, but also further cause inflammatory response damage and pyroptosis, which simulates the changes of testis microenvironment mediated by hypoxia and high pressure combined conditions in VC. This cell model can be used for studying the pathogenesis of VC-associated male infertility, evaluating drug efficacy, and exploring pharmacological mechanisms.
Male ; Animals ; Varicocele/pathology* ; Mice ; Testis/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Cell Hypoxia ; Cobalt ; Sertoli Cells/metabolism* ; Osmotic Pressure ; Spermatogenesis ; Cellular Microenvironment ; Infertility, Male ; Disease Models, Animal

Objective:To explore relevant factors to accurately diagnose BPPV in vertigo children. Methods:A retrospective study was conducted on the proportion of BPPV in children（<18 years） with vertigo who visited the Hearing and Vertigo Diagnosis and Treatment Center of Tianjin Medical University General Hospital from September 2017 to August 2023. The clinical characteristics of BPPV children, including general demographics, medical history, first visit department, comorbidities, canal involvement, response to treatment, and incidence of recurrence, were analyzed. Data analysis was conducted using SPSS 25.0 software. Results:BPPV was diagnosed in 22.8% of patients seen for vertigo during the study period. There are differences in the proportion of BPPV diagnosis among children with dizziness in different age groups（P<0.05）, and the diagnosis of BPPV in the 7-12-year-old group has a longer disease course than in the 13-17-year-old group（P<0.05）. 72.3%（47/65） of patients or their families were able to provide a typical history of positional vertigo. 49.2%（32/65） of BPPV patients had comorbidities, and there were differences in the proportion of comorbidities among different age groups of BPPV patients（P<0.05）. With the progress of study, the proportion of BPPV in children with vertigo has shown an upward trend, and the proportion of children with otolaryngology as the first diagnosis department has also increased（P<0.05）. The proportion of horizontal semicircular canals in children with BPPV has increased. All BPPV patients underwent canalith repositioning maneuvers, with good treatment outcomes and a recurrence rate of 12.3%（8/65）. The recurrence rate in the group of BPPV patients with comorbidities was 21.9%, which was higher than that in the group without comorbidities（P<0.05）. Conclusion:Childhood BPPV has clinical characteristics such as unclear medical history, high proportion of comorbidities, easy recurrence in BPPV children with comorbidities and high proportion of horizontal semicircular canal involvement. For children diagnosed with other vertigo diseases, do not ignore the BPPV diagnostic test. It is recommended to perform routine position tests on children with vertigo if conditions permit to reduce missed diagnosis of BPPV in children.
Humans ; Benign Paroxysmal Positional Vertigo/diagnosis* ; Child ; Retrospective Studies ; Adolescent ; Female ; Male ; Recurrence ; Vertigo/diagnosis* ; Comorbidity ; Child, Preschool

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Objective To observe the value of quantitative analysis technique for evaluating left atrial function in children with Kawasaki disease(KD).Methods Totally 43 children with KD(KD group)who would undergo intravenous immunoglobulin(IVIG)therapy were prospectively enrolled,including 23 with(ectasia subgroup)and 20 without coronary artery ectasia(non-ectasia subgroup),while 50 healthy children were enrolled as control group.Children in KD group.Echocardiography was performed in acute phase(10-12 hours before IVIG therapy),subacute phase(1 week after therapy)and convalescent phase(6-10 weeks after therapy)of KD.The left atrial reservoir strain(LASr),early diastolic conduit strain(LAScd),late diastolic contractile strain(LASct),left ventricular global longitudinal strain(LVGLS),basal segment,middle segment and apical segment longitudinal strain(LS)were measured.Strain parameters of different periods were compared between groups and subgroups in KD group,and left atrial strain parameters in KD subgroup were compared among different periods.Pearson correlation analysis was used for evaluation of the correlations of left atrium and left ventricle strain parameters in children with acute KD.Results LASr,LAScd,LASct,LVGLS and left ventricular segment LS of KD group in acute and subacute phase were all lower than those of control group(all P＜0.05),while the basal segment LS of KD group in convalescent phase was lower than that of control group(P＜0.05).In KD group,compared with acute stage,LASr,LAScd,LASct,LVGLS and left ventricular segment LS significantly increased in subacute phase(all P＜0.05),while in convalescent phase,LASr,LAScd,LASct,LVGLS,middle segment LS and apical LS further increased(all P＜0.05).LASr and LAScd in acute phase of KD group were positively correlated with LVGLS,middle segment LS and apical segment LS(r=0.43-0.67,all P＜0.05).In the acute and subacute phases,no significant difference of left artial LS parameters was found between subgroups within KD group(all P＞0.05).LASr and LAScd in convalescent phase of ectasia subgroup were lower than those of non-ectasia subgroup(all P＜0.05),while no significant difference of LASct was found between subgroups within KD group(P＞0.05).Conclusion Quantitative analysis technique could be used to evaluate left atrial function in KD children.Changes of left atrial function in KD children were closely related to left ventricular systolic function,which was affected by coronary artery ectasia in convalescent phase.