BACKGROUND: Gait impairment is closely related to quality of life in patients with Parkinson's disease (PD). This study aimed to explore alterations in brain microstructure in PD patients and healthy controls (HCs) and to identify the correlation of gait impairment in the ON and OFF states of patients with PD, respectively. METHODS: We enrolled 24 PD patients and 29 HCs from the Movement Disorders Program at Beijing Friendship Hospital Capital Medical University between 2019 and 2020. We acquired magnetic resonance imaging (MRI) scans and processed the diffusion kurtosis imaging (DKI) images. Preprocessing of diffusion-weighted data was performed with Mrtrix3 software, using a directional distribution function to track participants' main white matter fiber bundles. Demographic and clinical characteristics were recorded. Quantitative gait and clinical scales were used to assess the status of medication ON and OFF in PD patients. RESULTS: The axial kurtosis (AK), mean kurtosis (MK), and radial kurtosis (RK) of five specific white matter fiber tracts, the bilateral corticospinal tract, left superior longitudinal fasciculus, left anterior thalamic radiation, forceps minor, and forceps major were significantly higher in PD patients compared to HCs. Additionally, the MK values were negatively correlated with Timed Up and Go Test (TUG) scores in both the ON and OFF in PD patients. Within the PD group, higher AK, MK, and RK values, whether the patients were ON or OFF, were associated with better gait performance (i.e., higher velocity and stride length). CONCLUSIONS PD exhibits characteristic regional patterns of white matter microstructural degradation. Correlations between objective gait parameters and DKI values suggest that dopamine-responsive gait function depends on preserved white matter microstructure. DKI-based Tract-Based Spatial Statistics (TBSS) analysis may serve as a tool for evaluating PD-related motor impairments (e.g., gait impairment) and could yield potential neuroimaging biomarkers.
Humans ; Parkinson Disease/diagnostic imaging* ; White Matter/physiopathology* ; Male ; Female ; Middle Aged ; Aged ; Gait/physiology* ; Diffusion Magnetic Resonance Imaging/methods* ; Diffusion Tensor Imaging/methods*

Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals ; MicroRNAs/physiology* ; Obesity/metabolism* ; Mice ; Adipose Tissue, White/metabolism* ; Metabolic Diseases ; Subcutaneous Fat/metabolism* ; Male ; Uncoupling Protein 1/metabolism* ; Diet, High-Fat ; Mice, Inbred C57BL

OBJECTIVES: To evaluate preterm white matter injury (PWMI) in neonatal rats using multimodal magnetic resonance imaging (MRI) combined with histological assessments and to explore its underlying mechanisms. METHODS: Healthy 3-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group and a PWMI group (n=12 in each group). A PWMI model was established in neonatal rats through hypoxia-ischemia. Laser speckle imaging was used to observe changes in cerebral oxygen saturation and blood flow at different time points post-modeling. Multimodal MRI was employed to assess the condition of white matter injury, while hematoxylin-eosin staining was utilized to observe morphological changes in the striatal area on the injured side. Immunofluorescence staining was performed to detect the proliferation and differentiation of oligodendrocyte precursor cells. RESULTS: At 0, 6, 12, 24, and 72 hours post-modeling, the relative blood flow and relative oxygen saturation on the injured side in the PWMI group were significantly lower than those in the sham operation group (P<0.05). At 24 hours post-modeling, T2-weighted imaging showed high signals in the white matter of the injured side in the PWMI group, with relative apparent diffusion coefficient values and Lorenz differential values being lower than those in the sham operation group (P<0.001); additionally, the arrangement of nerve cells in the PWMI group was disordered, and the number of EdU⁺PDGFR-α⁺ cells was higher than that in the sham operation group (P<0.001). At 28 days post-modeling, the relative fractional anisotropy values, the number of EdU⁺Olig2⁺ cells, and the fluorescence intensity of myelin basic protein and neurofilament protein 200 in the white matter region of the PWMI group were all lower than those in the sham operation group (P<0.001). CONCLUSIONS Multimodal MRI can evaluate early and long-term changes in PWMI in neonatal rat models in vivo, providing both imaging and pathological evidence for the diagnosis and treatment of PWMI in neonates. Hypoxia-ischemia inhibits the proliferation and differentiation of oligodendrocyte precursor cells in neonatal rats, leading to PWMI.
Animals ; Rats, Sprague-Dawley ; Magnetic Resonance Imaging/methods* ; Rats ; White Matter/injuries* ; Animals, Newborn ; Female ; Multimodal Imaging ; Male ; Hypoxia-Ischemia, Brain/pathology*

OBJECTIVES: To explore the relationship between white matter injury (WMI) and cerebral perfusion in preterm infants using arterial spin labeling (ASL). METHODS: A total of 293 preterm infants (gestational age <34 weeks) hospitalized at the Third Affiliated Hospital of Zhengzhou University between June 2022 and June 2024 were included. After achieving clinical stability, the infants underwent brain magnetic resonance imaging (MRI) and ASL. Based on MRI findings, infants were classified into WMI (n=66) and non-WMI (n=227) groups. Cerebral perfusion parameters were compared between groups, and the association between WMI and perfusion alterations was evaluated. RESULTS: The WMI group showed a higher incidence of mild intraventricular hemorrhage (IVH) than the non-WMI group (P<0.05). Significantly lower cerebral perfusion was observed in the WMI group across bilateral frontal, temporal, parietal, and occipital lobes, as well as the basal ganglia and thalamus (P<0.05). After adjusting for gestational age, corrected gestational age at ASL scan, and mild IVH, WMI remained significantly associated with reduced regional perfusion (P<0.05). CONCLUSIONS WMI in preterm infants correlates with localized cerebral hypoperfusion. ASL-detected perfusion abnormalities may provide novel insights into WMI pathogenesis.
Humans ; White Matter/blood supply* ; Infant, Newborn ; Spin Labels ; Infant, Premature ; Female ; Male ; Cerebrovascular Circulation ; Magnetic Resonance Imaging

White matter injury (WMI) is a major form of brain injury in preterm infants. Its characteristic pathological features primarily involve impaired development of oligodendrocyte precursor cells and structural damage to axons, which can lead to the neurological sequelae such as motor, behavioral, and cognitive dysfunctions. Chondroitin sulfate proteoglycans (CSPGs), as the important components of extracellular matrix, can participate in neuroinflammatory response mediated by microglial cells and dynamically balance glial scar reconstruction and axon growth by regulating specific receptors and signaling pathways. This article reviews the relationship between CSPGs and WMI, as well as the mechanisms by which CSPGs inhibit axon growth, focusing on the role of multi-target regulation of CSPGs in promoting axon plasticity and functional brain recovery, thereby providing a theoretical basis for improving the prognosis of preterm infants with WMI.
Humans ; Chondroitin Sulfate Proteoglycans/physiology* ; White Matter/pathology* ; Axons/physiology* ; Infant, Premature ; Infant, Newborn ; Animals

OBJECTIVES: To investigate whether mesenchymal stem cell-derived exosomes (MSC-Exo) alleviate white matter damage (WMD) in neonatal rats by targeting the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). METHODS: Three-day-old Sprague-Dawley rats were randomly assigned to four groups: Sham, hypoxia-ischemia (HI), MSC-Exo, and MCC950 (NLRP3 inhibitor) (n=24 per group). The WMD model was established by unilateral common carotid artery ligation combined with hypoxia. Exosomes (1×10⁸ particles/μL) were transplanted into the lateral ventricle using stereotaxic guidance. Fourteen days after modeling, hematoxylin-eosin staining was used to observe pathological changes in brain tissue, and transmission electron microscopy was used to assess myelinated axons. Western blotting was performed to detect the expression of myelin basic protein (MBP), NLRP3, caspase-1, and interleukin-1β (IL-1β). Immunohistochemistry was used to measure NLRP3, caspase-1, and IL-1β expression. Twenty-eight days post-modeling, behavioral changes were evaluated using the Morris water maze. RESULTS: In the HI group, marked inflammatory cell infiltration, extensive vacuolation, and decreased numbers of myelinated axons were observed compared to the Sham group. The MSC-Exo group showed reduced inflammatory infiltration, fewer vacuoles, and increased myelinated axons compared to the HI group, while the MCC950 group showed nearly normal cell morphology. Compared to the Sham group, the HI group exhibited decreased MBP expression, fewer platform crossings, shorter time in the target quadrant, increased expression of NLRP3, caspase-1, and IL-1β, and longer escape latency (all P<0.05). Compared to the HI group, the MSC-Exo and MCC950 groups showed increased MBP expression, more platform crossings, longer target quadrant stay, and reduced NLRP3, caspase-1, and IL-1β expression, as well as shorter escape latency (all P<0.05). CONCLUSIONS MSC-Exo may attenuate white matter damage in neonatal rats by targeting the NLRP3 inflammasome and promoting oligodendrocyte maturation.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors* ; Rats, Sprague-Dawley ; White Matter/pathology* ; Inflammasomes/physiology* ; Rats ; Animals, Newborn ; Mesenchymal Stem Cells ; Interleukin-1beta/analysis* ; Male ; Caspase 1/analysis* ; Hypoxia-Ischemia, Brain/therapy* ; Myelin Basic Protein/analysis*

OBJECTIVES: To investigate the risk factors for white matter damage (WMD) in preterm infants with necrotizing enterocolitis (NEC). METHODS: A retrospective analysis was conducted on the clinical data of 249 preterm infants with NEC admitted to Children's Hospital of Fudan University between January 2021 and December 2023. Based on brain magnetic resonance imaging (MRI) white matter scores, the infants were categorized into a WMD group (≥7 points) and a non-injury group (<7 points). A multivariable logistic regression analysis was performed to identify risk factors for WMD. RESULTS: Compared with the non-injury group, the WMD group had significantly higher rates of Gram-negative bacterial infection (43.1% vs 28.2%), surgical treatment (47.2% vs 23.2%), and moderate-to-severe abnormalities on video electroencephalography (VEEG) (51.4% vs 11.9%) (all P<0.05). The multivariable logistic regression analysis showed that surgical treatment (OR=1.822, 95%CI: 1.199-2.777), longer hospital stay (OR=1.041, 95%CI: 1.004-1.080), and moderate-to-severe VEEG abnormalities (OR=7.045, 95%CI: 3.349-14.855) were independent risk factors for WMD (all P<0.05). CONCLUSIONS Surgical treatment, prolonged hospitalization, and moderate-to-severe VEEG abnormalities are independent risk factors for WMD in preterm infants with NEC, providing a basis for early clinical identification and intervention to improve neurological outcomes.
Humans ; Enterocolitis, Necrotizing/complications* ; Infant, Newborn ; Male ; Female ; Risk Factors ; Retrospective Studies ; Infant, Premature ; White Matter/diagnostic imaging* ; Logistic Models ; Magnetic Resonance Imaging

OBJECTIVES: To investigate whether human umbilical cord mesenchymal stem cells (HUC-MSCs) play protective effects against white matter injury (WMI) in neonatal rats via activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/heme oxygenase-1 (HO-1) signaling pathway. METHODS: A neonatal WMI model was established in 3-day-old Sprague-Dawley rats by unilateral common carotid artery ligation combined with hypoxia. The study comprised two parts. (1) Rats were randomized into sham, hypoxia-ischemia (HI), and HUC-MSC groups (n=36 per group); brain tissues were collected at 7, 14, and 21 days after modeling. (2) Rats were randomized into sham, HI, HUC-MSC, and HUC-MSC+ML385 (Nrf2 inhibitor) groups (n=12 per group); tissues were collected 14 days after modeling. Hematoxylin-eosin staining assessed histopathology, and Luxol fast blue staining evaluated myelination. Immunohistochemistry examined the localization and expression of Nrf2, myelin basic protein (MBP), and proteolipid protein (PLP). Immunofluorescence assessed synaptophysin (SYP) and postsynaptic density-95 (PSD-95). Western blotting quantified Nrf2, Keap1, HO-1, SYP, PSD-95, MBP, and PLP. Spatial learning and memory were evaluated by the Morris water maze. RESULTS: At 7, 14, and 21 days after modeling, the sham group showed intact white matter, whereas the HI group exhibited white matter disruption, cellular vacuolation, and disorganized nerve fibers. These pathological changes were attenuated in the HUC-MSC group. Compared with the HI group, the HUC-MSC group showed increased Nrf2 immunopositivity and protein levels, increased HO-1 protein levels, and decreased Keap1 protein levels (P<0.05). Compared with the HI group, the HUC-MSC group had higher SYP and PSD-95 immunofluorescence intensities and protein levels, higher MBP and PLP positivity and protein levels, increased mean optical density of myelin, more platform crossings, and longer time in the target quadrant (all P<0.05). These improvements were reduced in the HUC-MSC+ML385 group compared with the HUC-MSC group (P<0.05). CONCLUSIONS HUC-MSCs may promote oligodendrocyte maturation and synaptogenesis after neonatal WMI by activating the Nrf2/Keap1/HO-1 pathway, thereby improving spatial cognitive function.
NF-E2-Related Factor 2/physiology* ; Animals ; Rats, Sprague-Dawley ; Signal Transduction/physiology* ; Humans ; Rats ; White Matter/pathology* ; Kelch-Like ECH-Associated Protein 1/physiology* ; Umbilical Cord/cytology* ; Heme Oxygenase-1/physiology* ; Animals, Newborn ; Male ; Mesenchymal Stem Cell Transplantation ; Heme Oxygenase (Decyclizing)/physiology* ; Mesenchymal Stem Cells/physiology* ; Female ; Hypoxia-Ischemia, Brain

OBJECTIVE: To study the genetic polymorphism of red blood cell blood group among in Shenzhen Han, Indian and Xinjiang Uyghur populations, to provide scientific basis for the demand prediction and collection strategy of rare blood group, and to explore the genetic differences of blood group between Han and Caucasians. METHODS: The haplotypes of antigen coding genes of 10 target blood group systems from 87 Han Chinese and 50 Indian blood donors in Shenzhen, and 49 healthy Uyghur people in Xinjiang were obtained by three-generation sequencing technology, and the polymorphism and frequency characteristics were analyzed. RESULTS: Only a single genotype was detected the Langereis and Vel blood group systems in samples from three different populations. Only one genotype of Dombrock blood group was detected in Shenzhen Han, and Junior blood group in Xinjiang Uygur populations. In the MNS, Duffy, Kidd, Dombrock and Junior blood group systems, the haplotype frequency of Indian and Uyghur people was significantly different from that of Han people. Compared with the Han ethnic group, the rare blood group s-, Fy(a-), Jk(a-b-), and Do(a+b-) have a higher frequency among the Uyghur and Indian populations. CONCLUSION Haplotype frequencies of antigen genes for MNS, Duffy, Kidd, Dombrock and Junior blood group system in Shenzhen Han, Indian and Uyghur populations displayed a polymorphic difference with unique distribution characteristics different from the ethnic groups in other regions.
Humans ; Blood Group Antigens/genetics* ; China/ethnology* ; Erythrocytes ; Ethnicity/genetics* ; Gene Frequency ; Genotype ; Haplotypes ; India/ethnology* ; Polymorphism, Genetic ; White People/genetics* ; Central Asian People/genetics* ; East Asian People/genetics*

OBJECTIVES: To analyze the differences in the prognosis of gastric signet ring cell carcinoma (SRCC) among different races using the US Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database. METHODS: We analyzed the data of patients with gastric SRCC from the SEER database from 2000 to 2020, and divided the patients into cohorts of whites, blacks, Asians or Pacific Islanders, American Indians/Alaska Natives according to their race. The prognosis and treatment of the cohorts were evaluated using baseline demographic analysis, Kamplan-Meier survival curve, and nomogram analysis. RESULTS: We analyzed the data of a total of 2058 patients, including 8.6% blacks, 72.4% whites, 16.6% Asians or Pacific Islanders, 1.0% American Indians/Alaska Natives, and 1.4% other races. The tumor grade varied among different races, and the prevalence and survival rates of patients differed significantly across races. The differences in the white cohort were the most prominent, and all the differences were statistically significant (P<0.05). Racial differences were also noted in patient management and prognosis. CONCLUSIONS There are racial differences in tumor grades and prognosis of gastric SRCC, and these differences provide evidence for optimizing clinical diagnosis and treatment strategies for this malignancy.
Aged ; Female ; Humans ; Male ; Middle Aged ; Carcinoma, Signet Ring Cell/therapy* ; Databases, Factual ; Prognosis ; Racial Groups ; SEER Program ; Stomach Neoplasms/therapy* ; Survival Rate ; United States/epidemiology* ; White ; Asian American Native Hawaiian and Pacific Islander ; American Indian or Alaska Native ; Black or African American