ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.

ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

OBJECTIVE: To investigate the effect of the sequence of intermediate instrumentation and distraction-reduction of the injured vertebra on the surgical efficacy of short-segment percutaneous pedicle screw fixation for thoracolumbar burst fractures with high rate of spinal canal encroachment. METHODS: From January 2016 to January 2022, 38 patients with thoracolumbar burst fractures with high rate of spinal canal encroachment (spinal canal encroachment rate >40%, complete posterior longitudinal ligament, no flipping bone block in the posterior marginal of the vertebra) without spinal cord injury who were were treated with short-segment percutaneous pedicle screw fixation were retrospectively analyzed. During the operation, 18 cases were used distraction-reduction first and then intermediate instrumentation on injured vertebral and sequential distraction-reduction again(the distraction-reduction first group) including 8 females and 10 males with a mean age of 46.5 (38.5, 50.0) years old, and the other 20 cases were used intermediate instrumentation on injured vertebral first and then direct distraction-reduction(the intermediate instrumentation first group) including 10 males and 10 females with a mean age of 46.0 (35.8, 50.8) years. The anterior height ratio of the injured vertebra, local Cobb's angle of the injured vertebrae, the spinal canal encroachment rate, and the improvement rate of spinal canal encroachment were compared and evaluated. RESULTS: All patients were followed up for more than 1 year, and no complications such as spinal cord and root injury, screw loosening and screw rod fracture were found. The anterior height ratio of the injured vertebra, local Cobb' angle of the injured vertebra in the two groups were significantly improved compared with preoperative data(P<0.05), and those at 3 months and 1 year after operation was lost compared with that at the previous time point(P<0.05). Although the spinal canal encroachment rate of the two groups 1 day and 1 year after operation was improved compared with that before operation(P<0.05), the improvement of spinal canal volume in the distraction-reduction first group was significantly better than that in the intermediate instrumentation first group (P<0.01). CONCLUSION In the treatment of patients with thoracolumbar fractures with high rate of spinal canal encroachment, short-segment percutaneous pedicle screw internal fixation with distraction-reduction first and then intermediate instrumentation and sequential distraction-reduction again can more effectively reduce the bony encroachment in the spinal canal and achieve indirect decompression effect better.
Humans ; Female ; Male ; Adult ; Middle Aged ; Spinal Fractures/surgery* ; Thoracic Vertebrae/surgery* ; Lumbar Vertebrae/surgery* ; Fracture Fixation, Internal/instrumentation* ; Pedicle Screws ; Retrospective Studies ; Spinal Canal/surgery*

The pandemic of coronavirus disease 2019 (COVID-19) has impacted our lifestyles. On the one hand, the patients with hematological malignancies (HM) are more vulnerable to COVID-19 infection. Once infected with COVID-19, these patients tend to develop into severe type with a higher mortality rate. Although patients with HM demonstrated a reduced response to COVID-19 vaccines, they still can benefit from vaccine injection with reduced rates of viral infection and incidence of severe cases. The combination of monoclonal antibodies and antiviral drugs is helpful to the COVID-19 treatment of patients with HM. On the other hand, COVID-19 infection can lead to a delay of hematopoietic recovery and low immunity in patients with HM. For HM patients with COVID-19 infection, to reduce the intensity and shorten the course of radiotherapy and chemotherapy is needed. This article will review the interaction between COVID-19 infection and HM.
Humans ; COVID-19/complications* ; Hematologic Neoplasms/complications* ; SARS-CoV-2

OBJECTIVES: A stable, reliable, and easily implementable clinical diagnostic method for marginal velopharyngeal insufficiency (MVPI) was established on the basis of the subjective hearing judgement of hypernasality and objective examination of velopharyngeal closure to address the lack of unified diagnostic criteria for MVPI. METHODS: Nasopharyngeal fiberscopy and speech assessment results were collected from postoperative patients with cleft palate. These results were used to analyze the differences in the distribution of nasal resonance in patients with different velopharyngeal closure ratios and the correlation between velopharyngeal closure ratios and nasal resonance status. Mild-to-moderate hypernasality with its corresponding elopharyngeal closure ratio was employed to establish the diagnostic criteria of MVPI. The reproducibility of the criteria and whether the patients with MVPI diagnosed by using the criteria exhibited significantly different speech characteristics compared with other patients were verified. RESULTS: A strong correlation was found between velopharyngeal closure ratios and nasal resonance (P<0.001). Mild-to-moderate hypernasality mainly corresponded to velopharyngeal closure ratios ranging from 90% to 99%, and the combination of the two characteristics as the diagnostic criteria for MVPI demonstrated good consistency (Kappa value=0.789, P<0.001). Moreover, under the diagnostic criteria, significant differences in nasal resonance (P<0.001), nasal emission (P=0.007), and misarticulation (P<0.001) were found between patients with velopharyngeal insufficiency and those with MVPI. CONCLUSIONS Combining the subjective hearing judgement of mild-to-moderate hypernasality with velopharyngeal closure ratios over 90% under nasopharyngeal fiberscopy provides a reliable and effective clinical method for diagnosing MVPI.
Humans ; Velopharyngeal Insufficiency/physiopathology* ; Reproducibility of Results ; Cleft Palate/surgery* ; Male ; Female ; Child

Medical device related infections caused by bacteria are common complications in clinical practice,and preventing bacterial colonization on the surface of medical materials is one of the important challenges in the medical field.Therefore,there is an urgent need to construct medical coatings that combine antibacterial properties and biocompatibility.In this study,a γ-polyglutamic acid(γ-PGA)complex with long-chain alkyl quaternary ammonium salts formed by electrostatic and hydrophobic interactions was prepared,which was insoluble in water but soluble in organic solvents(e.g.,ethanol),and was capable of constructing antimicrobial coatings on the surfaces of medical materials in a simple and efficient manner.The bactericidal effect of the coating was verified using viable bacteria counting experiments,and the results showed that the bactericidal rate of the coated thermoplastic polyurethane(TPU)membrane against Staphylococcus aureus was greater than 99.9%compared with that of the uncoated TPU membrane.In addition,a cytotoxicity assay was performed using the L929 fibroblast and cell proliferation detection kit(CCK-8),which showed that the survival rate of L929 fibroblasts on coated TPU was greater than 90%.Meanwhile,the hemolysis rate of coated erythrocytes was tested using fresh rabbit red blood cells(RBCs),and the hemolysis rate on the coated TPU surface was 1.5%.The above results indicated that the coating had good biocompatibility.The preparation method of medical antibacterial coating reported in this study provided a new idea for preventing bacterial infections related to implantable/interventional medical devices.

Objective:To analyze the correlation between bone metabolism indicators,ultrasound quantitative parameters,and prediction of osteoporosis fracture risk assessment tool(FRAX)in elderly patients with osteoporosis(OP).Methods:A total of eighty elderly patients with OP who admitted to Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine from December 2023 to December 2024 were selected.Based on the results of measuring bone quality by dual energy X-ray absorptiometry(DXA),they were divided into bone loss group(26 cases),moderate group(41 cases),and severe group(13 cases).All patients underwent measurements for N-terminal osteocalcin(N-MID OCN),total type I collagen N-terminal extended peptide(TP1NP),25 hydroxyvitamin D(25-OH VitD),parathyroid hormone(PTH),and β-collagen specific sequence(CROSSL)bone metabolism indicators when they were enrolled in groups.They underwent examinations of ultrasonic quantitative parameters included ultrasonic bone density(T value),ultrasound conduction velocity(SOS)and bone quality index(BQI),as well as FRAX prediction.The results of bone metabolism indicators,the examination of ultrasound quantitative parameter,and FRAX prediction were compared among the three groups of elderly patients with OP.Using Pearson linear correlation analysis analyzed the relationship among the three factors.Results:The N-MID OCN and 25-OH VitD levels in the severe group were lower respectively than those in the moderate group and the bone loss group,while the TP1NP,PTH,and CROSSL levels were higher than those in the moderate group and the bone less group,and the differences among the three groups were statistically significant(F=31.646,75.055,110.274,93.321,59.246,P<0.05).The T value,SOS,and BQI in the severe group were lower than those in the moderate group and the bone loss group,and the differences among the three groups were statistically significant(F=81.980,108.985,76.327,P<0.05).The levels of proximal humeral fracture(PHF)and postmenopausal osteoporosis fracture(PMOF)in the severe group were higher than those in the moderate group and the bone loss group,and the differences among the three groups were statistically significant(F=57.086,118.079,P<0.05).Pearson linear correlation analysis showed that the N-MID OCN and 25-OH VitD levels were positively correlated with T value,SOS,and BQI in elderly patients with OP(r=0.398,0.617,0.769,0.752,0.500,0.654,P<0.05),and were negatively correlated with PHF and PMOF(r=-0.504,-0.534,-0.572,-0.662,P<0.05).The TP1NP,PTH,CROSSL levels were negatively correlated with T value,SOS and BQI(r=-0.745,-0.751,-0.634,-0.733,-0.728,-0.569,-0.709,-0.648,-0.611,P<0.05),and were positively correlated with PHF and PMOF(r=0.612,0.558,0.602,0.700,0.695,0.740,P<0.05).Conclusion:The bone metabolism indicators of elderly patients with OP are correlated significantly with ultrasound quantitative parameters and FRAX prediction,which can be used as an important scheme in clinical assessment for bone strength and fracture risk.