Publications by authors named "Jingping Shi"

53 Publications

Drainage of senescent astrocytes from brain via meningeal lymphatic routes.

Brain Behav Immun 2022 Apr 12;103:85-96. Epub 2022 Apr 12.

Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China; Department of Neurology, the Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, 210029, China; Center for Global Health, Nanjing Medical University, Nanjing, 211166, China. Electronic address:

Recent progress on the central lymphatic system has greatly increased our understanding of how the brain maintains its own waste homeostasis. Here, we showed that perivascular spaces and meningeal lymphatic vessels form a functional route for clearance of senescent astrocytes from the aging brain. Blocking meningeal lymphatic drainage by ligation of the deep cervical lymph nodes impaired clearance of senescent astrocytes from brain parenchyma, subsequently increasing neuroinflammation in aged mice. By contrast, enhancing meningeal lymphatic vessel diameter by a recombinant adeno-associated virus encoding mouse vascular endothelial growth factor-C (VEGF-C) improved clearance of senescent astrocytes and mitigated neuroinflammation. Mechanistically, VEGF-C was highly expressed in senescent astrocytes, contributing themselves to migrate across lymphatic vessels along C-C motif chemokine ligand 21 (CCL21) gradient by interacting with VEGF receptor 3. Moreover, intra-cisternal injection of antibody against CCL21 hampered senescent astrocytes into the lymphatic vessels and exacerbated short memory defects of aged mice. Together, these findings reveal a new perspective for the meningeal lymphatics in the removal of senescent astrocytes, thus offering a valuable target for therapeutic intervention.
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http://dx.doi.org/10.1016/j.bbi.2022.04.005DOI Listing
April 2022

An immune subtype-related prognostic signature of hepatocellular carcinoma based on single-cell sequencing analysis.

Aging (Albany NY) 2022 Apr 12;14(7):3276-3292. Epub 2022 Apr 12.

Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and is often associated with a poor prognosis. The main reason for this poor prognosis is that inconspicuous early symptoms lead to delayed diagnosis. Treatment options for advanced HCC remain limited and ineffective. In this context, the exploration of the immune microenvironment in HCC becomes attractive. In this study, we divided HCC into immune cell and non-immune cell subtypes, by single-cell sequencing analysis of GEO dataset GSE146115. We found differentially expressed genes in the two subtypes, which we used to construct a prognostic model for HCC through Cox and Lasso regressions. Our prognostic model can accurately evaluate the prognosis of HCC patients, and provide a reference for the design of immunotherapy for HCC.
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http://dx.doi.org/10.18632/aging.204012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037256PMC
April 2022

Correction to: Endoscope-Assisted Minimally Invasive Surgery for the Treatment of Glandular Gynecomastia.

Aesthetic Plast Surg 2022 Mar 21. Epub 2022 Mar 21.

Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.

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http://dx.doi.org/10.1007/s00266-022-02862-2DOI Listing
March 2022

A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases.

Front Immunol 2022 15;13:847624. Epub 2022 Feb 15.

Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

Background: Uveal melanoma(UVM) is the most common intraocular malignancy and has a poor prognosis. The clinical significance of necroptosis(NCPS) in UVM is unclear.

Methods: We first identified necroptosis genes in UVM by single-cell analysis of the GSE139829 dataset from the GEO database and weighted co-expression network analysis of TCGA data. COX regression and Lasso regression were used to construct the prognostic model. Then survival analysis, immune microenvironment analysis, and mutation analysis were carried out. Finally, cell experiments were performed to verify the role of ITPA in UVM.

Result: By necroptosis-related prognostic model, UVM patients in both TCGA and GEO cohorts could be classified as high-NCPS and low-NCPS groups, with significant differences in survival time between the two groups (P<0.001). Besides, the high-NCPS group had higher levels of immune checkpoint-related gene expression, suggesting that they might be more likely to benefit from immunotherapy. The cell experiments confirmed the role of ITPA, the most significant gene in the model, in UVM. After ITPA was knocked down, the activity, proliferation, and invasion ability of the MuM-2B cell line were significantly reduced.

Conclusion: Our study can provide a reference for the diagnosis and treatment of patients with UVM.
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http://dx.doi.org/10.3389/fimmu.2022.847624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886618PMC
May 2022

Endoscope-Assisted Minimally Invasive Surgery for the Treatment of Glandular Gynecomastia.

Aesthetic Plast Surg 2022 Mar 2. Epub 2022 Mar 2.

Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.

Background: Gynecomastia (GYN) is the most common benign disease in males. A vacuum-assisted biopsy is a minimally invasive surgical technique for GYN treatment that achieves satisfactory aesthetic results. However, due to the operation under non-direct vision, it is difficult to localize the bleeding points and assess the residual glandular tissue. Endoscopy was applied to observe the operative field after subcutaneous mastectomy. The present study aimed to recommend our initial experience in glandular GYN with endoscope-assisted minimally invasive subcutaneous mastectomy.

Methods: A total of 34 patients diagnosed with glandular GYN (50 breasts), treated with endoscope-assisted minimally invasive surgery at The First Affiliated Hospital with Nanjing Medical University between June 2018 and June 2020, were enrolled in this study. According to Simon's classification of the breast, 10 was grade I, 25 was grade IIA, and 15 was grade IIB. The characteristics of patients, operative data, postoperative complications, cosmetic outcome, and patient satisfaction were recorded.

Results: Endoscope-assisted minimally invasive mastectomy was performed successfully in all cases. The operative duration of the operation was 55-120 min/side. The total weight of the resected tissue of the 50 breasts was 55-350 g, and the blood loss was 10-105 mL/breast. Endoscopy detected five breasts with bleeding and three with residual glandular during the operation. Postoperative bleeding occurred in 1 breast, subcutaneous seroma in 3 breasts, dysesthesia of the nipple-areolar complex in 2 breasts, and skin redundancy in a bilateral patient. None of the patients experienced severe pain, infection, nipple necrosis, and nipple retraction, a saucer-like deformity. With a median follow-up of 21 months, all patients were satisfied with their cosmetic outcome (100%), and no recurrence occurred.

Conclusion: Endoscope-assisted minimally invasive mastectomy could be used as a feasible technique for the treatment of glandular GYN.

Level Of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online. Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-022-02807-9DOI Listing
March 2022

A novel long-term intravenous combined with local treatment with human amnion-derived mesenchymal stem cells for a multidisciplinary rescued uremic calciphylaxis patient and the underlying mechanism.

J Mol Cell Biol 2022 Feb 10. Epub 2022 Feb 10.

Department of Obstetrics, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis, with high mortality and no proven therapy. Here, we reported a severe uremic calciphylaxis patient with progressive skin ischemia, large areas of painful malodorous ulcers, and mummified legs. Because of the worsening symptoms and signs refractory to conventional therapies, treatment with human amnion-derived mesenchymal stem cells (hAMSCs) was approved. Pre-clinical release inspections of hAMSCs, efficacy, and safety assessment including cytokine secretory ability, immunocompetence, tumorigenicity, and genetics analysis in vitro were introduced. We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats, abnormal immune response tests in C57BL/6 mice, and tumorigenicity tests in neonatal Balbc-nu nude mice. After the pre-clinical research, the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers. When followed up to 15 months, the blood-based markers of bone and mineral metabolism improved, with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells. Skin biopsy after 1-month treatment showed vascular regeneration with mature non-calcified vessels within the dermis, and 20 months later, the re-epithelialization restored the integrity of the damaged site. No infusion or local treatment-related adverse events occurred. Thus, this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis with effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, anti-inflammatory and immune modulation, multi-differentiation, re-epithelialization, and restoration of integrity.
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http://dx.doi.org/10.1093/jmcb/mjac010DOI Listing
February 2022

Clinical significance of anti-SSA/Ro antibody in Neuromyelitis optica spectrum disorders.

Mult Scler Relat Disord 2022 Feb 10;58:103494. Epub 2022 Jan 10.

Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS), also described as CNS autoimmune astrocytopathy, due to the production of pathogenic antibodies against aquaporin-4 (AQP4) expressed on the foot of astrocytes. NMOSD coexists with autoimmune diseases and related autoantibodies [anti-Sjogren's syndrome A (anti-SSA)/Ro antibody, anti-Sjogren's syndrome B (anti-SSB)/La antibody, anti-nuclear (anti-ANA) antibodies, anti-double-stranded DNA (anti-dsDNA) antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody].

Objectives: No precise conclusion has been drawn on the role of the anti-SSA/Ro antibody in NMOSD. Therefore, the aim of this work was to evaluate whether the anti-SSA/Ro antibody has an impact on the clinical manifestation or prognosis of NMOSD.

Methods: Data were retrospectively collected from 102 patients with NMOSD diagnosed by experienced neurologists. The study population was divided into two groups based on the serum anti-SSA/Ro antibody status: NMOSD with or without anti-SSA/Ro antibody. The clinical, neuroimaging and laboratory parameters were compared between the two groups, including the neurological symptoms, MRI results, frequency of systemic autoantibodies, Expanded Disability Status Scale (EDSS), and NMOSD relapse rate. The EDSS and relapse were applied as measures of the NMOSD patient prognostic value. Cox regression analysis was used to evaluate the prognostic impact of anti-SSA/Ro antibody on NMOSD.

Results: Among the 102 NMOSD patients, striking differences were observed in the positive rate of AQP4-IgG (89.2% vs. 72.3%, p = 0.046) between those patients with and without the anti-SSA/Ro antibody. In addition, NMOSD patients with anti-SSA/Ro antibody showed the presence of more frequent anti-ANA antibodies (p = 0.002), anti-SSB/La antibody (p < 0.001), anti-dsDNA antibody (p < 0.002), Sjogren's syndrome (SS, p < 0.001) and systemic lupus erythematosus (SLE, p = 0.045). Univariate and multivariate Cox regression analysis were performed to confirm that the anti-SSA/Ro antibody affected the EDSS score and the relapse of NMOSD patients. The analysis of the survival curve revealed that the EDSS score in the NMOSD patients positive for the anti-SSA/Ro antibody reached 4.0 (p = 0.035) and relapsed (p = 0.039) earlier than in the negative group.

Conclusion: The anti-SSA/Ro antibody could be associated with disease activity and severe disability in NMOSD.
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http://dx.doi.org/10.1016/j.msard.2022.103494DOI Listing
February 2022

Altered effective connectivity in migraine patients during emotional stimuli: a multi-frequency magnetoencephalography study.

J Headache Pain 2022 Jan 15;23(1). Epub 2022 Jan 15.

Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.

Background: Migraine is a common and disabling primary headache, which is associated with a wide range of psychiatric comorbidities. However, the mechanisms of emotion processing in migraine are not fully understood yet. The present study aimed to investigate the neural network during neutral, positive, and negative emotional stimuli in the migraine patients.

Methods: A total of 24 migraine patients and 24 age- and sex-matching healthy controls were enrolled in this study. Neuromagnetic brain activity was recorded using a whole-head magnetoencephalography (MEG) system upon exposure to human facial expression stimuli. MEG data were analyzed in multi-frequency ranges from 1 to 100 Hz.

Results: The migraine patients exhibited a significant enhancement in the effective connectivity from the prefrontal lobe to the temporal cortex during the negative emotional stimuli in the gamma frequency (30-90 Hz). Graph theory analysis revealed that the migraine patients had an increased degree and clustering coefficient of connectivity in the delta frequency range (1-4 Hz) upon exposure to positive emotional stimuli and an increased degree of connectivity in the delta frequency range (1-4 Hz) upon exposure to negative emotional stimuli. Clinical correlation analysis showed that the history, attack frequency, duration, and neuropsychological scales of the migraine patients had a negative correlation with the network parameters in certain frequency ranges.

Conclusions: The results suggested that the individuals with migraine showed deviant effective connectivity in viewing the human facial expressions in multi-frequencies. The prefrontal-temporal pathway might be related to the altered negative emotional modulation in migraine. These findings suggested that migraine might be characterized by more universal altered cerebral processing of negative stimuli. Since the significant result in this study was frequency-specific, more independent replicative studies are needed to confirm these results, and to elucidate the neurocircuitry underlying the association between migraine and emotional conditions.
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http://dx.doi.org/10.1186/s10194-021-01379-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903691PMC
January 2022

Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases Identified That TNC Is a Novel Biomarker for Keloid.

Front Immunol 2021 22;12:783907. Epub 2021 Dec 22.

Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: The pathophysiology of keloid formation is not yet understood, so the identification of biomarkers for kelod can be one step towards designing new targeting therapies which will improve outcomes for patients with keloids or at risk of developing keloids.

Methods: In this study, we performed single-cell RNA sequencing analysis, weighted co-expression network analysis, and differential expression analysis of keloids based on public databases. And 3 RNA sequencing data from keloid patients in our center were used for validation. Besides, we performed QRT-PCR on keloid tissue and adjacent normal tissues from 16 patients for further verification.

Results: We identified the sensitive biomarker of keloid: Tenascin-C (TNC). Then, Pseudotime analysis found that the expression level of TNC decreased first, then stabilized and finally increased with fibroblast differentiation, suggesting that TNC may play an potential role in fibroblast differentiation. In addition, there were differences in the infiltration level of macrophages M0 between the TNC-high group and the TNC-low group. Macrophages M0 had a higher infiltration level in low TNC- group (P<0.05).

Conclusion: Our results can provide a new idea for the diagnosis and treatment of keloid.
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http://dx.doi.org/10.3389/fimmu.2021.783907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728089PMC
February 2022

Construction and validation of the diagnostic model of keloid based on weighted gene co-expression network analysis (WGCNA) and differential expression analysis.

J Plast Surg Hand Surg 2022 Jan 8:1-9. Epub 2022 Jan 8.

Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Keloid is a disease that seriously affects the aesthetic appearance of the body. In contrast to normal skin or hypertrophic scars, keloid tissue extends beyond the initial site of injury. Patients may complain of pain, itching, or burning. Although multiple treatments exist, none is uniformly successful. Genetic advances have made it possible to explore differences in gene expression between keloids and normal skin. Identifying the biomarker for keloid is beneficial to the mechanism exploration and treatment development of keloid. In this study, we identified seven genes with significant differences in keloids through weighted gene co-expression network analysis(WGCNA) and differential expression analysis. Then, by the Lasso regression, we constructed a keloid diagnostic model using five of these genes. Further studies found that keloids could be divided into high-risk and low-risk groups by this model, with differences in immunity, m6A methylation, and pyroptosis. Finally, we verified the accuracy of the diagnostic model in clinical RNA-sequencing data.
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http://dx.doi.org/10.1080/2000656X.2021.2024557DOI Listing
January 2022

Comparison of Serum Triiodothyronine with Biomarkers for Alzheimer's Disease Continuum in Euthyroid Subjects.

J Alzheimers Dis 2022 ;85(2):605-614

Jiangsu Province, Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.

Background: Accumulating studies have implicated thyroid dysfunction in the pathogenesis of Alzheimer's disease (AD).

Objective: This study aimed to explore the association between thyroid hormone (TH) levels and cerebrospinal fluid (CSF) biomarkers for AD continuum among euthyroid subjects.

Methods: In all, 93 clinically euthyroid subjects with a cognitive decline were included in this prospective cross-sectional study and were divided into groups with abnormal AD biomarkers (belonging to the "Alzheimer's continuum"; A+ patients) and those with "normal AD biomarkers" or "non-AD pathological changes" (A-patients), according to the ATN research framework classification for AD. A partial correlation analysis of serum thyroid-stimulating hormone (TSH) or TH levels with CSF biomarkers was conducted. The predictor for A+ patients was analyzed via binary logistic regressions. Finally, the diagnostic significance of individual biochemical predictors for A+ patients was estimated via receiver operating characteristic curve analysis.

Results: Serum total triiodothyronine (TT3) and free triiodothyronine (FT3) levels were found to affect the levels of CSF amyloid-β (Aβ)42 and the ratios of Aβ42/40. Further, FT3 was found to be a significant predictor for A+ via binary logistic regression modeling. Moreover, FT3 showed a high diagnostic value for A+ in euthyroid subjects.

Conclusion: Even in a clinical euthyroid state, low serum FT3 and TT3 levels appear to be differentially associated with AD-specific CSF changes. These data indicate that serum FT3 is a strong candidate for differential diagnosis between AD continuum and non-AD dementia, which benefits the early diagnosis and effective management of preclinical and clinical AD patients.
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http://dx.doi.org/10.3233/JAD-215092DOI Listing
February 2022

Systemic inflammasome activation and pyroptosis associate with the progression of amnestic mild cognitive impairment and Alzheimer's disease.

J Neuroinflammation 2021 Dec 2;18(1):280. Epub 2021 Dec 2.

Department of Neurology, Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing, 210029, Jiangsu, China.

Background: Growing evidence indicates that inflammasome-mediated inflammation plays important roles in the pathophysiology of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). Pyroptosis induced by inflammasome, and Gasdermin D (GSDMD) is involved in several neurodegenerative disorders. However, it is not clear whether peripheral inflammasome and pyroptosis are activated in aMCI and AD patients, influencing on neuroinflammation. The aim of this study was to examine the association between systemic inflammasome-induced pyroptosis and clinical features in aMCI and AD.

Methods: A total of 86 participants, including 33 subjects with aMCI, 33 subjects with AD, and 20 cognitively normal controls, in this study. The Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale were used for cognitive assessment. Levels of inflammasome-related genes/proteins in peripheral blood mononuclear cells (PBMCs) were determined using quantitative polymerase chain reaction and Western blotting. The levels of IL-1β, Aβ1-42, Aβ1-40, p-tau, and t-tau in cerebrospinal fluid (CSF), as well as the plasma IL-1β level, were measured by enzyme-linked immunosorbent assay. Finally, lipopolysaccharides (LPS) were used to investigate the effects of systemic inflammasome-induced pyroptosis in an AD mice model.

Results: Several genes involved in the inflammatory response were enriched in PBMCs of AD patients. The mRNA and protein levels of NLRP3, caspase-1, GSDMD, and IL-1β were increased in PBMCs of aMCI and AD patients. The IL-1β level in plasma and CSF of aMCI and AD patients was significantly higher than that in controls and negatively correlated with the CSF Aβ1-42 level, as well as MMSE and MoCA scores. Furthermore, there was a positive correlation between the IL-1β level in plasma and CSF of aMCI or AD patients. In vivo experiments showed that systemic inflammasome-induced pyroptosis aggravated neuroinflammation in 5 × FAD mice.

Conclusions: Our findings showed that canonical inflammasome signaling and GSDMD-induced pyroptosis were activated in PBMCs of aMCI and AD patients. In addition, the proinflammatory cytokine IL-1β was strongly associated with the pathophysiology of aMCI and AD. As such, targeting inflammasome-induced pyroptosis may be a new approach to inhibit neuroinflammation in aMCI and AD patients.
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http://dx.doi.org/10.1186/s12974-021-02329-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638109PMC
December 2021

Analysis of Multiple Human Tumor Cases Reveals the Carcinogenic Effects of PKP3.

J Healthc Eng 2021 25;2021:9391104. Epub 2021 Oct 25.

The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.

Plakophilins (PKPs) act as a key regulator of different signaling programs and control a variety of cellular processes ranging from transcription, protein synthesis, growth, proliferation, and tumor development. The function and possible mechanism of PKP3 in ovarian cancer (OC) remain unknown. It is extremely important to investigate the expression and prognostic values of PKP3, as well as their possible mechanisms, and immune infiltration in OC. Therefore, in this paper we explored the potential oncogenic role of PKP3 in 33 tumors based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The result outcomes showed that PKP3 is highly expressed in most cancers, and the expression level and prognosis of PKP3 showed little significance in cancer patients. Moreover, oncologists have found that members of the plakophilin family have different degrees of abnormality in ovarian cancer. PKP3 played a key part in carcinogenesis and aggressiveness of OC as well as malignant biological activity and can be used as a biomarker for early diagnosis and prognosis evaluation in OC.
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http://dx.doi.org/10.1155/2021/9391104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560240PMC
March 2022

A Novel Pyroptosis-Related lncRNA Signature for Predicting the Prognosis of Skin Cutaneous Melanoma.

Int J Gen Med 2021 8;14:6517-6527. Epub 2021 Oct 8.

Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Purpose: To construct a prognosis model of melanoma based on pyroptosis related genes.

Methods: Melanoma RNA-sequencing data was downloaded from TCGA. First, the lnRNAs related to pyroptosis were obtained through Pearson correlation analysis. Then, the prognosis model of pyroptosis related genes was constructed by Cox regression and Lasso regression. Melanoma patients were divided into high-risk and low-risk groups by risk score, and the differences in prognosis and immune microenvironment between the two groups were explored.

Results: We found that the high-risk group had a significantly poorer prognosis, and different groups differed in immune infiltration, m6A methylation, and immune checkpoint.

Conclusion: Our prognostic model can provide a reference for the study of pyroptosis in melanoma cells and provide a new idea for melanoma treatment.
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http://dx.doi.org/10.2147/IJGM.S335396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518699PMC
October 2021

ADM-assisted prepectoral breast reconstruction is not associated with high complication rate as before: a Meta-analysis.

J Plast Surg Hand Surg 2021 Sep 28:1-9. Epub 2021 Sep 28.

Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Implant-related breast reconstruction can be divided into subpectoral breast reconstruction (SPBR) and prepectoral breast reconstruction (PPBR) according to the different anatomical planes. The previous stereotype was that PPBR had a high complication rate and was not suitable for clinical use. However, with the emergence of acellular dermal matrix (ADM), the clinical effect of PPBR has been improved. To compare the outcomes difference between SPBR and PPBR, We conducted this meta-analysis. Articles on SPBR versus PPBR were searched in PubMed, Web of Sciences, Embase, and Cochrane databases, strictly following the PRISMA guidelines. According to the set criteria, we included the literature that met the requirements. Extracted data were the incidence of adverse events and the duration of drainage. Results show that SPBR has a higher incidence rate in capsular contracture, animation deformity, infection, hematoma and delayed healing wound than PPBR. There are no significant differences in skin flap necrosis, seroma, implant loss, reoperation and duration of drainage between the two groups. Hence, PPBR is no longer a high complication surgical method and can be used in the clinical practice. However, there are few large sample studies at present, so it is necessary to carry out further studies on PPBR.
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http://dx.doi.org/10.1080/2000656X.2021.1981351DOI Listing
September 2021

The Role of Thyroid Function in Alzheimer's Disease.

J Alzheimers Dis 2021 ;83(4):1553-1562

Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.

The thyroid gland is crucial for the regulation of metabolism, growth, and development of various tissues, organs, systems, including the central nervous system. Recent studies have implicated the role of thyroid dysfunction in the etiology of Alzheimer's disease (AD), while AD leads to a significant increase in the prevalence of thyroid dysfunction. In this review, we have analyzed the role of thyroid function in the pathophysiology of AD as well as its biomarkers. The present review aims to provide encouraging targets for early screening of AD risk factors and intervention strategies.
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http://dx.doi.org/10.3233/JAD-210339DOI Listing
December 2021

Database mining analysis revealed the role of the putative H/sugar transporter solute carrier family 45 in skin cutaneous melanoma.

Channels (Austin) 2021 12;15(1):496-506

Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Metabolic reprogramming is common in various cancers. Targeting metabolism to treat tumors is a hot research topic at present. Among them, changes in glucose metabolism in cancer have been widely studied. The Warburg effect maintains a high metabolic level in the tumor, accompanied by changes in glucose transporters. The transmembrane transport of sugar was previously thought to be mediated by SGLT and GLUT. Recently, the Solute Carrier Family(SLC) 45 family may be the third sugar transporter. But the role and value of the SLC45 family in melanoma, a highly malignant skin tumor, is unclear. Our study found that the four members of the SLC45 family, SLC45A1-SLC45A4, were differentially expressed in melanoma, but only SLC45A2 and SLC45A3 had prognostic guiding values. Further analysis revealed that the co-expression patterns of SLC45A2 and SLC45A3 were enriched in multiple metabolic pathways, suggesting their potential role in melanoma. In addition, SLC45A2 and SLC45A3 are also associated with immune cell infiltration. In conclusion, SLC45A2 and SLC45A3 are good prognostic indicators for melanoma and have guiding value for the treatment of melanoma in the future.
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http://dx.doi.org/10.1080/19336950.2021.1956226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331014PMC
December 2021

Solute carrier transporter superfamily member SLC16A1 is a potential prognostic biomarker and associated with immune infiltration in skin cutaneous melanoma.

Channels (Austin) 2021 12;15(1):483-495

Department of Burn and Plastic Surgery, The First Hospital Affiliated to Nanjing Medical University, Nanjing, China.

Melanoma is a type of cancer with a relatively poor prognosis. The development of immunotherapy for the treatment of patients with melanoma has drawn considerable attention in recent years. It is of great clinical significance to identify novel promising prognostic biomarkers and to explore their roles in the immune microenvironment. The solute carrier (SLC) superfamily is a group of transporters predominantly expressed on the cell membrane and are involved in substance transport. SLC16A1 is a member of the SLC family, participating in the transport of lactate, pyruvate, amino acids, ketone bodies, etc. The role of SLC16A1 in tumor immunity has been recently elucidated, while its role in melanoma remains unclear. In this study, bioinformatics analysis was performed to explore the role of SLC16A1 in melanoma. The results showed that high SLC16A1 expression was correlated with decreased overall survival in patients with melanoma. The genes co-expressed with SLC16A1 were significantly enriched in metabolic regulation, protein ubiquitination, and substance localization. Moreover, SLC16A1 was correlated with the infiltration of immune cells. In conclusion, SLC16A1 is a robust prognostic biomarker for melanoma and may be used as a novel target in immunotherapy.
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http://dx.doi.org/10.1080/19336950.2021.1953322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279094PMC
December 2021

Differences Changes in Cerebellar Functional Connectivity Between Mild Cognitive Impairment and Alzheimer's Disease: A Seed-Based Approach.

Front Neurol 2021 17;12:645171. Epub 2021 Jun 17.

Department of Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.

Recent studies have discovered that functional connections are impaired among patients with Alzheimer's disease (AD), even at the preclinical stage. The cerebellum has been implicated as playing a role in cognitive processes. However, functional connectivity (FC) among cognitive sub-regions of the cerebellum in patients with AD and mild cognitive impairment (MCI) remains to be further elucidated. Our study aims to investigate the FC changes of the cerebellum among patients with AD and MCI, compared to healthy controls (HC). Additionally, we explored the role of cerebellum FC changes in the cognitive performance of all subjects. Resting-state functional magnetic resonance imaging (rs-fMRI) data from three different groups (28 AD patients, 26 MCI patients, and 30 HC) was collected. We defined cerebellar crus II and lobule IX as seed regions to assess the intragroup differences of cortico-cerebellar connectivity. Bias correlational analysis was performed to investigate the relationship between changes in FC and neuropsychological performance. Compared to HC, AD patients had decreased FC within the caudate, limbic lobe, medial frontal gyrus (MFG), middle temporal gyrus, superior frontal gyrus, parietal lobe/precuneus, inferior temporal gyrus, and posterior cingulate gyrus. Interestingly, MCI patients demonstrated increased FC within inferior parietal lobe, and MFG, while they had decreased FC in the thalamus, inferior frontal gyrus, and superior frontal gyrus. Further analysis indicated that FC changes between the left crus II and the right thalamus, as well as between left lobule IX and the right parietal lobe, were both associated with cognitive decline in AD. Disrupted FC between left crus II and right thalamus, as well as between left lobule IX and right parietal lobe, was associated with attention deficit among subjects with MCI. These findings indicate that cortico-cerebellar FC in MCI and AD patients was significantly disrupted with different distributions, particularly in the default mode networks (DMN) and fronto-parietal networks (FPN) region. Increased activity within the fronto-parietal areas of MCI patients indicated a possible compensatory role for the cerebellum in cognitive impairment. Therefore, alterations in the cortico-cerebellar FC represent a novel approach for early diagnosis and a potential therapeutic target for early intervention.
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http://dx.doi.org/10.3389/fneur.2021.645171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248670PMC
June 2021

Standoff tracking of a ground target based on coordinated turning guidance law.

ISA Trans 2022 Jan 2;119:118-134. Epub 2021 Mar 2.

School of Automation, Northwestern Polytechnical University, 1 Dongxiang Road, Chang'an District, Xi'an Shaanxi, 710129, PR China; Shaanxi Province Key Laboratory of Flight Control and Simulation Technology, 1 Dongxiang Road, Chang'an District, Xi'an Shaanxi, 710129, PR China.

Target tracking is a typical application of unmanned aerial vehicles(UAVs). However, it is difficult for the existing guidance laws to meet the requirements of convergence speed and tracking accuracy at the same time. A new guidance law based on a coordinated turning equation is proposed to achieve target tracking, and its asymptotic stability is proved. Linear analysis is provided to help select the control parameters. This guidance law is improved to track the moving ground object with time-varying states. Compared with existing methods through numerical simulations, the proposed guidance law offers a faster convergence speed and a higher level of precision. The effectiveness and robustness of the guidance law in different situations are verified by hardware-in-the-loop (HIL) simulations.
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http://dx.doi.org/10.1016/j.isatra.2021.02.043DOI Listing
January 2022

Association of Static Posturography With Severity of White Matter Hyperintensities.

Front Neurol 2021 11;12:579281. Epub 2021 Feb 11.

Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing Brain Hospital, Nanjing, China.

Impaired gait and balance are associated with severity of leukoaraiosis. Evaluation of balance is based on neurological examination using Romberg's test with bipedal standing, assessment scale, and posturographic parameters. The goal of this study was to determine the relationship between static equilibrium and grades of white matter hyperintensities (WMHs) using static posturography as a quantitative technical method. One hundred and eighteen (118) patients with lacunar infarct were recruited and assessed on MRI with Fazekas's grading scale into four groups. On admission, age, gender, height, weight, Berg Balance Scale (BBS), mini-mental state examination (MMSE), and static posturography parameters were recorded, and their correlations with WMHs were determined. Age was significantly and positively correlated with severity of WMHs ( = 0.39, < 0.05). WMH score was negatively correlated with BBS score ( = -0.65, < 0.05) and MMSE score ( = -0.79, < 0.05). There was a significant positive correlation between track length anteroposterior (AP, with eyes closed) and severity of WMHs ( = 0.70, < 0.05). Partial correlation analysis and multiple logistic regression analysis indicated that track length AP with eyes closed, was a predictor for the severity of WMHs (< 0.05). The severity of WHMs is associated with age, cognitive decline, and impairment in balance. Posturography parameter in track length in AP direction with eyes closed in relation to cognition and balance, may be a potential marker for disease progression in WMHs.
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http://dx.doi.org/10.3389/fneur.2021.579281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905220PMC
February 2021

Nicotinamide Improves Cognitive Function in Mice With Chronic Cerebral Hypoperfusion.

Front Neurol 2021 25;12:596641. Epub 2021 Jan 25.

Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing Brain Hospital, Nanjing, China.

Normal brain function requires steady blood supply to maintain stable energy state. When blood supply to the brain becomes suboptimal for a long period of time, chronic cerebral hypoperfusion (CCH) and a variety of brain changes may occur. CCH causes white matter injury and cognitive impairment. The present study investigated the effect of nicotinamide (NAM) on CCH-induced cognitive impairment and white matter damage in mice. Male C57Bl/6J mice aged 10-12 weeks (mean age = 11 ± 1 weeks) and weighing 24 - 29 g (mean weight = 26.5 ± 2.5 g) were randomly assigned to three groups (eight mice/group): sham group, CCH group and NAM group. Chronic cerebral hypoperfusion (CCH) was induced using standard methods. The treatment group mice received intraperitoneal injection of NAM at a dose of 200 mg/kg body weight (bwt) daily for 30 days. Learning, memory, anxiety, and depression-like behaviors were measured using Morris water maze test (MWMT), open field test (OFT), sucrose preference test (SPT), and forced swim test (FST), respectively. White matter damage and remodeling were determined via histological/ immunohistochemical analyses, and western blotting, respectively. The results showed that the time spent in target quadrant, number of crossings and escape latency were significantly lower in CCH group than in sham group, but they were significantly increased by NAM ( < 0.05). Mice in NAM group moved significantly faster and covered longer distances, when compared with those in CCH group ( < 0.05). The percentage of time spent in open arms and the number of entries to the open arms were significantly lower in CCH group than in NAM group ( < 0.05). Moreover, anhedonia and histologic scores (index of myelin injury) were significantly higher in CCH group than in sham group, but they were significantly reduced by NAM ( < 0.05). The results of immunohistochemical staining and Western blotting showed that the protein expressions of 2', 3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) and synaptophysin were significantly downregulated in CCH group, relative to sham group, but they were significantly upregulated by NAM ( < 0.05). These results indicate that NAM improves cognitive function in mice with CCH.
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http://dx.doi.org/10.3389/fneur.2021.596641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868534PMC
January 2021

Association of RAGE with acute ischemic stroke prognosis in type 2 diabetes.

Ir J Med Sci 2021 May 28;190(2):625-630. Epub 2020 Sep 28.

Department of Neurology, The Affiliated Brain Hospital to Nanjing Medical University, Nanjing Brain Hospital, No. 264,Guangzhou Road, Nanjing, 210000, Jiangsu Province, People's Republic of China.

Background: In experimental models, the receptor for advanced glycation end products (RAGE) has been reported as a key mediator in cerebral ischemia. In this study, the clinical significance of serum RAGE levels in acute ischemic stroke patients with type 2 diabetes was determined.

Method: Three hundred seven patients (165 patients without diabetes and 142 patients with diabetes) with acute cerebral infarction (ACI) were enrolled over 3 consecutive months. On admission, their National Institute of Health Stroke Scale (NIHSS) scores were recorded. The clinical laboratory data of all subjects were collected, and their serum levels of RAGE were assayed using enzyme-linked immunosorbent assay (ELISA). On admission and 3 months after stroke, the clinical outcomes were assessed using the Barthel index (BI) and modified Rankin scale (mRS).

Results: Patients with diabetes (PwD) had significantly higher levels of triglycerides (TGs), RAGE, fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c), and worse stroke prognosis than patients without diabetes (p < 0.05). Hypertension history, RAGE, and FBG in patients without diabetes in ischemic stroke were increased, relative to stroke prognosis. Weight, RAGE, and FBG data showed significant correlation with stroke outcome in PwD (p < 0.05). Multiple logistic regression analysis indicated that the RAGE level was an independent risk factor for poor prognosis of stroke, especially in PwD with ACI (p < 0.05).

Conclusion: Acute ischemic stroke is associated with elevated serum RAGE level, which, at admission, is an independent predictor of poor outcome for stroke in type 2 diabetes.
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http://dx.doi.org/10.1007/s11845-020-02385-2DOI Listing
May 2021

Baicalein Attenuates Neuroinflammation by Inhibiting NLRP3/caspase-1/GSDMD Pathway in MPTP Induced Mice Model of Parkinson's Disease.

Int J Neuropsychopharmacol 2020 Aug 6. Epub 2020 Aug 6.

Department of Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Background: Inflammasome-induced neuroinflammation is a major pathogenic mechanism underlying the degeneration of nigral dopaminergic neurons in Parkinson's disease (PD). Baicalein is a flavonoid isolated from the traditional Chinese medicinal herbal Scutellaria baicalensis Georgi with known anti-inflammatory and neuroprotective efficacy in models of neurodegenerative diseases, including PD. However, its effects on inflammasome-induced neuroinflammation during PD remain unclear.

Methods: We used N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD-like pathology in mice. Behavioral assessments including the pole test, rotarod test and open filed test were conducted to evaluate the effects of baicalein on MPTP-induced motor dysfunction. The efficacies of baicalein against MPTP-induced dopaminergic neuron loss and glial cell activation in the substantia nigra compact (SNc) were examined by immunohistochemistry, effects on proinflammatory cytokines by qPCR and enzyme-linked immunosorbent assay (ELISA), effects on inflammasome pathway activation by immunoblotting and flow cytometry.

Results: Administration of baicalein reversed MPTP-induced motor dysfunction, loss of dopaminergic neurons, and pro-inflammatory cytokine elevation. Baicalein also inhibited NLRP3 and caspase-1 activation and suppressed gasdermin D (GSDMD)-dependent pyroptosis. Additionally, baicalein inhibited the activation and proliferation of disease-associated proinflammatory microglia.

Conclusions: These findings suggest that baicalein can reverse MPTP-induced neuroinflammation in mice by suppressing NLRP3/caspase-1/GSDMD pathway. Our study provides potential insight of baicalein in PD therapy.
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http://dx.doi.org/10.1093/ijnp/pyaa060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745250PMC
August 2020

Clinical characteristics and outcomes of autoimmune encephalitis patients associated with anti-glutamate decarboxylase antibody 65.

Clin Neurol Neurosurg 2020 09 10;196:106082. Epub 2020 Jul 10.

Department of Neurology, The Nanjing Brain Hospital Affiliated Nanjing Medical University, 210029, Nanjing, China.

Objective: This study was to investigate the clinical characteristics and prognosis of autoimmune encephalitis (AE) associated with anti-Glutamic Acid Decarboxylase 65 (GAD65).

Patients And Methods: From Jan 2016 to Aug 2018, three patients diagnosed as anti-GAD65 AE in our hospital were retrospectively analyzed for their general demographic characteristics, clinical presentation, cerebrospinal fluid (CSF) cytology, brain imaging, EEG, treatment and prognosis.

Results: We found that Anti-GAD65 AE may be more common in young and middle-aged women, with initial presentations of refractory status epilepticus or cognitive decline following the disease progresses, but with less psychiatric symptoms than other types of AEs. The abnormal signals of MRI may be obvious in bilateral frontal, temporal lobe and hippocampus.

Conclusion: The production of anti-GAD65 may have a certain latency period, and it is usually negative at the onset stage. More studies need to be performed on larger populations and further understand the potential mechanisms underlying the above clinical features of anti-GAD65 AE.
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http://dx.doi.org/10.1016/j.clineuro.2020.106082DOI Listing
September 2020

Angiotensin (1-7) through modulation of the NMDAR-nNOS-NO pathway and serotonergic metabolism exerts an anxiolytic-like effect in rats.

Behav Brain Res 2020 07 11;390:112671. Epub 2020 May 11.

Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, PR China. Electronic address:

Although recent studies have shown that angiotensin (1-7) (Ang [1-7]) exerts anti-stress and anxiolytic-like effects, the underlying mechanisms remain elusive. The ventral hippocampus (VH) is proposed to be a critical brain region for mood and stress management through the N-methyl-d-aspartate receptor (NMDAR) signaling pathway. However, the role of VH NMDAR signaling in the effects of Ang (1-7) remains unclear. In the present study, Ang (1-7) was injected into the bilateral VH of stressed rats, or in combination with a Fyn kinase inhibitor, NMDAR antagonist, neuronal nitric oxide synthase (nNOS) inhibitor, or nitric oxide (NO) scavenger. Anxiety-like behaviors were assessed using the open field test and elevated plus maze test, while alterations in NMDAR-nNOS-NO signaling and serotonergic metabolism were examined in the VH. After 21 days of chronic restraint stress, anxiety-like behaviors were evident. Levels of phosphorylated NR2B (a key NMDAR subunit), its upstream kinase Fyn, as well as activity of nNOS and monoamine oxidase (MAO) were markedly reduced. In contrast, levels of serotonin were increased. Bilateral VH infusion of Ang (1-7) recovered NMDAR-nNOS-NO signaling and MAO-mediated serotonin metabolism, as well as reducing anxiety-like behaviors in stressed rats. These effects were diminished by blockade of MasR (Ang [1-7]-specific receptor), Fyn kinase, NMDAR, nNOS, or NO production. Altogether, these findings indicate that Ang (1-7) exerts anxiolytic effects through modulation of the NMDAR-nNOS-NO pathway and serotonergic metabolism. Future translational research should focus on the relationship between Ang (1-7), glutamatergic neurotransmission, and serotonergic neurotransmission in the VH.
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http://dx.doi.org/10.1016/j.bbr.2020.112671DOI Listing
July 2020

IL-37 Represses the Autoimmunity in Myasthenia Gravis via Directly Targeting Follicular Th and B Cells.

J Immunol 2020 04 28;204(7):1736-1745. Epub 2020 Feb 28.

Department of Neurology, Drum Tower Hospital, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu 210008, China;

IL-37 is a newly identified immune-suppressive factor; however, the function, cellular sources, and mechanism of IL-37 in humoral immunity and Myasthenia gravis (MG) are still unclear. In this study, we found IL-37 were substantially downregulated in the serum and PBMCs of MG patients compared with healthy controls. The lower IL-37 was associated with severer disease (quantitative MG score) and higher follicular Th (Tfh)/Tfh17 and B cell numbers. Flow cytometry analysis revealed that IL-37 was mainly produced by CD4 T cells without overlapping with Th1, Th17, and Tfh subsets in MG patients. Regulatory IL-37 T cell rarely expressed Foxp3 and CD25 but produced numerous IL-4. Tfh and B cell expressed high levels of SIGIRR, the receptor of IL-37, in MG patients. Mechanically, IL-37 directly bond to SIGIRR, repressed the proliferation, cytokine production of Tfh and B cells, and the secretion of autoantibody via inhibition of STAT3 signaling in Tfh and B cells.
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http://dx.doi.org/10.4049/jimmunol.1901176DOI Listing
April 2020

Chinese multicentre prospective registry of breast cancer patient-reported outcome-reconstruction and oncoplastic cohort (PRO-ROC): a study protocol.

BMJ Open 2019 12 15;9(12):e032945. Epub 2019 Dec 15.

Department of Breast Surgery, Shanghai Cancer Hospital, Fudan University, Shanghai, China

Introduction: Available patient-reported outcome (PRO) studies are mainly from single institution or of small sample size, and the variations across hospitals and regions were not fully analysed. A multicentre, prospective, patient-reported outcome-reconstruction and oncoplastic cohort (PRO-ROC) will be planned to assess the PROs of Chinese patients with breast cancer who will undergo breast reconstruction (BR) or oncoplastic breast-conserving surgery (OBCS).

Methods And Analysis: The inclusion criteria are female patients with breast cancer aged >18 years old who will undergo BR or OBCS. This cohort will include at least 10 000 consecutive patients (about 5000 patients who will undergo BR and 5000 patients who will undergo OBCS). The exposures were surgery types: BR and OBCS regardless of the techniques and materials used. The primary endpoint will be PROs, which include BREAST-Q and quality of life (European Organisation for Research and Treatment (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and EORTC QoL Breast Cancer-specific version (QLQ-BR23)). All patients will be followed up to 24 months after operations. All data will be prospectively collected using an app software. Data will be analysed using SPSS and Stata software.

Ethics And Dissemination: This study follows the Helsinki Declaration. All patients will be asked to sign an informed consent before enrolment. The results of this study will be presented at national and international meetings and published in a scientific peer-reviewed journal.

Trial Registration Number: NCT04030845; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2019-032945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924782PMC
December 2019

Topological Disruption of Structural Brain Networks in Patients With Cognitive Impairment Following Cerebellar Infarction.

Front Neurol 2019 19;10:759. Epub 2019 Jul 19.

Department of Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.

Cerebellar lesions can lead to a series of cognitive and emotional disorders by influencing cerebral activity via cerebro-cerebellar loops. To explore changes in cognitive function and structural brain networks in patients with posterior cerebellar infarction, we conducted the current study using diffusion-weighted MRI (32 cerebellar infarction patients, 29 controls). Moreover, a series of neuropsychological tests were used to assess the subject's cognitive performance. We found cognitive impairment following cerebellar infarction involving multiple cognitive domains, including memory, executive functions, visuospatial abilities, processing speed and language functions, and brain topological abnormalities, including changes in clustering coefficients, shortest path lengths, global efficiency, local efficiencies, betweenness centrality and nodal efficiencies. Our results indicated that measures of local efficiency, mainly in the precuneus, cingulate gyrus and frontal-temporal cortex, were significantly reduced with posterior cerebellar infarction. At the same time, The correlation analysis suggested thatthe abnormal alterations in the right PCG, bilateral DCG, right PCUN may play a core role in the cognitive impairment following cerebellar infarctions. The differences in topological features of the structural brain networks within the cerebro-cerebellar circuits may provide a new approach to explore the pathophysiological mechanisms of cognitive impairment following cerebellar infarction.
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http://dx.doi.org/10.3389/fneur.2019.00759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659410PMC
July 2019

Angiotensin II triggers autophagy and apoptosis in PC12 cell line: An in vitro Alzheimer's disease model.

Brain Res 2019 09 2;1718:46-52. Epub 2019 May 2.

Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China. Electronic address:

Objective: The activation of renin angiotensin system is involved in multiple pathological processes. Growing evidence reveal that Angiotensin II (Ang II) contributes to the pathogenesis of Alzheimer disease (AD). However, the underlying mechanisms are still not fully understood.

Methods: In this study, the effect of Ang II on Aβ induced neurotoxicity was evaluated in PC12 cells. Apoptosis was examined by flow cytometry analysis and caspase-3 activity assay. Autophagy-related markers were also measured in each group.

Results: The results indicated that Ang II activated autophagy and triggered apoptosis in PC12 cells in a dose-dependent manner, as demonstrated byincreased LC3 II/I ratio and decreased p62 expression. Moreover, inhibition of autophagy by 3-methyladenine markedly attenuated the apoptosis caused by Ang II. In addition, an AT1R antagonist losartan, rather than the AT2R antagonist PD123319, completely reversed the Ang II induced autophagic activation and subsequent cell apoptosis.

Conclusions: Taken together, our study strengthen the crucial function of Ang II/AT1R axis in the pathogenesis of AD in vitro. These findings have deepened our understanding on the role of Ang II in the pathogenesis of AD and support the use of AT1R antagonists for the treatment of this devastating neurodegenerative disease.
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http://dx.doi.org/10.1016/j.brainres.2019.05.002DOI Listing
September 2019
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