Identification of core genes of craniopharyngioma angiogenesis based on single-cell nuclear transcriptome sequencing.

This study aimed to explore the core genes of craniopharyngioma angiogenesis for targeted vascular therapy based on single-cell nuclear transcriptome sequencing. For single-cell nuclear transcriptome sequencing, we collected six samples from the tumor center and adjacent hypothalamic tumor tissues from three patients with craniopharyngioma, as well as four normal brain tissues based on Gene Expression Omnibus. We screened genes with differential up-regulation between vascular endothelial cells of craniopharyngioma and those of normal brain tissues, performed GO and KEGG analysis, constructed the protein-protein interaction network, and selected key genes verified using immunofluorescence. After data cleaning and quality control, 623 craniopharyngioma endothelial cells and 439 healthy brain endothelial cells were obtained. Compared with normal brain endothelial cells, craniopharyngioma endothelial cells were screened for 394 differentially up-expressed genes (DEGs). GO and KEGG results showed that DEGs probably modulated endothelial cells, adherens junction, focal adhesion, migration, actin cytoskeleton, and invasion via the PI3K-AKT, Rap1, Ras, Wnt, and Hippo pathways. The core genes screened were CTNNB1, PTK2, ITGB1, STAT3, FYN, HIF1A, VCL, SMAD3, PECAM1, FOS, and CDH5. This study obtained possible anti-angiogenic genes in craniopharyngioma. Our results shed novel insights into molecular mechanisms and craniopharyngioma treatment.

Sunitinib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers.

Currently, renal cell carcinoma (RCC) is the most prevalent type of kidney cancer. Targeted therapy has replaced radiation therapy and chemotherapy as the main treatment option for RCC due to the lack of significant efficacy with these conventional therapeutic regimens. Sunitinib, a drug used to treat gastrointestinal tumors and renal cell carcinoma, inhibits the tyrosine kinase activity of a number of receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), c-Kit, rearranged during transfection (RET) and fms-related receptor tyrosine kinase 3 (Flt3). Although sunitinib has been shown to be efficacious in the treatment of patients with advanced RCC, a significant number of patients have primary resistance to sunitinib or acquired drug resistance within the 6-15 months of therapy. Thus, in order to develop more efficacious and long-lasting treatment strategies for patients with advanced RCC, it will be crucial to ascertain how to overcome sunitinib resistance that is produced by various drug resistance mechanisms. In this review, we discuss: 1) molecular mechanisms of sunitinib resistance; 2) strategies to overcome sunitinib resistance and 3) potential predictive biomarkers of sunitinib resistance.

Association of central arterial blood pressure and left ventricular hypertrophy in patients with chronic kidney disease.

AIMS: In the general population, central arterial blood pressure has proved to be more closely related to left ventricular hypertrophy (LVH) than brachial arterial blood pressure. We aimed to investigate whether this relationship was true in patients with chronic kidney disease (CKD). METHODS: In this retrospective study, we reviewed the medical records of 289 adult patients with CKD from the Zhejiang Provincial People's Hospital in Zhejiang, China. Demographic, echocardiographic and brachial and central blood pressure parameters were retrieved from medical records. Central blood pressure was measured using the SphygmoCor® CvMS (AtCor, Australia) device and its corresponding software. Multivariate logistic regression analyses were performed to identify independent predictors of LVH. Receiver operating characteristic curves were used to determine the ability of central and brachial blood pressure to predict LVH. RESULTS: The left ventricular mass index was positively associated with both central and brachial blood pressures. However, multiple logistic regression analysis demonstrated that a central pulse pressure (CPP) ≥ 58 mm Hg was an independent risk factor for LVH (OR = 5.597, 95%CI 2.363-13.259, p < .001). Brachial pulse pressure is not superior to CPP in predicting LVH (area under the curve [AUC] = 0.695, 95%CI 0.634-0.756, p < .001 vs. AUC = 0.687, 95%CI: 0.626-0.748, p < .001, respectively; p = .4824). CONCLUSION: Our results suggested that, similarly to the general population, CPP is a better parameter for predicting the occurrence of LVH in patients with CKD.

Position-deviation-compensation demodulation method for multi-channel polarized low-coherence interferometry.

A position-deviation-compensation demodulation method is proposed to improve the channel adaptability of Fabry-Perot (F-P) sensor in a multi-channel optical fiber F-P sensing system. By combining the envelope peak position (EPP) retrieval process and the position compensation process, the proposed method enables the accurate demodulation of F-P sensors in all channels. Thereinto, the EPP retrieval process uses the phase information to recover the EPP with high precision; the position compensation process compensates the position deviation by an optical-path-based model, which is established to illustrate the principle of the position deviation between different channels. We carried out the pressure experiment to verify the effectiveness of the proposed method. The experiment results showed that the demodulation errors of all channels are no more than 0.13 kPa, which demonstrated that our approach is reliable for improving the channel adaptability of F-P sensors.

The temozolomide derivative 2T-P400 inhibits glioma growth via administration route of intravenous injection.

The aim of this study is to investigate the inhibitory effects of 2T-P400, a derivative of temozolomide (TMZ), on glioma growth. SHG-44 and U373 human glioblastoma cell lines and SHG-44 cell subcutaneous and intracranial xenograft mouse models were used as the model system for these studies. Cell growth was analyzed using MTT assay. For intracranial glioma xenograft model, mouse brains were obtained and made as paraffin section for immunohistochemical staining. Tumor volume was calculated with this formula: tumor volume = length × width2/ 2. The results showed that 2T-P400 or TMZ significantly inhibits cell growth in a concentration dependent manner with the IC50 values of 12.90 ± 1.05 or 9.73 ± 2.12 µg/ml on SHG-44 cell line and 13.12 ± 0.86 or 10.13 ± 1.02 µg/ml on U373 cell line respectively. In SHG-44 cell subcutaneous xenograft model, the tumor volume of 2T-P400 or TMZ treated group was 1,062.12 ± 204.76 or 803.59 ± 110.32 mm3 respectively, which was significantly smaller than that in physiological saline (with volume of 1,968.85 ± 348.37 mm3) treated group. In intracranial xenograft model, the tumor volume of 2T-P400 or TMZ group was 6.12 ± 1.69 or 5.58 ± 1.45 mm3 respectively, significantly smaller than that in physiological saline group of 33.08 ± 6.88 mm3. Moreover, polyethylene glycol 400 (PEG400) exhibited no significant tumor growth inhibition. Our results indicated that 2T-P400 posses the same growth inhibitory effect as TMZ on glioblastoma cell lines and the subcutaneously and intracranially transplanted gliomas in xenograft mouse models. It may be a suitable alternate of TMZ for the treatment of glioma via intravenous administration route.

[Establishment and characterization of dual-color fluorescence nude mouse models of glioma].

OBJECTIVE: To establish red-green dual-color fluorescence glioma model in nude mice and to explore its practical values. METHODS: CM-DiI-stained rat glioma C6 cells (C6-CM- DiI cells) expressing red fluorescence were inoculated into the brain of athymic nude mice expressing green fluorescence protein (NC-C57BL/6J-EGFP). Then the whole-body dual-color fluorescence imaging was detected dynamically. Finally whole brains of the tumor-bearing mice were removed and 5 µm thick serial frozen slices were made. Light microscopy, fluorescence microscopy and confocal laser scanning microscopy were performed to observe the transplanted tumor tissue structure and fluorescent cells. RESULTS: Tumor mass with red fluorescence increased gradually under continuous in-vivo fluorescence imaging monitoring. Under the fluorescence microscope, cells with red, green and yellow fluorescence were observed in the frozen sections of transplanted tumor tissue and the mutual structural relationship among them could be defined. The tumor cells migration, implantation and cell fusion between transplanted tumor cells and host cells could be observed. It could be distinguished according to the fluorescence, that blood vessels of tumor-origin displayed red fluorescence, blood vessels of host-origin displayed green fluorescence and mosaic blood vessels appeared yellow fluorescence. It was depicted that host innate astrocytes and oligodendrocytes in the microenvironment at the tumor periphery could be activated and dedifferentiated into nestin-positive cells. CONCLUSIONS: In contrast to traditional animal model, the dual-color fluorescence imaging of nude mouse models of glioma possesses enormous advantages in investigating tumor mass in-vivo fluorescence imaging, tumor cells migration and metastasis, tumor angiogenesis and reactive activation of host innate cells in the microenvironment at tumor periphery, thus, has highly practical application value.

Multiomics integration-based immunological characterizations of adamantinomatous craniopharyngioma in relation to keratinization.

Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG+ epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.

[Host glial cell canceration induced by glioma stem cells in GFP/RFP dual fluorescence orthotopic glioma models in nude mice].

OBJECTIVE: During the process of tissue remodeling in human tumor transplantation models, the roles of the inoculated tumor cells and host tissue in tumor progression is still largely unknown. The aim of this study was to investigate the relationships and interactions between these two sides using GFP-RFP double fluorescence tracing technique. METHODS: Red fluorescence protein (RFP) gene was stably transfected into glioma stem cell line SU3, then SU3-RFP cells were transplanted into the brain of athymic nude mice with green fluorescence protein (GFP) expression. After the intracerebral tumors were formed, the relationship and interaction between GFP cells and RFP cells were analyzed. Highly proliferative GFP cells were screened out, and monocloned with micro-pipetting. DNA content assay, chromosome banding and carcinogenicity test of the GFP cells were performed to observe the GFP cells' cancerous phenotype in nude mice. RESULTS: In the transplantable tumor tissue, besides a great quantity of RFP cells, there were still a proportion of GFP cells and GFP/RFP fusion cells. The proportion of RFP cells, GFP cells and GFP/RFP cells were (88.99 ± 1.46)%, (5.59 ± 1.00)%, and (4.11 ± 1.020)%, respectively. Two monoclonal host GFP cells (H1 and H9) were cloned, which demonstrated the properties of immortality, loss of contact inhibition, and ultra-tetraploid when cultured in vitro. Both H1 and H9 cells expressed CNP, a specific marker of oligodendrocytes. The GFP cells also demonstrated 100% tumorigenic rate and high invasive properties in vivo. CONCLUSIONS: In this glioma transplantation model, the transplanted tumor tissues contained not only transplanted glioma stem cells but also cancerous host GFP cells. Our findings offer important clues to further research on the relationships among different members in the tumor microenvironment.

Budding uninhibited by benzimidazoles 1 promotes cell proliferation, invasion, and epithelial-mesenchymal transition via the Wnt/ß-catenin signaling in glioblastoma.

The pathogenesis and progression of GBM (glioblastoma), as one of the most frequently occurring malignancies of the central nervous system, are regulated by several genes. BUB1 (budding uninhibited by benzimidazoles 1) is a mitotic checkpoint that plays an important role in chromosome segregation as well as in various tumors. However, its role in glioma is unknown. The current study discovered prominently elevated BUB1 in glioma and a significant relationship between BUB1 expression, a high World Health Organization grade, and a poor prognosis in glioma patients. Moreover, BUB1 triggered EMT (epithelial-mesenchymal transition) apart from promoting glioma cell proliferation, migration, and infiltration. Besides, BUB1 promoted EMT by activating the Wnt/ß-catenin axis. As implied by our study, BUB1 probably has the potential as a target for GBM management.

The Role of Ferroptosis in Acute Kidney Injury.

Ferroptosis is a novel cell death method discovered in recent years. It is usually accompanied by massive accumulations of iron and lipid peroxidation during cell death. Recent studies have shown that ferroptosis is closely associated with the pathophysiological processes of many diseases, such as tumors, neurological diseases, localized ischemia-reperfusion injury, kidney injury, and hematological diseases. How to intervene in the incidence and development of associated diseases by regulating the ferroptosis of cells has become a hot topic of research. This article provides a review of the role of ferroptosis in the pathogenesis and potential treatment of acute kidney injury.

Novel mutation in the SALL1 gene in a four-generation Chinese family with uraemia: A case report.

BACKGROUND: Approximately 10% of adults and nearly all children who receive renal replacement therapy have inherited risk factors or are related to genetic factors. In the past, due to the limitations of detection technology and the nonspecific manifestations of uraemia, the etiological diagnosis is unclear. In addition to common monogenic diseases and complex disorders, advanced testing techniques have led to the recognition of more hereditary renal diseases. Here, we report a four-generation Chinese family in which four individuals had a novel SALL1 mutation and presented with uraemia or abnormal urine tests. CASE SUMMARY: A 32-year-old man presented with end-stage renal disease with a 4-year history of dialysis. His father and paternal aunt both had a history of unexplained renal failure with haemodialysis, and his 10-year-old daughter presented with proteinuria. The patient had multiple congenital abnormalities, including bilateral overlapping toes, unilateral dysplastic external ears, and sensorineural hearing loss. His family members also presented with similar defects. Genetic testing revealed that the proband carried a novel heterozygous shift mutation in SALL1_exon 2 (c.3437delG), and Sanger sequencing confirmed the same mutation in all affected family members. CONCLUSION: We report a novel SALL1 exon 2 (c.3437delG) mutation and clinical syndrome with kidney disease, bilateral overlapping toes, unilateral dysplastic external ears, and sensorineural hearing loss in a four-generation Chinese family.

[Corrigendum] Exosomal­miR­1184 derived from mesenchymal stem cells alleviates cisplatin­associated acute kidney injury.

Subsequently to the publication of this paper, the authors have noticed that Fig. 5 was published with inadvertent errors; essentially, the y­axis label in Fig. 5D should have read "TNF­α" instead of "IL­1ß" and conversely, in Fig. 5E, the y­axis label should have read "IL­1ß" instead of "TNF­α". The revised version of Fig. 5, with Figs. 5D and E now labelled correctly, is shown below. Note that these errors did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree to this corrigendum. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 24: 795, 2021; DOI: 10.3892/mmr.2021.12435].

Large mismatch profile predicts rapidly progressing brain edema in acute anterior circulation large vessel occlusion patients undergoing endovascular thrombectomy.

Background: Brain edema is a severe complication in patients with large vessel occlusion (LVO) that can reduce the effectiveness of endovascular therapy (EVT). This study aimed to investigate the association of the perfusion profile at baseline computed tomography (CT) perfusion with rapidly progressing brain edema (RPBE) after EVT in patients with acute anterior LVO. Methods: We retrospectively reviewed consecutive data collected from 149 patients with anterior LVO who underwent EVT at our center. Brain edema was measured by the swelling score (0-6 score), and RPBE was defined as the swelling score increased by more than 2 scores within 24 h after EVT. We investigated the effect of RPBE on poor outcomes [National Institute of Health Stroke Scale (NIHSS) score and modified Rankin scale (mRS) score at discharge, the occurrence of hemorrhagic transformation, and mortality rate in the hospital] using the Mann-Whitney U-test and chi-square test. A multivariate logistic regression model was used to assess the relationship between perfusion imaging parameters and RPBE occurrence. Results: Overall, 39 patients (26.2%) experienced RPBE after EVT. At discharge, RPBE was associated with higher NIHSS scores (Z = 3.52, 95% CI 2.0-12.0, P < 0.001) and higher mRS scores (Z = 3.67, 95% CI 0.0-1.0, P < 0.001) including the more frequent occurrence of hemorrhagic transformation (χ2 = 22.17, 95% CI 0.29-0.59, P < 0.001) and higher mortality rates in hospital (χ2 = 9.54, 95% CI 0.06-0.36, P = 0.002). Univariate analysis showed that intravenous thrombolysis, baseline ischemic core volume, and baseline mismatch ratio correlated with RPBE (all P < 0.05). After dividing the mismatch ratio into quartiles and performing a chi-square test between quartiles, we found that the occurrence of RPBE in Q4 (mismatch ratio > 11.3) was significantly lower than that in Q1 (mismatch ratio ≤ 3.0) (P < 0.05). The result of multivariate logistic regression analysis showed that compared with baseline mismatch ratio <5.1, baseline mismatch ratio between 5.1 and 11.3 (OR:3.85, 95% CI 1.06-14.29, P = 0.040), and mismatch ratio >11.3 (OR:5.26, 95% CI 1.28-20.00, P = 0.021) were independent protective factors for RPBE. Conclusion: In patients with anterior circulation LVO stroke undergoing successful EVT, a large mismatch ratio at baseline is a protective factor for RPBE, which is associated with poor outcomes.

Yi-Shen-Hua-Shi granules inhibit diabetic nephropathy by ameliorating podocyte injury induced by macrophage-derived exosomes.

Objective: To observe the therapeutic effect of Yi-Shen-Hua-Shi (YSHS) granule in podocyte damage and diabetic nephropathy (DN) proteinuria and to explore the corresponding mechanism. Methods: The db/db mice were used to establish the DN model. Serum creatinine (SCr), blood urea nitrogen (BUN), and 24 h urinary proteinuria were detected with specific kits. Glomerular structural lesions and podocyte apoptosis were detected through HE staining, TUNEL assay, and immunofluorescence. The medicated serum of YSHS granule (YSHS-serum) or control serum was prepared. Macrophage-derived exosomes were extracted using an exosome extraction kit. Morphology and the protein concentration of exosomes were evaluated by a transmission electron microscope (TEM) and BCA kit. The activity and apoptosis of podocyte MPC5 cells, the M1 macrophage polarization, and the protein expression of an exosome marker and cleaved caspase were detected by the CCK8 experiment, flow cytometry, and Western blot, respectively. The miR-21a-5p expression in podocytes and the exosomes from macrophages were measured by qRT-PCR. The effect of YSHS granule on the infiltration of M1 macrophages in the kidney tissue in db/db mice was measured by immunofluorescence. Results: The YSHS granule could improve renal function, reduce proteinuria, and inhibit glomerular structural lesions and podocyte apoptosis in db/db mice. High-glucose (HG) stimulation and YSHS granule treatment did not affect the protein concentration in macrophage-derived exosomes. Macrophage-derived exosomes could inhibit the cell viability and increase apoptosis of podocytes, especially the exosomes from macrophages treated with HG and control serum. Compared with the exosomes secreted by macrophages after an HG treatment, the exosome from macrophages treated with HG and YSHS granule showed lower inhibitory effects on podocyte activity, accompanied by the decreased upregulating effects of macrophage-derived exosomes on the miR-21a-5p in podocytes. miR-21a-5p mimics could reduce podocyte activity and promote caspase-3 shearing. M1 polarization of macrophages could change the content of miR-21a-5p in macrophage-derived exosomes. In addition, YSHS granule could inhibit HG-induced M1 polarization of macrophages and M1 macrophage infiltration in renal tissues. Conclusion: The YSHS granule could improve the podocyte injury induced by macrophage-derived exosomes and alleviate the progression of DN. This regulation might be related to the inhibition of M1 macrophage polarization by YSHS granule and the reduction of the miR-21a-5p content in macrophage-derived exosomes.

Mortality in chronic kidney disease patients with COVID-19: a systematic review and meta-analysis.

At the beginning of 2020, the outbreak of coronavirus disease 2019 (COVID-19) led to a worldwide pandemic and mass panic. The number of infected people has been increasing exponentially since, and the mortality rate has also been concomitantly increasing. At present, no study has summarized the mortality risk of COVID-19 in patients with chronic kidney disease (CKD). Therefore, the aim of the present study was to conduct a literature review and meta-analysis to understand the frequency of mortality among CKD patients infected with COVID-19. A comprehensive systematic search was conducted on the PubMed, Embase, and Cochrane databases to find articles published until May 15, 2020. Study quality was assessed using a modified version of the Newcastle-Ottawa Scale. After careful screening based on the inclusion and exclusion criteria, 3,867,367 patients from 12 studies were included. The mortality rate was significantly higher among CKD patients with COVID-19 infection than among CKD patients without COVID-19 infection, as indicated by a pooled OR of 5.81 (95% CI 3.78-8.94, P < 0.00001, I2 = 30%). The patients were then stratified into ≥ 70 and < 70 years, and subgroup analysis revealed that among CKD patients with COVID-19 infection, the mortality rate was higher in the < 70 years group (OR 8.69, 95% CI 7.56-9.97, P < 0.0001) than in the ≥ 70 years group (OR 2.44, 95% CI 0.75-6.63, P = 0.15). Thus, COVID-19 patients with CKD have a high mortality risk and require a comprehensive multidisciplinary management strategy.

Exosomal­miR­1184 derived from mesenchymal stem cells alleviates cisplatin­associated acute kidney injury.

Acute kidney injury (AKI) poses a severe threat to human health. MicroRNAs (miRNAs/miRs) are known to be involved in the progression of AKI; however, the function of miR­1184 in AKI remains unclear. Thus, the aim of the present study was to examine the role of this miRNA in kidney injury. In order to mimic AKI in vitro, HK­2 cells were treated with cisplatin. Bioinformatics analysis was performed to explore the differentially expressed miRNAs in AKI. A Cell Counting Kit­8 assay and flow cytometry were performed to examine cell viability and apoptosis, respectively. mRNA expression levels were detected via reverse transcription­quantitative PCR, and protein levels were investigated by western blot analysis. ELISA was performed to examine the levels of IL­1ß and TNF­α in the cell supernatants. The results revealed that miR­1184 expression was downregulated in AKI. Exosomes derived from miR­1184 agomir­treated mesenchymal stem cells (MSCs) significantly reversed cisplatin­induced cell growth inhibition by inhibiting apoptosis. Moreover, forkhead box O4 (FOXO4) was found to be the direct target of miR­1184, and exosomes expressing miR­1184 notably inhibited cisplatin­induced inflammatory responses in HK­2 cells via the mediation of IL­1ß and TNF­α. Furthermore, exosomes derived from miR­1184 agomir­treated MSCs significantly induced G1 phase arrest in HK­2 cells via the regulation of FOXO4, p27 Kip1 and CDK2. In conclusion, the present study demonstrated that exosomal­miR­1184 derived from MSCs alleviates cisplatin­associated AKI. Thus, the findings presented herein may shed new light onto the exploration of novel strategies for the treatment of AKI.

Integrative analysis of miRNA-mRNA network in idiopathic membranous nephropathy by bioinformatics analysis.

BACKGROUND: Currently, several specific antigens, M-type receptor for secretory phospholipase A2(PLA2R1), thrombospondin type-1 domain-containing 7A(THSD7A), and neural epidermal growth factor-like 1 protein (NELL-1), are discovered associated with the onset of idiopathic membranous nephropathy (IMN). But the pathomechanisms of IMN still need to be further claried. Understanding the mechanisms of IMN is required to improve its diagnosis and treatment. METHODS: In this study, we constructed miRNA regulatory networks to investigate IMN development. Moreover, miRNAs and mRNAs that were differentially expressed between Idiopathic Membranous Nephropathy (IMN) patients and normal controls were examined using the GSE115857 dataset and our previous sequence study. DE miRNA target genes were determined based on the FUNRICH software, starBase, miRDB, and miRWalk, and an miRNA-mRNA network was designed using DE-mRNAs that were negatively correlated with DE-miRNAs. The miRNA-mRNA network contained 228 miRNA-mRNA pairs. Thereafter, we conducted KEGG pathway, GO functional annotation, immune-related gene screening, protein interaction networks, and potential hub gene analyses. Furthermore, 10 miRNAs and 10 genes were determined and preliminarily validated using the validation dataset from GEO. Finally, we identified which pair may offer more accurate diagnosis and therapeutic targets for IMN. RESULTS: Two miRNA-mRNA pairs, miR-155-5p-FOS and miR-146a-5p-BTG2, were differentially expressed in IMN, indicating that these genes may affect IMN through immune processes. These findings may offer more accurate diagnoses and therapeutic targets for IMN.

Outcomes of Traumatic Brain-Injured Patients With Glasgow Coma Scale < 5 and Bilateral Dilated Pupils Undergoing Decompressive Craniectomy.

Objective: Decompressive craniectomy (DC) plays an important role in the treatment of patients with severe traumatic brain injury (sTBI) with mass lesions and intractably elevated intracranial hypertension (ICP). However, whether DC should be performed in patients with bilateral dilated pupils and a low Glasgow Coma Scale (GCS) score is still controversial. This retrospective study explored the clinical outcomes and risk factors for an unfavorable prognosis in sTBI patients undergoing emergency DC with bilateral dilated pupils and a GCS score <5. Methods: The authors reviewed the data from patients who underwent emergency DC from January 2012 to March 2019 in a medical center in China. All data, such as patient demographics, radiological findings, clinical parameters, and preoperative laboratory variables, were extracted. Multivariate logistic regression analysis was performed to determine the factors associated with 30-day mortality and 6-month negative neurological outcome {defined as death or vegetative state [Glasgow Outcome Scale (GOS) score 1-2]}. Results: A total of 94 sTBI patients with bilateral dilated pupils and a GCS score lower than five who underwent emergency DC were enrolled. In total, 74 patients (78.7%) died within 30 days, and 84 (89.4%) had a poor 6-month outcome (GOS 1-2). In multivariate analysis, advanced age (OR: 7.741, CI: 2.288-26.189), prolonged preoperative activated partial thromboplastin time (aPTT) (OR: 7.263, CI: 1.323-39.890), and low GCS (OR: 6.162, CI: 1.478-25.684) were associated with a higher risk of 30-day mortality, while advanced age (OR: 8.812, CI: 1.817-42.729) was the only independent predictor of a poor 6-month prognosis in patients undergoing DC with preoperative bilateral dilated pupils and a GCS score <5. Conclusions: The mortality and disability rates are extremely high in severe TBI patients undergoing emergency DC with bilateral fixed pupils and a GCS score <5. DC is more valuable for younger patients.

[The protective effects of cyclosporine A on aortic immunological injuries in STZ-induced diabetic rats].

OBJECTIVE: To investigate the autoimmune injuries of diabetic macrovascular disease (aorta) and the protective effects of immunosuppressive agent (cyclosporine A, CsA) on aortic injuries in streptozotocin (STZ)-induced diabetic rats. METHODS: STZ-induced diabetic rats were assigned randomly to 6 groups which received low (BML or AML, 1 mgxkg(-1)xd(-1)), middle (BMM or AMM, 4 mgxkg(-1)xd(-1)) or high (BMH or AMH, 8 mgxkg(-1)xd(-1)) dose of CsA from 1 week before or after STZ for 8 weeks. Diabetic rats without any treatment, insulin-treated diabetic rats and normal rats were also monitored simultaneously and served as control groups. The pathologic abnormalities of the aorta were verified by HE, Masson staining and electronmicroscopy. The depositions of immunoglobulins (IgG, IgM and IgA) were determined by immunohistochemistry and immunofluorescence methods. RESULTS: At the end of study, lymphocytes infiltration and collagen content (26 582 +/- 6901) were significantly higher in diabetic aorta than those in non-diabetic aorta (Collagen: 7482 +/- 3491, P < 0.01). The deposited IgG and IgA were also significantly increased in diabetic aorta compared with non-diabetic aorta (IgG: 11 789 +/- 2491 vs. 2518 +/- 1066, P < 0.01; IgA: 17 430 +/- 3159 vs. 1135 +/- 758, P < 0.01). These changes were not affected by insulin while CsA intervention significantly reduced aortic collagen content (BMH: 13 518 +/- 5440, P < 0.01 vs. STZ) and immunoglobulin deposition (BMH: IgG: 7584 +/- 4462; IgA: 6176 +/- 1900, all P < 0.01 vs. STZ). These immunoglobulin deposition changes were confirmed by results of immunofluorescence. Aortic collagen accumulation was positively correlated to aortic immunoglobulin deposition (IgG, r = 0.556, P < 0.01; IgA, r = 0.661, P < 0.01). CONCLUSIONS: Our data suggest that the autoimmune injuries might be a promoting factor in the pathogenesis of the diabetic macrovascular disease which could lead to the development of macrovascular disease. Immunosuppressive agent, such as CsA, could inhibit the abnormal deposition of immunoglobulins and therefore, delay the development of diabetic macrovascular disease in this model.

Differential Expression of Urinary Exosomal Small RNAs in Idiopathic Membranous Nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is a major cause of adult nephrotic syndromes, and reliable noninvasive biomarkers for diagnosis and monitoring are urgently needed. In this study, we performed small RNA (sRNA) sequencing to explore sRNA profiles of urinary exosomes derived from IMN patients and healthy controls (CON) to provide clues for identifying novel noninvasive sRNA biomarkers for IMN. METHODS: Urine samples were collected from five healthy controls and six patients with IMN. High-throughput sequencing was used to screen sRNA expression profiles of urinary exosomes from patients with IMN in two independent cohorts. RESULTS: Urinary exosomes were successfully isolated and used to obtain exosomal sRNAs. We screened 131 differentially expressed miRNAs, including 28 specifically expressed miRNAs, then explored the top 10 specifically expressed miRNAs in all IMN individuals. The specifically expressed miRNAs and differentially expressed miRNAs provide potential biomarkers for IMN. Additionally, we discovered numerous sRNAs derived from genomic repetitive sequences, which could represent an exciting new area of research. CONCLUSION: Herein, we revealed significant differences in expression profiles of urinary exosomal miRNAs and repetitive region-derived sRNAs between patients with IMN and healthy controls. The findings could facilitate the development of potential molecular targets for membranous nephropathy.