Characteristics and predictors of low-grade renal artery stenosis in female patients with CKD.

AIM: Renal artery stenosis (RAS) is an important cause of chronic kidney disease (CKD). The main purpose of this study was to explore the clinical characteristics and predictors of low-grade RAS in female patients with CKD. METHODS: One hundred and five female CKD patients from Huadong Hospital affiliated with Fudan University who underwent 3 T non-contrast renal artery magnetic resonance angiography (MRA) were analyzed. Basic statistics methods were used in the study, such as independent-sample t test,non-parametric test, binary logistic regression analysis and ROC analysis. RESULTS: In this cross-sectional study, there were 50 patients with RAS and 55 without RAS (47.6% versus 52.4%). Binary logistic regression analysis demonstrated that low-level ALB and lymphocyte count, high-level SP, BUN and NLR were independent risk factors for low-grade RAS in female patients with CKD. ROC analysis indicated that eGFR, FeNa and UBCR, ALB, lymphocyte count and NLR had the best predictive value for low-grade RAS, especially eGFR with a sensitivity of 65.50% and specificity of 72.00% and FeNa with a sensitivity of 71.10% and specificity of 72.20% and BUCR with a sensitivity of 71.10% and specificity of 68.10%. CONCLUSION: In female patients with CKD, FeNa, eGFR, ALB, UBCR, lymphocyte count and NLR may be good predictors of low-grade RAS, especially eGFR, FeNa and BUCR.

Identification of key cuproptosis-related genes and their targets in patients with IgAN.

BACKGROUND: IgA nephropathy (IgAN) is one of the most common forms of chronic glomerulonephritis, but the aetiology and pathogenesis remain unclear. Cuproptosis is a newly identified form of cell death that plays an important role in many diseases. Researchers have not clearly determined whether the expression of cuproptosis-related genes (CRGs) is involved in the pathogenesis of IgAN. METHODS: The GSE93798, GSE50469 and GSE37460 datasets containing microarray data from patients with IgAN (63) and healthy controls (31) were downloaded from the GEO database. Immune cells and immune-related functions were analysed in patients with IgAN and controls, and genes were identified that may be related to cuproptosis. A logistic regression model was established according to the results, and then GO and KEGG enrichment analyses were performed. Finally, possible drugs were selected using the DSigDB database. RESULTS: The subjects in the different groups showed significantly different fractions of immune cells and immune-related functions, and 11 genes related to cuproptosis may be involved in these processes. Based on these 11 genes, the ROC curve was plotted, and the AUC value was calculated (0.898, 95% CI: 0.839-0.958). The result revealed good predictability. Then, genes with P < 0.05 (lipoyltransferase 1, LIPT1) were selected to plot an ROC curve, and the AUC value was calculated (0.729, 95% CI: 0.636-0.821). Enrichment analyses showed that the TCA cycle and multiple metabolic pathways may also be involved in the occurrence of IgAN. Finally, 293 potential drugs that may be used to treat IgAN were identified based on these genes. CONCLUSION: In this study, we identified some novel CRGs that may be involved in IgAN, among which LIPT1 was significantly differentially expressed. It may predict the risk of IgAN and provides a possible target for the treatment of IgAN. Further experimental studies are needed to explore how these CRGs mediate the occurrence and development of IgAN.

Polymer-based planar waveguide chirped Bragg grating for high-resolution tactile sensing.

A novel tactile sensor for two-dimensional force location measurements, based on polymer-based planar waveguide chirped Bragg gratings (PPCBGs) fabricated on sheet PMMA substrate, is presented. The planar waveguide and chirped Bragg grating are simultaneously generated using a KrF excimer laser and a phase mask covered by a quartz chrome mask. Location and magnitude of an applied force is measured by observing the change of the wavelength of a dip in the measured spectrum and a change in the reflectivity intensity. Experimental characterization indicates submillimeter spatial resolution of applied force in the range of 1-4 N with a sensitivity of 947.02 pm/mm.

Autophagy-dependent Na+-K+-ATPase signalling and abnormal urate reabsorption in hyperuricaemia-induced renal tubular injury.

Increasing evidence indicates that hyperuricaemia (HUA) is not only a result of decreased renal urate excretion but also a contributor to kidney disease. Na+-K+-ATPase (NKA), which establishes the sodium gradient for urate transport in proximal tubular epithelial cells (PTECs), its impairment leads to HUA-induced nephropathy. However, the specific mechanism underlying NKA impairment-mediated renal tubular injury and increased urate reabsorption in HUA is not well understood. In this study, we investigated whether autophagy plays a key role in the NKA impairment signalling and increased urate reabsorption in HUA-induced renal tubular injury. Protein spectrum analysis of exosomes from the urine of HUA patients revealed the activation of lysosomal processes, and exosomal expression of lysosomal-associated membrane protein-2 was associated with increased serum levels and decreased renal urate excretion in patients. We demonstrated that high uric acid (UA) induced lysosome dysfunction, autophagy and inflammation in a time- and dose-dependent manner and that high UA and/or NKA α1 siRNA significantly increased mitochondrial abnormalities, such as reductions in mitochondrial respiratory complexes and cellular ATP levels, accompanied by increased apoptosis in cultured PTECs. The autophagy inhibitor hydroxychloroquine (HCQ) ameliorated NKA impairment-mediated mitochondrial dysfunction, Nod-like receptor pyrin domain-containing protein 3 (NLRP3)-interleukin-1ß (IL-1ß) production, and abnormal urate reabsorption in PTECs stimulated with high UA and in rats with oxonic acid (OA)-induced HUA. Our findings suggest that autophagy plays a pivotal role in NKA impairment-mediated signalling and abnormal urate reabsorption in HUA-induced renal tubular injury and that inhibition of autophagy by HCQ could be a promising treatment for HUA.

The association of urinary prostaglandins with uric acid in hyperuricemia patients.

PURPOSE: To explore the association between uric acid and urinary prostaglandins in male patients with hyperuricemia. METHODS: A total of 38 male patients with hyperuricemia in outpatients of Huadong Hospital from July 2018 to January 2020 were recruited. Serum uric acid (SUA), 24 h urinary uric acid excretion and other indicators were detected respectively. 10 ml urine was taken to determine prostaglandin prostaglandin D (PGD), prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), 6-keto-PGF1α, thromboxane A2 (TXA2) and thromboxane B2 (TXB2). Fraction of uric acid excretion (FEua) and uric acid clearance rate (Cua) were calculated. According to the mean value of FEua and Cua, patients were divided into two groups, respectively. The independent-samples t test and the Mann-Whitney U test were applied for normally and non-normally distributed data, respectively. RESULTS: After adjusting confounding factors (age, BMI, eGFR, TG, TC, HDL and LDL), SUA was negatively correlated with urinary PGE1(r = -0.615, P = 0.009) and PGE2(r = -0.824, P < 0.001). Compared with SUA1 group (SUA < 482.6 mg/dl), SUA2 (SUA [Formula: see text] 482.6 mg/dl) had lower urinary PGE1(P = 0.022) and PGE2(P = 0.019) levels. Cua was positively correlated with PGE2 (r = 0.436, P = 0.01). The correlation persisted after adjustment for age, BMI, eGFR, TG, TC, HDL and LDL by multiple linear regression analysis. In the Cua1 group (Cua < 4.869 mL /min/1.73 m2), PGE2 were lower than that in Cua2 (Cua [Formula: see text] 4.869 mL /min/1.73 m2) group (P = 0.011). CONCLUSIONS: In male patients with hyperuricemia, SUA was negatively correlated with urinary PGE2, Cua was positively correlated with urinary PGE2. Urinary PGE2 were significantly different between different SUA and Cua groups.

High Level of Serum Uric Acid induced Monocyte Inflammation is Related to Coronary Calcium Deposition in the Middle-Aged and Elder Population of China: A five-year Prospective Cohort Study.

Background: Serum uric acid (SUA) is suspected to be associated with atherosclerosis and calcium deposition in atherosclerosis is known to related poor prognosis, yet there is no cohort study on the aged in China. We aimed to investigate the relationships between SUA levels and coronary calcium deposition in the middle-aged and elderly populations in China. Methods: A total of 326 participants between the ages of 50 and 85 who had undergone a coronary CT scan in 2015 at the Huadong Hospital Affiliated to Fudan University (Shanghai, China) were included in this study. Univariate and multivariate binary logistic regression was performed to analyze the correlation between SUA levels and coronary artery calcium score (CACS). The changes in CACS during a five-year follow-up were analyzed through Kaplan-Meier survival and binary cox regression analysis. An observational study was done on another 104 asymptomatic middle-aged and elderly patients to compare relative mRNA expressions of proinflammatory factors in peripheral blood mononuclear cells (PBMCs) from 104 subjects. Results: Based on the first year of follow-up data analysis, the elevation of SUA levels (P<0.001) is an independent risk factor for the increase of CACS after coordinating the confounding factors. According to five-year follow-up data, cox regression analysis proved that SUA was a risk factor for CACS (HR =5.86, P<0.001). The mRNA expression of IL-6 and CXCL8 in the HUA and HUA patients with CAC (HUA-CAC) groups was significantly higher than that in the normal control (NC) and coronary calcium deposition (CAC) groups. Conclusion: Taken together, the findings in this study indicate that high SUA levels (P<0.001) are an independent risk factor for CACS and elevated SUA levels increase the risk of developing coronary calcium deposition among middle-aged and old people in the Chinese population, which may be related to an increase of pro-inflammatory cytokines in the PBMCs.

Gegen Qinlian Decoction Ameliorates Hyperuricemia-Induced Renal Tubular Injury via Blocking the Inflammatory Signaling Pathway.

Background: Gegen Qinlian decoction (GGQLD) is a typical traditional Chinese medicine (TCM) prescription documented in Shang Han Lun. Clinically, GGQLD has been utilized to manage the inflammatory symptoms of metabolic diseases and to protect against renal damage in China. In the present study, a hypothesis was proposed that the multi-target solution of GGQLD produced anti-inflammatory effects on ameliorating hyperuricemia (HUA). Methods: A total of 30 primary HUA patients receiving GGQLD treatment (two doses daily) for 4 weeks were selected. Then, differences in uric acid (UA) levels and expression of peripheral blood mononuclear cells (PBMCs) and urinary exosomes before and after treatment were analyzed. The therapeutic indexes for the active ingredients in GGQLD against HUA were confirmed through pharmacological subnetwork analysis. Besides, the HUA rat model was established through oral gavage of potassium oxonate and treated with oral GGQLD. In addition, proximal tubular epithelial cells (PTECs) were stimulated by UA and intervened with GGQLD for 48 h. Subsequently, RNA-seq, flow cytometry, and confocal immunofluorescence microscopy were further conducted to characterize the differences in UA-mediated inflammation and apoptosis of human renal tubular epithelial cells pre- and post-administration of GGQLD. In the meanwhile, quantitative real-time PCR (qPCR) was carried out to determine gene expression, whereas a western blotting (WB) assay was conducted to measure protein expression. Results: Our network analysis revealed that GGQLD treated HUA via the anti-inflammatory and antiapoptotic pathways. Additionally, NLPR3 expression significantly decreased in PBMCs and urinary exosomes of HUA patients after GGQLD treatment. In vivo, GGQLD treatment alleviated HUA-induced renal inflammation, which was associated with decreased expression of NLRP3 inflammasomes and apoptosis-related mRNAs. Moreover, GGQLD promoted renal UA excretion by inhibiting the activation of GSDMD-dependent pyroptosis induced by NLRP3 inflammasomes and by reducing apoptosis via the mitochondrial apoptosis signaling pathway in vitro. Conclusion: This study indicates that GGQLD efficiently reduces inflammatory responses while promoting UA excretion in HUA. Our findings also provide compelling evidence supporting the idea that GGQLD protects against the UA-mediated renal tubular epithelial cell inflammation through the mitochondrial apoptosis signaling pathways. Taken together, these findings have demonstrated a novel therapeutic method for the treatment of HUA.

LncRNA and mRNA interaction study based on transcriptome profiles reveals potential core genes in the pathogenesis of human thoracic aortic dissection.

The aim of the present study was to determine the potential core genes in the pathogenesis of human thoracic aortic dissection (TAD) by analyzing microarray profiles of long non­coding (lnc)­RNAs between TAD and normal thoracic aorta (NTA). The differentially expressed lncRNA profiles of the aorta tissues between TAD patients (TAD group, n=6) and age­matched donors with aortic diseases (NTA group, n=6) were analyzed by lncRNAs microarray. Gene ontology (GO), pathway and network analyses were used to further investigate candidate lncRNAs and mRNAs. Differentially expressed lncRNAs and mRNAs were validated by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). In total, the present study identified 765 lncRNAs and 619 mRNAs with differential expression between TAD and NTA (fold change >2.0, P<0.01). GO analysis demonstrated that the differentially upregulated lncRNAs are associated with cell differentiation, homeostasis, cell growth and angiogenesis. Kyoto Encyclopedia of Gene and Genomes pathway analysis demonstrated that the differentially downregulated lncRNAs are mainly associated with arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy and dilated cardiomyopathy. To reduce the lncRNAs for further investigation and to enrich those potentially involved in TAD, a total of 16 candidate lncRNAs with a significant expression (fold change >4, P<0.01) were selected, that were associated with an annotated protein­coding gene through the GO term and scientific literatures. Then a set of significantly expressed lncRNAs [purinergic receptor P2X7 (P2RX7), hypoxia inducing factor (HIF)­1A­AS2, AX746823, RP11­69I8.3 and RP11­536K7.5) and the corresponding mRNAs (P2RX7, cyclin dependent kinase inhibitor 2B, HIF­1A, runt­related transcription factor 1, connective tissue growth factor and interleukin 2 receptor a chain] were confirmed using RT­qPCR. The present study revealed that the expression profiles of lncRNAs and mRNAs in aorta tissues from TAD were significantly altered. These results may provide important insights into the pathogenesis of TAD disease.

[Minimally invasive percutaneous pedicle screw fixation for the treatment of thoracolumbar fractures and posterior ligamentous complex injuries].

OBJECTIVE: To evaluate the efficacy and safety of minimally invasive percutaneous pedicle screw for the management of neurologically intact patients with thoracolumbar burst fractures and posterior ligamentous complex injuries. METHODS: In the study, 35 patients were reviewed,including 20 males and 15 females, with an average age of 34.1 years (18 to 52), and the mean follow-up for 25.8 months (24 to 36). RESULTS: The duration of surgery was (95.8±12.3) minutes and intraoperative blood loss was (83.0±40.7) mL. There were no major perioperative complications, with the exception of 2 patients who developed a superficial wound infection. LKA and VBH were significantly improved immediately after surgery (P<0.001). No significant loss of correction was observed in all the patients(P>0.05). Screw misplacement was observed in 9/140 (6.4%) and no patient showed neurological deficit as a result of screw misplacement. CONCLUSION: The minimally invasive percutaneous pedicle screw has a good clinical outcome in the treatment of thoracolumbar burst fractures with posterior ligamentous complex injury, which could maintain the fracture reduction effectively, and minimize the iatrogenic soft tissue injury.

[Treatment of lumbar disc herniation by modified transforaminal lumbar interbody fusion with a pedicle screw system].

OBJECTIVE: To evaluate the outcomes of modified transforaminal lumbar interbody fusion in patients with lumbar disc herniation. METHODS: Forty-six cases of lumbar disc herniation were treated by modified transforaminal lumbar interbody fusion. There were 32 males and 14 females with a mean age of 47 years old (range: 27 - 65). The mean course of disease was 7.5 years (range: 4 - 18). Eighteen cases were of single-level lumbar disc herniation, including L3/4 (n = 5), L4/5 (n = 8) and L5/S1 (n = 5). There were 28 cases with lumbar degenerative diseases at other levels. Preoperatively, the score of visual analogue scale (VAS) was 8.9 ± 1.3 and the score of Oswestry disability index (ODI) was 57.3 ± 5.2. All patients received a normal conservative treatment for at least 3 months with no therapeutic effect at pre-operation. RESULTS: Forty-six cases had an average follow-up of 20 months (range: 12 - 20). The operative duration was an average of 160 minutes (range: 120 - 180). And the average volume of intra-operative blood loss was 550 ml (range: 400 - 800). There was no severe complication. The symptoms became stable after three months. At 3 months postoperatively, the score of VAS was 2.0 ± 0.4 and the score of ODI 15.2 ± 3.4. And there were significant differences between preoperative and postoperative values (P < 0.05). The improvement rates of postoperative VAS and ODI were (80.1 ± 4.7)% and (73.6 ± 2.8)% respectively. All patients achieved lumbar interbody bone fusion at 12 months post-operation with a fusion rate of 100%. For the therapeutic effect, 34 cases were regarded as excellent, 8 good and 4 fair with an excellent/good rate of 91.3%. All patients began to walk with orthosis after 3 days and resumed their jobs and normal lives after 3 months. CONCLUSION: Modified transforaminal lumbar interbody fusion is effective for the treatment of lumbar disc herniation. Making a detailed operative plan on the basis of preoperative images and symptoms is essential.

Electroacupuncture promotes insulin-like growth factors system in ovariectomized osteoporosis rats.

Postmenopausal Osteoporosis (PMOP) is induced by the deficiency of estrogen in postmenopausal women. Electroacupuncture (EA) has been confirmed to be effective in clinic. We adopted ovariectomized osteoporosis model of rats to observe the role of EA in PMOP. Fifty female SD rats were divided randomly into 5 groups: intact (INT, n = 10), sham operation (Sham, n = 10), model (n = 10), estrogen (E, n = 10) and electroacupuncture (EA, n = 10). The bone mineral content (BMC) and the bone mineral density (BMD) were examined in lumbar(1-6) and right thigh-bone, respectively, and estrodiol (E(2)), insulin-like growth factor I (IGF-I) and insulin-like growth factor binding proteins (IGF-BPs) were tested by RIA or ELISA. The results showed that BMC and BMD of lumbar 1-6 and right thigh-bone in PMOP model rats decreased markedly, while the level of serum E(2), IGF-I and IGF-BP1 were lower than in INT and Sham. However, EA could upgrade the contents of IGF-I and IGF-BP1 to increase BMD in PMOP rats, while no significant difference was seen in E group. Therefore, EA may promote IGF system to improve PMOP.