Specialized cis-Acting RNA Elements Balance Genome Cyclization to Ensure Efficient Replication of Yellow Fever Virus.

Genome cyclization is essential for viral RNA (vRNA) replication of the vertebrate-infecting flaviviruses, and yet its regulatory mechanisms are not fully understood. Yellow fever virus (YFV) is a notorious pathogenic flavivirus. Here, we demonstrated that a group of cis-acting RNA elements in YFV balance genome cyclization to govern efficient vRNA replication. It was shown that the downstream of the 5'-cyclization sequence hairpin (DCS-HP) is conserved in the YFV clade and is important for efficient YFV propagation. By using two different replicon systems, we found that the function of the DCS-HP is determined primarily by its secondary structure and, to a lesser extent, by its base-pair composition. By combining in vitro RNA binding and chemical probing assays, we found that the DCS-HP orchestrates the balance of genome cyclization through two different mechanisms, as follows: the DCS-HP assists the correct folding of the 5' end in a linear vRNA to promote genome cyclization, and it also limits the overstabilization of the circular form through a potential crowding effect, which is influenced by the size and shape of the DCS-HP structure. We also provided evidence that an A-rich sequence downstream of the DCS-HP enhances vRNA replication and contributes to the regulation of genome cyclization. Interestingly, diversified regulatory mechanisms of genome cyclization, involving both the downstream of the 5'-cyclization sequence (CS) and the upstream of the 3'-CS elements, were identified among different subgroups of the mosquito-borne flaviviruses. In summary, our work highlighted how YFV precisely controls the balance of genome cyclization to ensure viral replication. IMPORTANCE Yellow fever virus (YFV), the prototype of the Flavivirus genus, can cause devastating yellow fever disease. Although it is preventable by vaccination, there are still tens of thousands of yellow fever cases per year, and no approved antiviral medicine is available. However, the understandings about the regulatory mechanisms of YFV replication are obscure. In this study, by a combination of bioinformatics, reverse genetics, and biochemical approaches, it was shown that the downstream of the 5'-cyclization sequence hairpin (DCS-HP) promotes efficient YFV replication by modulating the conformational balance of viral RNA. Interestingly, we found specialized combinations for the downstream of the 5'-cyclization sequence (CS) and upstream of the 3'-CS elements in different groups of the mosquito-borne flaviviruses. Moreover, possible evolutionary relationships among the various downstream of the 5'-CS elements were implied. This work highlighted the complexity of RNA-based regulatory mechanisms in the flaviviruses and will facilitate the design of RNA structure-targeted antiviral therapies.

Non-motor symptoms are associated with midline tremor in essential tremor.

OBJECTIVES: Essential tremor (ET) patients presenting tremor in the midline structures may be a distinct subtype of the syndrome. Therefore, we sought to explore the clinical manifestations, especially non-motor symptoms (NMS) of Chinese ET patients with midline tremor (MT). METHODS: In the cross-sectional study, we grouped 290 definite or probable ET patients based on their MT conditions. The NMS in ET patients were evaluated using the NMS scale (NMSS). NMS and other clinical correlates were then compared among subgroups with, and without MT. RESULTS: We revealed that 39.0%, 27.6%, and 6.9% of the patients respectively had neck, voice, and facial tremors. With the accumulation of tremor in midline structures, NMS became more severe and prevalent. Logistic regression analyses revealed that factors such as: female gender (OR = 2.164, 95% CI: 1.307-3.583), having least or highest action arm tremor (OR = 2.512, 95% CI: 1.520-4.151), having higher score of sleep/fatigue domain (OR = 1.692, 95% CI: 1.004-2.850) and mood/apathy (OR = 1.926, 95% CI: 1.143-3.246) domain, to be independently associated with MT manifestation. CONCLUSIONS: Our study demonstrates the heterogeneity of symptoms in ET patients with MT, especially in prominent NMS. In addition, the discrepancy of NMS between patients with, and without MT provides novel insight into the underlying pathophysiology and therapeutic of ET.

Lack of association between appendectomy and Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Accumulation of aggregated α-synuclein from the enteric nervous system is believed to be involved in the pathogenesis of Parkinson's disease (PD). The appendix contains abundant α-synuclein and lacks a blood-tissue barrier, suggesting that appendectomy might reduce α-synuclein aggregation, and therefore the risk of PD. Studies on this intriguing possibility have not come to consistent conclusions. METHODS: PubMed, Embase (via Ovid), and the Cochrane Controlled Register of Trials were searched for studies published through February 20, 2019 on the potential relationship between appendectomy and PD. Two reviewers independently screened literature, extracted data and evaluated the quality of included studies. Data were summarized as pooled effect sizes (RRs or SMDs) with 95% confidence intervals (CIs), which were calculated using the inverse variance method and a random-effects model. Heterogeneity was assessed using the I2 statistic and explored in subgroup analyses. RESULTS: Of the 408 references screened, six studies involving 3,554,540 people were included eventually. Appendectomy did not significantly affect PD risk (RR 1.02, 95% CI 0.87-1.20, I2 = 83.1%, P = 0.789) or delay its onset (SMD 0.21, 95% CI - 0.03 to 0.44, I2 = 43.4%, P = 0.083). CONCLUSION: The available evidence suggests no protective effect of appendectomy against PD. Future studies should seek to clarify the role of inflammation, α-synuclein pathology and the gut-brain axis in PD pathogenesis.

Evaluation of Quiescent-Interval Single-Shot Magnetic Resonance Angiography in Diabetic Patients With Critical Limb Ischemia Undergoing Digital Subtraction Angiography: Comparison With Contrast-Enhanced Magnetic Resonance Angiography With Calf Compression at 3.0 Tesla.

PURPOSE: To assess the diagnostic performance of quiescent-interval single-shot magnetic resonance angiography (QISS-MRA) at 3 tesla in diabetic patients with critical limb ischemia (CLI) vs contrast-enhanced MR angiography (CE-MRA) using digital subtraction angiography (DSA) as the standard of reference. METHOD: Thirty-seven consecutive diabetic patients (mean age 71.8±7.2 years; 30 men) with CLI (Fontaine stage III-IV) underwent QISS-MRA and CE-MRA with calf compression; DSA was the standard. Image quality (5-point Likert-type scale) and stenosis severity (5-point grading) for QISS-MRA and CE-MRA were evaluated by 2 blinded readers in 1147 and 654 vessel segments, respectively. Per-segment and per-region (pelvis, thigh, calf) sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Image quality of QISS-MRA was lower compared with CE-MRA in the pelvic region (p<0.001 in both readers) and thigh region (p=0.033 in reader 1 and p=0.018 in reader 2), whereas in the calf region, the image quality of QISS-MRA was better than CE-MRA (p=0.009 in reader 1 and p=0.001 in reader 2). In segment-based analyses, there was no difference between QISS-MRA and CE-MRA in sensitivity [89.5% vs 90.3% in reader 1 (p=0.774) and 87.6% vs 90.6% in reader 2 (p=0.266)] or specificity [94.2% vs 92.9% in reader 1 (p=0.513) and 92.9% vs 92.9% in reader 2 (p>0.999)]. In region-based analyses, QISS-MRA and CE-MRA yielded similar sensitivity and specificity in all areas but the pelvic region for reader 2 (specificity 95.5% vs 84.8%, p=0.041). CONCLUSION: QISS-MRA performed very well in diabetic patients with CLI and was a good alternative for patients with contraindications to CE-MRA.

MicroRNA-203 Acts as a Potent Suppressor in Septic Shock by Alleviating Lung Injury via Inhibition of VNN1.

BACKGROUND: Septic shock, the most serious complication of sepsis, is a life-threatening disease that is mainly characterized by hypoperfusion and multiple organ failure. Various aberrantly expressed microRNAs (miRNAs) have been reported to be related to septic shock. We explored the regulatory effect of microRNA-203 (miR-203) on lung injury in septic shock mice. METHODS: Microarray-based gene expression profiling related to septic shock identified the differentially expressed gene vanin-1 (VNN1) and potential regulatory miR-203. miR-203 was predicted to mediate VNN1 expression, thus affecting septic shock, which was investigated by treatment with miR-203 mimic, miR-203 inhibitor, and siRNA-VNN1 in septic shock mouse models. Polymorphonuclear neutrophils (PMNs) and pulmonary alveolar macrophages in bronchoalveolar lavage fluid (BALF) as well as the wet/dry ratio of the lung were also measured to assess lung injury. Additionally, the effects of miR-203 on inflammatory cytokines, oxidative stress indexes, blood biochemical indexes, serine-threonine protein kinase (AKT) signaling pathway-related factors, and apoptosis-related factors were determined. RESULTS: VNN1 was verified to be targeted and negatively regulated by miR-203. In mouse models of septic shock, weak expression of miR-203, high expression of VNN1, and inhibition of AKT signaling pathway were identified. In response to miR-203 mimic and VNN1 gene silencing, mouse models of septic shock displayed reduced apoptosis, MDA, ALT, and AST in lung tissues, decreased levels of TNF-α, IL-1ß, IFN-γ, IL-10, and IL-6, in serum, and reduced PMN and PAM levels in BALF, in addition to elevated SOD activity. Notably, the presence of miR-203 mimic led to AKT signaling pathway activation. CONCLUSION: This study shows that upregulating miR-203 can alleviate lung injury through activation of the AKT signaling pathway by downregulating VNN1 in septic shock.

Microwave ablation of hyperplastic parathyroid glands is a treatment option for end-stage renal disease patients ineligible for surgical resection.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a frequently encountered problem in patients with end-stage renal disease (ESRD). Some patients with severe SHPT could not be managed by medical treatment and are ineligible for surgical resection. PURPOSE: Our objective was to evaluate the efficacy, safety of microwave ablation (MWA) on these patients. MATERIALS AND METHODS: Between 1 April 2015 and 28 February 2017, 35 patients (M/F 19/16, age 49.8 ± 12.9 years) were enrolled. All patients were treated with MWA. Levels of intact parathyroid hormone (iPTH) and of serum calcium and phosphorus were compared pre- and post-ablation. Repeated-measures ANOVA was used to compare treatment outcomes pre- and post-ablation. RESULTS: Complete ablation was achieved in all 63 glands in the 35 patients with SHPT. The mean follow-up time was 15.9 ± 2.2 months. The maximum gland diameter was 6-31 mm (mean, 14.9 ± 5.5 mm). The trends of the changes in iPTH and calcium levels showed a curve: the level of iPTH and calcium at 6 months post-ablation were lower than those pre-ablation (both p < .0001); after then iPTH remained relatively stable and the end of follow up, with no rebound (p < .0001), while instead of calcium at the end of follow up was not significantly lower than pre-ablation (p = .462). The trend in the change in phosphate levels showed a straight line; the level of phosphate at 6 months post-ablation and at the end of follow up both were significantly lower than pre-MWA (p < .001). There was no major complication. CONCLUSIONS: In this series, MWA was used successfully to treat SHPT patients who are ineligible for surgical resection.

Morphological characteristics of chronic total occlusion: predictors of different strategies for long-segment femoral arterial occlusions.

OBJECTIVES: To investigate morphological characteristics used to predict recanalisation strategies in long-segment (>10 cm) femoral chronic total occlusion (LSF-CTO) angioplasty. METHODS: We retrospectively evaluated a range of morphological CTA and DSA features in patients who underwent recanalisation of LSF-CTO. The stage of CTO was classified into early (3-12 months) and late (>12 months) according to estimated duration. Characteristics including stump morphology, lesion length and calcification, proximal side branches, collaterals circulation, runoff vessels and concomitant arterial occlusion were used as predictors, and multivariate logistic regression analysis was performed to identify variables associated with late-stage CTO and retrograde technique. RESULTS: A total of 119 patients with 137 CTOs in 137 limbs were enrolled. Overall, successful recanalisation was achieved in 122 CTOs (89.1%). Flush occlusion [odds ratio (OR) 2.958; 95% confidence interval (CI) 1.172-7.465; p = 0.022], large collateral (OR 2.778; 95% CI 1.201-6.427; p = 0.017) and TransAtlantic Inter-Society Consensus II class D (TASC D) lesion (OR 1.743; 95% CI 1.019-2.981; p = 0.042) were predictors for late-stage CTO. Flush occlusion (OR 75.278; 95% CI 10.664-531.384; p < 0.001) and large collateral (OR 23.213; 95% CI 3.236-166.523; p = 0.002) were associated with high likelihood for retrograde approach. CONCLUSIONS: Flush occlusion and large collateral were associated with a CTO at late-stage which may require retrograde recanalisation. KEY POINTS: • CTO morphological characteristics help estimate lesion duration and optimise recanalisation strategies. • Flush occlusion and large collateral is associated with late-stage CTO and retrograde recanalisation. • Application of anterograde and retrograde recanalisation for long-segment femoral CTO is effective.

Correction to: Morphological characteristics of chronic total occlusion: predictors of different strategies for long-segment femoral arterial occlusions.

The original version of this article unfortunately contained mistakes. The legends to Figs. 2-4 were incorrectly interchanged. The correct versions are given below. The original article has been corrected.

String-like lumen in below-the-knee chronic total occlusions on contrast-enhanced magnetic resonance angiography predicts intraluminal recanalization and better blood flow restoration.

OBJECTIVES: To determine whether string-like lumina (SLs) on contrast-enhanced magnetic resonance angiography (CE-MRA) predict better outcomes in diabetic patients with below-the-knee (BTK) chronic total occlusions (CTOs). METHODS: This study involved 317 long-segment (>5 cm) BTK CTOs of 245 patients that were examined using CE-MRA and treated using endovascular angioplasty. An SL with a CTO was slowly filled with blood on conventional CE-MRA. Univariate and multivariate analyses were performed to identify predictors of procedural success, recanalisation method and immediate blood flow restoration. The target-lesion patency and limb-salvage rates were assessed. RESULTS: SL-positive CTOs (n = 60) achieved a higher technique success rate, preferred intraluminal angioplasty and better blood flow restoration than SL-negative CTOs (n = 257, P < 0.05). Multivariate analyses revealed that lesion length was the independent predictor of procedural success (P = 0.028). SL was a predictor of intraluminal angioplasty (P < 0.001) and good blood-flow restoration (P = 0.004). Kaplan-Meier analyses at 12 months revealed a higher target lesion patency rate (P = 0.04) and limb-salvage rate (P = 0.35) in SL-positive CTOs. CONCLUSIONS: In patients with BTK CTOs, SL predicted intraluminal angioplasty and good blood-flow restoration for BTK CTOs. KEY POINTS: • Intraluminal recanalisation was more frequently used for BTK-CTOs with SLs than without • CTO length was the only independent predictor of successful CTO recanalisation • SL was the only predictor of intraluminal angioplasty for BTK-CTOs • SL and CTO length were predictors of good blood-flow restoration after recanalisation • Restenosis-free and limb-salvage rates were better for SL-positive CTOs than SL-negative CTOs.

Rendezvous technique for recanalization of long-segmental chronic total occlusion above the knee following unsuccessful standard angioplasty.

PURPOSE: To assess the technical feasibility and efficacy of the rendezvous technique, a type of subintimal retrograde wiring, for the treatment of long-segmental chronic total occlusions above the knee following unsuccessful standard angioplasty. METHODS: The rendezvous technique was attempted in eight limbs of eight patients with chronic total occlusions above the knee after standard angioplasty failed. The clinical symptoms and ankle-brachial index were compared before and after the procedure. At follow-up, pain relief, wound healing, limb salvage, and the presence of restenosis of the target vessels were evaluated. RESULTS: The rendezvous technique was performed successfully in seven patients (87.5%) and failed in one patient (12.5%). Foot pain improved in all seven patients who underwent successful treatment, with ankle-brachial indexes improving from 0.23 ± 0.13 before to 0.71 ± 0.09 after the procedure (P < 0.001). At the end of the follow-up period, the visual analogue scale improved from 6.86 ± 1.57 to 1.57 ± 1.27 (P < 0.001). Non-healing ulcers in three patients either healed (n = 2) or improved (n = 1). No major amputation was necessary. Kaplan-Meier analyses revealed that stenosis-free rate was 83.3% at six months and 41.7% at 12 months. CONCLUSION: The rendezvous technique is a feasible and effective treatment for chronic total occlusions above the knee when standard angioplasty fails.

Runoff detected by magnetic resonance angiography as an indicator for better recanalization outcomes in below-the-knee chronic total occlusions in diabetic patients.

PURPOSE: To compare the feasibility and efficacy of recanalizing below-the-knee (BTK) chronic total occlusions (CTOs) between patients with good or poor distal runoff based on magnetic resonance angiography (MRA) scans. METHODS: Two hundred long-segment BTK CTOs in 171 limbs of 113 diabetic patients (58 men; mean age 69.8±1.9 years) were divided into good distal runoff (GDR: 119 lesions, 98 limbs) or poor distal runoff groups (PDR: 81 lesions, 73 limbs) based on baseline MRA findings. After angioplasty, modified thrombolysis in myocardial ischemia (mTIMI) grades and ankle-brachial index (ABI) were used to assess immediate outcomes. Regularly scheduled duplex or MRA imaging was performed in follow-up. The restenosis and limb salvage rates were compared. RESULTS: The success rates were 93.3% and 87.7% in the GDR and PDR groups, respectively (p=0.21); subintimal angioplasty was more common in the PDR group (93.0% vs. 63.1%, p<0.01). Completion angiography indicated an mTIMI grade 3 blood flow in 71.2% lesions in the GDR patients and in 52.1% in the PDR (p=0.01) group. Improvement in the ABI was greater in the GDR limbs (p<0.001 vs. PDR). Mean imaging follow-up was 10.8±6.9 months in the GDR group and 11.1±6.6 months in the PDR group. Kaplan-Meier analysis showed a better restenosis-free rate in the GDR group (80.6% vs. 61.7%; p=0.02) at 12 months and for lesions with mTIMI grade 3 flow (p<0.01). At 24 months, Kaplan-Meier analysis revealed a better limb salvage rate in the GDR group (84.2% vs. 54.6%; p=0.02). CONCLUSION: Distal runoff detected using MRA could be a predictor for successful intraluminal recanalization, better distal tissue perfusion, improved long-term patency, and better limb salvage for patients with BTK CTOs.

Excitotoxic effects of glutamate on cochlear organotypic cultures.

Glutamate (Glu) is the major afferent excitatory neurotransmitter in the auditory system, and excessive Glu may play an important role in cochlear dysfunction. It is unclear how excessive Glu plays roles in cochlear dysfunction in cochlear organotypic cultures. In this study neonatal rat cochlear organotypic cultures were prepared, and then the cochlear tissues were incubated with a new medium containing specific concentrations of Glu (0.1, 0.5, 1, 10 or 20 mmol/L) for 24 h, or incubated with the medium containing a concentration of 20 mmol/L Glu for 6, 12, 24 or 72 h, respectively. It was found that when the cochlear tissues were cultured for 24 h, the inner hair cells (IHCs) were damaged at the concentration of 0.5 mmol/L Glu, and with the increases of the concentrations, the injury was gradually aggravated, and 20 mmol/L Glu resulted in the significant loss of IHCs. In the 20 mmol/L Glu groups, the stereocilia bundles were missing or disarrayed on a few IHCs after culture for 6 h and the damage effect was time-dependent. The missing of IHCs was more significant in the basal turn of the cochlea than in the middle turn of the cochlea under the same concentration of Glu exposure. These results suggest that excessive exogenous Glu affects the morphology of IHCs, but not affects the outer hair cells (OHCs) in cochlear organotypic cultures, and the excitotoxic effects are different on IHCs of different parts of the cochlea under the same concentration of Glu exposure.

Patency of runoff detected by MR angiography at 3.0 T with cuff-compression: a predictor of successful endovascular recanalization below the knee.

OBJECTIVES: Our aim was to assess the reliability of detecting distal runoff vessels using contrast-enhanced MR angiography (CE-MRA) that were occult on digital subtraction angiography (DSA) for predicting the outcome of endovascular recanalization (ER). METHODS: This retrospective analysis comprised 63 patients with diabetes (98 limbs) who underwent ER for infrapopliteal lesions. Before ER, they underwent CE-MRA and DSA for peripheral arterial disease; runoff vessels were detected with CE-MRA, but not with DSA. Immediate and follow-up postoperative outcomes were assessed. Univariate analysis was performed to identify variables associated with successful ER. RESULTS: Successful ER was achieved in 85.7 % of limbs, and runoff score was significantly lower than in failure limbs (5.1 ± 1.1 vs. 6.2 ± 1.3; P < 0.05). During follow-up, sustained ankle-brachial index (ABI) improvement was found in 76.6 % claudication patients, and walking distance improvement in 86.5 %; pain was relieved in 70.6 % of critical limb ischemia (CLI) limbs, ulceration healed in 81.3 %, and limb-salvage rate was 100 %. Restenosis/occlusion rate was higher for patients with CLI at 12 months (48.8 % vs. 96.3 % in claudication; P < 0.01). Runoff score was associated with a significantly higher likelihood of ER success (odds ratio = 4.096, 95 % confidence interval: 2.056-8.158; P < 0.001). CONCLUSION: Runoff vessels detected using CE-MRA could indicate immediate success and better outcome of ER for infrapopliteal occlusions. KEY POINTS: • 3-T MRA with cuff compression displayed distal below-the-knee (BTK) runoffs better than DSA • Detected runoffs indicate high recanalization rate and good clinical outcome • Runoff display provides potential opportunity to perform other backup recanalization strategies.

Accuracy of 3.0T magnetic resonance angiography for the detection of arteriovenous fistula dysfunction in hemodialysis patients requiring interventional therapy: a prospective study.

Background: Color Doppler ultrasonography (CDUS) is feasible to detect arteriovenous fistula (AVF) dysfunction in hemodialysis patients but is not sufficient to map the structure of fistula required for interventions. This study is designed to evaluate the diagnostic accuracy of three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) at 3.0T versus CDUS for AVF dysfunction, by using digital subtraction angiography (DSA) as reference. Methods: This prospective study enrolled 68 consecutive patients with dysfunctional AVF who underwent both CDUS and TOF-MRA at Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The analysis of the dysfunctional AVFs was divided into three regions: the feeding artery, fistula and draining veins. In the whole- and per-regional-based analyses, two observers who were blinded to the clinical and DSA results independently analyzed all CDUS and TOF-MRA datasets. The image quality and stenosis severity of the lesions on TOF-MRA were evaluated. A receiver operating characteristic curve was applied to analyze the detection of AVF dysfunction with TOF-MRA. Results: A total of 204 vessel regions were evaluated. The whole-region-based image quality of TOF-MRA was poorer in patients with a total occlusion (1.8±0.8) than in those with stenosis (2.7±0.6, P<0.001). In the whole-region analyses, TOF-MRA had higher sensitivity [99.1% (94.6-100.0%) vs. 82.9% (74.6-89.0%), P<0.001] and similar specificity [93.1% (85.0-97.1%) vs. 94.3% (86.5-97.9%), P=0.755] than CDUS. The per-region-based analyses showed that TOF-MRA yielded higher sensitivity [fistula region, 98.1% (88.4-99.9%) vs. 80.8% (67.0-89.9%); P=0.004; draining vein region, 100.0% (92.5-100.0%) vs. 85.0% (72.9-2.5%); P=0.003] and similar specificity [fistula region, 88.2% (62.3-97.8%) vs. 88.2% (62.3-97.9%); P>0.99; draining vein region, 100.0% (59.8-100.0%) vs. 87.5% (46.7-99.3%); P>0.99] than CDUS. Sensitivity and specificity of TOF-MRA were comparable to those of CDUS in feeding artery region. Conclusions: TOF-MRA is a feasible and accurate method to display AVF dysfunction in hemodialysis patients, and this method might fulfill the endovascular treatment planning requirements.

Unraveling DDIT4 in the VDR-mTOR pathway: a novel target for drug discovery in diabetic kidney disease.

Introduction: Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within the VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery. Methods: Transcriptome data from the Gene Expression Omnibus Database were analyzed to assess the expression of mTOR and VDR expression in human renal tissues. Clinical samples from DKD patients and minimal change disease (MCD) controls were examined, and a DKD animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection was employed to modulate the VDR-mTOR pathway, with its components evaluated using immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). Results: Changes in the expression of the VDR-mTOR pathway were observed in both DKD patients and the animal model. Overexpression of DDIT4 increased VDR expression and decreased levels of mTOR, p70s6k, and 4E-BP1. Furthermore, DDIT4 treatment regulated autophagy by upregulating LC3I expression and downregulating LC3II expression. Notably, DDIT4 alleviated oxidative stress by reducing the levels of lipid peroxidation product MDA, while simultaneously increasing the levels of superoxide dismutase (SOD) and glutathione (GSH), underscoring the role of DDIT4 in the pathological process of DKD and its potential as a therapeutic target. Conclusion: Unraveling DDIT4's involvement in the VDR-mTOR pathway provides insights for innovative DKD drug discovery, emphasizing its potential as a therapeutic target for future interventions.

Expression of RACGAP1 in high grade meningiomas: a potential role in cancer progression.

Recently, Rac GTPase-activating protein 1 (RACGAP1) has been shown to have a critical role in various tumors. The aim of the present study was to investigate the expression of RACGAP1 in human meningiomas and to compare these results with the clinicopathological parameters. Thirty-two cases, classified as 13 World Health Organization grade I (40.6 %), 10 grade II (31.3 %) and 9 grade III (28.1 %) primary meningiomas, were selected from our pathological files. Clinico-pathological data, including survival data, were also available. RACGAP1 expression in the meningiomas was measured by real-time quantitative PCR and western blot. Our results showed the level of RACGAP1 expression in grade III meningioma is higher than that of grade I. Higher levels of RACGAP1 mRNA were significantly correlated with tumor size, higher Simpson grade, histological type and clinical course (P < 0.05). Furthermore, the level of RACGAP1 expression mRNA was positively correlated with MIB-1 labeling index in different meningiomas tissue (r(2) = 0.3237, P = 0.0007). Additionally, Kaplan-Meier curves demonstrated a significantly worse survival in patients with high levels of RACGAP1 mRNA (P = 0.008). In conclusion, these findings suggest that RACGAP1 may be used as a potential predictor for tumor proliferative and patient prognosis in meningiomas.

Application of protective stents in endovascular repair of acute complicated Stanford type B aortic dissections.

PURPOSE: To describe the use of protective stents in the endovascular repair of acute complicated Stanford type B aortic dissections. METHODS: From 2009 to 2011, 33 patients (27 men; mean age 47 years, range 31-73) with acute complicated Stanford type B aortic dissection underwent thoracic endovascular aortic repair (TEVAR) assisted by protective stents. In all cases, the proximal and distal landing zones differed in size by >5 mm, and the primary entry tear was in the proximal descending aorta. A bare self-expanding stent (protective stent) was deployed initially at the intended distal landing site of the primary stent-graft in the true lumen. The intention was that the bare stent would prevent excessive dilation of the distal end of the stent-graft in the vicinity of the entry tear, thus avoiding intimal rupture. RESULTS: Successful stent deployment and sealing of the entry tear was achieved in all patients. The median diameter and length of the protective bare stents was 20.3 mm (range 18-24) and 72.7 mm (range 60-80), respectively, while the corresponding dimensions of the covered stent-grafts were 32.8 mm (range 26-40) and 157.4 mm (range 120-200 mm), respectively. There was no stent twisting, migration, of rupture of the false or true lumen. Computed tomography 1 week postoperatively demonstrated closure of the primary entry tear with thrombosis of the false lumen in all cases. No patients were lost to follow-up, which has ranged from 3 months to 3 years. No late endoleaks or stent complications, such as angulation, dislodgment, persistent leaks, branch obstruction, or stent-graft migration, have been observed, and there has been no chronic progressive true or false lumen dilatation, recurrences, or deaths. CONCLUSION: Adjunctive use of a protective stent when treating acute Stanford type B aortic dissections in which the diameters of the proximal and distal landing zones differ by >5 mm is feasible and safe and provides good short-term outcomes.

Relationship Between the Expression of LC3 (Microtubule-Associated Protein 1A/1B-Light Chain 3) in Nasal Mucosa and Serum IL-5 and IL-4 Concentrations in Allergic Rhinitis Mice.

Objective: To investigate the expression and correlation of autophagy-related microtubule-associated protein 1 light chain 3 beta LC3 and interleukin-5 IL-5 in allergic rhinitis AR. Methods: Fifty-six 7-week-old BALC/C mice were randomly divided into experimental group (n = 56) and control group (n = 8). The experimental group used Dermatophagoides farinae (Der f) for AR modeling, and control group used PBS solution. As the experimental group sampled at 6 time points, and 8 mice were sacrificed each time, while the control group was sacrificed 24 hours after the last dose. The contents of serum IL-4, IL-5, and dust mite specific IgE HDM-sIgE in mice were detected by enzyme-linked immunosorbent assay ELISA, and the morphological changes of nasal mucosa were detected by a hematoxylin-eosin H&E staining. The expression of LC3 in mouse nasal mucosa was detected by immunohistochemical staining. Spearman correlation coefficient was used to assess the relationship between LC3 and IL-5 levels. Results: In AR mice modelled with dust mites, the serum levels of IL-4 and HDM-sIgE increased gradually, and the serum IL-5 concentration had a peak at the early intraperitoneal administration stage similar to that at the end of modelling. The LC3 level in nasal mucosa of AR mice modelled with dust mites increased gradually in the early stages, but stabilized in the later stages. The expression of LC3 level in nasal mucosa was a positively correlated ration between serum IL-5 level in AR mice. Conclusion: In the early stage of AR mice, the level of nasal mucosal autophagy and serum IL-5 levels were significantly increased and correlated, suggesting that nasal mucosal autophagy played a promoting role in the early stage of AR.

[Characteristics and Source Apportionment of Volatile Organic Compounds in Zhanjiang in Summer].

Ozone pollution is intensifying in China, and its related studies are weak in non-focus regions and non-focus cities. Here, we investigated the characteristics and sources of volatile organic compounds (VOCs) at three sampling sites in Zhanjiang. We analyzed 101 VOCs using a gas chromatography-mass spectrometry/hydrogen ion flame detector (GC-MS/FID) and high-performance liquid chromatography (HPLC) using a Summa canister and DNPH adsorption tube. We calculated the ozone formation potential (OFP) of VOCs and used the positive matrix factorization (PMF) model for source apportionment. The results showed that the mean φ(TVOCs) was 1.28×10-7, and the dominant contributors were OVOCs (52%), followed by alkanes (36%), alkenes (7%), halogenated hydrocarbons (2.42%), aromatic hydrocarbons (1.61%), and alkynes (0.78%). The diurnal variation in VOCs was influenced by photochemical reactions; the ratio of aromatic hydrocarbons and alkanes was high in the morning and evening and low at noon, whereas OVOCs had a low ratio in the morning and noon and high in the evening, influenced by primary emissions and the upwind transport of pollutants. The OFP was 3.28×10-7, and the dominant species were formaldehyde, butene, n-butane, butanone, and acetaldehyde.The analysis of X/E values (characterizing the aging degree of air masses) and backward trajectories of air masses showed that during the sampling, when influenced by air masses from the south or southwest, X/E was small, and the aging degree of air masses was high, indicating the influence of regional transport; when influenced by air masses from the east or southeast direction, X/E was large, and the air masses were fresh, and VOCs were mainly from local emissions. Six emission sources of VOCs, including industrial emissions, gasoline vehicle exhaust and gasoline evaporation, regional background and transport sources, biomass combustion, diesel vehicles and marine shipping emissions, and solvent use emission sources, were resolved using the PMF model, with contributions of 36.05%, 28.99%, 13.84%, 10.13%, 7.05%, and 3.95%, respectively.Zhanjiang should strengthen the supervision of formaldehyde, butene, n-butane and butanone, industry sources, and mobile sources as the focus of control.

[Characteristics and Health Risk Assessment of Volatile Organic Compounds in Different Functional Zones in Baoji in Summer].

The situation of air pollution in Guanzhong Plain has been increasing in recent years; hence, it is very important to study the characteristics of volatile organic compounds (VOCs) and their health risks in urban functional zones. We analyzed 115 VOCs using gas chromatography-mass spectrometry/hydrogen ion flame detector (GC-MS/FID) and high performance liquid chromatography (HPLC) at four sampling sites in the traffic, comprehensive, industrial, and scenic zones of Baoji. We analyzed the main components and key species in the different functional zones. Ozone formation potential (OFP),·OH consumption rate (L·OH), and secondary organic aerosol formation potential (SOAFP) were used to evaluate the environmental impact, and the hazard index (HI) and lifetime cancer risk (LCR) methods were employed. The results revealed that the mean values of φ(TVOCs) in the traffic, comprehensive, industrial, and scenic zones were (59.63±23.85)×10-9, (42.92±11.88)×10-9, (60.27±24.09)×10-9, and (55.54±7.44)×10-9, respectively. The dominant contributors at the traffic zone were alkanes, and those at the other functional zones were OVOCs. Acetaldehyde, acetone, n-butane, and isopentane were abundant at different functional zones. According to the characteristic ratios of VOCs, the average ratio of toluene to benzene (T/B) at the traffic, comprehensive, industrial, and scenic zones were 1.84, 2.39, 1.28, and 1.64, respectively, and the ratio of iso-pentane to n-pentane (i/n) was mainly between 1 and 4. The results indicated that VOCs in Baoji were significantly affected by vehicle emissions and gasoline evaporation, biomass and coal combustion, and industrial coatings and foundry. The ratio of m/p-xylene to ethylbenzene (X/E) was lower than 2 at the four functional zones, and the minimum was 1.79 at the scenic zones; the results revealed that X/E was small, and the aging degree of air masses was high, indicating the influence of regional transport. According to the ratio of formaldehyde to acetaldehyde (C1/C2) and the ratio of acetaldehyde to propanal (C2/C3), it was suggested that there may have been evident anthropogenic emission sources, and the photochemical reaction had an important effect on aldehydes and ketones. Environmental impact assessment results revealed that OVOCs and alkenes contributed significantly to OFP and OFP from large to small was as follows:industrial zone>scenic zone>traffic zone>comprehensive zone. The range of L·OH in each functional zone was 8.77-15.82 s-1, with isoprene contributing the most in the industrial zone and acetaldehyde contributing the most at other functional zones. The SOAFP of each functional zone was as follows:scenic zone>comprehensive zone>traffic zone>industrial zone. Toluene, m/p-xylene, and isoprene were the notable species. According to the health risk assessment of EPA, the HI of toxic VOCs in all functional zones was lower than 1, which was at an acceptable level. However, the number of days with HI>1 in industrial zones accounted for 42.86% of the total sampling days, indicating a high risk. The lifetime carcinogenic risk (LCR) of the traffic, comprehensive, industrial, and scenic zones were 1.83×10-5, 1.21×10-5, 1.85×10-5, and 1.63×10-5, respectively, which were all in grade Ⅲ of the rating system, indicating a high probability of cancer risk. Species with LCR greater than 10-6 were formaldehyde; acetaldehyde; 1,2-dibromoethane; 1,2-dichloroethane; 1,2-dichloropropane; and chloroform.