CT imaging using variable helical pitch scanning for lower extremity arterial disease: Reduced contrast medium dose, improved image quality and diagnostic accuracy.

OBJECTIVES: This study aimed to explore the feasibility of reducing contrast medium (CM) volume, improving image quality and diagnostic accuracy using variable helical pitch (VHP) scanning for patients with lower extremity arterial disease (LEAD). MATERIALS AND METHODS: Eighty patients who underwent lower extremity CT angiography (CTA) were prospectively enrolled and randomly assigned to either the VHP group (n = 40) or the conventional group (n = 40). Quantitative parameters and qualitative scores were compared between the two groups. Additionally, out of these patients, 72 arteries from 18 patients had DSA as the reference standard, and the diagnostic accuracy for the degree of vessel stenosis was assessed and compared. RESULTS: In the VHP group, the contrast volume was significantly lower than in the conventional group (79.55 ± 11.87 mL vs. 89.63 ± 10.03 mL, p < 0.001), showing a reduction of 12.7 %. For all image quality characteristics, scores in VHP group were significantly superior to those in the conventional groups (all p < 0.05). Quantitative analysis revealed that images from the VHP group exhibited superior CT enhancement, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in the anterior tibial arteries (ATA) and dorsali pedis arteries (DPA) compared to the conventional group (all p < 0.001). Moreover, segment-based analysis showed the VHP group had significantly higher positive predictive value (PPV) and accuracy than the conventional group (PPV: 100 % vs. 76.19 %, p = 0.01; accuracy: 100 % vs. 84.38 %, p = 0.01, respectively). CONCLUSIONS: The implementation of the VHP protocol led to a 12.7 % decrease in contrast medium dosage compared to the conventional lower extremity CTA scanning protocol. Furthermore, it improved image quality and diagnostic accuracy, particularly for arteries below the knee.

Application of Femoral Nerve Block in Treating Great Saphenous Vein Insufficiency by Endovenous Radiofrequency Ablation Combined with Punctate Stripping.

PURPOSE: To evaluate the efficacy and safety of ultrasound-guided femoral nerve block (FNB) in treating great saphenous vein (GSV) insufficiency by endovenous radiofrequency ablation (EVRA) combined with punctate stripping (PS). METHODS: This was a single-center, retrospective cohort study. A total of 135 patients were divided into Group A (59 patients) and Group B (76 patients). All patients received tumescent anesthesia during the operation, and group A received an additional ultrasound-guided FNB before the procedure. Intraoperative and postoperative pain score, the volume of tumescent anesthesia solution (TAS), and other indicators were compared in two groups. RESULTS: Group A had a significantly lower intraoperative pain visual analog scale than group B (2.7 ± 1.2 vs 5.2 ± 1.5, P < 0.001). The volume of TAS in group A was significantly lower than that in group B (198 ± 26.6 ml vs 338 ± 34.7 ml, P < 0.001). Postoperative muscle strength of group A was significantly decreased compared with group B (54.2% vs 3.90%, P < 0.001); no patient had severe limitation of active movements in both groups, and all motor blocks recovered within 24 h. The incidence of skin ecchymosis in group A was lower than that in group B (18.6% vs 46.1%, P = 0.001). The operation duration of the two groups had no statistically significant difference. CONCLUSIONS: Ultrasound-guided FNB in treating GSV insufficiency by EVRA combined with PS significantly relieved intraoperative pain and reduced the dosage of TAS and the incidence of skin ecchymosis without increasing the complications of anesthesia or any other surgical complications.

Changing trends of deep neck infections in southern China: A review of 127 cases.

This study aimed to review our experience with the clinical characteristics and management of deep neck infections (DNIs) and determine the changing trends of their characteristics over time in southern China. Patients diagnosed with a DNI between January 2009 and December 2018 were screened retrospectively for their demographic characteristics, etiology of infection, site of infection, microbiology, treatment, and complications. In total, 127 patients were included: 41 (32.3%) were treated between 2009 and 2013 (group A), and 86 (67.7%) were treated between 2014 and 2018 (group B). The most common site of infection in group A was the parapharyngeal space (15 patients, 36.6%), while that in group B involved multiple spaces (36 patients, 41.9%). The leucocyte count (×109 cells/L) was 13.23 ± 4.19 in group A and 16.04 ± 4.33 in group B (p < 0.001). Streptococcus viridans was the most common bacteria in both groups. The mean hospital stay was 21.46 ± 33.09 days in group A and 10.44 ± 6.19 days in group B. The rate of diabetes mellitus (DM) in group A was lower than that in group B (8/41 and 33/86, respectively; p = 0.034). Airway obstruction was the most common complication in both groups. DNIs are more likely to show multi-space involvement, affect more DM patients, and be associated with higher leucocyte counts over time. We infer that the duration from morbidity to admission and that from admission to operation play roles in the successful management of DNIs, possibly causing fewer complications, lower mortality rates, and shorter hospital stays. DM patients require increased attention.

TLR3 polymorphisms are associated with the severity of hand, foot, and mouth disease caused by enterovirus A71 in a Chinese children population.

Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is a contagious viral disease, and toll-like receptors (TLRs) play essential roles in resisting the pathogen. The aim of this study was to assess the potential relationship between several TLRs polymorphisms and the HFMD severity in a Chinese children population. A total of 328 Chinese children with HFMD were included in the present study. The polymorphisms of TLR3 (rs3775290, rs3775291, rs3775296, rs1879026, rs5743312, rs5743313, rs5743303, rs13126816, and rs3775292), TLR4 (rs4986790, rs4986791, rs2149356, rs11536889, and rs41426344), TLR7 (rs179009, rs179010, rs179016, rs3853839, rs2302267, rs1634323, and rs5741880), and TLR8 (rs3764880, rs2159377, rs2407992, rs5744080, rs3747414, rs3764879, and rs5744069) genes were selected. The study indicated that individuals with the GG genotype of TLR3 single-nucleotide polymorphism rs1879026 had a higher risk of developing severe cases (GG vs. GT: OR = 1.875; 95% CI, 1.183-2.971; p = .007). Meanwhile, TLR3 rs3775290 CC genotype and C allele were associated with lower disease severity in females (CC vs. CT: OR = 0.350; 95% CI, 0.163-0.751; p = .006; C vs. T: OR = 0.566; 95% CI, 0.332-0.965; p = .036). TLR3 rs3775291 CC genotype showed 2.537 folds higher risk of developing severe cases in females (CC vs. CT: OR = 2.537; 95% CI, 1.108-5.806; p = .026). Moreover, TLR3 rs1879026 GG genotype was found to be related to increased risk of severe cases in males (GG vs. GT: OR = 2.076; 95% CI, 1.144-3.768; p = .016). The current findings show that the genetic variants of TLR3 rs1879026, rs3775290, and rs3775291 are associated with the severity of EV-A71-associated HFMD in a Chinese children population.

The perplexity of catheter-directed thrombolysis for deep venous thrombosis: the approaches play an important role.

The recent adjunctive catheter-directed thrombolysis (ATTRACT) trial rose a controversy about the treatment effect of catheter-directed thrombolysis (CDT) in deep venous thrombosis (DVT). In fact, most studies including the ATTRACT trial did not perform subgroup analysis of catheterization approaches. Different approaches would confound the conclusions. Therefore, a single-center retrospective analysis was performed to compare the differences between the antegrade (AGA) and retrograde (RGA) approaches. Total 217 DVT patients treated with CDT were enrolled from January 2010 to December 2017, with mean age of 55.3 years (67 received antegrade approach, 150 received retrograde approach). The clot burden reduction by segment was evaluated. The mean access establishment time and thrombolytic time were compared. The patency of the iliofemoral vein at 6 months was evaluated. The rate of PTS, quality of life and venous insufficiency were assessed at 1 year. AGA group showed better thrombolytic effect in popliteal and femoral vein than RGA group. The rate of iliofemoral clot burden reduction in RGA group was mostly at Grade II, while most were at Grade III in AGA group. The retrograde approach showed better thrombolysis effect in iliofemoral DVT than popliteal to iliac DVT. The RGA group reported longer mean access establishment time (5.4 ± 1.8 vs 27.0 ± 7.5 min, p < 0.001) and thrombolytic time (6.9 ± 1.5 days vs 6.8 ± 1.5 days, p = 0.586). At 6 months, RGA group had a lower rate of femoral vein patency (52.0% vs 89.6%, p < 0.001) and a higher rate of venous insufficiency (52.0% vs 29.9%, p < 0.001), compared with AGA group. Although there was no difference in the rate of PTS, the RGA group showed higher Villalta scores in the free and mild PTS. The antegrade approach was preferably recommended over the retrograde approach for CDT treatment.

Geranylgeranyl Transferase-I Knockout Inhibits Oxidative Injury of Vascular Smooth Muscle Cells and Attenuates Diabetes-Accelerated Atherosclerosis.

The proliferation of vascular smooth muscle cells (VSMCs) induced by oxidative injury is one of the main features in diabetes-accelerated atherosclerosis. Geranylgeranyl transferase-I (GGTase-I) is an essential enzyme mediating posttranslational modification, especially the geranylgeranylation of small GTPase, Rac1. Our previous studies found that GGTase-I played an important role in diabetes-accelerated atherosclerosis. However, its exact role is largely unclear. In this study, mouse conditional knockout of VSMC GGTase-I (Pggt1b Δ/Δ mice) was generated using the CRISPR/Cas9 system. The mouse model of diabetes-accelerated atherosclerosis was induced by streptozotocin injections and an atherogenic diet. We found that GGTase-I knockout attenuated diabetes-accelerated atherosclerosis in vivo and suppressed high-glucose-induced VSMC proliferation in vitro. Moreover, after a 16-week duration of diabetes, Pggt1b Δ/Δ mice exhibited lower α-smooth muscle actin (α-SMA) and nitrotyrosine level, Rac1 activity, p47phox and NOXO1 expression, and phospho-ERK1/2 and phosphor-JNK content than wild-type mice. Meanwhile, the same changes were found in Pggt1b Δ/Δ VSMCs cultured with high glucose (22.2 mM) in vitro. In conclusion, GGTase-I knockout efficiently blocked diabetes-accelerated atherosclerosis, and this protective effect must be related to the inhibition of VSMC proliferation. The potential mechanisms probably involved interfering Rac1 geranylgeranylation, inhibiting the assembly of NADPH oxidase cytosolic regulatory subunits, reducing oxidative injury, and decreasing ERK1/2 and JNK phosphorylation.

MicroRNA­125a­mediated regulation of the mevalonate signaling pathway contributes to high glucose­induced proliferation and migration of vascular smooth muscle cells.

Hyperglycemia contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMC), which are closely associated with atherosclerosis. MicroRNAs (miRNAs/miRs) constitute a novel class of gene regulators, which have important roles in various pathological conditions. The aim of the present study was to identify miRNAs involved in the high glucose (HG)­induced VSMC phenotype switch, and to investigate the underlying mechanism. miRNA sequencing and reverse transcription­quantitative PCR results indicated that inhibition of miR­125a expression increased the migration and proliferation of VSMCs following HG exposure, whereas the overexpression of miR­125a abrogated this effect. Furthermore, dual­luciferase reporter assay results identified that 3­hydroxy­3-methyglutaryl­coA reductase (HMGCR), one of the key enzymes in the mevalonate signaling pathway, is a target of miR­125a. Moreover, HMGCR knockdown, similarly to miR­125a overexpression, suppressed HG­induced VSMC proliferation and migration. These results were consistent with those from the miRNA target prediction programs. Using a rat model of streptozotocin­induced diabetes mellitus, it was demonstrated that miR­125a expression was gradually downregulated, and that the expressions of key enzymes in the mevalonate signaling pathway in the aortic media were dysregulated after several weeks. In addition, it was found that HG­induced excessive activation of the mevalonate signaling pathway in VSMCs was suppressed following transfection with a miR­125a mimic. Therefore, the present results suggest that decreased miR­125a expression contributed to HG­induced VSMC proliferation and migration via the upregulation of HMGCR expression. Thus, miR­125a­mediated regulation of the mevalonate signaling pathway may be associated with atherosclerosis.

Effect of Moringa oleifera supplementation on productive performance, colostrum composition and serum biochemical indexes of sow.

Moringa oleifera has been considered as a potential functional feed or food, since it contains multiple components beneficial to animal and human. However, little is known about the effects of Moringa oleifera supplementation on productive performances in sows. In the current study, the results showed that dietary Moringa oleifera significantly decreased the farrowing length and the number of stillborn (p < .05), while had an increasing trend in the number of live-born (0.05 < p < .10). Furthermore, 8% Moringa oleifera supplementation significantly elevated protein levels in the colostrum (p < .05); 4% Moringa oleifera lowed serum urea nitrogen of sows after 90 days of gestation (p < .05) and significantly decreased serum glucose on 10 days of lactation (p < .05). Both groups showed significant elevation in serum T-AOC activity (p < .05). The serum malondialdehyde (MDA) of sows declined significantly in 4% Moringa oleifera addition group (p < .05). 8% Moringa oleifera meal significantly elevated serum CAT activity after 60 days of gestation (p < .05), while decreased the serum MDA level and increased the serum GSH-Px activity of sows at 10 days of lactation (p < .05). Of piglets, both two dosages of Moringa oleifera supplementation essentially reduced the serum urea nitrogen (p < .05), and 4% Moringa oleifera meal increased serum total protein (p < .05). In addition, piglets that received 8% Moringa oleifera had the highest serum CAT and SOD activities among all groups (p < .05). The present study indicated that Moringa oleifera supplementation could enhance the reproduction performances, elevate protein levels in the colostrum and improve the serum antioxidant indices in both sows and piglets.

PPWD1 is associated with the occurrence of postmenopausal osteoporosis as determined by weighted gene co­expression network analysis.

Postmenopausal osteoporosis (PMO) is the most common type of primary osteoporosis (OP), a systemic skeletal disease. Although many factors have been revealed to contribute to the occurrence of PMO, specific biomarkers for the early diagnosis and therapy of PMO are not available. In the present study, a weighted gene co­expression network analysis (WGCNA) was performed to screen gene modules associated with menopausal status. The turquoise module was verified as the clinically significant module, and 12 genes (NUP133, PSMD12, PPWD1, RBM8A, CRNKL1, PPP2R5C, RBM22, PIK3CB, SKIV2L2, PAPOLA, SRSF1 and COPS2) were identified as 'real' hub genes in both the protein­protein interaction (PPI) network and co­expression network. Furthermore, gene expression analysis by microarray in blood monocytes from pre­ and post­menopausal women revealed an increase in the expression of these hub genes in postmenopausal women. However, only the expression of peptidylprolyl isomerase domain and WD repeat containing 1 (PPWD1) was correlated with bone mineral density (BMD) in postmenopausal women. In the validation set, a similar expression pattern of PPWD1 was revealed. Functional enrichment analysis revealed that the fatty acid metabolism pathway was significantly abundant in the samples that exhibited a higher expression of PPWD1. Collectively, PPWD1 is indicated as a potential diagnostic biomarker for the occurrence of PMO.

Modified unilateral video-assisted thoracoscopic extended thymectomy for myasthenia gravis using 5-mm incisions: A case report.

RATIONALE: Myasthenia gravis (MG) is the most common cause of acquired neuromuscular junction disorder. Thymectomy has been established as an effective therapy for MG, as it attenuates the natural course of the disease and may result in complete remission. PATIENT CONCERNS: We report the case of a 22-year-old female with a 6-year history of MG presented with bilateral ptosis, diplopia, and intermittent dysphagia. She denied shortness of breath, dysarthria, and fatigue. DIAGNOSES: She had been diagnosed with MG 6 years previously at the Neurology Department of our hospital. A computed tomography (CT) scan revealed thymic hyperplasia INTERVENTIONS:: She was treated with modified unilateral VATET that minimized incision size. OUTCOMES: Unilateral VATET was performed using two 5-mm incisions to minimize pressure on intercostal soft tissues/nerves and reduce postoperative pain. LESSONS: The lesson learnt from this case report is that this modified VATET method could be a useful approach to the management of non-thymomatous MG. The ability to achieve complete dissection with good cosmetic results may lead to wider acceptance of this technique by patients with MG and their neurologists for earlier thymectomy and improved outcomes. Additional studies are needed to determine the superiority of this approach to established methods.

MiRNA-mRNA crosstalk in laryngeal squamous cell carcinoma based on the TCGA database.

BACKGROUND: The functional characterization of non-coding microRNAs (miRNAs) has been shown to be associated with the pathophysiology of the disease, but it is still a challenging task to elucidate the pathogenesis of microRNAs and disease. In addition, the understanding of the role of miRNAs in the development of LSCC still needs further exploration. MATERIALS AND METHODS: In this study, to identify miRNAs that play a key role in LSCC, we analyzed miRNA and mRNA sequence data from 162 LSCC samples from the TCGA database, and screened specific miRNAs and mRNAs by differential gene expression analysis. And then, construct a differentially expressed miRNAs and mRNAs interaction network. RESULTS: In our investigation, 23 miRNAs (P < 0.01, log2FoldChange > 2) and 331 mRNAs (P < 0.01, log2FoldChange > 4) were identified differentially expressed in LSCC and reduced the number of loosely linked miRNAs and mRNAs according to appropriate thresholds. Finally, 13 miRNAs and 35 mRNAs were enriched in a network. CONCLUSIONS: Our study provides the most comprehensive information on the expression of miRNAs in LSCC and identifies the known oncogenic miRNAs (such as miR-163a), as well as aberrant expression of novel miRNAs involved in cell regulation and metabolic defects that occur during development of LSCC.

Relationship between CaSRs and LPS-injured cardiomyocytes.

OBJECTIVE: Calcium-sensing receptors (CaSRs) regulate systemic calcium homeostasis. Intracellular calcium concentration changes are initiating factors of endoplasmic reticulum stress and cell autophagy. Recent research has revealed that CaSRs play an important role in myocardial ischemia/reperfusion injury and other cardiovascular diseases. However, it remains unclear whether CaSRs are involved in lipopolysaccharide (LPS)-induced cardiomyocyte injury. METHODS: Cultured neonatal rat cardiomyocytes were treated with LPS, with or without pretreatment by a CaSR specific agonist SC-211006 or CaSR specific antagonist SC-207394. The ultrastructure of cardiomyocytes was observed using a transmission electron microscope, and the expression of CaSR, GRP78, LC3B, CytC and Bcl-2 proteins were detected by western blot. RESULTS: Compared with the control group, LPS increased cardiomyocyte injury and the expression of CaSR, GRP78, LC3B and CytC proteins, but decreased the expression of Bcl-2. Compared with the LPS group, pretreatment with SC-211006 further enhanced cardiomyocyte damage and the expression of CaSR, GRP78, LC3B and CytC, but reduced the expression of Bcl-2. Conversely, pretreatment with SC-207394 decreased cardiomyocyte injury and the protein expression of CaSR, GRP78, LC3B and CytC, but increased the expression of Bcl-2. CONCLUSION: Our results suggest that CaSRs are involved in LPS-induced rat cardiomyocyte injury via the activation of endoplasmic reticulum stress and autophagy.

Inhibition of farnesyl pyrophosphate synthase attenuates high glucose­induced vascular smooth muscle cells proliferation.

The proliferation of vascular smooth muscle cells (VSMCs) is one of the main features of atherosclerosis accelerated by hyperglycemia. Our previous studies found that farnesyl pyrophosphate synthase (FPPS, EC 2.5.1.10), an essential enzyme in the mevalonate pathway, was upregulated in aorta media from diabetic mice along with the process of atherosclerosis. However, the exact role of FPPS in high glucose­induced proliferation of VSMCs is largely unclear. In our study, we found that alendronate (an FPPS inhibitor) attenuated diabetic accelerated atherosclerosis in vivo and suppressed high glucose­induced VSMCs proliferation in vitro. Moreover, in aorta from streptozotocin (STZ)­induced diabetic mice, 16­week treatment of alendronate decreased the activation of small GTPase (Ras, RhoA, and Rac1), but had no effect on the expression of cystathionine γ­lyase (CSE), the pivotal H2S­producing enzyme. Meanwhile, in VSMCs cultured in high glucose­containing media, alendronate remarkably decreased total CoQ content, increased the H2S level, depressed small GTPases (Ras, RhoA, and Rac1) activation, but yet had no effect on expression of CSE. In conclusion, FPPS inhibition by alendronate attenuated the high glucose­induced proliferation of VSMCs both in vivo and in vitro, probably though depressing H2S metabolism and suppressing small GTPases (Ras, RhoA, and Rac1) activation.

Rrp15 affects cell cycle, proliferation, and apoptosis in NIH3T3 cells.

Riken 2810430M08 (hereinafter referred to as Rrp15) is a newly identified and reported gene from the mouse genome. In our previous work, we found that the gene had a relationship with the proliferation and activation of T cells. Rrp15 protein is highly homologous with RRP15 (budding yeast), which has an important role in ribosomal RNA processing. We explored the potential function of Rrp15 in apoptosis, cell proliferation, and its involvement with RNA in the nucleus. We constructed a knockdown of the Rrp15 gene in NIH3T3 cells and then performed real-time PCR, western blotting, flow cytometry, and immunofluorescence to determine the function of the Rrp15 gene. Knockdown of the Rrp15 gene suppresses proliferation and induces apoptosis. We also found that the Rrp15 protein was normally distributed in the nucleus and bound to RNA or pre-RNA in the nucleus. Additionally, Rrp15 altered the activity of the 20S proteasome. Rrp15 promotes proliferation and inhibits apoptosis in NIH3T3 cells and may have a relationship with RNA in the nucleus.

Evaluation of Distal Hemodynamic Changes of Lower Extremity after Endovascular Treatment: Correlation between Measurements of Color-Coded Quantitative Digital Subtraction Angiography and Ankle-Brachial Index.

PURPOSE: To confirm the feasibility of using time-to-peak (TTP) measurements derived from color-coded digital subtraction angiography (ccDSA) imaging to assess improvements in distal circulation in relation to the ankle-brachial index (ABI). MATERIALS AND METHODS: Nineteen patients who underwent percutaneous transluminal angioplasty and/or stent placement (in 20 lower extremities) were evaluated. A region of interest (ROI) at the proximal superficial femoral artery (SFA) was selected for a reference TTP for quantitative assessments. The ROI measurements of the TTP interval between medial and lateral plantar/dorsalis pedis relative to the reference was regarded as the ΔTTP and used to assess distal hemodynamic improvement achieved by the revascularization. The ABI was obtained with a handheld Doppler ultrasound machine with a manually operated blood-pressure cuff. Correlation between the two methods was analyzed. RESULTS: The ABI improved significantly from 0.44 ± 0.18 to 0.79 ± 0.20 (t = 10.11; P < .0001) after the intervention. TTP, which reflected the blood flow time from the proximal SFA to the foot, became much faster, from 11.86 seconds ± 4.26 to 6.75 seconds ± 2.03 (t = 6.57; P < .001). A good correlation was observed between the improvement ratios of ΔTTP and ABI (r = 0. 863). CONCLUSIONS: TTP measurements derived from ccDSA provide an easy and objective method for assessment of distal hemodynamic changes after endovascular treatment of lower-extremity peripheral arterial disease (PAD). It may provide a quantitative method to assess the adequacy of endovascular interventions and provide more objective suggestions for procedure endpoints, with potentially better clinical outcomes for patients with PAD.

Solely lung-involved IgG4-related disease : a case report and review of the literature.

By analyzing the clinical data of 1 case of IgG4-related lung disease(IgG4-RLD) and the review of literature, the author investigated the clinical characteristics of IgG4-RLD. IgG4-RLD is a rare disease characterized by significant elevation of serum IgG4 and infiltration of a large number of IgG4+ plasma cells. The clinical manifestations of the disease were nonspecific, and the imaging features were mixed with several types. The disease can only be involved in the lung, but also multiple organ involvement. Solely lung-involved IgG4-RD is not only extremely rare but also easily misdiagnosed as tuberculosis, lung cancer, lymphoma and other common pulmonary diseases. Histopathological examination is the key to the diagnosis of the disease. Corticosteroids are the first choice of treatment, and the overall prognosis is good.

Alteration of mevalonate pathway in proliferated vascular smooth muscle from diabetic mice: possible role in high-glucose-induced atherogenic process.

The proliferation of vascular smooth muscle cells (VSMCs) is one of the main features of atherosclerosis induced by high glucose. Mevalonate pathway is an important metabolic pathway that plays a key role in multiple cellular processes. The aim of this study was to define whether the enzyme expression in mevalonate pathway is changed in proliferated VSMCs during atherogenic process in diabetic mice. Diabetes was induced in BALB/c mice with streptozotocin (STZ, 50 mg/kg/day for 5 days). Induction of diabetes with STZ was associated with an increase of lesion area and media thickness after 8 and 16 weeks of diabetes. In aorta, there were overexpressions of some enzymes, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), farnesyl pyrophosphate synthase (FPPS), geranylgeranyl pyrophosphate synthase (GGPPS), farnesyltransferase (FNT), and geranylgeranyltransferase-1 (GGT-1), and unchanged expression of squalene synthase (SQS) and phosphor-3-hydroxy-3-methylglutaryl-coenzyme A reductase (P-HMGR) in 8 and 16 weeks of diabetes. In vitro, VSMCs were cultured and treated with different glucose concentrations for 48 h. High glucose (22.2 mM) induced VSMC proliferation and upregulation of HMGR, FPPS, GGPPS, FNT, and GGT-1 but did not change the expressions of SQS and P-HMGR. In conclusion, altered expression of several key enzymes in the mevalonate pathway may play a potential pathophysiological role in atherogenic process of diabetes macrovascular complication.

Left ovarian vein dilation or pelvic congestion syndrome secondary to abdominal aortic dissection: incidental findings on CT angiography.

BACKGROUND: In the study, we describe eight cases in which pelvic congestion syndrome (PCS) was a direct complication of abdominal aortic dissection (AD). METHODS: We recorded computed tomographic (CT) details of the AD and PCS. The patterns of pelvic varices and reflux were identified as well. RESULTS: All eight had abdominal AD (diameter, 23.44-33.98 mm). The compressed left renal vein revealed stenosis in situ (diameter, 1.17-2.69 mm). CT also revealed dilation of left ovarian vein with left pelvic varices in all cases. CONCLUSIONS: Some cases of PCS and dilation of the left ovarian vein can be directly correlated with abdominal AD.

Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced cardiac hypertrophy and fibrosis in vivo.

Farnesyl pyrophosphate synthase (FPPS), as a key branchpoint of the mevalonate pathway, catalyzes the synthesis of isoprenoid intermediates. The isoprenoid intermediates are needed for protein isoprenylation to participate in cardiac remodeling. We have previously demonstrated that both knockdown of FPPS with small interfering RNA and inhibition of FPPS by alendronate could prevent Ang II-induced hypertrophy in cultured cardiomyocytes. In this study, we evaluated the effects of FPPS inhibition in Ang II-mediated cardiac hypertrophy and fibrosis in vivo. Wild type mice were separately treated with saline, Ang II (2.88 mg/kg per day), FPPS inhibitor alendronate (0.1 mg/kg per day), or the combination of Ang II (2.88 mg/kg per day) and alendronate (0.1 mg/kg per day) for 4 weeks. The results showed that Ang II increased FPPS expression, and the increases of Ang II-induced synthesis of the isoprenoid intermediates, FPP and GGPP, were significantly inhibited by FPPS inhibitor. In the meantime, FPPS inhibition attenuated Ang II-mediated cardiac hypertrophy and fibrosis as indexed by the heart weight to body weight ratio, echocardiographic parameters, histological examinations and expression of ANP and BNP mRNA. Furthermore, it was also found that FPPS inhibitor attenuated Ang II-induced increases of RhoA activity and p-38 MAPK phosphorylation and TGF-ß1 mRNA expression. In conclusion, FPPS might play an important role in Ang II-induced cardiac hypertrophy and fibrosis in vivo, at least in part through RhoA, p-38 MAPK and TGF-ß1.