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.

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.

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.

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.

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.

Expression of inducible co-stimulator on peripheral blood T lymphocytes in patients with lupus nephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease and lupus nephritis (LN) represents a major clinical manifestation. Studies have shown that elevated inducible co-stimulator (ICOS) in SLE. The purpose of the study was to investigate the expression of ICOS on T cells in patients with LN. Flow cytometry (FCM) was used to analyze the expression of ICOS on peripheral blood T lymphocytes in LN patients, SLE patients without nephritis, and healthy controls. The expression of ICOS on CD4 + CD45RO + and CD8 + CD4RO + T cells was significantly increased in SLE patients when compared with healthy controls (P < 0.001). In addition, ICOS expression in patients with nephritis was higher than those without nephritis (P < 0.01). Taken together, our results suggest that ICOS co-stimulatory pathway is important in the pathogenesis of LN; blockade of the pathway might represent a novel therapeutic strategy for the treatment of LN.

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.

Dual effects of sodium aescinate on vascular tension in rat thoracic aorta.

OBJECTIVE: Sodium aescinate (SA) is used as a vasoactive drug in clinical treatment. This study was designed to investigate the effects of SA on rat isolated thoracic aorta and the possible mechanisms. METHODS: Isometric tension was recorded in response to drugs in organ bath. RESULTS: The effects of SA obeyed an all-or-nothing response. SA in relatively low dose (> or = 50 microg/ml) had an endothelium-independent contractile effect in rat aorta (P<0.01), which depended on extracellular Ca(2+) influx via L-type Ca(2+) channel (P<0.05). SA in relatively high dose (> or = 100 microg/ml) also induced vasoconstriction in Ca(2+)-free medium (P<0.01), which was independent of the activity of inositol-1,4,5-trisphosphate receptor (IP(3)R), ryanodine receptor (RYR), and protein kinase C (PKC). SA in relatively high dose (> or = 100 microg/ml) dilated both endothelium-intact and endothelium-denuded aortic rings precontracted by phenylephrine (PE) or KCl (each P<0.01). SA inhibited extracellular Ca(2+) influx induced by PE or KCl (each P<0.01) and had no activation effect on K(+) channels on vascular smooth muscle. The relaxant effect of SA partly depended on the activity of NO synthase but not on the activity of cyclooxygenase. CONCLUSIONS: Taken together, this study indicated that SA had dual effects on vascular tension in rat isolated thoracic aorta.

Increased serum interleukin 17 in patients with systemic lupus erythematosus.

Interleukin 17 (IL-17) is a Th17 cytokine associated with inflammation, autoimmunity and defense against some bacteria, it has been implicated in many chronic autoimmune diseases including psoriasis, multiple sclerosis and systemic sclerosis. However, whether IL-17 plays a role in the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. In the present study, we aimed to investigate the serum IL-17 level in patients with SLE and it's associations with disease manifestations and activity. Fifty-seven patients with SLE and 30 healthy volunteers were recruited. Serum IL-17 levels were examined by enzyme linked immunosorbent assay (ELISA). Statistic analyzes were performed by SPSS 10.01. Results show that serum IL-17 levels were significantly elevated in SLE patients as compared with normal controls. Nevertheless, no associations of serum IL-17 level with clinical and laboratory parameters were found; no significant difference regarding serum IL-17 level between SLE patients with nephritis and those without nephritis was found; no significant difference was found between Less active SLE and More active SLE; Correlation analysis between serum IL-17 levels and SLEDAI showed no association. Taken together, our results indicate increased serum IL-17 levels in SLE patients, suggesting that this cytokine may trigger the inflammatory process in SLE. However, no associations of serum IL-17 level with disease manifestations were found. Therefore, further studies are required to confirm this preliminary data.

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.

Effects of atorvastatin on calcium-regulating proteins: a possible mechanism to repair cardiac dysfunction in spontaneously hypertensive rats.

Previous clinical and experimental studies have demonstrated that statins, the inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, can improve left ventricular function in damaged hearts. Also, the normal expression of Ca(2+) regulatory proteins is critical for efficient myocardial function. However, it is still unclear whether the beneficial effect of statins on cardiac function is associated with alterations of Ca(2+) regulatory proteins. In this study, we investigated the effect of atorvastatin on cardiac function in spontaneously hypertensive rats (SHRs), focusing in particular on its impact on the expression of sarcoplasmic reticulum Ca(2+)-adenosine triphosphatase (SERCA2a), phospholamban (PLB) and its phosphorylated form (phosphorylated PLB), all of which are Ca(2+) regulatory proteins in myocardium. SHRs showed decreases in gene expression of SERCA2a and phosphorylated PLB, and reduction in SERCA activity in the left ventricular myocardium, as well as reduced cardiac function, compared to age-matched Wistar Kyoto rats (WKYs). Furthermore, we showed that in SHRs atorvastatin preserved cardiac dysfunction accompanied by positive alterations in calcium regulatory proteins, with up-regulation in expression of SERCA2a and phosphorylated PLB, and with improvement of SERCA activity. Thus, atorvastatin has positive effects on calcium regulatory proteins, which may be one of the mechanisms of the beneficial effect of statins on cardiac function in spontaneously hypertensive rats.

Endothelium-independent vasorelaxant effect of sodium ferulate on rat thoracic aorta.

AIMS: This study was designed to investigate the effects of sodium ferulate (SF) on rat isolated thoracic aortas and the possible mechanisms. MAIN METHODS: Isometric tension was recorded in response to drugs in organ bath. Cytosolic free Ca(2+) concentration ([Ca(2+)](i)) was measured using Fluo-3 in cultured rat aortic smooth muscle cells (RASMC). KEY FINDINGS: SF (0.1-30 mM) relaxed the isolated aortic rings precontracted with phenylephrine (PE) and high-K(+) in a concentration-dependent manner with respective pD(2) of 2.7+/-0.02 and 2.6+/-0.06. Mechanical removal of endothelium did not significantly modify the SF-induced relaxation. In Ca(2+)-free solution, SF noticeably inhibited extracellular Ca(2+)-induced contraction in high-K(+) and PE pre-challenged rings, and suppressed the transient contraction induced by PE and caffeine. The vasorelaxant effect of SF was unaffected by various K(+) channel blockers such as tetraethylammonium, glibenclamide, 4-aminopyridine, and barium chloride. In addition, SF concentration-dependently reduced the contraction induced by phorbol-12-myristate-13-acetate, an activator of protein kinase C (PKC), in the absence of extracellular Ca(2+), with the pD(2) of 2.9+/-0.03. In RASMC, SF had no effect on PE- or KCl-induced [Ca(2+)](i) increase either in the presence or in the absence of external Ca(2+). SIGNIFICANCE: These results indicate that SF acts directly as a non-selective relaxant to vascular smooth muscle. The direct inhibition of the common pathway after [Ca(2+)](i) increase may account for the SF-induced relaxation in Ca(2+)-dependent contraction, while the blockage of the PKC-mediated contractile mechanism is likely responsible for the SF-induced relaxation in Ca(2+)-independent contraction.

Cardioprotection by polysaccharide sulfate against ischemia/reperfusion injury in isolated rat hearts.

AIM: Polysaccharide sulfate (PSS) is a new type of heparinoid synthesized with alginic acid as the basic material and then by chemical introduction of effective groups. Although PSS is successfully applied in ischemic cardio-cerebrovascular disease, its effect on cardiac function after ischemia/reperfusion (I/R) injury has previously not been investigated. The aim of the present study was to investigate whether PSS can protect the heart from I/R injury and the underlying mechanism of protection. METHODS: Isolated rat hearts were perfused (Langendorff) and subjected to 20 min global ischemia followed by 60 min reperfusion with Kreb's Henseleit solution or PSS (0.3-100 mg/L). Myocardial contractile function was continuously recorded. Creatine kinase (CK) and lactate dehydrogenase (LDH) leakage were measured. Tumor necrosis factor-alpha (TNF-alpha) expression in cardiomyocytes was investigated. Western blot analysis for extracellular regulated kinases (ERKs), c-jun amino-terminal kinase (JNKs) and p38 mitogen-activated protein kinase (MAPK) activity was performed. RESULTS: After I/R, cardiac contractility decreased, CK and LDH levels increased in the coronary effluent, and TNF-alpha expression increased in cardiomyocytes. PSS administration at concentrations of 1-30 mg/L improved cardiac contractility, reduced CK and LDH release and inhibited TNF-alpha production. Phosphorylated-p38MAPK (p-p38MAPK) and p-p54/p46-JNK increased in I/R rat hearts but diminished in PSS (1-30 mg/L) treated hearts. P-p44/p42-ERK levels were unchanged. In contrast, high concentrations of PSS (100 mg/L) had adverse effects that caused a worsening of heart function. CONCLUSION: PSS has dose-dependent cardioprotective effects on the rat heart after I/R injury. The beneficial effects may be mediated through normalization of the activity of p38 MAPK and JNK pathways as well as controlling the level of TNF-alpha expression.

Rapid prototyping drill guide template for lumbar pedicle screw placement.

OBJECTIVE: To develop a novel method of spinal pedical stereotaxy by reverse engineering and rapid prototyping techniques, and to validate its accuracy by experimental and clinical studies. METHODS: A 3D reconstruction model for the desired lumbar vertebra was generated by using the Mimics 10.11 software, and the optimal screw size and orientation were determined using the reverse engineering software. Afterwards, a drill template was created by reverse engineering principle, whose surface was the antitemplate of the vertebral surface. The drill template and its corresponding vertebra were manufactured using the rapid prototyping technique. RESULTS: The accuracy of the drill template was confirmed by drilling screw trajectory into the vertebral biomodel preoperatively. This method also showed its ability to customize the placement and size of each screw based on the unique morphology of the lumbar vertebra.The drill template fits the postural surface of the vertebra very well in the cadaver experiment. Postoperative CT scans for controlling the pedicle bore showed that the personalized template had a high precision in cadaver experiment and clinical application. No misplacement occurred by using the personalized template. During surgery, no additional computer assistance was needed. CONCLUSIONS: The authors have developed a novel drill template for lumbar pedicle screw placement with good applicability and high accuracy. The potential use of drill templates to place lumbar pedicle screws is promising. Our methodology appears to provide an accurate technique and trajectory for pedicle screw placement in the lumbar spine.

[Primary clinical result of digital template as navigation to supper cervical pedicle instrumentation].

OBJECTIVE: To observe the primary clinical result of digital template as navigation to the upper cervical pedicle instrumentation. METHODS: CT scan of upper cervical vertebrae was performed. 3-D model of upper cervical vertebrae was reconstructed by software Amira 3.1 and was preserved in STL format. Then 3-D model was run in software UG Imageware 12.0, the best pedicle channel was extracted according to the reverse engineering principle. A virtual navigational template was established according to he lamina anatomic trait, and the best pedicle channel. The virtual vertebrae and navigational template were manufactured using rapid prototyping. The navigational template was sterilized and used intra operative to assist with the placement of pedicle screw. The Accuracy of screw placement was confirmed with postoperative X-ray and CT scanning. RESULTS: The digital navigational template had been established and used in the 3 cases, the good trajectory of cervical pedicle had been showed by the CT scan of post operation. There were not complications of related pedicle screw insertion. CONCLUSIONS: A novel method of upper cervical pedicle location using Reverse Engineering and rapid prototyping has been developed; the navigational template is found to be highly accuracy and has great expectation.

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.

Tissue-specific effects of atorvastatin on 3-hydroxy-3-methylglutarylcoenzyme A reductase expression and activity in spontaneously hypertensive rats.

AIM: Cardiovascular remodeling is closely associated with cholesterol and is attenuated by statins. The spontaneously hypertensive rat (SHR) has a low serum cholesterol level and evident cardiovascular remodeling. The aims of the present study were to characterize the effects of atorvastatin on tissue cholesterol content and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase expression and activity in four tissues from SHR: liver, heart, aorta and kidney. METHODS: SHR and normotensive Wistar-Kyoto rats (WKY) were treated daily with atorvastatin (50 mg/kg) for 8 weeks. Cholesterol levels of serum and tissues (liver, heart, aorta and kidney) were determined by commercial enzymatic methods. Western blot analysis and high performance liquid chromatogram (HPLC) were used to assay the expression and activity of enzyme respectively. RESULTS: Treatment with atorvastatin decreased cholesterol content and HMGCoA reductase expression and activity in all four tissues of SHR. However, in WKY, atorvastatin only altered HMG-CoA reductase in liver, where the protein expression was upregulated but the enzyme activity was decreased. CONCLUSION: The present study demonstrates that the effects of atorvastatin on tissue cholesterol content and HMG-CoA reductase are strain- and tissue-specific.