Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are the major cause of in-stent restenosis (ISR). Intervention proliferation and migration of VSMCs is an important strategy for antirestenotic therapy. Roscovitine, a second-generation cyclin-dependent kinase inhibitor, can inhibit cell cycle of multiple cell types. We studied the effects of roscovitine on cell cycle distribution, proliferation and migration of VSMCs in vitro by flow cytometry, BrdU incorporation and wound healing assay, respectively. Our results showed that roscovitine increased the proportion of G0/G1 phase cells after 12 h (69.57±3.65 vs. 92.50±1.68, P=0.000), 24 h (80.87±2.24 vs. 90.25±0.79, P=0.000) and 48 h (88.08±3.86 vs. 88.87±2.43, P=0.427) as compared with control group. Roscovitine inhibited proliferation and migration of VSMCs in a concentration-dependent way. With the increase of concentration, roscovitine showed increased capacity for growth and migration inhibition. Roscovitine (30 μmol/L) led to an almost complete VSMCs growth and migration arrest. Combined with its low toxicity and selective inhibition to ISR-VSMCs, roscovitine may be a potential drug in the treatment of vascular stenosis diseases and particularly useful in the prevention and treatment of ISR.
Cardiotrophin-1 (CT-1) activates a distinct form of cardiac muscle cell hypertrophy in which the sarcomeric units are assembled in series. The aim of the study was to determine the expression pattern of sarcomeric contractile protein α-actin, specialized cytoskeletal protein α-actinin and mitochondrial uncoupling protein-2 (UCP2) in myocardial remodeling induced by chronic exposure to CT-1. Kunming mice were intraperitoneally injected with carboxy-terminal polypeptide (CP) of CT-1 (CT-1-CP, 500 μg·kg−1· day−1) for 1, 2, 3 and 4 week (s), respectively (4 groups obtained according to the injection time, n=10 each, with 5 males and 5 females in each group). Those injected with physiological saline for 4 weeks served as controls (n=10, with 5 males and 5 females). The heart tissues of mice were harvested at 1, 2, 3 or 4 week (s). Immunohistochemistry (IHC) and Western blotting (WB) were used to detect the distribution and expression of sarcomeric α-actin, α-actinin and mitochondrial UCP2 in myocardial tissues. IHC showed that α-actin was mainly distributed around the nuclei of cardiomyocytes, α-actinin concentrated around the striae and UCP2 scattered rather evenly in the plasma. The expression of α-actin was slightly greater than that of α-actinin and UCP2 in the control group (IHC: χ2=6.125; WB: F=0.249, P>0.05) and it gradually decreased after exposure to CT-1-CP. There was no significant difference in the expression of α-actin between the control group and the CT-1-CP-treated groups (χ2=7.386, P>0.05). But Western blotting revealed significant difference in the expression of α-actin between the control group and the 4-week CT-1-CP-treated group (F=2.912; q=4.203, P<0.05). Moreover, it was found that the expression of α-actinin increased stepwise with the exposure time in CT-1-CP-treated groups and differed significantly between CT-1-CP-treated groups and the control group (ICH: χ2=21.977; WB: F=50.388; P<0.01). The expression of UCP2 was initially increased (WB: control group vs. 1- or 2-week group, q values: 5.603 and 9.995, respectively, P<0.01) and then decreased (WB: control group vs. 3-week group, q=4.742, P<0.01; control group vs. 4-week group, q=0.558, P>0.05). It was suggested that long-term exposure to CT-1-CP could lead to the alteration in the expression of sarcomeric α-actin, α-actinin and mitochondrial UCP2. The different expressions of sarcomeric structure proteins and mitochondrial UCP2 may be involved in myocardial remodeling.
Stellate ganglion blockade (SGB) protects patients from focal cerebral ischemic injury, and transection of the cervical sympathetic trunk (TCST) in a rat model can mimic SGB in humans. The purpose of this study was to investigate the mechanisms underlying the neuroprotective effects of TCST on neuronal damage in the hippocampus in a rat model of middle cerebral artery occlusion (MCAO) in an attempt to elucidate the neuroprotective effects of SGB. The modified method of Zea Longa was used to establish the permanent MCAO model. Male Wistar rats were randomly divided into three groups: sham-operated group, MCAO group, and TCST group. The animals in TCST group were sacrificed 48 h after TCST which was performed after the establishment of the MCAO model. Proteins were extracted from the ipsilateral hippocampus and analyzed by two-dimensional difference gel electrophoresis (2D-DIGE) and peptide mass fingerprinting (PMF). The levels of N-ethylmaleimide-sensitive factor (NSF) were measured as well. The results showed that 11 types of proteins were identified by 2D-DIGE. The expressions of eight proteins were changed both in the sham-operated and TCST groups, and the expressions of the other three proteins were changed in all three groups. Moreover, the expression of NSF was higher in the TCST group than in the MCAO group but lower in the MCAO group than in sham-operated group. The ratio of NSF expression between the MCAO group and shamoperated group was −1.37 (P<0.05), whereas that between the TCST group and MCAO group was 1.35 (P<0.05). Our results imply that TCST increases the expression of NSF in the hippocampus of adult rats with focal cerebral ischemia, which may contribute to the protection of the injured brain. Our study provides a theoretical basis for the therapeutic application of SGB to patients with permanent cerebral ischemia.
To investigate the known and new factors associated with uninvestigated dyspepsia (UD), we surveyed 8600 Chinese navy personnel with offshore training shorter than 1 month or longer than 9 months per year. All respondents were required to complete a questionnaire covering demographics, the Chinese version of the Rome III survey, eating habits, life styles, and medical and family history. The response rate was 94.3% (8106/8600) with 4899 respondents qualified for analysis, including 1046 with offshore training and 3853 with onshore training. The prevalence of UD was higher in the offshore group than in the onshore group (12.6% vs. 6.9%, P<0.001), with a general prevalence of 8.1%. The subjects with offshore training were more likely to suffer from UD and postprandial distress syndrome (OR=1.955, 95% CI 1.568–2.439, P<0.001 and OR=1.789, 95% CI 1.403–2.303, P<0.001, respectively). The multivariate logistic regression analysis showed UD was associated with offshore training (OR=1.580, 95% CI 1.179–2.118, P=0.002), family history (OR=1.765, 95% CI 1.186–2.626, P=0.005) and smoking (OR=1.270, 95% CI 1.084–1.488, P=0.003), but not with alcohol drinking. The association between dysentery history and UD was undetermined/borderline (P=0.056–0.069). In conclusion, we identified offshore training as a new factor associated with UD, and also confirmed 2 known associated factors, family history and smoking.
This study was aimed to investigate the role of the delta-opioid receptor (DOR)-β-arrestin1-Bcl-2 signal transduction pathway in the pathogenesis of ulcerative colitis (UC) and the intervention effects of oxymatrine on UC. Forty Sprague-Dawley rats were divided into normal group, model group, oxymatrine-treated group and mesalazine-treated group (n=10 each) at random. The rat UC model was established by intra-colonic injection of trinitrobenzene sulfonic acid in the model group and two treatment groups. The rats in oxymatrine-treated group were subjected to intramuscular injection of oxymatrine [63 mg/(kg·day)] for 15 days, and those in mesalazine-treated group given mesalazine solution [0.5 g/(kg·day)] by gastric lavage for the same days. Animals in normal group and model group were administered 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the rats were sacrificed for the removal of colon tissues. The expression levels of DOR, β-arrestin1 and Bcl-2 were determined in colon tissues by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR), respectively. It was found that the expression levels of DOR, β-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group as compared with the other groups (P<0.05). They were conspicuously decreased in both mesalazine-treated and oxymatrine-treated groups in contrast to the model group (P<0.05). No statistically significant difference was noted in these indices between mesalazine- and oxymatrinetreated groups (P>0.05). This study indicated that the DOR-β-arrestin1-Bcl-2 signal transduction pathway may participate in the pathogenesis of UC. Moreover, oxymatrine can attenuate the development of UC by regulating the DOR-β-arrestin1-Bcl-2 signal transduction pathway.
The aim of this study was to examine the effects of endoplasmic reticulum (ER) stress on aldosterone (Aldo)-induced apoptosis of endothelial cells. Glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP, a hallmark of ER-associated apoptosis) were used to evaluate ER stress. Western blotting and real-time PCR were used to analyze indicators of ER molecule. Apoptosis was detected by annexin V/propidium iodide staining and flow cytometry. Human umbilical vein endothelial cells (HUVECs) were stimulated with different concentrations of Aldo for different durations. Aldo promoted apoptosis of HUVECs and induced ER stress, as evidenced by increased expression of GRP78 and CHOP. siRNA knockdown of CHOP attenuated Aldo-mediated apoptosis. These results indicate that ER stress may be involved in Aldo-induced apoptosis of HUVECs.
This study was aimed to examine the effect of ovariectomy on visceral fat, serum adiponectin levels and lipid profile. Forty-five female Sprague Dawley rats were divided into three groups (n=15 each): ovariectomized group (OVX), ovariectomized plus estrogen-treated group (OVX+E2), and sham-operated group (SHAM). Body weight, abdominal adipose tissues, serum adiponectin and lipid profile were measured and compared among the groups after three-month feeding post-surgery. Significant increases in body weight and visceral fat were found in ovariectomized rats when compared with sham-operated ones and significant increases were also observed in serum adiponectin, triglyceride and very low density lipoprotein cholesterol levels in ovariectomized rats. Body weight, visceral fat and serum adiponectin levels were profoundly reduced in OVX+E2 group as compared with OVX group. It was concluded that ovarian hormone deficiency induced by ovariectomy leads to significant increases in body weight and visceral fat, along with increased serum adiponectin, triglyceride and very low density lipoprotein cholesterol levels in rats. Attenuation in these changes can be achieved by estrogen supplementation.
Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic constituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the production and secretion of the proinflammatory cytokine interleukin-1β (IL-1β), which plays a critical role in the development and maintenance of neuropathic pain. In the present study, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were significantly decreased after spinal nerve ligation (SNL), and the changes were accompanied by inhibited autophagy in the spinal microglia and increased mRNA and protein levels of IL-1β in the ipsilateral spinal cord. We then investigated the antinociceptive effect of rapamycin, a widely used autopahgy inducer, on SNL-induced neuropathic pain in rats and found that treatment with intrathecal rapamycin significantly attenuated the mechanical allodynia and thermal hyperalgesia. Moreover, rapamycin significantly enhanced autophagy in the spinal microglia, whereas it reduced the mRNA and protein levels of IL-1β in the ipsilateral spinal cord. Our results showed that rapamycin could ameliorate neuropathic pain by activating autophagy and inhibiting IL-1β in the spinal cord.
In recent years, more attention has been paid to the role of the glutamate transporter 1 (GLT-1, EAAT2) in major depressive disorder (MDD). However, experimental data on brain GLT-1 levels are, to some extent, inconsistent in human postmortem and animal studies. These discrepancies imply that the role of GLT-1 in the pathophysiology of MDD and the action of antidepressants remain obscure. This work was designed to study the impact of chronic unpredictable stress (CUS) for 2 sessions per day for 35 days and four weeks of fluoxetine (FLX) on depressive-like behaviors in rats, as well as the concomitant expression of the GLT-1 protein in the hippocampus. Behavioral changes were assessed by the sucrose preference and open field tests. GLT-1 levels were detected by immunohistchemistry and Western blot analysis. Our study demonstrated that the animals exposed to CUS showed depressive-like behaviors and exhibited a significant decrease in GLT-1 expression in the hippocampus. Chronic FLX treatment reversed the behavioral deficits and the CUS-induced decrease in GLT-1 levels. Taken together, our results support the reduction of GLT-1 in human postmortem studies in MDD and suggest that GLT-1 may be involved in the antidepressant activity of FLX. Our studies further support the notion that GLT-1 is an attractive candidate molecule associated with the fundamental processes of MDD and may be a potential, and novel pharmacological target for the treatment of MDD.
Novel uniform-sized magnetic molecularly imprinted polymers (MMIPs) were synthesized for selective recognition of active antitumor ingredients of kaempferol (KMF) and protoapigenone (PA) in Macrothelypteris torresiana (M. torresiana) by surface molecular imprinting technique in this study. Super paramagnetic core-shell nanoparticles (γ-MPS-SiO2@Fe3O4) were used as seeds, KMF as template molecule, acrylamide (AM) as functional monomer, and N, N′-methylene bisacrylamide (BisAM) as cross-linker. The prepared MMIPs were characterized by X-ray diffraction (XRD), Fourier transform infrared spectrum (FTIR), transmission electron microscopy (TEM) and thermo-gravimetric analysis (TGA), respectively. The recognition capacity of MMIPs was 2.436 times of non-imprinted polymers. The adsorption results based on kinetics and isotherm analysis were in accordance with the pseudo-second-order model (R2=0.9980) and the Langmuir adsorption model (R2=0.9944). The value of E (6.742 kJ/mol) calculated from the Dubinin-Radushkevich isotherm model suggested that the physical adsorption via hydrogen-bonding might be predominant. The Scatchard plot showed a single line (R2=0.9172) and demonstrated the homogeneous recognition sites on MMIPs for KMF. The magnetic solid phase extraction (MSPE) based on MMIPs as sorbent was established for fast and selective enrichment of KMF and its structural analogue PA from the crude extract of M. torresiana and then KMF and PA were detected by HPLC-UV. The established method showed good performance and satisfactory results for real sample analysis. It also showed the feasibility of MMIPs for selective recognition of active structural analogues from complex herbal extracts.
The purpose of the current study was to examine the pharmacokinetic profiles and tissue distribution of clevidipine, an ultra-short-acting calcium antagonist in Beagle dogs and Sprague-Dawley rats, respectively. The pharmacokinetics and biodistribution of its primary metabolite H152/81 were also evaluated. Dogs received intravenous infusion of clevidipine at a dose rate of 17 μg/(kg·min), and rats were given intravenous administration of clevidipine at a dose of 5 mg/kg. Dog plasma and rat tissues were collected and assayed by HPLC-MS/MS. It was found that plasma clevidipine quickly reached the steady state concentration. The terminal half-life was short (16.8 min), pointing out a rapid elimination after the end of the infusion. The total clearance was 5 mL/(min·kg). In comparison, plasma concentration of H152/81 was increased more slowly and was significantly higher than that of clevidipine. After intravenous administration, clevidipine was distributed rapidly into all tissues examined, with the highest concentrations found in the brain, heart and liver. Maximal concentrations of clevidipine were found in most tissues at 10 min post-dosing. However, the proportion of clevidipine distributed in all tissues was quite small (0.042‰) compared to the total administration dose. It was suggested that clevidipine was mainly distributed in blood and it transformed to inactive metabolite rapidly.
A rapid, sensitive, and selective liquid chromatography-tandem mass spectrometry was developed for the simultaneous determination of lycorine and galanthamine, two major constituents in Lycoris radiata extract, in rat plasma. Liquid-liquid extraction with ethyl ether was carried out using diphenhydramine as the internal standard. The two bioactive alkaloids were separated on a Zorbax SB-C18 reserved-phase column (150 mm × 4.6 mm, i.d., 5 μm) by gradient elution using a mobile phase consisting of methanol with 0.1% formic acid (A) and water with 0.1% formic acid (B) at a flow rate of 0.6 mL/min. All analytes showed good linearity over a wide concentration range (r2>0.99) and the lower limit of quantification was 3.00 ng/mL for each analyte. The average extraction recovery of the analytes from rat plasma was more than 82.15%, and the intra-day and inter-day accuracy and precision of the assay were less than 12.6%. The validated method was successfully applied to monitoring the concentrations and pharmacokinetic studies of two Amaryllidaceous alkaloids in rat plasma after an oral administration of Lycoris radiata extract.
Postpartum visits (PPVs) are still underutilized in rural China, and identification of factors that influence PPV use is important in ensuring the utilization of maternal health services and for wellbeing of women. A cross-section study was undertaken to collect related data from 347 rural women interviewed six weeks or more after delivery, and an ANOVA was performed to find whether there were significant differences in the number of PPVs among different rural areas in China. According to Andersen’s socio-behavioral model of health service use, factors were divided into equitable and inequitable ones. Chi-squared test, univariate and multiple analyses were used to determine the equity of PPV use by identifying factors that were most strongly associated with the use of a PPV. The results showed that 20.2% of the respondents (n=70) did not receive any PPVs, and 62.5% (n=173) of those who had PPVs (n=277) did not receive standard PPVs (referring to at least 3 visits). There was no significant difference among different rural areas in terms of the number of PPVs (F=1.514, P=0.211). Multiple regression analyses revealed that enabling factors such as compensation for delivery expense [OR (95% CI)=2.825 (1.331, 5.995)], village type [OR (95% CI)=1.802 (1.021, 3.182)] and service quality [OR (95% CI)=1.847 (1.074, 3.176)] were strongly associated with PPV use. Both enabling factors such as home visits [OR (95% CI)=1.855 (1.085, 3.174)], service quality [OR (95% CI)=1.993 (1.155, 3.439)] and need factors such as low birth weight [OR (95% CI)=4.424 (1.482, 13.203)] were significantly associated with standard PPV use. Our results suggested that the equitable access to PPVs has been considerably improved in rural areas in China. The associations between inequitable factors and PPV use warrant further exploration, and policies aimed at improving quality and patterns of service supply are needed in order to ensure a full equitable access to maternal health services.
Estrogen-related receptor alpha (ERRα) plays an important role in the development of hormone-dependent cancers, but its roles in lung cancer remain elusive. The present study was aimed to investigate the effects of ERRα on the proliferation and metastasis of lung cancer A549 cells. The mRNA and protein levels of ERRα were detected in lung cancer A549 and MCF-7 cells and bronchial epithelial BEAS-2B cells by qRT-PCR and Western blotting, respectively. ERRα plasmid transfection and XCT-790 (an inverse agonist of ERRα) were used to up-regulate or down-regulate ERRα expression in A549 cells, respectively. The viability of A549 cells was measured by cell counting kit-8 (CCK-8) and the motility of A549 cells by wound healing assay and Transwell migration/invasion assay. The epithelial markers E-cadherin (E-Cad) and zona occludin-1 (ZO-1), the mesenchymal markers fibronectin (FN) and vimentin (Vim) and the transcription factors (Snail, Zeb1 Twist and Slug) were further detected at mRNA and protein levels by qRT-PCR and Western blotting, respectively. The results showed that ERRα promoted the growth of lung cancer A549 cells in vitro. XCT-790 significantly inhibited the migration and invasion of A549 cells. Over-expression of ERRα promoted the epithelial-to-mesenchymal transition (EMT) of A549 cells, down-regulated the epithelial makers E-Cad and ZO-1, and up-regulated the mesenchymal makers FN and Vim. Silencing of Slug, but not other transcription factors, significantly abolished the ERRα-induced EMT of A549 cells. It was suggested that ERRα promoted the migration and invasion of A549 cells by inducing EMT, and Slug was involved in the process. Targeting ERRα might be an efficient approach for lung cancer treatment.
This study investigated the effects of miRNA-155 on malignant biological characteristics of NK/T-cell lymphoma cell lines and the possible mechanism. The expression of miRNA-155 was detected in lymphoma cell lines from different sources (SNK-6, YTS, Jurkat and DOHH2) by real-time PCR. Lentiviral vectors (pLL3.7) that could overexpress or downexpress miRNA-155 were constructed. Recombinant lentiviral particles were prepared and purified, and their titers determined. The expression of miRNA-155 in the infected SNK-6 cells and the cell proliferation were detected by PCR and CCK-8, respectively. Flow cytometry was used to determine the apoptosis of infected SNK-6 cells. The target of miRNA155 was predicted from Targetscan website. The effect of miRNA155 on FOXO3a expression was examined by Western blotting. The results showed that among the human NK/T-cell lymphoma cell lines SNK-6, YTS, Jurkat and DOHH2, the expression of miRNA-155 was highest in SNK-6. The infection efficiency of the recombinant lentivirus in SNK-6 was more than 70% at multiplicity of infection (MOI) of 100. The expression of miRNA-155 was significantly increased in SNK-6 cells infected by lentivirus vectors with high expression of miRNA-155 (4 times higher than the control group), and profoundly decreased in those infected with lentiviruses with low expression of miRNA-155. The proliferation of letivirus-infected SNK-6 cells was decreased as the expression of miRNA-155 reduced. The apoptosis rate was increased with the reduction in the expression of miRNA-155. FOXO3a was found to be a possible target of miRNA155, as suggested by Targetscan website. Western blotting showed that the expression of FOXO3a was significantly elevated in SNK-6 cells with miRNA-155 inhibition. It was concluded that reduction in miRNA-155 expression can inhibit the proliferation of SNK-6 lymphoma cells and promote their apoptosis, which may be associated with regulation of FOXO3a gene.
Studies have proved that microRNA-101 (miR-101) functions as a tumor suppressor and is associated with growth and apoptosis of various human cancers. However, the role of miR-101 in osteosarcoma and the possible mechanism by which miR-101 affects the tumor growth and apoptosis have not been fully elucidated. In this study, we found that the expression of miR-101 was down-regulated in osteosarcoma tissues and Saos-2 cell line as compared with that in adjacent non-neoplastic bone tissues and the osteoblastic cell line. To better characterize the role of miR-101 in osteosarcoma, we used a gain-of-function analysis by transfecting human osteosarcoma cell line Saos-2 with chemically synthesized miR-101 mimics. The results showed that overexpression of miR-101 inhibited the proliferation and promoted the apoptosis of Saos-2 cells. Meanwhile, bioinformatic analysis demonstrated that mTOR gene was a direct target of miR-101. Overexpression of miR-101 significantly decreased the expression of mTOR at both mRNA and protein levels in Saos-2 cells, consequently inhibiting Saos-2 cells proliferation and promoting cells apoptosis in an mTOR-dependent manner. Taken together, these data suggest that miR-101 may act as a tumor suppressor, which is commonly downregulated in both osteosarcoma tissues and cells. mTOR plays an important role in mediating miR-101 dependent biological functions in osteosarcoma. Reintroduction of miR-101 may be a novel therapeutic strategy by down-regulating mTOR expression.
Forkhead Box c2 (FOXC2) is a member of forkhead/winged-helix family of transcription factors. The relationship between FOXC2 and invasive breast cancers, including basal-like breast cancer (BLBC, a subtype of breast cancer), remains to be elucidated. In this study, immunohistochemistry was used to detect the expression of FOXC2 in samples from 103 cases of invasive breast cancers and 15 cases of normal mammary glands. The relationship between FOXC2 and clinical parameters of invasive breast cancers such as patient’s age, tumor size, lymph node metastasis, tumor grade, the expression of ER, PR, HER-2 and p53, and Ki-67 labeling index (LI) was evaluated. The expression of FOXC2 was detected in parent MCF7 cells, MCF cells transfected with FOXC2 expression vectors and MDA-MB-435 cells by immunohistochemistry and Western blotting. Transwell assay was used to determine the invasive ability of these cells. The results showed that FOXC2 was strongly expressed in basal epithelial cells in normal mammary glands and weakly expressed or even not expressed in glandular epithelial cells. The majority of invasive breast cancers (71.8%, 74/103) had negative or weak expression of FOXC2. However, FOXC2 was strongly expressed in 60.7% of BLBCs. Moreover, FOXC2 was related with tumor grade, p53 expression, ki-67 LI and lymph nodes metastasis. It was expressed in FOXC2-transfected MCF cells and MDA-MB-435 cells but not in parent MCF cells. Transwell assay revealed that MCF cells transfected with FOXC2 expression vectors were more aggressive than the parent MCF cells, suggesting a positive correlation between FOXC2 and the invasion of breast cancer. It was concluded that there is a significant association between FOXC2 and the metastasis of invasive breast cancer. FOXC2 may be used as a new marker for the diagnosis and prognosis prediction of different subtypes of invasive breast cancers.
The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients (620 females, mean age of 36.8±7.7 years) admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study (warfarin plus 75–100 mg aspirin) or control (warfarin only) groups. International normalized ratio (INR) and prothrombin time were maintained at 1.8–2.5 and 1.5–2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respectively (P>0.05). The incidence of overall thromboembolic events in study group was lower than that in control group (2.16% vs. 4.35%, P=0.049). No statistically significant differences were found in hemorrhage events (3.53% vs. 3.95%, P=0.722) or mortality (0.20% vs. 0.40%, P=0.559) between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.
Anterior lumbar interbody fusion (ALIF) followed by posterior pedicle screw fixation (PSF) in a second procedure is mostly used to implement lumbar spine fusion. ALIF followed by anterior lumbar screw-plate has a lot of advantages, but its biomechanical stability requires confirmation. This study evaluated the biomechanical stability of a novel anterior lumbar locked screw-plate (ALLSP) by comparison with posterior lumbar PSF. Twelve fresh human cadaveric lumbar specimens (L4–L5) were assigned to four groups: ALIF+PSF group, ALIF+ALLSP (both fixed) group, ALIF group and an untreated control (both non-fixed) group. The first three groups received implantation of a rectangular titanium cage. Tests under axial compression, flexion, extension, lateral bending, or rotation showed that the fixed groups had significantly stronger stability than the non-fixed groups (P=0.000 for all). The ALIF+ALLSP group had significantly greater axial stiffness under applied axial compression and significantly less angular displacement under rotational forces than the ALIF+PSF group. The angular displacement of the ALIF+ALLSP group was less under flexion than that of the ALIF+PSF, and the angular displacement under lateral bending and extension was greater, but these differences were not statistically significant. In summary, the ALLSP conforms to the anterior lumbar spine and has good biomechanical stability. It is a reliable choice for enhancing the stability of ALIF.
Complex segmental femoral fractures are usually not amenable to closed reduction. The purpose of this study was to evaluate a series of patients who had undergone four pins assisted reduction and intramedullary nail fixation to determine the therapeutic effect of this closed reduction technique. Between December 2010 and January 2013, 15 consecutive patients with segmental femoral fractures were treated with four pins assisted reduction at our hospital. The patient was placed in a supine position on a radiolucent fracture table and a gentle traction was attempted on the limb. Usually, the proximal fracture segment exhibited the typical deformity of flexion, external rotation, and abduction, the middle segment exhibited adduction and distal fracture segment exhibited flexion. Four Schanz pins were placed percutaneously to fix one cortex and did not penetrate into the medullary cavity, and the “T” sharp handles were fixed on the Schanz pins. The fragments were then reduced by reversing the deforming forces for segmental fractures by two assistants. And then, the reduction could be easily achieved and intramedullary nail fixation was performed. Radiographs were evaluated for the quality of the reduction and fracture union. Closed reduction was achieved in all patients using the four pins technology. All 15 fractures united uneventfully. No patient had a rotational malunion or limb length discrepancy at the time of the last follow-up. Thirteen of the fifteen (86.7%) patients had anatomic reduction and two of them (13.3%) had minor varus alignment of 3° and 5°. Knee stiffness was observed in 2 patients and no implant failure was observed. Surgical treatment of complex segmental femoral fractures with four pins assisted reduction and intramedullary nail fixation techniques can result in excellent reductions and a high union rate.
Conventional pedicled-flap based surgeries in treating breast cancer have their limitations. New surgical regimens are yet to be explored, which will follow the oncological principle of being “total tumor free”, whilst fit into the unique characteristics of China’s own medical system as well as patients’ demand. From 2007 to 2013, 143 patients with early stage breast cancer were included in the study, with the average age of 46.1 years. Fifty-three patients were subjected to modified breast conserving surgery (MBCS)+latissimus dorsi (LD) flap reconstruction, 41 to skin sparing mastectomy (SSM)+implant+LD flap reconstruction, 29 to MBCS+distal transverse rectus abdominis myocutaneous (DTRAM) flap reconstruction, and 20 to SSM+DTRAM flap reconstruction. The results showed that out of the 143 patients, there was no graft loss. Minor complications included 4 cases of fat liquefaction, and 6 cases of seratoma, which all resolved after conservative treatment. Five patients had visible protuberance in the abdomen, but not leading to any gastrointestinal symptoms. The reconstructed breasts all presented good shape. 96.7% of the patients were satisfied with the outcome. The follow-up period varied from 6 months to 60 months, and only one patient died from tumor metastasis in the brain. No local recurrence occurred. It was concluded that these two modified pedicled-flap surgeries are readily practical, and aesthetically satisfactory, with high applicability in China. They do not compromise the oncological outcomes, but also are well-accepted by Chinese patients.
Nonalcoholic and alcoholic rabbit models of fatty liver were established by feeding on high-fat diet and alcohol, respectively, and fatty liver stiffness at different pathological stages was assessed with real-time shear-wave elastography (SWE), so as to investigate the fibrosis process during the development of fatty liver. The fatty liver stiffness of rabbit in nonalcoholic and alcoholic groups was higher than that in the control group, and that in alcohol group was higher than that in the nonalcoholic group (P<0.01). The elasticity modulus of liver in fatty liver rabbits of nonalcoholic and alcoholic groups showed a positive correlation with progression of liver fibrosis (P<0.01). Real-time SWE, as a noninvasive diagnostic method, can objectively reflect the liver stiffness change and progression of liver fibrosis during the development of fatty liver.
The elastic and functional coupling of heart and vessels makes the stroke work (SW) of the heart optimal. Speckle tracking imaging (STI) can evaluate the myocardial strain and function. We studied ventricular-vascular coupling in 80 diabetic patients with different systolic function using STI. The patients were divided into two groups according to ejection fraction (EF): the diabetes mellitus with normal EF (DMN) group and the diabetes mellitus with abnormal EF (DMA) group. Forty-two volunteers served as control group. The relative wall thickness (RWT), left ventricular mass index (LVMI), stroke volume (SV), SW, rate-pressure product (RPP), systemic vascular resistance index (SVRI), left ventricular end-systolic elastance (Ees), effective arterial elasticity (Ea) and ventricular-vascular coupling index (VVI) were measured and calculated by conventional echocardiography. The longitudinal strain (LS) at basement (LSBA), papillary muscle (LSPM) and cardiac apex (LSAP) was assessed with STI. It was found: (A) compared with control group, in DMN and DMA groups, LSBA, LSPM and LSAP decreased, and they were lower in DMA group. (B) VVI, RPP and SVRI increased, and they were higher in DMN group; Ees decreased, and it was lower in DMA group. (C) LSBA, LSPM, and LSAP had negative correlation with VVI. LSAP, RWT, LVMI and SW were independent predictors for VVI. The area under the receiver operating characteristic (ROC) curves was used for identification of DMA and DMN with LSBA, LSPM, and LSAP, and the area under the ROC of LSAP was the largest. This study supports that myocardial LS could reflect the ventricular-vascular coupling. Different segments had an order to “respond to” the state of the coupling, and the cardiac apex might be the earliest.
The purpose of this study was to evaluate whether the cranial and circumaxillary sutures react differently to maxillary expansion (ME) and alternate maxillary expansions and constrictions (Alt-MEC) in a rat model. Twenty-two male Sprague-Dawley rats (6 weeks old) were used and divided into three groups. In ME group (n=9), an expander was activated for 5 days. In Alt-MEC group (9 animals), an alternate expansion and constriction protocol (5-day expansion and 5-day constriction for one cycle) was conducted for 2.5 cycles (25 days total). The control group comprised 4 animals with no appliances used, each of two sacrificed on day 5 and day 25 respectively. Midpalatal suture expansion or constriction levels were assessed qualitatively and quantitatively by bite-wing X-rays and cast models. Distances between two central incisors and two maxillary first molars were measured on cast models after each activation. Circumaxillary sutures (midpalatal, maxillopalatine, premaxillary, zygomaticotemporal and frontonasal suture) in each group were characterized histologically. Results showed that midpalatal suture was widened and restored after each expansion and constriction. At the end of activation, the widths between both central incisors and first molars in Alt-MEC group were significantly larger than those in ME group (P<0.05). Histologically, all five circumaxillary sutures studied were widened in multiple zones in Alt-MEC group. However, only midpalatal suture was expanded with cellular fibrous tissue filling in ME group. Significant osteoclast hyperplasia was observed in all circumaxillary sutures after alternate expansions and constrictions, but osteoclast count increase was only observed in midpalatal suture in ME group. These results suggested that cranial and circumaxillary sutures were actively reconstructed after Alt-MEC, while only midpalatal suture had active reaction after ME.
There is continuous debate regarding the effectiveness of thymectomy in the treatment of non-thymomatous myasthenia gravis (MG). This systematic review was undertaken to determine whether thymectomy was effective in non-thymomatous MG. We retrieved articles published between January 1980 and September 2013. Sixteen cohort studies were included. Given the considerable heterogeneity, we used a descriptive method instead of statistical synthesis. The median relative rates (RRs) and their interquartile ranges were used to estimate the magnitude of benefit. Compared to conservatively treated MG patients, thymectomized patients had higher survival, clinical remission, pharmacologic remission and improvement rates, and RRs were 1.07 (1.01–1.17), 1.83 (0.82–2.99), 1.55 (1.22–1.95) and 1 (1.00–1.09), respectively. Subgroup analyses showed that patients with moderate to severe generalized MG benefited more from thymectomy, with RRs of survival and pharmacologic remission increasing to 1.35 (1.24–1.49) and 2.68 (1.73–4.17), respectively. These results suggested that thymectomy might be an effective procedure in non-thymomatous MG patients. The patients with moderate to severe generalized MG might benefit more. Taking into account the poor methodological quality of present studies, more well-designed prospective randomized controlled trials (RCTs) are still required to reach unequivocal conclusion.
There have been numerous studies done to explore the diagnostic performance of quantitative diffusion-weighted (DW) MR imaging to differentiate between benign and malignant pancreatic masses. However, the results have been inconsistent. We performed a meta-analysis to investigate whether DW-MR imaging can differentiate between these two diseases. Databases including MEDLINE, EMBASE and Cochrane Library were utilized to find relevant articles published between January 2001 and January 2014. A Stata version 12.0 and a Meta-Disc version 1.4 were used to describe primary results. Twelve studies with 594 patients, which fulfilled the inclusion criteria, were enrolled for the analysis. The pooled sensitivity and specificity of DW imaging was 0.91 (95% CI: 0.84, 0.95) and 0.86 (95% CI: 0.76, 0.93) respectively. The area under the curve of the summary receiver operating characteristic was 0.95 (95% CI: 0.93, 0.96). The results indicated that DW imaging might be a valuable tool for differentiating benign and malignant pancreatic masses.