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The aim of the present study was to evaluate the predictors for advanced liver fibrosis in patients with chronic hepatitis B virus (HBV) infection with persistently normal alanine aminotransferase (PNALT), or persistently or intermittently mildly elevated ALT (PIEALT). A total of 305 patients were included in the present study. Liver biopsies were evaluated using the METAVIR scoring system. Liver stiffness (LS) was measured using Fibroscan. Multivariate logistic regression and the area under the receiver operating characteristic curve (AUROC) were used to examine the diagnostic value of the predictors for advanced liver fibrosis. HBV DNA viral load in the PNALT group was significantly lower compared with the PIEALT group (4.57±1.68 vs. 5.71±1.69 log10 IU/ml; P<0.001). Body mass index and LS were also significantly lower in the PNALT group compared with the PIEALT group (P<0.001). The proportion of patients with liver fibrosis was significantly higher in the PIEALT group compared with the PNATL group (P=0.001). High ALT levels were an independent predictor for liver fibrosis, with an odds ratio (OR) of 2.69 (P=0.002). Male sex (OR=0.34, P=0.007), high ALT levels (OR=2.37, P=0.029) and a high HBV DNA load (OR=1.39, P=0.005) were independent predictors for advanced liver fibrosis. The AUROC was 0.65 (P=0.003) when using ALT levels to predict advanced liver fibrosis. ALT levels at ≥0.88 upper limit of normal (ULN; 35 IU/l) were considered as positive for advanced liver fibrosis, the sensitivity and specificity were 87.8 and 47.4%, respectively. The AUROC was 0.64 (P=0.004) when using the HBV DNA value to predict advanced liver fibrosis. When an HBV DNA value of ≥4.99 log10 IU/ml was considered as positive for advanced liver fibrosis, the sensitivity and specificity were 78.0 and 49.5%, respectively. The AUROC was 0.72 (P<0.001) when combining ALT, HBV DNA load and sex into a formulation to predict advanced liver fibrosis. When the formulation score at >-2.22 was considered as positive for advanced liver fibrosis, the sensitivity and specificity were 61.5 and 70.7%, respectively. Therefore, normal ALT levels do not always indicate the absence of hepatic fibrosis. A combination of ALT levels, sex and serum HBV DNA load may more effectively identify patients with CHB at high risk of developing fibrosis. These patients may benefit from liver biopsy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) represents a major endpoint of chronic liver diseases and is the third leading cause of cancer-related mortality. Long intergenic non-coding RNA-integrin subunit ß1 ITGB1 (linc-ITGB1) is a novel long non-coding RNA, which is implicated in the development and progression of human tumors. However, its involvement in hepatocarcinogenesis remains to be elucidated. In the present study, the specific roles of linc-ITGB1 on cell proliferation and metastasis in HCC were investigated. It was initially observed that the expression of linc-ITGB1 was significantly elevated in 30 cases of clinical HCC tissues relative to their adjacent non-cancerous tissues. Expression of linc-ITGB1 was particularly elevated in the highly invasive cell line, HCCLM3. Knockdown of linc-ITGB1 in HCCLM3 cells using a specific short hairpin RNA decreased cell viability and colony formation in vitro. In addition, cell cycle analysis demonstrated that linc-ITGB1-depleted cells accumulated in the G0/G1 phase. HCCLM3 cells with linc-ITGB1 depletion exhibited significantly decreased migration and invasion abilities, when compared with control cells (P<0.05). These data suggest that linc-ITGB1 promotes HCC progression by inducing cell-cycle arrest. Therefore, targeted therapy against linc-ITGB1 may be a novel strategy to treat HCC. [ABSTRACT FROM AUTHOR]

Phascolarctobacterium can produce short-chain fatty acids, including acetate and propionate, and can be associated with the metabolic state and mood of the host. The present study investigated the colonization characteristics of Phascolarctobacterium faecium in healthy individuals <1-80 years old in Southern China. A total of 150 fresh fecal samples were collected, and bacterial DNA was isolated from these samples for quantitative polymerase chain reaction analysis. Phascolarctobacterium faecium demonstrated a high colonization rate and abundant colonization in the human gastrointestinal tract. The colonization rate varied between 43.33-93.33%, and the abundance of Phascolarctobacterium faecium ranged between 3.22-5.76 log cells g-1 (<1 years old) and 3.06-9.33 log cells g-1 (>1 year old). The permillage of Phascolarctobacterium faecium in total bacteria ranged between 0.004-1.479. There was presence of Phascolarctobacterium faecium-like bacteria in younger individuals with a gradual increase in the number of bacteria maintained at a high level with increasing ages (between 1 and 60 years old), but with a decrease in elderly individuals (>60 years old). The results of the present study demonstrated that Phascolarctobacterium faecium is abundantly colonized in the human gastrointestinal tract. [ABSTRACT FROM AUTHOR]

The aim of the present study was to identify whether sepsis-induced vascular hyporeactivity is associated with microcirculation disturbance and multiple organ injuries. The current study assessed the impact of resveratrol (Res) treatment on lipopolysaccharide (LPS) challenge mediated vascular hyporeactivity. Effects of Res treatment (30 mg/kg; i.m.) at 1 h following LPS stimulation (5 mg/kg; i.v.) on the survival time, mean arterial pressure (MAP), and maximal difference of MAP (ΔMAP) to norepinephrine (NE; 4.2 μg/kg) in mice were observed. The reactivity to gradient NE of isolated mesenteric arterioles and the association with the RhoA-RhoA kinase (ROCK)-myosin light chain phosphatase (MLCP) pathway were investigated by myography, and the signaling molecule protein levels were assessed using ELISA. Res treatment prolonged the survival time of mice subjected to LPS challenge, but did not prevent the LPS-induced hypotension and increase in ΔMAP. Res treatment and RhoA agonist U-46619 incubation prevented LPS-induced vascular hyporeactivity ex vivo, which were suppressed by incubation with ROCK inhibitor Y-27632. LPS-induced vascular hyporeactivity was not affected by the MLCP inhibitor okadaic acid incubation, but was further downregulated by the co-incubation of OA plus Y-27632. The inhibiting effect of Y-27632 on Res treatment was eradicated by incubation with U-46619. Furthermore, RhoA inhibitor C3 transferase did not significantly inhibit the enhancing role of Res treatment, which was further increased by U-46619 plus C3 transferase co-incubation. In addition, Res treatment eradicated the LPS-induced decreases in p-RhoA and p-Mypt1 levels and increases in MLCP levels. The results of the present study indicate that post-treatment of Res significantly ameliorates LPS-induced vascular hyporeactivity, which is associated with the activation of the RhoA-ROCK-MLCP pathway. [ABSTRACT FROM AUTHOR]

Vitiligo is a common acquired depigmentation disorder for which many treatments have previously been used with varying effects. The aim of the present study was to evaluate the efficacy and safety of targeted high-intensity (TH) and narrow band (NB) ultraviolet B light (UVB) for vitiligo treatment. A total of 33 patients with vitiligo were enrolled in the present study. Patients with a symmetrical or near-symmetrical distribution of lesions on their bodies were selected for the present study. For each patient, half of the body was treated with TH-UVB and the other with NB-UVB twice weekly over a period of 12 weeks (24 times total). The patients were assessed each week for repigmentation of lesions. All data were analyzed using SPSS software, and a total of 30 patients were evaluated. The effective rate was significantly higher in the TH-UVB group (56.7%) compared with the NB-UVB group (20.0%; P<0.05). Additionally, the mean number of radiations necessary for initial repigmentation was significantly lower in the TH-UVB group (7.95±3.43) compared with the NB-UVB group (15.36±3.43; P<0.05). No correlation was found between the clinical features of patients and the efficacy of treatment. In summary, the results of the present study suggest that TH-UVB is a more effective treatment for vitiligo than NB-UVB. [ABSTRACT FROM AUTHOR]

The aim of the present study was to compare the efficacy and safety of fosfomycin combinational therapy with other antibiotics for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). This retrospective cohort study examined 104 cases of sepsis caused by CRKP occurring between January 2012 and November 2014 in Shanghai Tenth People's Hospital. Three categories of patient outcome were assessed: Survival/mortality, duration of intensive care unit stays and duration of medical ventilation. Univariate ordinal analyses were adopted to evaluate the correlations between outcome and treatment. A total of 104 patients with physician-diagnosed CRKP were involved in the study. The overall mortality rate was 25.0%. The majority of the infections (84; 80.8%) were hospital acquired. Critical infections received more than one active antibiotic as therapy. Patients treated with fosfomycin combinational therapy were less likely to fail therapy (OR: 4.71, 95% CI: 1.03-21.65, P=0.034) and tended to have a shorter duration of mechanical ventilation. Gender (OR: 4.35, 95% CI: 1.08-3.60, P=0.037), history of chronic obstructive pulmonary disease (OR: 9.35, 95% CI: 0.06-0.19, P=0.007) and peripheral catheter use (OR: 3.00, 95% CI: 0.07-0.19, P=0.002) are risk factors for clinical outcome. Therefore, the use of fosfomycin combinational therapy for treatment of infection due to CRKP appears to be associated with improved survival rate. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS), which is triggered by endothelial cell injury, evolves into a chronic inflammatory disease. Oxidized low-density lipoprotein (ox-LDL) is an important risk factor for the development of atherosclerosis; ox-LDL induces atherosclerotic plaque formation via scavenging receptors. The present study used ox-LDL-treated human umbilical vein endothelial cells (HUVECs) to investigate the effect of ox-LDL on angiogenesis. ox-LDL decreased HUVEC proliferation by MTT, induced apoptosis by Annexin V-fluorescein isothiocyanate (FITC) staining and markedly suppressed HUVEC tube formation by the Matrigel assay in a dose-dependent manner. Angiogenesis has been correlated with monocyte invasion, plaque instability and atherosclerotic lesion formation. In addition, ox-LDL induced the overproduction of reactive oxygen species using DCFH-DA staining and increased caspase-3 activity. Vascular endothelial growth factor receptor 2 (VEGFR2) were detected by quantitative polymerase chain reaction and western blot analysis and has previously been observed to have a key role in angiogenesis. Furthermore, the present study demonstrated that the abundance of VEGFR2 was decreased in ox-LDL-treated HUVECs. These results suggested that ox-LDL impairs angiogenesis via VEGFR2 degradation, thus suggesting that VEGFR2 may be involved in adaptation to oxidative stress and AS. [ABSTRACT FROM AUTHOR]

The main function of adipocyte fatty acid-binding protein (A-FABP) is to regulate fatty acid metabolism as its molecular chaperone. The clinical significance of A-FABP in hypoxic-ischemic brain damage (HIBD) neonates is not yet clear. Free fatty acid (FFA) in cerebral cortex increases along with hypoxia ischemia degree. Thus, we aimed to investigate whether FFA can induce A-FABP expression and elevate the serum A-FABP level in HIBD neonates. In the present study, 42 HIBD neonates were selected including 11 cases as mild, 16 cases as moderate and 15 cases as severe. The serum was collected from peripheral vein at 72 h after the first visit (acute stage) and 7 days after birth (recovery stage), and the serum from 10 normal neonates was used as the control. The serum level of A-FABP and FFA in 42 neonates with acute phase and recovery phase HIBD were detected using ELISA and copper colorimetric method. The overall serum A-FABP content in HIBD neonates at the acute stage was significantly higher compared to the normal neonates (P<0.05). The serum A-FABP level in severe HIBD neonates was significantly higher than that in mild HIBD, moderate HIBD and normal neonates (P<0.05). The serum FFA level in HIBD neonates at the acute stage was 1,521.57±605.63 µmol/l, which was significantly higher than that in the normal neonates 838.24±294.22 µmol/l. The serum FFA levels in mild, moderate and severe HIBD neonates were significantly higher than those in the normal neonates. The overall A-FABP level in HIBD neonates at the recovery stage was significantly lower compared to the acute stage, which was significant in severe HIBD neonates. A-FABP levels in mild and moderate HIBD neonates at recovery stage were decreased compared with the acute stage, although there was no statistical difference. There was a positive correlation between serum A-FABP and FFA in HIBD neonates at acute stage (r=0.369, P<0.05). In conclusion, serum A-FABP and FFA levels were significantly increased in HIBD neonates at acute stage, and were positively correlated. The serum A-FABP level in HIBD neonates at recovery stage was significantly lower than that in the acute stage. The results suggested that serum A-FABP and FFA levels at acute stage can reflect the severity of HIBD. The detection of serum A-FABP and FFA can be applied as indicators for the early diagnosis of HIBD, but also provides a basis for the clinical evaluation of HIBD treatment. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the therapeutic effect of a combined treatment of Buyang Huanwu decoction (BYHWD), a well-known formula of traditional Chinese medicine, and neural stem cells (NSCs) on spinal cord injury (SCI) and the associated underlying mechanisms. A SCI model was established by surgery via a complete transection of the T10 vertebra of female Sprague-Dawley rats. Gelatin sponges were used to absorb NSCs labeled with the thymidine analog, 5-bromo-2-deoxyuridine (BrdU), and were transferred into the transected spinal cords. BYHWD was administered once a day by introgastric infusion. Motor functions of the hind limbs were evaluated using the 21-point locomotor rating scale developed by Basso, Beattie and Bresnahan (BBB). The fate of the transplanted NSCs under the various conditions was examined by double immunofluorescence staining, using markers for neurons, astrocytes and oligodendrocytes, with BrdU. Ultrastructural changes of the SCI site following the various treatments were examined under a transmission electron microscope. The number of double positive cells for glial fibrillary acidic protein and BrdU in the BYHWD + NSC group was significantly decreased when compared with that in the NSC group (P<0.05). However, the number of cells that were labeled double positive for myelin basic protein and BrdU, as well as neuron specific enolase and BrdU, was greater in the BYHWD + NSC group when compared with the NSC group. Electron microscopy demonstrated that treatment with BYHWD combined with NSCs significantly alleviated demyelination. Results from the BBB motor function test exhibited a significant improvement in the BYHWD + NSC group when compared with the SCI, BYHWD and NSC only groups. In conclusion, the results demonstrated that the traditional Chinese medicine formula, BYHWD, exerted an effect on the differentiation and migration of NSCs. Combining the administration of BYHWD with NSCs was shown to have a synergistic effect on the recovery of neurological function, mitigating the progress of demyelination or ameliorating the recovery of myelination. [ABSTRACT FROM AUTHOR]

Physical exercise has been proved to be neuroprotective in clinical trials and animal experiments. However, the exact mechanism underlying this neuroprotective effect remains unclear. The aim of the present study was to explore whether pre-ischemic treadmill training could act as a form of ischemic preconditioning in a rat following ischemic stroke by reducing oxidative damage. Fifty-four rats were randomly divided into three groups (n=18 per group): Sham surgery, middle cerebral artery occlusion (MCAO) without exercise and MCAO with exercise. Subsequent to treadmill training, ischemic stroke was induced by occluding the MCA for 1.5 h, followed by reperfusion. Six rats in each group were evaluated for neurological deficits and then sacrificed by decapitation to calculate the infarct volume. The remaining rats in each group were sacrificed to detect the level of superoxide dismutase (SOD) activity (n=6) and malondialdehyde (MDA) concentration (n=6). The results indicated that pre-ischemic exercise training reduced brain infarct volume and neurological deficits, increased SOD activity and decreased the concentration of MDA following ischemic stroke. In conclusion, treadmill exercise training prior to MCAO/reperfusion increased the antioxidant ability and decreased the oxidative damage in the brain subsequent to ischemic stroke. [ABSTRACT FROM AUTHOR]

Previous studies have reported that renal size may change when the function is compromised. However, it is not known whether sonographically measured renal size reflects the residual renal function (RRF) in patients undergoing chronic hemodialysis. A total of 140 patients undergoing chronic hemodialysis (≥3 months) were investigated in the present study. The patients were divided into two groups according to the daily urine volume: Individuals with RRF (RRF+ group; ≥200 ml; n=65) and without RRF (RRF- group; <200 ml; n=75). Renal sizes were measured using sonography and renal volumes were calculated with the ellipsoid formula. Univariable and multivariable stepwise forward logistic regression analyses were performed to examine the correlation between the presence of RRF and various variables. The results indicated that there were statistically significant differences (P<0.001) between the RRF+ and RRF- groups with regard to renal length, width, thickness and volume of the left (length, 7.9±1.2 vs. 6.8±1.2 cm; volume, 60.0±26.7 vs. 40.2±18.1 ml, respectively) and right (length, 7.6±1.2 vs. 6.7±1.2 cm; volume, 50.2±26.5 vs. 33.9±15.3 ml, respectively) sides of the kidney. Multivariable stepwise forward logistic regression analyses showed that the mean renal length or volume and hemodialysis duration were independent predictors of the presence of RRF. Therefore, renal size assessment by ultrasonography may be useful for RRF evaluation in patients undergoing chronic hemodialysis. [ABSTRACT FROM AUTHOR]

The ratio between plasma kynurenine (Kyn) and tryptophan (Trp) serves as a marker of indoleamine 2,3-dioxygenase, a critical immunomodulatory molecule. Simultaneous detection of the two markers may be performed using high-pressure liquid chromatography (HPLC). However, for uremic patients, the conventional detection method may be affected by a range of accumulated toxins. The current study aimed to establish a method for the simultaneous measurement of Kyn and Trp in patients following maintenance hemodialysis via HPLC-ultraviolet detection. The procedure involved the use of a SinoChrom ODS-BP C18 column (4.6x150 mm; inner diameter, 4.5 µm) and a mobile phase of 15 mmol/l sodium acetate acetic acid solution (containing 5% acetonitrile, pH 4.8). The modified method was verified using plasma samples from 10 healthy controls and 91 maintenance hemodialysis patients. The results demonstrated that the modified method was successful in simultaneously detecting the concentrations of Trp and Kyn in the healthy controls and maintenance hemodialysis patients. The method is simple, fast, accurate and suitable for clinical and research purposes in maintenance hemodialysis patients. [ABSTRACT FROM AUTHOR]

Abstract. The aim of this study was to observe autophagy in chondrocytes from degenerative human cervical vertebral end-plates and to investigate the significance of variations in autophagy in the degeneration of cervical vertebral end-plate chondrocytes. Cartilage end-plates were obtained from 48 inpatients admitted to hospital between February 2011 and August 2012. The patients were divided into the control group (n=17) with cervical vertebral fracture or dislocation and the cervical spondylosis group (n=31) with cervical spondylotic myelopathy. End-plate chondrocytes were isolated via enzyme digestion and then cultured in vitro. The cells were stained with toluidine blue and hematoxylin-eosin (H&E). A laser scanning confocal microscope and monodansylcadaverine (MDC) were used to reveal autophagy in the end-plate chondrocytes. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect mRNA expression of type II collagen and aggrecan. Western blotting was conducted to detect LC3 proteins. The chondrocytes isolated from the degenerative human cervical end-plates were cultured successfully in vitro. The morphology of the cells from the cervical spondylosis group tended to exhibit changes in spindle morphology compared with the control group. Autophagic bodies were stained with MDC. LC3 proteins were visible in the intracellular and perinuclear regions under the laser scanning confocal microscope. The mRNA expression levels (relative to those of β-actin) of aggrecan (0.715±0.194) and type II collagen (0.628±0.254) in the cervical spondylosis group were markedly decreased compared with those in the control group (0.913±0.254 and 0.845±0.186, respectively; both P<0.05). The LC3-II/LC3-I ratio was observed to be significantly reduced in the cervical spondylosis group by Western blot analysis. Autophagy has an important role in human cervical disc degeneration. The regulation of autophagy may prevent disc degeneration in cartilage end-plate cells. [ABSTRACT FROM AUTHOR]

The Chinese population are at an increased risk of autoimmune hepatitis (AIH). The aims of this study were to determine the demographic and clinical features of AIH in China. A total of 83 patients with AIH diagnosed by the revised scoring system were re-analyzed, and the clinical presentations among the different ages were compared. The patients were classified according to age at presentation. AIH occurred in patients aged ≤30 years (9.6%), 31-39 years (10.8%), 40-49 years (16.9%), 50-59 years (31.3%) and ≥60 years (31.3%). There were no differences in the form of the clinical presentation, concurrent autoimmune diseases, cirrhosis distribution and autoantibodies among the groups. However, patients aged ≥60 years presented with higher levels of alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ-GT) compared with patients aged ≤30 years (P=0.034, P=0.043, respectively), and patients aged 31-39 years had a significantly lower immunoglobulin G (IgG) level compared with those aged 50-59 years (P=0.049) and those aged ≥60 years (P=0.012). By contrast, patients aged ≤30 years had a significantly higher total bilirubin (TBIL) level compared with those aged 31-39 years (P=0.007), 50-59 years (P=0.002) and ≥60 years (P=0.013). A substantial portion of patients with AIH were aged >60 years, indicating a poor liver-associated outcome under current management strategies. Elderly patients appeared to be more asymptomatic compared with the younger patients. [ABSTRACT FROM AUTHOR]

Coronary heart disease (CHD) is the leading cause of mortality worldwide. The Chinese medicinal formula Guanxin II has been shown to have a favorable effect in the attenuation of angina. The aim of this study was to compare the pharmacokinetics of ferulic acid (FA), which is a vasorelaxant compound present in Guanxin II, in healthy volunteers and patients with angina pectoris following the administration of Guanxin II. Ex vivo experiments were performed in order to investigate the vasorelaxant effect of FA on the human internal mammary artery (IMA) to provide evidence that it is a bioactive component of Guanxin II. Following the oral administration of Guanxin II, the FA levels in the serum were quantified by a simple and rapid high-performance liquid chromatography (HPLC) method. Treatment with FA (10-8-10-3 M) caused a concentration-dependent relaxation of endothelial IMA rings following precontraction with KCl. Statistically significant differences were identified between the pharmacokinetic parameters Cmax, t1/2 α, t1/2 ß and t1/2 Ka of the healthy volunteers and the patients with angina pectoris following the oral administration of Guanxin II. FA is a bioactive compound absorbed from Guanxin II that attenuates angina pectoris, a condition that may modify the pharmacokinetics of FA. Not only do the pharmacokinetic parameters direct the clinical use of Guanxin II, but they may also be useful for exploring the pathology of angina pectoris. [ABSTRACT FROM AUTHOR]