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Type 2 diabetes mellitus (T2DM) is a leading cause of blindness, non-traumatic amputation and end-stage renal disease, as well as a major cardiovascular risk factor. To determine whether miR-125b and miR-34a serve an important role in the development of T2DM, the current study investigated the expression profile of two microRNAs (miR-34a and miR-125b) and their relative genes in peripheral blood mononuclear cells from 73 patients with T2DM and 52 healthy donors by reverse transcription-quantitative polymerase chain reaction In addition, the association between miR-34a, miR-125b and their relevant genes expression profile were analyzed with respect to the pathogenesis of T2DM. The present study demonstrated that the expression levels of miR-125b and miR-34a were elevated in peripheral blood mononuclear cell samples from patients with T2DM. Furthermore, miR-34a and miR-125b were positively correlated with low-density lipoprotein/ high-density lipoprotein (HDL) and Foxp3 and negatively related to triglyceride/HDL. However, no correlation among miR-34a, miR-125b and the value of homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function and the genes of B lymphocyte-induced maturation protein-1, interferon regulatory factor-4, P53 and retinoid-related orphan receptor γt were observed. These results indicate that the alteration of miR-34a and miR-125b exists in patients with T2DM, which may be involved in the pathogenesis of T2DM, and could be a potential novel biomarker of T2DM. [ABSTRACT FROM AUTHOR]

Pancreatic necrosectomy (PN) following percutaneous catheter drainage (PCD) is an effective method of treating patients with necrotizing pancreatitis, however, the predictive factors for PN after PCD have not yet been identified. A total of 74 patients with suspected infected necrotizing pancreatitis (INP) and peripancreatic fluid collection were enrolled in the current study between October 2010 and October 2015. These patients received ultrasound or computer topography guided PCD followed by PN. Patients were divided into two groups: i) A PCD-alone group (n=32) and ii) a PCD+necrosectomy group (n=42). Multivariate analysis revealed that reduction of fluid collection after PCD (P=0.021), maximum extent of peripancreatic necrosis (P=0.019) and multiple organ failure (P=0.017) were predictors of PN following PCD. A prediction model was produced to evaluate the aforementioned factors and indicated that the area under the receiver operating characteristic curve was 0.827. The probability of successful PCD was determined using a prognostic nomogram. Thus, the results of the current study demonstrated that a reduction of fluid collection by <50% following PCD, a maximum extent of peripancreatic necrosis of >50% and multiple organ failure are effective predictors of necrosectomy in patients with INP following PCD failure. [ABSTRACT FROM AUTHOR]

The present study was designed to analyze the difference of the adeB gene expression levels under conditions of induced resistance and to verify the significance of the AdeABC efflux pump in the in vitro induction of Acinetobacter baumannii (A. baumannii). Strains were isolated from blood or drainage samples in the First Hospital of China Medical University. The minimum inhibitory concentration (MIC) was determined by a broth microdilution method. In addition, an in vitro induction of drug-resistance tests was confirmed with the three drugs. The expression level of the adeB was determined by quantitative polymerase chain reaction (qPCR), and there were 19, 17 and 25 strains isolated from this test that were susceptible to amikacin, netilmicin and imipenem, respectively. Furthermore, 11, 15 and 8 stably resistant strains generated against amikacin, netilmicin and imipenem, respectively, by in vitro induction. The MIC values of all the imipenem-sensitive and imipenem-resistant strains decreased by no more than 2-fold under carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-containing conditions. The MIC values of 10 amikacin-resistant and 14 netilmicin-resistant strains decreased 4-fold or more under CCCP-containing conditions. Furthermore, qPCR revealed that none of the imipenem-sensitive or the imipenem-resistant strains expressed the adeB gene, but there were 10 amikacin-resistant and 5 netilmicin-resistant strains that expressed the adeB gene. In conclusion, the present study confirmed that in vitro induction of drug-resistance tests in sensitive A. baumannii strains could produce drug-resistance following long-term exposure to low doses of antibacterial drugs. In addition, amikacin and netilmicin are more prone to producing drug-resistance compared to imipenem in vitro. The results of the efflux phenotype indicate the possible application of CCCP in the inhibition of the efflux system in some drugs. The inconsistency between efflux phenotype and qPCR of adeB indicates that other mechanisms may also be included in the induction of drug-resistance that work with the active mechanism in order to increase drug resistance to common clinically-used antimicrobial drugs. [ABSTRACT FROM AUTHOR]

Forkhead box P3 (FOXP3), which is a transcription factor, has a primary role in the development and function of regulatory T cells, and thus contributes to homeostasis of the immune system. A previous study generated a cell-permeable fusion protein of mouse FOXP3 conjugated to a protein transduction domain (PTD-mFOXP3) that successfully blocked differentiation of type 17 T helper cells in vitro and alleviated experimental arthritis in mice. In the present study, the role of PTD-mFOXP3 in type 1 T helper (Th1) cell-mediated immunity was investigated and the possible mechanisms for its effects were explored. Under Th1 polarization conditions, cluster of differentiation 4+ T cells were treated with PTD-mFOXP3 and analyzed by flow cytometry in vitro, which revealed that PTD-mFOXP3 blocked Th1 differentiation in vitro. Mice models of delayed type hypersensitivity (DTH) reactions were generated by subcutaneous sensitization and challenge with ovalbumin (OVA) to the ears of mice. PTD-mFOXP3, which was administered via local subcutaneous injection, significantly reduced DTH-induced inflammation, including ear swelling (ear swelling, P<0.001; pinnae weight, P<0.05 or P<0.01 with 0.25 and 1.25 mg/kg PTD-mFOXP3, respectively), infiltration of T cells, and expression of interferon-γ at local inflammatory sites (mRNA level P<0.05) compared with the DTH group. The results of the present study demonstrated that PTD-mFOXP3 may attenuate DTH reactions by suppressing the infiltration and activity of Th1 cells. [ABSTRACT FROM AUTHOR]

Outer membrane proteins (OMPs) of microorganisms play important roles in directly interacting with host cells. Brucella species inhibit the apoptosis of host cells to benefit their own intracellular survival and replication. However, the association between OMP31 of Brucella and host cell apoptosis, and the underlying mechanism are unclear. In this study, an OMP31 gene deletion mutant based on B. melitensis 16M was constructed. Following the infection of RAW264.7 cells with B. melitensis 16M or the mutant strain, colony formation, apoptosis, tumor necrosis factor (TNF)-a levels and the levels of key downstream factors of the apoptosis pathways triggered by TNF-a, namely caspase-3, -8 and -9, cytochrome c, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected. The mutant strain was shown to have the same phenotype as the parent strain using traditional microbiological tests. However, the mutant strain had impaired intracellular survival, with higher levels of apoptosis and TNF-a expression in infected RAW164.7 macrophages than the parent strain. The downstream factors of apoptosis triggered by TNF-a, including increased caspase-8, -3 and -9, cytochrome c and Bax, and decreased Bcl-2, indicated that the classical and mitochondrial cell death pathways were involved. It may be concluded that OMP31 from Brucella inhibited apoptosis and benefitted the intracellular survival of this microorganism. Furthermore, TNF-a may have served as a switch triggering classical death and mitochondrial cell death pathways. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) are a class of short and non-coding RNA molecules, which function as either oncogenes or tumor suppressors in the development of various human cancers, including nasopharyngeal carcinoma (NPC). The aim of the present study was to investigate the expression of miR-133b in NPC tissue samples, as compared with adjacent normal tissues, and to examine its roles and underlying mechanisms. Analysis using reverse transcription-quantitative polymerase chain reaction demonstrated that miR-133b was downregulated in NPC tissue samples, as compared with adjacent tissues. In vitro experiments using NPC cell lines transfected with miR-133b mimics or antisense oligonucleotides further demonstrated that the overexpression of miR-133b mimics impaired, whereas knockdown of its expression promoted, the proliferation of NPC cells. Sphingosine-1-phosphate receptor 1 (S1PR1) was predicted to be a target of miR-133b. Luciferase reporter assays showed that miR-133b inhibited the protein expression of S1PR1 by targeting its 3'-untranslated region. Furthermore, western blot analysis demonstrated that miR-133B altered the regulation of the signal transducer and activator of transcription-3 (STAT3) signaling pathway and the expression of downstream proteins in NPC cells. Therefore, the results of the present study suggested that a previously unknown miR-133b/S1PR1 molecular network may regulate NPC progression. [ABSTRACT FROM AUTHOR]

During liver surgery, hepatic blood flow needs to be blocked in order to reduce bleeding, which inevitably results in hepatic ischemia/reperfusion injury (HI/R). Paeoniflorin (PF) is the main active ingredient of the traditional Chinese herbal medicine peony, which has been shown to exert anti-oxidative and anti-apoptotic properties. In the present study, a mouse model of HI/R was generated by clamping the hepatoportal vein, hepatic artery, and hepatic duct of BALB/c mice with a vascular clamp for 30 min, followed by reperfusion for 6 h under anesthesia. Six mice in the three PF treatment groups (5, 10 and 20 mg/kg) were then injected with PF, via the tail vein. A sham group, consisting of six mice that did not undergo the procedure, and a vehicle group, consisting of 6 mice that underwent the procedure but subsequently received injections of physiological saline only, were used as controls. Liver injury was indicated by serum levels of the enzymes alanine transaminase (ALT) and aspartate transaminase (AST). The activities of oxidative stress biomarkers, including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA), were also measured. Furthermore, the activity of caspase-3 was analyzed in hepatic tissue using a commercial kit. Treatment with PF significantly attenuated HI/R injury histologically, as compared with the vehicle group. In addition, significant reductions in the serum levels of ALT and AST were observed in the PF-treated ischemic mice. Furthermore, treatment with PF enhanced the activities of hepatic tissue SOD, GSH and GSH-PX, but decreased the MDA content. Treatment of ischemic mice with PF markedly reduced the expression levels of inflammatory mediators, including nuclear factor-κB, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β, and decreased the HI/R injury-induced expression of caspase-3. The results of the present study suggest that PF attenuates the HI/R injury of mice via anti-oxidative, anti-inflammatory and anti-apoptotic activities. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the role of survivin in adenoid cystic carcinoma of the lacrimal gland (LGACC) and the effect of arsenic trioxide (As2O3) intervention in vitro. In total, 13 patients with LGACC were recruited from Renmin Hospital of Wuhan University between 2007 and 2012. The patients were divided into different groups, namely tumor-node-metastasis (TNM)1-2 and TNM3-4, according to the TNM classification. A total of eight samples were included in the TNM1-2 group, while five samples were included in the TNM3-4 group. In addition, six patients that suffered from other diseases (no tumor), but underwent eye surgery, were selected as the controls. The mRNA and protein expression levels of survivin were analyzed. In addition, primary adenoid cystic carcinoma (ACC) cells were cultured and the expression of survivin was silenced using short interfering RNA (siRNA), after which the cell proliferation was determined. Furthermore, the primary cultured ACC cells were treated with different doses of As2O3 to observe the effect on the apoptosis rate. The mRNA and protein expression levels of survivin in the LGACC groups were higher when compared with the controls (P<0.01). In addition, the expression levels were higher in the TNM3-4 group when compared with the TNM1-2 group (P<0.01). After silencing survivin expression using siRNA, the rate of ACC cell proliferation was shown to decrease at days 2, 3, 4 and 5 following culture, particularly in the TNM3-4 group at days 2 and 3 (P<0.05), day 4 (P<0.01 vs. TNM1-2 + siRNA); and days 3 and 5 (P<0.05), and day 2 (P<0.01 vs. TNM3-4 + siRNA). The mRNA expression levels of survivin in the TNM1-2 and TNM3-4 groups were significantly decreased following treatment with the various doses of As2O3 (2, 4 and 6 µM) for 48 h, and the apoptosis rate of the ACC cells was markedly increased (TNM1-2 and 3-4: As2O3 6 µM vs. As2O3 2 µM, As2O3 6 µM vs. As2O3 4 Mm, P<0.01; TNF3-4, As2O3 4 µM VS. As2O3 2 µM, P<0.01; TNM1-2, As2O3 4 µM vs. As2O3 2 µM, P<0.05). Therefore, survivin was demonstrated to be highly expressed in ACC cells of the lacrimal gland, and inhibition of survivin gene expression was found to suppress the proliferation of the ACC cells. Furthermore, As2O3 treatment was demonstrated to inhibit the mRNA expression of survivin in the ACC cells, while significantly increasing the apoptosis rate. [ABSTRACT FROM AUTHOR]

Porous tantalum has been reported to be a promising material for use in bone tissue engineering. In the present study, the biocompatibility and osteogenic properties of porous tantalum were studied in vitro and in vivo. The morphology of porous tantalum was observed using scanning electron microscopy (SEM). Osteoblasts were cultured with porous tantalum, and cell morphology, adhesion and proliferation were investigated using optical microscopy and SEM. In addition, porous tantalum rods were implanted in rabbits, and osteogenesis was observed using laser scanning confocal microscopy and hard tissue slice examination. The osteoblasts were observed to proliferate over time and adhere to the tantalum surface and pore walls, exhibiting a variety of shapes and intercellular connections. The porous tantalum rod connected tightly with the host bone. At weeks 2 and 4 following implantation, new bone and small blood vessels were observed at the tantalum-host bone interface and pores. At week 10 after the porous tantalum implantation, new bone tissue was observed at the tantalum-host bone interface and pores. By week 12, the tantalum-host bone interface and pores were covered with new bone tissue and the bone trabeculae had matured and connected directly with the materials. Therefore, the results of the present study indicate that porous tantalum is non-toxic, biocompatible and a promising material for use in bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the efficacy and side-effects of preventive treatment with pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) on concurrent chemoradiotherapy-induced grade IV neutropenia and to provide a rational basis for its clinical application. A total of 114 patients with concurrent chemoradiotherapy-induced grade IV neutropenia were enrolled. A randomized approach was used to divide the patients into an experimental group and a control group. The experimental group included three subgroups, namely a P-50 group, P-100 group and P + R group. The P-50 group had 42 cases, which were given a single 50-µg/kg subcutaneous injection of PEG-rhG-CSF. The P-100 group had 30 cases, which received a single 100-µg/kg subcutaneous injection of PEG-rhG-CSF. The P + R group comprised 22 cases, which were given a single 50-µg/kg subcutaneous injection of PEG-rhG-CSF and rhG-CSF 5 µg/kg/day; when the absolute neutrophil count (ANC) was ≥2.0x109/l, the administration of rhG-CSF was stopped. The control group (RC group) comprised 20 patients, who received rhG-CSF 5 µg/kg/day by subcutaneous injection until the ANC was ≥2.0x109/l. Changes in the neutrophil proliferation rate and ANC values over time, the neutropenic symptom remission time and incidence of adverse drug reactions were analyzed statistically in each group of patients. In the experimental group, the neutrophil proliferation rate and ANC values were significantly higher than those in the control group; the clinical effects began 12-24 h after treatment in the experimental group, and indicated that the treatment improved neutropenia in ~48 h after treatment. There was no significant difference in the neutrophil proliferation rate and ANC values between the P-50 and P+R groups. In the experimental group, the remission time of neutropenia-induced fever and muscle pain after administration was significantly shorter than that in the control group, with a statistically significant difference (P<0.05). The adverse drug reaction rates showed no significant difference between the experimental group and the control group. PEG-rhG-CSF had good efficacy and safety in the treatment of concurrent chemotherapy-induced grade IV neutropenia. For the treatment of concurrent chemotherapy-induced grade IV neutropenia, a single subcutaneous injection of 50 µg/kg PEG-rhG-CSF is the recommended dose. The effects begin at 12-24 h; if the ANC values are not significantly improved during this time, no supplementary administration of rhG-CSF is necessary. [ABSTRACT FROM AUTHOR]

Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disease with early onset. PLA2G6 gene mutations have been identified in the majority individuals with INAD. In future, molecular diagnosis of INAD will replace the invasive biopsies used previously. In the present report, monozygotic male twins with INAD were referred The Children's Hospital (Zhejiang University School of Medicine, Zhejiang, China) at fifteen months old for delayed development. The older brother was found to have developmental stagnation when he was 6 months old. The patient could not stand securely without support, and had poor eye tracking and listening ability. Magnetic resonance imaging (MRI) of the patient's brain revealed cerebellar atrophy and electromyography identified signs of peripheral neuropathy. The younger brother displayed similar clinical features and findings. Two different phospholipase A2 group VI (PLA2G6; 22q13.1) gene mutations were detected in the twins by DNA sequencing. The results of the present study indicate that neurogenetic disease should be considered when child patients present with idiopathic developmental stagnation, particularly when similar cases have appeared in the same family. In addition, INAD should be considered as a possible diagnosis when the patient has developmental delay of the central and peripheral nerves. In the future, molecular genetic testing will be the primary method of INAD diagnosis, enabling better prevention of this genetic disease. [ABSTRACT FROM AUTHOR]

Successful drug treatment for sepsis-related acute lung injury (ALI) remains a major clinical problem. Thus, the aim of the present study was to investigate the beneficial effects of salidroside on ameliorating cecal ligation and puncture (CLP)-induced lung inflammation. Rats underwent CLP surgery to induce ALI and 800 mg/kg salidroside (i.v.) was administered 24 h after the CLP challenge. Subsequently, biochemical changes in the blood and lung tissues, as well as morphological and histological alterations in the lungs, that were associated with inflammation and injury were analysed. CLP was shown to significantly increase the serum levels of plasma tumour necrosis factor-α and interleukin-6, -1β and-10. In addition, CLP increased pulmonary oedema, thickened the alveolar septa and caused inflammation in the lung cells. These changes were ameliorated by the administration of 800 mg/kg salidroside (i.v.) 24 h after the CLP challenge. This post-treatment drug administration also significantly attenuated the lipopolysaccharide-induced activation of nuclear factor-κβ and increased the release of peroxisome proliferator-activated receptor γ in the lung tissue. Therefore, salidroside administered following the induction of ALI by CLP significantly prevented and reversed lung tissue injuries. The positive post-treatment effects of salidroside administration indicated that salidroside may be a potential candidate for the management of lung inflammation in CLP-induced endotoxemia and septic shock. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the clinical significance of the results of screening of newborn hearing and the incidence of deafness-susceptibility genes. One thousand newborn babies in the Handan Center Hospital (Handan, China) underwent screening of hearing and deafness-susceptibility genes. The first screening test was carried out using otoacoustic emissions (OAEs). Babies with hearing loss who failed to pass the initial screening were scheduled for rescreening at 42 days after birth. Cord blood was used for the screening of deafness-susceptibility genes, namely the GJB2, SLC26A4 and mitochondrial 12S rRNA (MTRNR1) genes. Among the 1,000 neonates that underwent the first hearing screening, 25 exhibited left-sided hearing loss, 21 exhibited right-sided hearing loss and 15 cases had binaural hearing loss. After rescreening 42 days later, only one of the initial 61 cases exhibited hearing loss under OAE testing. The neonatal deafness gene tests showed two cases with 1555A>G mutation and two cases with 1494C>T mutation of the MTRNR1 gene. In the SLC26A4 gene screening, four cases exhibited the heterozygous IVS7-2A>G mutation and one case exhibited heterozygous 1226G>A mutation. In the GJB2 gene screening, two cases exhibited the homozygous 427C>T mutation and 10 exhibited the heterozygous 235delC mutation. The genetic screening revealed 21 newborns with mutations in the three deafness-susceptibility genes. The overall carrier rate was 2.1% (21/1,000). The association of hearing and gene screening may be the promising screening strategy for the diagnosis of hearing loss. [ABSTRACT FROM AUTHOR]

Chemoresistance is one of the major barriers to chemotherapeutic treatment and it has been established that CD133+ cancer stem cells are responsible for drug resistance in laryngeal carcinoma. In the present study, curcumin and cisplatin were used as a combined treatment to induce the sensitivity of CD133+ cancer stem cells to chemotherapeutic agents and to enhance therapeutic effectiveness. The results revealed that in untreated and cisplatin-treated HEp-2 cell groups, the percentage of CD133+ cells was 4.50 and 6.89%, respectively. However, in the combined treatment group, the percentage of CD133+ cells was markedly reduced to 1.49%, indicating that curcumin may increase the sensitivity of CD133+ cells to cisplatin, leading to the suppression of chemoresistance in HEp-2 cells. Furthermore, the expression of ATP-binding cassette sub-family G member 2 (ABCG2), which is an important gene for chemoresistance, was demonstrated to be reduced in CD133+ cancer stem cells following combined treatment. These results suggest that the combined application of curcumin with chemotherapeutic drugs may be a reliable and effective approach for the treatment of laryngeal carcinoma. [ABSTRACT FROM AUTHOR]

In the present study, a set of self-designed measurement protocols for the precision of coaxial needle placement (PCNP) was proposed and applied in a computed tomography (CT)-guided transthoracic needle biopsy (TNB) audit of an interventional radiologist to determine if the PCNP was commensurate with the experience of the operator. A total of 102 patients (98 with lung lesions and four with mediastinum lesions) consented to be subjected to CT-guided TNB performed by staff interventional radiologists. The patients were divided into two groups based on appointment date. Group A consisted of the first 51 patients and group B comprised of the latter 51 patients. A set of self-designed measurement protocols for PCNP was proposed, and the PCNP was classified into four grades, from grade 1 (most accurate) to grade 4 (least accurate). PCNPs were independently measured by three staff radiologists who were blind to the grouping. The anatomical features of the lesions were also analyzed between the two groups. A significant difference in the PCNP gained after the first needle placement was identified between the two groups (P=0.003, two-tailed). The number of patients in group B with grade I PCNP (51.0%) was significantly higher than that in group A (21.6%) (P<0.05). The number of patients in group B with grade III PCNP (11.8%) was significantly lower than that in group A (29.4%, P<0.05). The PCNP was observed to be commensurate with the experience of the operator and should be considered as a routine audit index in CT-guided TNB. [ABSTRACT FROM AUTHOR]