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In the present study, it was aimed to evaluate whether there is an objective tongue image indicator that could be used to evaluate malignant risk of thyroid nodules through a cross sectional study. From December 2018 to December 2020, the TFDA-1 digital tongue-face diagnostic instrument was used to collect the tongue images. TDAS 2.0 software was used for tongue image analysis. A standardized database was constructed by combining patient physical examination results and tongue image analysis results. The relationship between tongue image index and TI-RADS classification of thyroid nodules was tested. A total of 5,900 cases were collected and 4,615 cases were included in the present study after excluding 154 cases due to incomplete information, 1,221 cases with thyroid nodules were separated into 417 cases TI-RADS 2 group, 693 cases in TI-RADS 3 group and 111 cases in TI-RADS 4 group. Without considering confounding factors, tongue image indexes zhiCon, zhiASM, zhiENT, zhiMEAN, zhiClrB, zhiClrR, zhiClrG, zhiClrI, zhiClrL and zhiClrY were significantly different among the three groups (P<0.05). Excluding the influence of age, sex, body mass index, smoking and drinking, the results of one-way variance linear trend analysis showed that the values of zhiCon, zhiENT and zhiMEAN increased with the increasing TI-RADS category, while the values of zhiASM decreased with the increase of TI-RADS category. Tongue texture index may be helpful for differentiating the benign and malignant of thyroid nodules. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the mechanisms driving the protective effects of squid ink polysaccharide (SIP) against cyclophosphamide (CP)-induced testicular damage, focusing on germ cells. In the testes of mice exposed to CP and/or SIP, the present study examined the levels of reactive oxygen species (ROS) and malondialdehyde, activity of superoxide dismutase levels, protein expression levels of B-cell lymphoma 2 (Bcl2), Bcl2-associated X protein (Bax), and total Caspase 3, activation of p-p38 and p-Akt proteins, and tissue morphology. The findings indicated that CP induced ROS production and oxidative stress, resulting in testicular damage. However, under administration of SIP, oxidative stress was impaired and the testicular toxicity induced by CP was weakened, which implied that SIP may have an important role in preventing chemotherapeutic damage to the male reproductive system via promoting antioxidant ability. Furthermore, the altered expression levels, including the upregulation of Bax and Caspase 3, downregulation of Bcl-2 and the increased Bax/Bcl-2 ratio, indicated that apoptosis occurred in CP exposed testes of mice; however, the alterations were reversed in mice treated with SIP. Moreover, in CP-exposed testes, p38 and Akt proteins were significantly phosphorylated (P<0.05), whereas in the testes of mice co-treated with SIP and CP, phosphorylation of the two proteins was inhibited, demonstrating that the two signalling pathways participated in the regulative processes of the deleterious effects caused by CP, and the preventive effects SIP mediated. [ABSTRACT FROM AUTHOR]

Members of the GATA‑binding factor protein family, including GATA1, GATA2 and GATA3, serve an inhibiting role in leukemia. The present study demonstrated that GATA4 was upregulated in children with acute lymphoblastic leukemia (ALL). Results from a number of functional experiments, including cell proliferation analysis, cell cycle analysis, cell apoptosis assay and Transwell migration and invasion analyses, have suggested that high expression of GATA4 may facilitate proliferation and metastasis, and suppress apoptosis in ALL cells. Chromatin immunoprecipitation assay and luciferase reporter assay revealed that GATA4 was a transcription factor that activated mouse double minute 2 homolog (MDM2) and B cell lymphoma 2 (BCL2) expression in ALL cells. BCL2 is a key anti‑apoptosis protein that was demonstrated to suppress cell apoptosis. In addition, GATA4 was revealed to regulate p53 through the transcriptional activation of MDM2, subsequently influencing cell cycle and apoptosis. Results from the present study suggested that GATA4 may be a key marker in ALL diagnosis and a potential target of molecular therapy. [ABSTRACT FROM AUTHOR]

Bile duct hamartoma (BDH) is a rare liver disease with a rising incidence in recent years. A retrospective study on BDH patients between June 2007 and December 2015 was conducted. All the medical records, including clinical, imaging and pathological characteristics, were retrieved. Follow-up data were obtained by telephone communication. The majority of the patients had no symptoms and the laboratory tests were normal. The appearance on ultrasound examination was variable. The lesion exhibited low density on plain computed tomography and no enhancement in 4 cases, and inhomogeneous enhancement in 1 case. Magnetic resonance imaging examination revealed hypointensity on T1-weighted imaging (WI), hyperintensity on T2WI, no enhancement in 1 case, and enhancement in 4 cases. Two patients underwent magnetic resonance cholangiopancreatography due to jaundice and intrahepatic bile duct dilation. The preoperative diagnosis was liver cancer in 4 cases, hepatic hilar biliary obstruction in 1, chronic calculous cholecystitis in 1, suspected hepatic abscess in 1, and benign liver tumor in 2 cases. All the patients underwent surgery. Nest-like cell arrangements were observed in 2 patients, and in 1 patient the lesion transformed to intrahepatic cholangiocarcinoma, resulting in the patient's death 25 months after surgery. Thus, BDH may transform into a life-threatening cholangiocarcinoma and it should be surgically removed. Furthermore, the mechanism underlying carcinogenesis in BDH requires further investigation. [ABSTRACT FROM AUTHOR]

Angiogenesis is important in the development of solid tumors. Vasohibin-1 (VASH-1) is an endothelium-derived protein that acts as an inhibitor of angiogenesis in many different types of cancer. However, the expression of VASH-1 and its clinical value in bladder cancer remain unknown. The current study analyzed the expression of VASH-1, as well as the expression of the angiogenesis-related factors vascular endothelial growth factor-A, hypoxia inducible factor-1a and cluster of differentiation 34 in bladder cancer tissues from 50 patients using immunohistochemistry. The associations between the expression of these factors and the clinicopathological characteristics of the patients were assessed. The current study demonstrated that VASH-1 is primarily expressed in the cytoplasm of bladder cancer cells and in a fraction of vascular endothelial cells. Furthermore, the expression of VASH-1 was positively associated with the tumor stage (P<0.01), pathological grade (P<0.01) and distant metastasis (P<0.05) but not with patient age or sex (P>0.05). Spearman rank correlation tests indicated that levels of those four factors were positively correlated with each other. Kaplan-Meier analysis indicated that high expression of these four factors was significantly associated with lower 5-year overall survival and progression-free survival rates. Collectively, the results of the current study suggest that VASH-1 is clinically significant in bladder cancer and its high expression may predict the progression and prognosis of patients with bladder cancer. The present study also implies that VASH-1 may be a novel target for vascular targeting therapy. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) function as oncogenes or tumor suppressors, and are involved in mediating tumorigenesis and resistance to chemotherapy by altering the expression of genes at various levels. Accumulating evidence suggests that the maternally expressed gene 3 (MEG3) lncRNA serves an important role in a number of cancers. However, its functional role in mediating cisplatin‑induced apoptosis of glioma cells is unknown. To investigate the role of MEG3, the mRNA levels of MEG3 under cisplatin treatment were investigated by reverse transcription‑quantitative polymerase chain reaction, and the cell viability and apoptosis were examined by MTT assay, and flow cytometry analysis and western blotting, respectively. The results demonstrated that MEG3 expression levels were increased in U87 cells following cisplatin treatment. Elevated MEG3 by lentiviral transfection enhanced the chemosensitivity of U87 cells to cisplatin, whereas knockdown of MEG3 expression by small interfering RNA transfection increased the resistance of U87 cells to cisplatin. Subsequent mechanistic studies revealed that MEG3 eliminated autophagy induced by cisplatin. Decreased MEG3‑induced autophagy improved the chemosensitivity of U87 cells to cisplatin. The results present a novel therapeutic strategy for the treatment of patients with glioblastoma multiforme. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the diagnostic concordance of plasma epidermal growth factor receptor (EGFR) mutation using droplet digital polymerase chain reaction (ddPCR) with tumor tissue samples and the predictive clinical significance of plasma EGFR mutation concentration. Plasma DNA samples from patients with non-small cell lung cancer (NSCLC) were analyzed for EGFR exon 21 codon 858 (L858R) mutation, deletion of exon 19 (ex19del) and exon 20 codon 790 (T790M) mutation using ddPCR. Firstly, the mutations in the plasma samples were compared with the matched tumor samples to determine the concordance. Secondly, image examination follow-ups were analyzed to assess the association between plasma EGFR mutation concentration and patients' response to EGFR-tyrosine kinase inhibitors (TKIs). A total of 51 patients with NSCLC were enrolled, including 48 newly diagnosed patients. Compared with tumor tissue samples, the sensitivity and specificity of ddPCR were 76.19% (16/21) and 96.55% (28/29) for mutant L858R, and 88.89% (8/9) and 100% (41/41) for ex19del, respectively. No patient exhibited the T790M mutation in the tumor tissue or plasma samples. Furthermore, 5 patients with the L858R mutation and 4 patients with ex19del in plasma and tumor tissue samples had been followed up with image examination for ≥3 months following EGFR-TKI treatment. The baseline mutant EGFR concentrations were positively correlated with a reduction in tumor burden (Spearman's r=0.7000, P=0.0358). When analyzed separately, ex19del concentrations (Spearman's r=1.0000, P<0.0001) were also positively correlated with the reduction, while mutant L858R concentrations were not (Spearman's r=0.7000, P=0.1881). In the present study, detection of plasma EGFR mutations using ddPCR exhibited sufficient concordance with tumor tissue sample results. Baseline plasma mutant EGFR and ex19del concentrations were significantly and positively correlated with response to EGFR-TKIs. [ABSTRACT FROM AUTHOR]

Progress in the treatment options for small cell lung cancer (SCLC) remains poor. Concerns exist regarding the efficacy of bevacizumab in SCLC. The present study aimed to evaluate the efficacy of bevacizumab in extensive stage (ES)‑SCLC. A meta‑analysis on studies conducted and listed on the Medline, Cochrane Trials, ASCO, ESMO and Clinical-Trial databases, and Chinese databases prior to April 2015 was performed. All clinical trials in which patients with ES‑SCLC were treated with bevacizumab were considered. Survival rates at specific time points were extracted from the reported survival curves. Hazard ratios (HR) for progression‑free survival (PFS) and overall survival (OS), rates for PFS, OS, overall response rate (ORR), and side‑effects were synthesized using random‑effects or fixed‑effects model. Two randomized control trials (RCT) (176 patients) and six single‑arm trials (292 patients) were identified. In RCTs, no statistically significant differences were observed in PFS [HR, 0.70; 95% confidence interval (CI), 0.41‑1.19; P=0.19] or OS (HR, 1.21; 95% CI, 0.84‑1.75; P=0.31). In the first‑line trials, pooled 6‑month and 1‑year PFS rates were 57% (95% CI, 39‑76%) and 10% (95% CI, 4‑16%), respectively. Synthesized 1‑year and 2‑year OS rates were 45% (95% CI, 36‑54%) and 10% (95% CI, 6‑14%), respectively. Reported median PFS and OS times for pretreated patients were 2.7‑4.0 months and 6.3‑7.4 months, respectively. Pooled ORRs were 71% (95% CI, 59‑82%) in the first‑line trials and 18% (95% CI, 11‑25%) in the second‑line trials. The most common types of reported toxicities were chemotherapy‑associated, including neutropenia, leukopenia, fatigue and thrombocytopenia. According to the RCTs, bevacizumab did not appear to improve the PFS or OS for patients with ES‑SCLC, with low quality of evidence. Due to the disappointing pooled efficacy in the single‑arm trials, more clinical studies on bevacizumab in SCLC may not be valuable, although the evidence was with low quality. [ABSTRACT FROM AUTHOR]

Repeat transcatheter arterial chemoembolization (TACE) becomes more challenging for patients with intrahepatic biloma following TACE for hepatocellular carcinoma (HCC).The purpose of this study was to investigate the clinical course, incidence, imaging features and outcome and to explore the reasonable therapy scheme for intrahepatic biloma following TACE for HCC.A total of 4,695 TACE procedures were performed for 1,923 patients with HCC. Twenty patients with intrahepatic biloma following TACE were studied retrospectively. The incidence of intrahepatic biloma was 1.04% in this study. The 20 patients underwent 55 TACE procedures (mean, 2.75). Portal vein invasion was found in half of the patients. Eleven patients developed round solitary or multiple cystic biloma, 6 patients had branched biloma and 3 patients developed both cystic and branched biloma. Percutaneous drainage was applied for 4 patients. One patient underwent partial hepatectomy and one mortality occurred due to progressive biloma and multiple organ failure. Although severe intrahepatic biloma following TACE is rare, the procedure should be performed with caution. Timely and appropriate management, including percutaneous drainage, partial hepatectomy and antibiotic administration should be performed in the case of any signs of infection. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the clinical, pathological and prognostic characteristics of Chinese patients with resected pancreatic neuroendocrine neoplasms (p-NENs). Data from patients who were surgically treated and pathologically diagnosed with p-NENs at the Department of Pancreatic Oncology of the Fudan University Shanghai Cancer Center (Shanghai, China), between January 2003 and July 2015, were evaluated using univariate and multivariate analyses. A total of 162 patients with p-NENs met the criteria of the present study and were included in the analysis. Patients with poorly differentiated pancreatic neuroendocrine carcinoma (p-NEC) exhibited a significantly increased rate of lymph node metastasis, as compared with patients with grade (G)1/G2 pancreatic neuroendocrine tumors (p-NETs) (62.5 vs. 20.5%, P=0.003). Univariate analysis identified that the following factors led to decreased overall survival (OS): Lymph node metastasis (P=0.001, vs. the absence of lymph node metastasis); distant metastasis (P=0.043, vs. the absence of distant metastasis); resection margin R1/R2 (P=0.030, vs. R0 resection); NEC G3 (P<0.001, vs. NET G1). Following the multivariate analysis, NEC G3 remained a statistically significant risk factor (HR=12.593; 95% CI, 3.476-45.622; P<0.001, vs. NET G1/G2). Furthermore, according to the proliferation marker protein Ki-67 staining index, assigning a grade using the proliferative index (G1, ≤5%; G2, >5-20%; G3, >20%) was more efficient for prognostic stratification compared with the European Neuroendocrine Tumor Society (Berlin, Germany)/World Health Organization (Geneva, Switzerland) 2010 grading classification. The present study indicated that p-NEC was an important predictor of decreased OS in Chinese patients. Furthermore, a Ki-67 staining index of 5% represented a more efficient value for the distinction between G1 and G2. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion (I/R) injury can occur during small-for-size liver transplantation, resulting in delayed graft function and decreased long-term graft survival. The aim of the present study was to evaluate the effects of genetic overexpression of endothelial nitric oxide synthase (eNOS) in protecting hepatocytes against I/R injury in a rat model of small-for-size liver transplantation. L02 liver cells were transfected with the eNOS gene using an adenovirus (Ad-eNOS). eNOS expression was detected using quantitative polymerase chain reaction and western blot analysis. To evaluate the effect of eNOS overexpression, L02 cells were placed in a hypoxic environment for 12 h and immediately transferred to an oxygen-enriched atmosphere. For in vivo testing, rats pretreated with Ad-eNOS or control underwent small-for-size liver transplantation. At 6 h after reperfusion, the bile quantity, serum transaminase and nitric oxide (NO) levels, and histological outcomes were evaluated. Cell apoptosis was assessed by flow cytometry or TUNEL assay. In vitro, Ad-eNOS prevented apoptosis in L02 cells with an increase in the level of NO in culture supernatant. In vivo, Ad-eNOS pre-treatment significantly increased bile production, improved abnormal transaminase levels, diminished apoptosis among liver cells, and decreased hepatocellular damage at 6 h after I/R injury. The eNOS-mediated renal protective effects might be associated with the downregulation of tumor necrosis factor-α and a reduction in macrophage activation in the early stage of reperfusion in small-for-size liver allografts. eNOS-derived NO production significantly attenuates hepatic I/R injury. Thus, eNOS overexpression constitutes a promising therapeutic approach to prevent liver I/R injury following small-for-size liver transplantation. [ABSTRACT FROM AUTHOR]

Cancer cachexia remains a leading cause of morbidity and mortality worldwide, despite extensive research and clinical trials. The prominent clinical feature of cancer cachexia is the continuous loss of skeletal muscle that cannot be fully reversed by conventional nutritional support, and that leads to progressive functional impairment. The mechanism underlying muscle loss in patients with cachexia is poorly understood. The present study analyzed 21 cancer patients with or without cachexia, and demonstrated that mitofusin-2 (Mfn2) was downregulated in the rectus abdominis of patients with cachexia, which was associated with body weight loss. In vitro cell experiments indicated that loss of Mfn2 was associated with atrophy of the C2C12 mouse myoblast cell line. Furthermore, in vivo animal experiments demonstrated that cachexia decreased gastrocnemius muscle mass and Mfn2 expression, and overexpression of Mfn2 in gastrocnemius muscle was able to partially attenuate cachexia-induced gastrocnemius muscle loss. The results of the present study suggested that Mfn2 is involved in cachexia-induced muscle loss and may serve as a potential target for therapy of cachexia. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) regulate the proliferation and metastasis of numerous cancer cell types. It was previously reported that miR-143 levels were downregulated in non-small cell lung cancer (NSCLC) tissues and cell lines, and that the migration and invasion of NSCLC cells was inhibited upon suppression of cell proliferation and colony formation by the upregulation of miR-143. Epidermal growth factor receptor (EGFR), which is a vital factor in the promotion of cancer cell proliferation and has been investigated as a potential focus in cancer therapy, has been reported to be a possible target of miR-143. The present study aimed to investigate the role of miR-143 in NSCLC using NSCLC cell lines and primary cells from NSCLC patients. NSCLC cells were co-transfected with EGFR and miR-143, and the mRNA and protein expression of EGFR were analyzed. Furthermore, the activity of the transfected cancer cells with regard to colony formation, migration, invasion and apoptosis were evaluated. The levels of miR-143 were decreased in the NSCLC cell lines and primary cells from patients with NSCLC compared with the controls. Following transfection with miR-143, the ability of NSCLC cells to proliferate, form colonies, migrate and invade was inhibited. Similarly, knockdown of EGFR led to the suppression of NSCLC cell proliferation. The mRNA and protein expression levels of EGFR were signiicantly reduced following miR-143 overexpression, and the level of miR-143 was inversely correlated with that of EGFR in NSCLC cells. The results of the present study demonstrated that miR-143 was able to suppress NSCLC cell proliferation and invasion by inhibiting the effects of EGFR, suggesting that EGFR may be considered a potential target for NSCLC therapy. [ABSTRACT FROM AUTHOR]

Lower back pain (LBP) is a common and remitting problem. One of the primary causes of LBP is thought to be degeneration of the intervertebral disc (IVD). The aim of the present study was to investigate the role of the myeloid differentiation primary-response protein 88 (MyD88)-dependent Toll-like receptor 4 (TLR4) signal pathway in the mechanism of IVD degeneration. IVD nucleus pulposus cells isolated and cultured from the lumbar vertebrae of Wistar rats were stimulated by various doses of lipopolysaccharide (LPS; 0.1, 1, 10 and 100 µg/ml) to simulate IVD degeneration. Cells were rinsed and cultured in serum-free Dulbecco's modified Eagle's medium/F12. Reverse transcription-quantitative polymerase chain reaction was used to determine the levels of TLR4, MyD88, tumor necrosis factor α (TNFα), and interleukin-1β (IL-1β) mRNA expression after 1, 3, 6, 9 and 12 h of incubation. Additionally, western blot and enzyme-linked immunosorbent assay analyses were used to determine the levels of TLR4, MyD88, TNFα, and IL-1β protein expression after 24, 48 and 72 h of incubation. The levels of TLR4, MyD88, TNFα and IL-1β mRNA all increased in the cells stimulated by 10 µg/ml LPS at 3, 6 and 9 h (all P<0.001). Furthermore, the levels of TLR4, MyD88, TNFα and IL-1β protein all increased at 24, 48 and 72 h (all P<0.001). Additionally, the mRNA and protein levels of TLR4, MyD88, TNFα and IL-1β increased significantly in the cells stimulated by 1, 10 and 100 µg/ml LPS compared with the control group, and reached a peak in the 10 µg/ml LPS group (all P<0.001). These results suggest that the MyD88-dependent TLR4 signal pathway is a target pathway in IVD degeneration. This pathway is time phase- and dose-dependent, and when activated can lead to the release of inflammatory factors that participate in IVD degeneration. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a human malignancy with one of the highest mortality rates and little progress has been achieved in its treatment in recent decades. Further improvement to the understanding of the biological and molecular mechanisms underlying the initiation and development of pancreatic ductal adenocarcinoma (PDAC) is required. Previous studies using genetically engineered mouse models have demonstrated that oncogenic GTPase KRas (KRAS) mutation is involved in the formation of pancreatic intraepithelial neoplasia and promotes the progression of PDAC. However, attempts to target KRAS directly by pharmacological inhibition have been unsuccessful. This has resulted in increased efforts to identify pharmacological targets and nodes associated with the mutated KRAS. The present review discusses the recent progress and prospects of KRAS signaling in pancreatic cancer. [ABSTRACT FROM AUTHOR]

The Chinese herbal formula, Shu-Yu capsule (SYC), has been successfully used to treat depression-like disorders in clinical settings. To rapidly identify the chemical constituents of SYC and its metabolites in rat serum, a simple and sensitive liquid chromatography-tandem mass spectrometry method was established in the present study. By comparing the retention times, MS and MSn spectra data in the literature and reference standards, a total of 73 compounds were identified from SYC. In rat serum, 62 components, including 13 prototype compounds and 49 metabolites were identified. Of these components, 14 metabolites were confirmed as novel metabolites of SYC. The results of the present study indicated that certain flavonoid glycosides and monoterpene glycosides were absorbed directly. Glucuronidation and sulfation were identified as the predominant metabolic pathways of the components in SYC. In addition, certain phase I reactions, including hydrolysis, demethylation and hydroxylation occurred in the rats. These results provide scientific evidence, which support further investigations of the pharmacology and mechanism of SYC. [ABSTRACT FROM AUTHOR]

The current study aimed to present the neuro-radiological and histopathological features of intracranial hemangioendothelioma (HE). The computed tomography (CT; n=3) and magnetic resonance imaging (MRI; n=7) features, and the clinical presentations of 7 patients with pathologically documented HEs were retrospectively analyzed. Lesions were observed in the right side of the skull (the frontal bone in 1 patient and the parietal bone in 1 patient), the tentorium (2 patients), the cerebral falx (1 patient), the right cavernous sinus (1 patient) and the right temporal lobe (1 patient). The tumor was lobulated in 5 cases and round in 2 cases. The majority of tumors appeared isointense or hypointense with multiple scattered hyperintensities on T1-weighted MRI. Moreover, the lesions appeared as inhomogeneous hyperintense regions with multiple enlarged and tortuous blood flow voids on T2-weighted MRI. The lesions also showed marked gadolinium enhancement in a honeycomb pattern. CT scan results showed a isoattenuation region (32-47 HU), with numerous small, round, high-density foci. The 2 cases with skull lesions presented with local bone destruction and discontinuous bone lines of the tabula interna ossis cranii. In 1 case, MR angiography revealed abnormal vessels in the basilar region. A total of 4 cases were epithelial HE, 2 were retiform HE and 1 was kaposiform HE. Histological examination revealed endothelial cell proliferation with vascular lesions and a mucous matrix or dense fibrous mesenchyme. In conclusion, intracranial HE is rare, but should be considered in the differential diagnosis when evaluating intracranial neoplasms. A well-defined lobulated mass and imaging features that include internal heterogeneity, small scattered hemorrhages and thromboses, signal voids of vessels, and marked and delayed enhancement may confirm the diagnosis of HE. [ABSTRACT FROM AUTHOR]

The Chinese herbal formula, Shu-Yu capsule (SYC), has been successfully used to treat depression-like disorders in clinical settings. To rapidly identify the chemical constituents of SYC and its metabolites in rat serum, a simple and sensitive liquid chromatography-tandem mass spectrometry method was established in the present study. By comparing the retention times, MS and MSn spectra data in the literature and reference standards, a total of 73 compounds were identified from SYC. In rat serum, 62 components, including 13 prototype compounds and 49 metabolites were identified. Of these components, 14 metabolites were confirmed as novel metabolites of SYC. The results of the present study indicated that certain flavonoid glycosides and monoterpene glycosides were absorbed directly. Glucuronidation and sulfation were identified as the predominant metabolic pathways of the components in SYC. In addition, certain phase I reactions, including hydrolysis, demethylation and hydroxylation occurred in the rats. These results provide scientific evidence, which support further investigations of the pharmacology and mechanism of SYC. [ABSTRACT FROM AUTHOR]

Hypoxic pulmonary hypertension (PH) is a common disease characterized by a disturbance to the balance of apoptosis and cell proliferation in pulmonary artery smooth muscle cells (PASMCs). The anti-apoptotic protein, survivin, has been observed to be upregulated in pulmonary arteries (PAs) of chronic hypoxia-induced PH rats. The present study aimed to investigate the therapeutic potential of sepantronium bromide (YM155), a selective survivin inhibitor, on hypoxic human PASMCs and examine the potential underlying mechanisms. Cultured human PASMCs (HPASMCs) were randomly divided into the following groups: i) Normoxia (N); ii) normoxia + 100 nmol/l YM155 (NY100); iii) hypoxia (H); iv) hypoxia + 1 nmol/l YM155 (HY1); v) hypoxia + 10 nmol/l YM155 (HY10); and hypoxia + 100 nmol/l YM155 (HY100) groups. The cells were exposed to the different conditions for 24 h, according to the group. Cell viability was then determined using a Cell Counting Kit-8 assay, and apoptosis was detected using a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. The expression levels of survivin were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunocytochemistry and Western blot analyses. The expression levels of the voltage-dependent K+ (Kv) channels, Kv1.5 and Kv2.1, were measured using RT-qPCR and Western blotting. Cell proliferation in the hypoxic PASMCs was significantly increased by hypoxia, however, apoptosis of the HPASMCs was suppressed, the expression of survivin were upregulated and the expression levels of Kv1.5 and Kv2.1 were downregulated. YM155 treatment ameliorated the hypoxia-induced increase in cell proliferation and expression of survivin in a concentration-dependent manner, increased apoptosis, and increased the expression levels of Kv1.5 and Kv2.1 (P<0.05). By contrast, YM155 treatment in normoxic HPASMCs had no significant effects on proliferation, apoptosis, or the expression levels of survivin and Kv channels in the PASMCs. The present study is the first, to the best of our knowledge, to demonstrate that YM155, a selective survivin inhibitor, has a beneficial therapeutic effect on hypoxic HPASMCs, and that YM155 induces a pro-apoptotic effect by downregulating the apoptosis inhibitor, survivin, possibly through a Kv channel-mediated mechanism. [ABSTRACT FROM AUTHOR]

Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome (NS) in adults. The latest study of the chronic kidney disease-prognosis consortium showed that a 30% decrease in the estimated glomerular filtration rate (eGFR) within 2 years could cover more patients and showed a better correlation with end-stage renal disease (ESRD), as compared with serum creatinine (SCr). The aim of the present study was to analyze prognostic factors of ESRD using a 30% decrease in eGFR within 2 years as the end-point. The medical records of patients who were diagnosed as having IMN by clinical pathology between February 2011 and August 2012 and had been followed up for ≥ 24 months were analyzed retrospectively. A 30% decrease in eGFR or the occurrence of ESRD were the end-points. Factors affecting the prognosis were analyzed by the χ² test and multivariate logistic regression analysis, and the cumulative risk of risk factors was analyzed by Kaplan-Meier curve. A total of 73 patients with IMN were confirmed by clinical pathology. Blood pressure, tubulointerstitial injury area (TIA), glomerular sclerosis ratio, SCr, blood urea nitrogen, cystatin C, serum albumin and 24-h urine protein. In total, 28 patients (38.4%) reached the observation end-point. Multivariate logistic regression analysis showed that only age ≥60 years, serum albumin <25 g/l and TIA >25% were independent risk factors for predicting the occurrence of end-point events in the two groups (P<0.05), which increased the risk of the occurrence of end-point events in IMN patients by 3.471-, 3.195- and 6.724-fold, respectively. Kaplan-Meier curve showed that the occurrence of end-point events within 2 years was significantly higher in IMN patients whose age was ≥60 years, serum albumin <25 g/l and TIA >25% (log-rank P=0.004, P=0.024 and P=0.001). The results of the present study revealed that age ≥60 years, low serum albumin concentrations and severe tubulointerstitial injury are independent risk factors for the occurrence of ESRD in IMN patients. [ABSTRACT FROM AUTHOR]

Primary lung enteric adenocarcinoma is a rare type of invasive lung carcinoma. Its morphology and immunohistochemistry are those of colorectal carcinoma, but there is no associated primary colorectal carcinoma. The present study describes the case of a 53-year-old female who presented with an irritating cough and a mass around the right sternoclavicular joint. Comprehensive evaluation revealed involvement of the mediastinum, lungs, right sternoclavicular joint and right kidney. Biopsies from the mediastinal and right sternoclavicular joint tumors showed features of adenocarcinoma. Immunohistochemistry was positive for cytokeratin (CK)20 and caudal type homeobox transcription factor 2, and negative for CK7, thyroid transcription factor-1 and napsin A. Genotypic analysis identified the expression of wild-type epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene homolog, serine/threonine-protein kinase B-Raf and UDP-glucuronosyltransferase 1-1. There was no expression of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase and a moderate expression of excision repair cross-complementation group 1, ribonucleoside-diphosphate reductase large subunit and tubulin β-3 chain. A strong expression of thymidylate synthase and 677TC genotype expression of methylenetetrahydrofolate reductase was observed. Gastroscopy, enteroscopy, colorectal colonoscopy and positron emission tomography-computed tomography failed to find evidence of a gastrointestinal malignancy and primary lung enteric adenocarcinoma was diagnosed. The presence of multiple metastases did not permit curative surgery. The patient was treated with 3 monthly cycles of the XELOX chemotherapy regimen; the response was poor with progression of supraclavicular lesions. Treatment was switched to the TP regimen for 4 monthly cycles, which resulted in a significant reduction in the size of the lung lesions; however, the supraclavicular lesion responded poorly to the treatment. The patient then received 2 cycles of the FOLFIRI regimen; however, the lung and right supraclavicular lesions progressed, causing increased right upper limb pain. The pain was alleviated by palliative surgery. Following surgery, the DP regimen was employed. Follow-up of the patient remains ongoing. The present findings suggest that the early diagnosis and treatment of primary lung enteric adenocarcinoma is likely to improve patient outcome. [ABSTRACT FROM AUTHOR]

Eukaryotic translation initiation factor 4E (eIF4E) was shown to be upregulated in malignant human tumors. To assess the effect of downregulation of eIF4E on the proliferation and invasiveness of a human lung adenocarcinoma cell line, a short hairpin (sh)RNA targeting eIF4E was constructed and transfected into A549 human lung adenocarcinoma cells. The expression of eIF4E was determined by reverse transcription-quantitative polymerase chain reaction and western blotting. Cell viability was assessed using a Cell Counting kit-8, and apoptosis levels and cell cycle distribution were assessed by flow cytometry. Invasiveness was assessed using Transwell chambers. Transfection of the A549 cells with eIF4E targeting shRNA reduced the mRNA and protein expression levels of eIF4E by >70% 48 and 72 h following transfection, and eIF4E targeting shRNA-transfected cells were significantly less viable compared with the cells transfected with scrambled shRNA. The rate of apoptosis was also significantly increased, significantly more cells were in the G0/G1 phase and fewer were in the S phase, indicating cell cycle arrest. The fraction of transfected cells migrating across Transwell inserts were also reduced. In conclusion, inhibition of eIF4E suppressed cell growth and invasion, induced apoptosis and cell cycle arrest, suggesting that eIF4E may be a potential therapeutic target in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Non-small-cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation is resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib, but responds to the ALK-TKI crizotinib. Characterization of EML4-ALK translocation may provide invaluable information to facilitate disease diagnosis and improve the outcome of customized treatment. Although the occurrence of EML4-ALK translocation is likely to be affected by the smoking habits and gender of patients, the translocation has not been characterized extensively in female never-smokers with NSCLC. Therefore, 280 female never-smokers that were diagnosed with NSCLC were enrolled in the present study, and characteristics of EML4-ALK translocation, including the frequency, were determined in these NSCLC patients. EML4-ALK fusion variants were detected using Multiplex one-step reverse transcription-polymerase chain reaction and subsequently confirmed by DNA sequencing and Vysis ALK Break Apart fluorescence in situ hybridization analysis. The EML4-ALK fusion variants were detected in 21 carcinoma tissue specimens, accounting for 7.5% of the enrolled patients. Out of these patients with EML4-ALK fusion variants, EML4-ALK fusion variant 1 was identified in 12 patients, indicating that variant 1 is the most common type of EML4-ALK fusion gene in the present cohort of patients. ALK mRNA was aberrantly expressed in all the tissues with EML4-ALK translocation, but not in the carcinoma tissues without EML4-ALK translocation. In addition, the EML4-ALK translocation was more frequently found in younger patients. The median age of patients with EML4-ALK translocation was 50.95±2.29 years, which was significantly younger (P<0.01) than the median age of the patients without EML4-ALK translocation (57.15±0.56). The EML4-ALK translocation was detected exclusively in undifferentiated tumors that were graded as poorly- or moderately-differentiated carcinomas and suspected to be more malignant compared with well-differentiated tumors. In summary, the present study found that 7.5% of patients with NSCLC that are female never-smokers harbor EML4-ALK translocations, which are associated with the aberrant expression of ALK mRNA, early onset of disease and undifferentiated carcinomas. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the effect of astragalosides (ASTs) on angiogenesis, as well as the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) following myocardial infarction (MI). MI was induced in rats by ligation of the left coronary artery. Twenty-four hours after surgery, the rats were divided into low-dose, high-dose, control and sham surgery groups (n=8 per group). The low- and high-dose groups were treated with ASTs (2.5 and 10 mg/kg/day, respectively, via intraperitoneal injection), while, the control and sham surgery group rats received saline. Serum levels, and mRNA and protein expression levels of VEGF and bFGF, as well as the microvessel density (MVD) were determined four weeks post-treatment. Twenty-four hours post-surgery, VEGF and bFGF serum levels were observed to be comparable between the groups; while at four weeks, the VEGF and bFGF levels were higher in the AST-treated rats (P<0.01). Similarly, VEGF and bFGF mRNA and protein expression levels were higher following AST treatment (P<0.05). No difference in VEGF mRNA expression between the low- and high-dose groups was noted, however, an increase in the bFGF expression levels was detected in the high-dose group. Newly generated blood vessels were observed following MI, with a significant increase in MVD observed in the AST-treated groups (P<0.05). AST promotes angiogenesis of the heart and increases VEGF and bFGF expression levels. Thus, it is hypothesized that increased VEGF and bFGF levels may contribute to the AST-induced increase in angiogenesis in rat models of MI. [ABSTRACT FROM AUTHOR]

Hypoxic conditions regulate several metabolic enzymes and transcription factors that are involved in cancer, ischemia and pulmonary diseases. The Ras homolog (Rho) family, including Rho member A (RhoA), is involved in reorganization of the actin cytoskeleton, cell migration and in the regulation of apoptosis and gene transcription. The aim of the present study was to investigate the expression of hypoxia-inducible factor (HIF)-α and the activity of RhoA in PC12 neuroblastoma cells under hypoxic conditions. The upregulation of HIF-α and RhoA by hypoxia was determined using reverse transcription-quantitative polymerase chain reaction and western blot assays, cell apoptosis was analyzed using flow cytometry, and the activity of caspase 3 was examined using a western blot assay and caspase 3 activity assay kit. The PC12 cells were induced to apoptosis following exposure to hypoxia, and exhibited increased expression of HIF-α and increased mRNA and protein expression levels of RhoA. The overexpression of HIF-α attenuated the hypoxia-induced apoptosis of the PC12 cells. In addition, RhoA knockdown using small interfering RNA abrogated the antagonism of HIF-1α towards hypoxia-induced apoptosis. The results of the present study confirmed the protective role of HIF-1α and RhoA in hypoxia-induced PC12 cell apoptosis, and that the upregulation of HIF-1α by hypoxia is RhoA-dependent. [ABSTRACT FROM AUTHOR]

Aberrant microRNA (miRNA) expression has been linked to cancer development. In this study, we aimed to investigate whether the anti-cancer effect of miRNA-299-3p on laryngeal cancer Hep-2 cells is mediated through targeting human telomerase reverse transcriptase (hTERT). The expression of miR-299-3p in laryngeal cancer Hep-2 cells and human osteosarcoma U2OS cells was quantified by stem-loop-mediated reverse transcription quantitative polymerase chain reaction. miR-299-3p mimic was transfected into Hep-2 cells to induce overexpression of miR-299-3p. A CCK-8 assay was performed to identify the effects of miR-299-3p overexpression on the proliferation of Hep-2 cells. Western blot analysis was carried out to determine the expression of hTERT protein. A significant decrease was noted in the expression of miR-299-3p in Hep-2 cells compared with that of U2OS cells (P<0.05). Overexpression of miR-299-3p resulted in a notable inhibition of cellular proliferation (P<0.05), as well as downregulation of hTERT mRNA and protein in Hep-2 cells (P>0.05). The expression of miR-299-3p is downregulated in human laryngeal cancer Hep-2 cells. Overexpression of miR-299-3p inhibits Hep-2 cell growth by targeting the 3'-untranslated region of hTERT mRNA. [ABSTRACT FROM AUTHOR]

The aim of the present study was to identify the major factors correlated with early postoperative seizures in elderly patients who had undergone a meningioma resection, and subsequently, to develop a logistic regression equation for assessing the seizures risk. Fourteen factors possibly correlated with early postoperative seizures in a cohort of 209 elderly patients who had undergone meningioma resection, as analyzed by multifactorial stepwise logistic regression. Phenobarbital sodium (0.1 g, intramuscularly) was administered to all 209 patients 30 min prior to undergoing surgery. All the patients had no previous history of seizures. The correlation of the 14 clinical factors (gender, tumor site, dyskinesia, peritumoral brain edema (PTBE), tumor diameter, pre- and postoperative prophylaxes, surgery time, tumor adhesion, circumscription, blood supply, intraoperative transfusion, original site of the tumor and dysphasia) was assessed in association with the risk for post-operative seizures. Tumor diameter, postoperative prophylactic antiepileptic drug (PPAD) administration, PTBE and tumor site were entered as risk factors into a mathematical regression model. The odds ratio (OR) of the tumor diameter was >1, and PPAD administration showed an OR >1, relative to a non-prophylactic group. A logistic regression equation was obtained and the sensitivity, specificity and misdiagnosis rates were 91.4, 74.3 and 25.7%, respectively. Tumor diameter, PPAD administration, PTBE and tumor site were closely correlated with early postoperative seizures; PTBE and PPAD administration were risk and protective factors, respectively. [ABSTRACT FROM AUTHOR]

Early detection of epidermal growth factor receptor (EGFR) mutation, particularly EGFR T790M mutation, is of clinical significance. The aim of the present study was to compare the performances of amplification refractory mutation system-based quantitative polymerase chain reaction (ARMS-qPCR) and droplet digital polymerase chain reaction (ddPCR) approaches in the detection of EGFR mutation and explore the feasibility of using ddPCR in the detection of samples with low mutation rates. EGFR gene mutations in plasmid samples with different T790M mutation rates (0.1-5%) and 10 clinical samples were detected using the ARMS-qPCR and ddPCR approaches. The results demonstrated that the ARMS-qPCR method stably detected the plasmid samples (6,000 copies) with 5 and 1% mutation rates, while the ddPCR approach reliably detected those with 5% (398 copies), 1% (57 copies), 0.5% (24 copies) and 0.1% (average 6 copies) mutation rates. For the 10 clinical samples, the results for nine samples by the ARMS-qPCR and ddPCR methods were consistent; however, the sample N006, indicated to be EGFR wild-type by ARMS-qPCR, was revealed to have a clear EGFR T790M mutation with seven copies of mutant alleles in a background of 6,000 wild-type copies using ddPCR technology. This study demonstrates the feasibility of applying the ddPCR system to detect EGFR mutation and identified the advantage of ddPCR in the detection of samples with a low EGFR mutation abundance, particularly the secondary EGFR T790M resistance mutation, which enables early diagnosis before acquired resistance to tyrosine kinase inhibitors becomes clinically detectable. [ABSTRACT FROM AUTHOR]

The development of chemoresistance in patients represents a major challenge in cancer treatment. Lactate dehydrogenase-A (LDHA) is one of the principle isoforms of LDH that is expressed in breast tissue, controlling the conversion of pyruvate to lactate and also playing a signifi- cant role in the metabolism of glucose. The aim of this study was to identify whether LDHA was involved in oral cancer cell resistance to Taxol and whether the downregulation of LDHA, as a result of cisplatin treatment, may overcome Taxol resistance in human oral squamous cells. The OECM-1 oral epidermal carcinoma cell line was used, which has been widely used as a model of oral cancer in previous studies. The role of LDHA in Taxol and cisplatin resistance were investigated and the synergistic cytotoxicity of cisplatin and/or Taxol in oral squamous cells was analyzed. Cell viability was analyzed by MTT assay, LDHA expression was analyzed by western blot analysis and siRNA tranfection was performed to knock down LDHA expression. The present study results showed that decreased levels of LDHA were responsible for the resistance of oral cancer cells to cisplatin (CDDP). CDDP treatments downregulated LDHA expression, and lower levels of LDHA were detected in the CDDP-resistant oral cancer cells compared with the CDDP-sensitive cells. By contrast, the Taxol-resistant cancer cells showed elevated LDHA expression levels. In addition, small interfering RNA-knockdown of LDHA sensitized the cells to Taxol, but desensitized them to CDDP treatment, while exogenous expression of LDHA sensitized the cells to CDDP, but desensitized them to Taxol. The present study also revealed the synergistic cytotoxicity of CDDP and Taxol for killing oral cancer cells through the inhibition of LDHA. This study highlights LDHA as a novel therapeutic target for overcoming Taxol resistance in oral cancer patients using the combined treatments of Taxol and CDDP. [ABSTRACT FROM AUTHOR]

Primary hemangioendotheliomas (HEs) of the spleen are rare, low-grade borderline-malignant vascular tumors. To date, only a few splenic HE cases have been reported in adults. In infants, one 9-year-old male patient has previously been reported, and the patient succumbed to the disease shortly following surgery. Currently, the clinical treatment and prognosis of the disease remains challenging to define, due to the extremely low number of cases reported. The current report presents the case of a 9-year-old pediatric patient with splenic HE, who survived with no recurrence or complications following a partial splenectomy. Additionally, a literature review was conducted to analyze the treatment and prognosis of the disease. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate whether low frequency low energy ultrasound combined with microbubbles induces apoptotic cell death of A7r5 rat aortic vascular smooth muscle cells, and to identify the possible mechanisms underlying this effect. Ultrasonic waves (45 kHz with 0.3 Wcm² of intensity for 0, 10, 20 and 30 sec) were used together with different dosages of SonoVue™ microbubbles (0, 14, 28, 42 and 56 µl), respectively. The cell viability and apoptotic rate were determined by trypan blue staining immediately following treatment and flow cytometry 24 h thereafter. The treatment conditions resulting in the lowest amount of necrosis, highest apoptotic rate and lowest microbubble dosage was selected for the US+MB group, which was treated with ultrasound combined with microbubbles. The cell proliferation 24 h following treatment was determined and western blot analysis was applied to examine the expression of apoptosis-associated proteins, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). The harmonic acoustic pressure amplitude was measured to obtain the cavitation intensity. The combination of 20 sec ultrasound irradiation and 14 µl SonoVue™ was selected as the treatment conditions for the US+MB group. The results demonstrated that both ultrasound alone (the US group) and in combination with microbubbles significantly inhibited the proliferation of A7r5 cells compared with that of the control (P<0.01), and the suppression in the US+MB group was significantly greater (P<0.01). The apoptotic rate in A7r5 cells induced by this combination treatment (16.62±0.93%) was significantly higher than that in the control (3.93±0.39%; P<0.01) and US (6.88±1.87%; P<0.01) groups. Treatment with ultrasound combined with microbubbles increased the expression of Bax and decreased the ratio of Bcl-2/Bax compared with those in the control and US groups. The cavitation induced by ultrasound combined with microbubble treatment was more intense than that by ultrasound alone. The results demonstrated that the cell death and apoptosis of A7r5 cells were associated with ultrasound duration and microbubble dosage. Low frequency ultrasound combined with microbubbles induced apoptosis in A7r5 cells through the upregulation of Bax and the downregulation of the Bcl-2/Bax ratio, where the cavitation effect may have an important role. [ABSTRACT FROM AUTHOR]

The aim of the present study was to observe the effects of Fuzheng Huayu capsule combined with Pegasys (peginterferon a-2a) on hepatic fibrosis in rats and in the treatment of patients with genotype 1 hepatitis C and hepatic cirrhosis. A dimethylnitrosamine (DMN)-induced rat model of liver injury was established. Fuzheng Huayu capsule combined with Pegasys was administered to the rats and the DMN-induced hepatocyte apoptosis was observed. In addition, a total of 100 patients with genotype 1 hepatitis C and hepatic cirrhosis were treated by oral administration of Fuzheng Huayu capsule combined with Pegasys or with Pegasys alone. The therapeutic effect of Fuzheng Huayu capsule combined with Pegasys was analyzed. Following the oral administration of Fuzheng Huayu capsule combined with Pegasys to the DMN model rats, the expression of a-smooth muscle actin was found to be significantly reduced, hemopoietic stem cell apoptosis was increased and liver cell apoptosis was reduced. These indices were significantly different compared with those in the model group (P<0.05). Liver function and liver fibrosis were markedly recovered in hepatitis C patients with hepatic cirrhosis following treatment with the combination treatment compared with those in the patients treated with Pegasys alone (P<0.05). In conclusion, the combination of Fuzheng Huayu capsule with Pegasys inhibited liver fibrosis and cell apoptosis, and may be a novel therapeutic strategy for the treatment of patients with compensated cirrhosis due to hepatitis C. This study provides a method for the optimization of existing treatment strategies and for the establishment of potentially effective combination therapies. [ABSTRACT FROM AUTHOR]