Application of Continuous Sacral Block Guided by Ultrasound After Comprehensive Sacral Canal Scanning in Children Undergoing Laparoscopic Surgery: A Prospective, Randomized, Double-Blind Study.

Purpose: The present study aimed to explore the effects of continuous sacral block on the postoperative pain of children and the satisfaction of the nurses in post-anesthesia care unit (PACU). Also, the influence of the modified protocol of continuous sacral block was investigated. Patients and Methods: A total of 60 children undergoing laparoscopic surgery were randomly divided into two groups: GI and GC groups. The general anesthesia was induced with midazolam, propofol, sufentanil and succinylcholine in both groups. In addition, the patients were subjected to continuous sacral block with levobupivacaine in group GC. The modified protocol of continuous sacral block was divided into three steps: comprehensive lumbar and sacral vertebral canal scanning by ultrasound, catheterization and administration. The EVENDOL pain scales and pediatric anesthesia emergence delirium scales of the children were evaluated at 5 min after extubation (T3), 90 min (T4), and 4 h (T5) after the operation. The nurses' satisfaction scores at T3 -T4 and adverse events, such as nausea and vomiting, were also recorded, after the operation. Results: After ultrasonic scanning, one patient in group GC was excluded due to the sacral hiatus atresia, which might lead to failure of catheterization. Data of 59 patients were collected for statistical analysis. Compared to the GI group, the EVENDOL scores and the pediatric anesthesia emergence delirium scales were reduced at T3, T4, and T5 (P < 0.05) in group GC. Furthermore, there was a higher rank of PACU nurses' satisfaction in the GC group compared to the GI group (P < 0.05). Conclusion: Based on the modified protocol, continuous sacral block provides reliable and safety analgesia for children undergoing laparoscopic surgery, thereby improving the satisfaction of PACU nurses.

Metformin abrogates Fusobacterium nucleatum-induced chemoresistance in colorectal cancer by inhibiting miR-361-5p/sonic hedgehog signaling-regulated stemness.

BACKGROUND: Chemotherapy resistance is the major cause of recurrence in patients with colorectal cancer (CRC). A previous study found that Fusobacterium (F.) nucleatum promoted CRC chemoresistance. Additionally, metformin rescued F. nucleatum-induced tumorigenicity of CRC. Here, we aimed to investigate whether metformin could revert F. nucleatum-induced chemoresistance and explore the mechanism. METHODS: The role of metformin in F. nucleatum-infected CRC cells was confirmed using cell counting kit 8 assays and CRC xenograft mice. Stemness was identified by tumorsphere formation. Bioinformatic analyses were used to explore the regulatory molecules involved in metformin and F. nucleatum-mediated regulation of the sonic hedgehog pathway. RESULTS: We found that metformin abrogated F. nucleatum-promoted CRC resistance to chemotherapy. Furthermore, metformin attenuated F. nucleatum-stimulated stemness by inhibiting sonic hedgehog signaling. Mechanistically, metformin diminished sonic hedgehog signaling proteins by targeting the MYC/miR-361-5p cascade to reverse F. nucleatum-induced stemness, thereby rescuing F. nucleatum-triggered chemoresistance in CRC. CONCLUSIONS: Metformin acts on F. nucleatum-infected CRC via the MYC/miR-361-5p/sonic hedgehog pathway cascade, subsequently reversing stemness and abolishing F. nucleatum-triggered chemoresistance. Our results identified metformin intervention as a potential clinical treatment for patients with chemoresistant CRC with high amounts of F. nucleatum.

Silybin alleviates hepatic lipid accumulation in methionine-choline deficient diet-induced nonalcoholic fatty liver disease in mice via peroxisome proliferator-activated receptor α.

Nonalcoholic fatty liver disease (NAFLD) is regarded as the most common liver disease with no approved therapeutic drug currently. Silymarin, an extract from the seeds of Silybum marianum, has been used for centuries for the treatment of various liver diseases. Although the hepatoprotective effect of silybin against NAFLD is widely accepted, the underlying mechanism and therapeutic target remain unclear. In this study, NAFLD mice caused by methionine-choline deficient (MCD) diet were orally administrated with silybin to explore the possible mechanism and target. To clarify the contribution of peroxisome proliferator-activated receptor α (PPARα), PPARα antagonist GW6471 was co-administrated with silybin to NAFLD mice. Since silybin was proven as a PPARα partial agonist, the combined effect of silybin with PPARα agonist, fenofibrate, was then evaluated in NAFLD mice. Serum and liver samples were collected to analyze the pharmacological efficacy and expression of PPARα and its targets. As expected, silybin significantly protected mice from MCD-induced NAFLD. Furthermore, silybin reduced lipid accumulation via activating PPARα, inducing the expression of liver cytosolic fatty acid-binding protein, carnitine palmitoyltransferase (Cpt)-1a, Cpt-2, medium chain acyl-CoA dehydrogenase and stearoyl-CoA desaturase-1, and suppressing fatty acid synthase and acetyl-CoA carboxylase α. GW6471 abolished the effect of silybin on PPARα signal and hepatoprotective effect against NAFLD. Moreover, as a partial agonist for PPARα, silybin impaired the powerful lipid-lowering effect of fenofibrate when used together. Taken together, silybin protected mice against NAFLD via activating PPARα to diminish lipid accumulation and it is not suggested to simultaneously take silybin and classical PPARα agonists for NAFLD therapy.

New Phenylpropanoid Glycosides from Illicium majus and Their Radical Scavenging Activities.

Chemical investigation of the ethanol extract of the branch and leaves of Illicium majus resulted in the isolation of four new phenylpropanoid glycosides (1-4) and one new phenolic glycoside (9), along with 13 known ones. Spectroscopic techniques were used to elucidate the structures of the new isolates such as 3-[(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-2,3-dihydro-1-benzofuran-5-yl]propyl ß-D-glucopyranoside (1), [(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-3-yl]methyl 2-O-α-L-rhamnopyranosyl-ß-D-glucopyranoside (2), [(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-3-yl]methyl 2-O-α-L-rhamnopyranosyl-ß-D-xylopyranoside (3), 3-[(2R,3S)-3-({[2-O-(4-O-acetyl-α-L-rhamnopyranosyl)-ß-D-xylopyranosyl]oxy}methyl)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-2,3-dihydro-1-benzofuran-5-yl]propyl acetate (4), and 4-(2-hydroxyethyl)phenyl 3-O-ß-D-glucopyranosyl-ß-D-glucopyranoside (9). Free radical scavenging activities of the isolates were elucidated through the DPPH assay method. The most active compounds, 1-O-caffeoyl-ß-D-glucopyranose (17) and soulieana acid 1 (18), exhibited moderate radical scavenging activities (IC50 =37.7±4.4 µM and IC50 =97.2±3.4 µM, respectively). The antibacterial activities of the isolates against Staphylococcus aureus and Escherichia coli were also assessed, and no activity was shown at the measured concentration (<32 µg/mL).

Association of anti-NXP2 antibody with clinical characteristics and outcomes in adult dermatomyositis: results from clinical applications based on a myositis-specific antibody.

OBJECTIVES: The aim was to study and compare the clinical manifestations, auxiliary examinations, and therapeutic responses in patients with different myositis-specific antibody (MSA) types. METHOD: We retrospectively investigated the medical records of 143 hospitalized dermatomyositis patients, all of whom were tested for MSAs, and performed follow-up. Patients were divided into groups with and without anti-nuclear matrix protein 2 (NXP2) antibodies (17 vs 126 patients). Demographic, clinical manifestation (occurring at any time during the disease course), imaging, laboratory, treatment response, and survival data were collected for statistical analyses. RESULTS: Adult dermatomyositis patients with anti-NXP2 antibodies were more prone to dysphagia (P<0.001), had higher levels of muscle injury markers (CK peak, P=0.007; CK peak>1000 IU/L, P<0.001; CK-MB, P=0.002), were younger at onset (P=0.008), and were less likely to present with interstitial lung disease (P=0.016) than the anti-NXP2 antibody-negative subgroup. Multivariable logistic regression analysis showed that onset age (OR=0.96 CI 95%: 0.924-0.999, P=0.043) and dysphagia (OR=7.088, CI 95%: 1.824-27.536, P=0.005) were independent risk factors for anti-NXP2 antibody positivity. Kaplan-Meier survival analysis did not reveal that dermatomyositis patients with anti-NXP2 antibodies have a relatively worse prognosis. However, the disease course was more frequently polycyclic, and 68.75% of patients had a relapsing-remitting disease course. More than half (52.94%) of those who showed no response to treatment used at least 3 disease-modifying antirheumatic drugs. CONCLUSIONS: We show the important clinical features of and risk factors for this unique antibody-mediated form of dermatomyositis. Although these patients had a relatively low mortality rate, they were prone to recurrence, and treatment was challenging. Key points • The clinical features and risk factors for adult dermatomyositis patients with anti-NXP2 antibodies. • The impact of anti-NXP2 antibody on survival outcomes.

SIS3, a good candidate for the reverse of type 2 diabetes mellitus in mice.

TGF-ß signaling plays an extremely important role in the occurrence and development of type 2 diabetes mellitus (T2DM), and the blockade of TGF-ß/Smad3 pathway protests against the high-fat diet-induced obesity and diabetes. As a specific small molecule inhibitor of Smad3 protein, the biological activities of compound SIS3 were evaluated by high-fat diet-induced T2DM model mice. In vivo results indicated that SIS3 can not only significantly reduce the body weight, fat mass, and fasting blood glucose in high-fat diet-induced T2DM model mice, but also improve insulin sensitivity and oral glucose tolerance of high-fat diet-induced T2DM model mice after the injection of SIS3 with 5 mg/kg for 45 days.

Semi-solid extrusion 3D printing ODFs: an individual drug delivery system for small scale pharmacy.

Orodispersible films (ODFs) are promising drug delivery systems for customized medicines as it provide an alternative approach to increase consumer acceptance by advantages of rapid dissolution and administration without water. The aim of this study was to develop a platform to support the realization of tailored treatments suitable for the extemporaneous production of ODFs by semi-solid extrusion (SSE) 3D printing (3DP). Hydroxypropyl methyl cellulose (HPMC) was used as the polymer of ODFs, and levocetirizine hydrochloride was used as the model drug. The optimal formulation was HPMC:API:PS:maltitol:sucralose at a ratio of 64:10:10:15:1. Seventeen percent HPMC solution and optimal formulation were used to prepare film precursors. The impact of dynamic viscosities and fluid mechanics difference on printing applicability was discussed. The ODFs of cube designs with aimed dose of 1.25 mg, 2.5 mg, and 5 mg were printed by SSE 3DP. Good linear relationship between theoretical model volume and drug content (R2 = 0.999) and good dose accuracy indicate that 3DP is a suitable method for preparing individualized ODFs.

Attentional bias toward emotional stimuli in type 2 diabetic Chinese patients with different self-management levels.

Extensive evidence has been obtained that supports an association between an attentional bias (AB) toward negative stimuli and vulnerability to mental and behavioral problems; however, diabetes self-management (DSM) behavior in type 2 diabetic patients has not specifically been assessed. The current study investigated whether type 2 diabetic Chinese patients who had different levels of self-management behaviors showed different patterns of AB toward either positive or negative stimuli. A sample of 195 patients completed questionnaires measuring DSM and a modified dot-probe task measuring AB. Patients with low levels of DSM had an avoidance bias for positive stimuli, the regression showed that negative orienting index significantly predicted lower DSM; patients with medium levels of DSM had difficulty in disengaging attention from negative stimuli, the regression showed that negative disengaging index significantly predicted lower DSM; while patients with high levels of DSM had an avoidance bias for negative stimuli and difficulty in disengaging from positive stimuli. An implication of this finding is that the understanding of information processing bias affects DSM and therefore suggests a novel target for prevention and treatment interventions.

[Renal Injury and Its Mechanisms in Lepr db/ db Mice].

OBJECTIVE: To study the mechanism of renal injury in Lepr db/ db mice with the leptin receptor homozygous deficiency. METHODS: Ten male of 28-week-old Lepr db/+ mice with leptin receptor heterozygous deficiency were selected as control group and ten male Lepr db/ db mice with leptin receptor homozygous deficiency were used in this study. After fasting for 8 hours, the body mass, fasting blood glucose (FBG) and glycosylated hemoglobulin (HbA1c) of the mice were measured. Blood of the mice was obtained from femoral artery before euthanasia. Serum creatinine (CRE), blood urea nitrogen (BUN), superoxide dismutase (SOD), glutathione (GSH) and malonaldehyde (MDA) were detected by corresponding kits, and serum interleukin-1ß (IL-1ß), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA) method. The kidney was taken for pathological observation. The expression levels of nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) in renal were analyzed by Western blot. The mitochondria of renal was isolated by the corresponding kit. Meanwhile, the expression level of lipoic acid synthase (LIAS) in renal mitochondria was measured by Western blot. RESULTS: The body mass, FPG, HbA1c, CRE and BUN levels of the Lepr db/ db mice were significantly increased in comparison with the Lepr db/+ mice ( P<0.05). Compared with the Lepr db/+ mice, the Lepr db/ db mice renal exhibited glomerular hypertrophy, thickened basement membrane and capillary wall, the mesangial matrix expansion and mesangial cell hyperplasia. Compared with the Lepr db/+ mice, the serum level of GSH in the Lepr db/ db mice was decreased significantly ( P<0.05). The levels of MDA and concentrations of MCP-1, IL-1ß and TNF-α in serum of the Lepr db/ db mice were higher than those of the Lepr db/+ mice ( P<0.05). Compared with the Lepr db/+ mice, the expression of LIAS and Nrf2 protein in the Lepr db/ db mice renal were decreased ( P<0.05), while the expression of NF-κB protein was increased ( P<0.05). CONCLUSION: LIAS, Nrf2 and NF-κB might play significant roles through regulation of oxidative stress and inflammation in the renal injury of Lepr db/ db mice.

Reverse transcription - loop-mediated isothermal amplification assay for the rapid detection of pathogenic Listeria monocytogenes in meat products.

This study reports the use of reverse transcription - loop-mediated isothermal amplification (RT-LAMP) to detect Listeria monocytogenes in meat. The assay was designed to target the iap gene of L. monocytogenes, to which four primers, recognizing six distinct iap sites, were designed. We optimized the RT-LAMP conditions and established the following optimal systems: 60 min, 63 °C, 2.0 mmol/L MgSO4, 1.0 mol/L betaine, 2.0 mmol/L dNTPs, 320 U/mL Bst DNA polymerase, 0.4 µmol/L outer primers, and 0.8 µmol/L inner primers. The RT-LAMP amplification products were identified by a visible white Mg2P2O7 precipitate or electrophoresis on a 2% agarose gel. RT-LAMP has a sensitivity of 7.3 × 101 CFU/mL, which is 2-fold higher than that of LAMP. When commercially available raw meat samples (including beef, pork, mutton, and rabbit) were analyzed simultaneously with RT-LAMP and the Chinese National Standard GB 4789.30-2016, their abilities to detect L. monocytogenes were the same. Samples containing L. monocytogenes killed by 15 psi at 121 °C for 15 min were used to confirm the specificity of RT-LAMP for live microorganisms. Thus, we used RT-LAMP to efficiently detect L. monocytogenes in meat products.

What Makes Lexical Tone Special: A Reverse Accessing Model for Tonal Speech Perception.

Previous studies of tonal speech perception have generally suggested harder or later access to lexical tone than segmental information, but the mechanism underlying the lexical tone disadvantage is unclear. Using a speeded discrimination paradigm free of context information, we confirmed multiple lines of evidence for the lexical tone disadvantage as well as revealed a distinctive advantage of word and atonal syllable judgments over phoneme and lexical tone judgments. The results led us to propose a Reverse Accessing Model (RAM) for tonal speech perception. The RAM is an extension of the influential TRACE model, with two additional processing levels specialized for tonal speech: lexical tone and atonal syllable. Critically, information accessing is assumed to be in reverse order of information processing, and only information at the syllable level and up is maintained active for immediate use. We tested and confirmed the predictions of the RAM on discrimination of each type of phonological component under different stimulus conditions. The current results have thus demonstrated the capability of the RAM as a general framework for tonal speech perception to provide a united account for empirical observations as well as to generate testable predictions.

Protective Effect of Zengye Decoction () on Submandibular Glands in Nonobese Diabetic Mice.

OBJECTIVE: To investigate the protective effect of Zengye Decoction (, ZYD) on the submandibular glands (SMGs) in nonobese diabetic (NOD) mice. METHODS: Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine (HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon (IFN-γ), interleukin-10 (IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide (VIP) in the submandibular glands were measured by real-time polymerase chain reaction. RESULTS: Compared with the model group, the salivary flow of the ZYD group significantly increased (P<0.05), the extent of the histological changes was ameliorated (P<0.05), and the Th1/Th2 cytokine imbalance was remedied (P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated (P<0.05). CONCLUSIONS: ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.

[Research on the blended learning mode of "Microbial Breeding Experiments" based on WeChat].

With the rapid development of the internet technology, the blended learning mode plays a more and more important role in education reforms by integrating traditional classroom teaching and online learning. WeChat is the most popular Chinese social software, and its public platform is also suitable for mobile learning. Here, we report an application of the blended learning method based on WeChat public platforms in microbiology breeding experiment courses, using the site-directed mutagenesis of the green fluorescent protein (GFP) as an example. The learning process was divided into five modules: teaching design, learning resource preparation, pre-class learning, classroom learning, post-class review and evaluation. By introducing one mutation (Y66H) in mutagenic primers, the mutated GFP gene was amplified by PCR using pGFPuv as templates, followed by removal of the original plasmid template by Dpn1 digestion. Students can monitor the color changes from green to blue in the fluorescence emission of the mutated proteins. As a useful addition to classroom teaching, WeChat is suitable for students to use fragmented time to learn and improve teaching interaction. Learning assessment results revealed the blended learning environment improves students' study interests and self-learning abilities, thus achieving a fruitful teaching result.

The distinct role of strand-specific miR-514b-3p and miR-514b-5p in colorectal cancer metastasis.

The abnormal expression of microRNAs (miRNAs) in colorectal cancer (CRC) progression has been widely investigated. It was reported that the same hairpin RNA structure could generate mature products from each strand, termed 5p and 3p, which binds different target mRNAs. Here, we explored the expression, functions, and mechanisms of miR-514b-3p and miR-514b-5p in CRC cells and tissues. We found that miR-514b-3p was significantly down-regulated in CRC samples, and the ratio of miR-514b-3p/miR-514b-5p increased from advanced CRC, early CRC to matched normal colorectal tissues. Follow-up functional experiments illustrated that miR-514b-3p and miR-514b-5p had distinct effects through interacting with different target genes: MiR-514b-3p reduced CRC cell migration, invasion and drug resistance through increasing epithelial marker and decreasing mesenchymal marker expressions, conversely, miR-514b-5p exerted its pro-metastatic properties in CRC by promoting EMT progression. MiR-514b-3p overexpressing CRC cells developed tumors more slowly in mice compared with control cells, however, miR-514b-5p accelerated tumor metastasis. Overall, our data indicated that though miR-514b-3p and miR-514b-5p were transcribed from the same RNA hairpin, each microRNA has distinct effect on CRC metastasis.

Attentional bias toward emotional stimuli in accidentally injured Chinese patients with different posttraumatic growth levels.

Extensive evidence has been obtained that supports an association between an attentional bias (AB) toward negative stimuli and vulnerability to stress-related psychopathology, little is known regarding the characteristics of individual AB in different posttraumatic growth (PTG) levels. The current study used a modified dot-probe task to investigate if individual differences in AB towards either positive or negative emotional stimuli, are related to self-reported PTG. A sample of 202 patients completed the experiment. Patients with low levels of PTG did not exhibit AB toward negative or positive stimuli, patients with medium levels of PTG had difficulty disengaging attention from negative stimuli, patients with high levels of PTG had difficulty disengaging attention from positive stimuli. And the AB towards positive stimuli was only predictive for PTG. An implication of this finding is that there are different characteristics of implicit cognitive processing in patients with different levels of PTG, suggesting the necessity of psychological intervention on the accidentally injured patients.

miR-508 Defines the Stem-like/Mesenchymal Subtype in Colorectal Cancer.

Colorectal cancer includes an invasive stem-like/mesenchymal subtype, but its genetic drivers, functional, and clinical relevance are uncharacterized. Here we report the definition of an altered miRNA signature defining this subtype that includes a major genomic loss of miR-508. Mechanistic investigations showed that this miRNA affected the expression of cadherin CDH1 and the transcription factors ZEB1, SALL4, and BMI1. Loss of miR-508 in colorectal cancer was associated with upregulation of the novel hypoxia-induced long noncoding RNA AK000053. Ectopic expression of miR-508 in colorectal cancer cells blunted epithelial-to-mesenchymal transition (EMT), stemness, migration, and invasive capacity in vitro and in vivo In clinical colorectal cancer specimens, expression of miR-508 negatively correlated with stemness and EMT-associated gene expression and positively correlated with patient survival. Overall, our results showed that miR-508 is a key functional determinant of the stem-like/mesenchymal colorectal cancer subtype and a candidate therapeutic target for its treatment.Significance: These results define a key functional determinant of a stem-like/mesenchymal subtype of colorectal cancers and a candidate therapeutic target for its treatment. Cancer Res; 78(7); 1751-65. ©2018 AACR.

High Expression of FAM83B Predicts Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma and Correlates with Cell Cycle and Cell Proliferation.

FAM83B (family with sequence similarity 83, member B) seems to emerge as a new class of players involved in the development of a variety of malignant tumors. Yet the molecular mechanisms are not well understood. The present study is intended to investigate the expression and function of FAM83B in pancreatic ductal adenocarcinoma (PDAC). In this study, we found that the expression of FAM83B was significantly increased both in PDAC cell lines and PDAC tumor tissues. FAM83B expression was positively related with advanced clinical stage and poor vital status. Higher FAM83B expression predicted shorter overall survival in PDAC patients, regardless of lymphatic metastasis status and histological differentiation. Actually, FAM83B may act as an independent prognostic indicator as well. What's more, down-regulation of FAM83B in PDAC cells contributed to G0/G1 phase arrest and inhibition of cell proliferation. Finally, a subcutaneous xenograft model indicated that knockdown of FAM83B significantly reduced the tumor volume in vivo. Our findings have provided supporting evidence for the potential molecular biomarker role of FAM83B in PDAC. It's of great interest and broad significance to target FAM83B in PDAC, which may conduce to develop a meaningful and effective strategy in the diagnosis and treatment of PDAC.

Assessment of high-sensitivity C-reactive protein tests for the diagnosis of hepatocellular carcinoma in patients with hepatitis B-associated liver cirrhosis.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide, with high morbidity and mortality. Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma and the majority (~80%) of hepatocellular carcinoma patients in China exhibit co-morbidity with HBV-associated liver cirrhosis. The goal of reliable early diagnostic and prognostic techniques for HBV-associated HCC remains unrealized. The aim of the present study was to explore the efficacy of serum high-sensitivity C-reactive protein (hs-CRP) tests in the early diagnosis of HCC in patients with HBV-associated liver cirrhosis. A cohort of 493 patients with HBV-associated liver disease was divided into three groups: Chronic HBV (CHB) group; liver cirrhosis without HCC (LC) group; and liver cirrhosis with HCC (HCC) group. A further 47 healthy individuals comprised the healthy control (CN) group. Comparative analyses of clinical symptoms, histopathology, ultrasound imagery, computed tomography, magnetic resonance imaging, biochemistry [α-fetoprotein (AFP) and liver function enzymes], and hs-CRP tests were conducted across these four groups. Immunohistochemical analysis showed that CRP is strongly expressed in HCC tumor tissue, but is not expressed elsewhere. Analyses of the correlations between serum hs-CRP levels and HCC clinical parameters indicated that there was no correlation between serum hs-CRP levels, tumor Edmondson grade, tumor-node-metastasis stage and AFP status. Serum hs-CRP and AFP levels were found to be significantly elevated in the HCC group compared to those in the LC, CHB and CN groups (P<0.01). Receiver operator characteristic analysis showed that measurement of serum hs-CRP could differentiate HCC from HBV-associated liver cirrhosis, as well as increase the accuracy of HCC diagnoses. Additionally, measurement of hs-CRP and AFP together improved diagnostic accuracy for HCC compared with either test alone. Serum hs-CRP could have potential as an effective diagnostic tool to complement AFP in diagnosing HCC and improving the identification of AFP-negative HCC in patients with HBV-associated liver cirrhosis. The present findings may facilitate the earlier diagnosis of hepatocellular carcinoma, permitting more effective treatment and a broader spectrum of treatment modalities for patients with advanced hepatic disease.

Oncogenic function and prognostic significance of Abelson interactor 1 in hepatocellular carcinoma.

Aberrant expression of Abelson interactor 1 (ABI1) has been reported in multiple cancers. However, its clinical significance and potential biological roles in hepatocellular carcinoma (HCC) have not been fully elucidated. In this study, we found that ABI1 was obviously upregulated in HCC tissues compared with non-tumor tissues. Moreover, high ABI1 expression was significantly correlated with tumor size (P=0.041), tumor number (P<0.001), tumor encapsulation (P<0.001) and BCLC stage (P=0.010). Importantly, Kaplan-Meier survival analysis showed that increased ABI1 expression predicted shorter overall survival time (P<0.001) and a higher tendency of tumor recurrence (P=0.001) in HCC patients. Multivariate Cox regression analysis further confirmed high ABI1 expression was an independent predictor for both overall survival (HR=1.795, P=0.025) and early recurrence (HR=1.893, P=0.012) after surgical resection. Furthermore, in vitro studies indicated that overexpression of ABI1 induced an increase in cell proliferation, migration and invasion of HCC cells, whereas knockdown of ABI1 did the opposite. Xenograft mouse models verified the promoting effects of ABI1 on HCC growth and lung metastasis in vivo. Collectively, our findings indicated that ABI1 contributes to the development and progression of HCC as an oncogene and may serve as a valuable prognostic marker for HCC patients.

Comparison of bioactive components and pharmacological activities of ophiopogon japonicas extracts from different geographical origins.

Ophiopogon japonicus (Linn. f.) Ker-Gawl (O. japonicas), mainly cultivated in Sichuan and Zhejiang province in China, has different bioactive components and therefore their pharmacological activities. To explain the different clinical efficacy of O. japonicas derived preparations, herein we report differences of pharmacological activities between Sichuan and Zhejiang O. japonicas and behind them the exact differences of bioactive components. Based on a LC/MS-IT-TOF method, the differences of bioactive components between Sichuan and Zhejiang O. japonicas extracts were analyzed and respective characteristic components were picked out. We determined 39 ophiopogonones and 71 ophiopogonins compounds in Sichuan and Zhejiang O. japonicas extracts and found the contents of these compositions have several times difference. Evidenced by experimental data of pharmacological activities in inhibiting cardiomyocyte damage induced by H2O2, mouse macrophage cell inflammation induced by lipopolysaccharide and cytotoxicity in vitro, Zhejiang O. japonicas extract had a stronger antioxidant and anti-inflammatory capacity than Sichuan O. japonicas extract, and the two O. japonicas extracts exhibited selective cytotoxicity on different cancer cell lines in vitro. These data shed light on the links between bioactive components and pharmacological activities of O. japonicas derived preparations. Thus, geographical origin of O. japonicas should be considered to be a key factor in efficacy studies and further clinical application.