High normal alanine aminotransferase is an indicator for better response to antiviral therapy in chronic hepatitis B.

Background: Evidence shows people living with CHB even with a normal ALT (40U/L as threshold) suffer histological disease and there is still little research to evaluate the potential benefit of antiviral benefits in them. Methods: We retrospectively examined 1352 patients who underwent liver biopsy from 2017 to 2021 and then obtained their 1-year follow-up data to analyze. Results: ALT levels were categorized into high and low, with thresholds set at >29 for males and >15 for females through Youden's Index. The high normal ALT group showed significant histological disease at baseline (56.43% vs 43.82%, p< 0.001), and better HBV DNA clearance from treatment using PSM (p=0.005). Similar results were obtained using 2016 AASLD high normals (male >30, female >19). Further multivariate logistic analysis showed that high normal ALT (both criterias) was an independent predictor of treatment (OR 1.993, 95% CI 1.115-3.560, p=0.020; OR 2.000, 95% CI 1.055-3.793, p=0.034) Both of the models had higher AUC compared with current scoring system, and there was no obvious difference between the two models (AUC:0.8840 vs 0.8835). Conclusion: Male >30 or female >19 and Male >29 or female>15 are suggested to be better thresholds for normal ALT. Having a high normal ALT in CHB provides a potential benefit in antiviral therapy.

Serum ammonia variation predicts mortality in patients with hepatitis B virus-related acute-on-chronic liver failure.

Background: Hyperammonemia is critical to the development of hepatic encephalopathy (HE) and is associated with mortality in end-stage liver disease. This study investigated the clinical value of ammonia variation in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. Methods: A total of 276 patients with HBV-ACLF were retrospectively recruited. Patients' ammonia levels were serially documented. Baseline ammonia, Peak ammonia (highest level), and Trough ammonia (lowest level) were particularly corrected to the upper limit of normal (AMM-ULN). The primary endpoint was 28-day mortality. Results: The 28-day, 3-month, and 12-month mortality rates were 19.2, 25.7, and 28.2%, respectively. A total of 51 (18.4%) patients had overt HE (grade 2/3/4). Peak AMM-ULN was significantly higher in patients with overt HE and non-survivors compared with their counterparts (P < 0.001). Following adjustment for significant confounders, high Peak AMM-ULN was an independent predictor of overt HE (hazard ratio, 1.031, P < 0.001) and 28-day mortality (hazard ratio, 1.026, P < 0.001). The cut-off of Peak AMM-ULN was 1.8, determined by using the X-tile. Patients with Peak AMM-ULN appearing on days 1-3 after admission had a higher proportion of overt HE and mortality compared to other groups. Patients with decreased ammonia levels within 7 days had better clinical outcomes than those with increased ammonia. Conclusion: Serum Peak ammonia was independently associated with overt HE and mortality in HBV-ACLF patients. Serial serum ammonia may have prognostic value.

Neck-to-height ratio is positively associated with diabetic kidney disease in Chinese patients with type 2 diabetes mellitus.

Introduction: The aim of this study was to investigate the associations of neck circumference (NC) and neck-to-height (NHR) with diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus (T2DM). Materials and methods: A total of 2,615 patients with prevalent T2DM were enrolled. NHR was calculated through NC (cm) divided by height (cm), and prevalent DKD was defined as the urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g or the estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 in the absence of other primary kidney diseases. Results: The levels of NC and NHR were higher in DKD patients compared with non-DKD patients (38.22 vs. 37.71, P = 0.003; 0.232 vs. 0.227, P < 0.001, respectively). After full adjustments, individuals at the highest tertile of NHR had higher odds of DKD than those at the lowest tertile (multivariate-adjusted OR = 1.63, 95% CI: 1.22, 2.18), but this association was not pronounced with NC (multivariate-adjusted OR = 1.24, 95% CI: 0.87, 1.76). Individuals at the highest tertile of NHR had lower eGFR (ß = -4.64, 95% CI: -6.55, -2.74) and higher UACR levels (ß = 0.27, 95% CI: 0.10, 0.45) than those at the lowest tertile. The adverse association between NHR and prevalent DKD remained statistically significant among most of the subgroups analyzed and no interaction effects were observed. Conclusion: The increase in NHR was adversely and independently associated with DKD in this Chinese T2DM population.

Differential expression of microRNAs in xenografted Lewis lung carcinomas subjected to intermittent hypoxia: a next-generation sequence analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased cancer mortality, but the underlying mechanism remains poorly understood. MicroRNAs (miRNAs) are confirmed to be involved in tumorigenesis and tumor progression. However, whether miRNAs have any differential expressions in OSA population needs to be elucidated. The aim of this experimental study was to determine the alterations of various miRNAs in xenograft mice exposed to chronic intermittent hypoxia (IH) which is considered a hallmark of OSA. METHODS: Sequencing was applied to screen the miRNAs of tumor tissues in xenograft mice exposed to IH and normoxia (control, CTL), respectively. Most differentially expressed miRNAs were verified by the quantitative real-time polymerase chain reaction (qRT-PCR). Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway were performed to reveal the functional enrichment of the target genes regulated by the miRNAs. RESULTS: A total of 485 miRNAs (259 novel miRNAs and 226 known miRNAs) were differentially expressed between the IH and CTL groups. 154 miRNAs were upregulated and 331 miRNAs were downregulated among them. The top 5 differentially expressed known (miR-767, miR-466f-5p, miR-5122, miR-124-3p and miR-590-3p) and novel (miR-140, miR-130, miR-301, miR-177 and miR-90) miRNAs were validated by qRT-PCR. MiR-767, miR-124-3p, miR-590-3p and all novel miRNAs were upregulated while miR-466f-5p and miR-5122 were downregulated in IH-induced xenograft mice. In addition, GO and KEGG pathway analysis demonstrated that the predicted target genes, which were regulated by differentially expressed miRNAs were markedly enriched in related biological processes and pathways, including biological processes, cell metabolic and biosynthetic processes and molecular functions. CONCLUSIONS: Several altered miRNAs were detected in xenograft mice exposed to IH. The differentially expressed miRNAs in IH indicates that these miRNAs might involve in the molecular mechanism of tumorigenesis and tumor progression in OSA. Further studies are required to determinate the exact intermediation of certain miRNAs between IH and tumor progression.

Some Wilker and Cusa type inequalities for generalized trigonometric and hyperbolic functions.

The authors obtain some Wilker and Cusa type inequalities for generalized trigonometric and hyperbolic functions and generalize some known inequalities.

An inequality for generalized complete elliptic integral.

In this paper, we show an elegant inequality involving the ratio of generalized complete elliptic integrals of the first kind and generalize an interesting result of Alzer.

Biomarker discovery and identification from non-small cell lung cancer sera.

Currently, serum biomarkers might usually be thought not to be used for early detection of lung cancer by some researchers. In this study, we used a highly optimized ClinProt-matrix-assisted laser desorption/ionization time-of flight mass spectrometer (MALDI-TOF-MS) to screen non-small cell lung carcinoma (NSCLC) markers in serum. A training set of spectra derived from 45 NSCLC patients, 24 patients with benign lung diseases (BLDs) and 21 healthy individuals, was used to develop a proteomic pattern that discriminated cancer from non-cancer effectively. A test set, including 74 cases (29 NSCLC patients and 45 controls), was used to validate this pattern. After cross-validation, the classifier showed sensitivity and specificity, 86.20% and 80.00%, respectively. Remarkably, 100% of early stage serum samples could be correctly classified as lung cancer. Furthermore, the differential peptides of 1865Da and 4209Da were identified as element of component 3 and eukaryotic peptide chain release factor GTP-binding subunit ERF, respectively. The patterns we described and peptides we identified may have clinical utility as surrogate markers for detection and classification of NSCLC.

Study of differential proteins in lung adenocarcinoma using laser capture microdissection combined with liquid chip-mass spectrometry technology.

BACKGROUND: In recent years the proportion of lung adenocarcinoma (adCA) which occurs in lung cancer patients has increased. Using laser capture microdissection (LCM) combined with liquid chip-mass spectrometry technology, we aimed to screen lung cancer biomarkers by studying the proteins in the tissues of adCA. METHODS: We used LCM and magnetic bead based weak cation exchange (MB-WCX) to separate and purify the homogeneous adCA cells and normal cells from six cases of fresh adCA and matched normal lung tissues. The proteins were analyzed and identified by matrix assisted laser desorption/ionization time-of-fight mass spectrometry (MALDI-OF-MS). We screened for the best pattern using a radial basic function neural network algorithm. RESULTS: About 2.895 × 10(6) and 1.584 × 10(6) cells were satisfactorily obtained by LCM from six cases of fresh lung adCA and matched normal lung tissues, respectively. The homogeneities of cell population were estimated to be over 95% as determined by microscopic visualization. Comparing the differentially expressed proteins between the lung adCA and the matched normal lung group, 221 and 239 protein peaks, respectively, were found in the mass-to-charge ration (M/Z) between 800 Da and 10 000 Da. According to t test, the expression of two protein peaks at 7521.5 M/Z and 5079.3 M/Z had the largest difference between tissues. They were more weakly expressed in the lung adCA compared to the matched normal group. The two protein peaks could accurately separate the lung adCA from the matched normal lung group by the sample distribution chart. A discriminatory pattern which can separate the lung adCA from the matched normal lung tissue consisting of three proteins at 3358.1 M/Z, 5079.3 M/Z and 7521.5 M/Z was established by a radial basic function neural network algorithm with a sensitivity of 100% and a specificity of 100%. CONCLUSIONS: Differential proteins in lung adCA were screened using LCM combined with liquid chip-mass spectrometry technology, and a biomarker model was established. It is possible that this technology is going to become a powerful tool in screening and early diagnosis of lung adCA.

Detection of lung adenocarcinoma using magnetic beads based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry serum protein profiling.

BACKGROUND: Recently, due to the rapid development of proteomic techniques, great advance has been made in many scientific fields. We aimed to use magnetic beads (liquid chip) based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) technology to screen distinctive biomarkers for lung adenocarcinoma (adCA), and to establish the diagnostic protein profiles. METHODS: Using weak cation exchange magnetic beads (MB-WCX) to isolate and purify low molecular weight proteins from sera of 35 lung adCA, 46 benign lung diseases (BLDs) and 44 healthy individuals. The resulting spectra gained by anchor chip-MALDI-TOF-MS were analyzed by ClinProTools and a pattern recognition genetic algorithm (GA). RESULTS: In the working mass range of 800 - 10 000 Da, 99 distinctive peaks were resolved in lung adCA versus BLDs, while 101 peaks were resolved in lung adCA versus healthy persons. The profile gained by GA that could distinguish adCA from BLDs was comprised of 4053.88, 4209.57 and 3883.33 Da with sensitivity of 80%, specificity of 93%, while that could separate adCA from healthy control was comprised of 2951.83 Da and 4209.73 Da with sensitivity of 94%, specificity of 95%. The sensitivity provided by carcinoembryonic antigen (CEA) in this experiment was significantly lower than our discriminatory profiles (P < 0.005). We further identified a eukaryotic peptide chain release factor GTP-binding subunit (eRF3b) (4209 Da) and a complement C3f (1865 Da) that may serve as candidate biomarkers for lung adCA. CONCLUSION: Magnetic beads based MALDI-TOF-MS technology can rapidly and effectively screen distinctive proteins/polypeptides from sera of lung adCA patients and controls, which has potential value for establishing a new diagnostic method for lung adCA.

[Application of liquid chip-mass spectrometry technology for screening serum biomarker proteins in lung squamous cell carcinoma].

OBJECTIVE: To screen the serum biomarker proteins of lung squamous cell carcinoma (SCCs) by liquid chip-mass spectrometry technology. METHODS: All serum samples, including 34 SCCs, 46 benign lung diseases (BLDs) and 44 healthy individuals, were analyzed by CLINPROT system in order to study the serum protein expression profiles. Then the discriminatory proteins were detected by FlexAnalysis 3.0 software. Biomarkers were identified by liquid chromatography-tandem mass spectrometry (LCMS/MS). RESULTS: Comparing the differential serum expression proteins between SCCs and healthy individuals, and SCCs and BLDs respectively. Ninety-six differential protein peaks [mass-to-charge ration (M/Z) between 800 and 10 000] were found between SCCs and healthy individuals. In these protein peaks, the expression of protein peaks at 4054.13 M/Z and 4267.46 M/Z had the largest difference between them. The two protein peaks could accurately separate SCCs from healthy individuals by the frame of axes. Similarly, 99 differential protein peaks were automatically detected between SCCs and BLDs. In these protein peaks, the expression of protein peaks at 5065.27 M/Z and 4054.02 M/Z had the largest difference between them. The two protein peaks could accurately separate SCCs from BLDs by the frame of axes. Identified by LC-MS/MS, 1778 M/Z and 1865 M/Z might be assayed jointly and corresponded to complements C3 fragment or C3f precursor. CONCLUSIONS: Differential protein expressions existed between SCCs versus healthy individuals and SCCs versus BLD patients. It is feasible to screen the diagnostic serum biomarkers of SCC with a high sensitivity and specificity by using CLINPROT system.

[The value of (18)F-FDG PET/CT in differential diagnosis of benign and malignant pulmonary lesions: a Meta-analysis.].

OBJECTIVE: Using Meta analysis to evaluate the value of (18)F-FDG PET/CT ((18)fluorine-fluorodeoxyglucose Positron emission tomography/computed tomography) in differentiating between benign and malignant pulmonary lesions. METHODS: Relevant documentations from PubMed and other 5 databases from 1980 to 2008 were searched, and the eligible literatures according to the inclusive criteria were selected. The statistical information and quality of science were assessed and classified. The data were analyzed using Meta-Disc1.4 software. The diagnostic value of PET/CT in distinguishing benign from malignant pulmonary lesions was evaluated by the pooled sensitivity, specificity, the likelihood ratio (LR) and summary receiver operating characteristic curve (SROC curve) statistical indicators. RESULTS: Seven literatures were collected including 5 in English and 2 in Chinese, and 795 cases were included in the study. Heterogeneity test showed that the homogeneity of the study was good. By using deterministic models to analyze the data, the value of the weighted sensitivity was 95% (93% - 97%), the specificity was 77% (71% - 82%), the positive likelihood ratio was 4.12, negative likelihood ratio was 0.08, and the SROC area under the curve (area under curve, AUC) was 94%. CONCLUSION: PET/CT is of high diagnostic value in differentiation between benign and malignant lung lesions, but large sized, multicenter, prospective studies are needed to assess its clinical value more accurately.