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.

Health insurance fraud detection by using an attributed heterogeneous information network with a hierarchical attention mechanism.

BACKGROUND: With the rapid growth of healthcare services, health insurance fraud detection has become an important measure to ensure efficient use of public funds. Traditional fraud detection methods have tended to focus on the attributes of a single visit and have ignored the behavioural relationships of multiple visits by patients. METHODS: We propose a health insurance fraud detection model based on a multilevel attention mechanism that we call MHAMFD. Specifically, we use an attributed heterogeneous information network (AHIN) to model different types of objects and their rich attributes and interactions in a healthcare scenario. MHAMFD selects appropriate neighbour nodes based on the behavioural relationships at different levels of a patient's visit. We also designed a hierarchical attention mechanism to aggregate complex semantic information from the interweaving of different levels of behavioural relationships of patients. This increases the feature representation of objects and makes the model interpretable by identifying the main factors of fraud. RESULTS: Experimental results using real datasets showed that MHAMFD detected health insurance fraud with better accuracy than existing methods. CONCLUSIONS: Experiment suggests that the behavioral relationships between patients' multiple visits can also be of great help to detect health care fraud. Subsequent research fraud detection methods can also take into account the different behavioral relationships between patients.

In situ encapsulation of SQDs by zinc ion-induced ZIF-8 growth strategy for fluorescent and colorimetric dual-signal detection of alkaline phosphatase.

Controllable encapsulation of sulfur quantum dots (SQDs) into metal-organic frameworks (ZIF-8) by a surface-bound zinc ion-induced growth strategy, and SQDs@ZIF-8 was successfully prepared for alkaline phosphatase (ALP) detection. The new synthesis procedure involves first binding Zn2+ to the surface of SQDs to form SQDs/Zn, and then via zinc ion-induced in situ ZIF-8 growth to obtain SQDs@ZIF-8, which greatly improved the luminous efficiency of SQDs. The specific process of detecting ALP using pH-triggered fluorescence quenching of SQDs@ZIF-8: firstly ALP hydrolyzes 2-phosphate-l-ascorbic acid trisodium salt (AAP) to ascorbic acid (AA), and then the leakage of SQDs in the SQDs@ZIF-8 leads to a decrease in fluorescence intensity based on the destruction of ZIF-8 skeleton by H+ released by AA. A linear relationship was obtained between the fluorescence intensity and the ALP concentration in the range of 0.15-50 U/L, and the detection limit was 0.044 U/L. Moreover, it was found that free SQDs can be complexed with Fe2+ to produce wine red complexes, and the obtained UV absorbance and ALP concentration have a linear relationship in the range of 10-200 U/L. The detection range of ALP is significantly broadened based on the combination of the above two detection methods. Furthermore, SQDs@ZIF-8 exhibited excellent stability in water and was successfully applied to the fluorescence and colorimetric detection of ALP in human serum.

Improving Na+ Diffusion and Performance of P2-Type Layered Na0.6Li0.07Mn0.66Co0.17Ni0.17O2 by Expanding the Interplanar Spacing.

Because of their high reversible capacity and wide operation voltage window, P2-type layered transition metal oxides are considered as one type of potential cathode candidate for sodium-ion batteries. However, they still suffer from low kinetics, phase degeneration, and ambiguous mechanism of Na+ diffusion. Here, we synthesized a P2-type Na0.6Li0.07Mn0.66Co0.17Ni0.17O2 with a high Na+ diffusion performance by sintering a nanoplate-structural precursor with alkali metal salt and proposed a possible mechanism for improving Na+ diffusion. The as-prepared P2-type layered oxide presents a quasi-hexagon shape and demonstrates a discharge capacity of 87 mAh g-1 at a current density of 875 mA g-1 (5 C rate), twice that of the sample synthesized from a non-nanoplate particle precursor. Rietveld refinement and results of X-ray photoelectron spectroscopy reveal the probable mechanism that the expanded interplanar spacing along the c-axis orientation would facilitate Na+ diffusion during Na+ intercalation/deintercalation processes, and the expanded interplanar spacing may arise from a high oxidation state of transition metal ions.

A novel genomic-clinicopathologic nomogram to improve prognosis prediction of hepatocellular carcinoma.

There is a lack of precise and clinical accessible model to predict the prognosis of hepatocellular carcinoma (HCC) in clinic practice currently. Here, an inclusive nomogram was developed by integrating genomic markers and clinicopathologic factors for predicting the outcome of patients with HCC. A total of 365 samples of HCC were obtained from the Cancer Genome Atlas (TCGA) database. The LASSO analysis was carried out to identify HCC-related mRNAs, and the multivariate Cox regression analysis was used to construct a genomic-clinicopathologic nomogram. As results, 9 mRNAs were finally identified as prognostic indicators, including RGCC, CDH15, XRN2, RAB3IL1, THEM4, PIF1, MANBA, FKTN and GABARAPL1, and used to establish a 9-mRNA classifier. Additionally, an inclusive nomogram was built up by combining the 9-mRNA classifier (P < 0.001) and clinicopathologic factors including age (P = 0.006) and metastasis (P < 0.001) to predict the mortality of HCC patients. Time-dependent receiver operating characteristic, index of concordance and calibration analyses indicated favorable accuracy of the model. Decision curve analysis suggested that appropriate intervention according to the established nomogram will bring net benefit when threshold probability was above 25%. The genomic-clinicopathologic model could be a reliable tool for predicting the mortality, helping determining the individualized treatment and probably improving HCC survival.

Nomogram predicting cancer-specific mortality in patients with esophageal adenocarcinoma: a competing risk analysis.

BACKGROUND: Many factors are reported to be related to the prognosis of patients with esophageal adenocarcinoma (EAC), but few reliable and straightforward tools for clinicians to estimate individual mortalities have been developed. This study aimed to evaluate the probability of cancer-specific death for patients with EAC and to build nomograms for predicting long-term cancer-specific mortality and overall mortality for EAC patients. METHODS: Between 2004 and 2013, a total of 20,623 patients were identified from the surveillance, epidemiology, and end results (SEER) database and randomly divided into training (N=14,436) and validation (N=6,187) cohorts. The cumulative incidence functions (CIFs) of EAC-specific death and other causes were evaluated at the 1st, 3rd, and 5th year after diagnosis. We integrated the significant prognostic factors to construct nomograms and subjected them to internal and external validation. RESULTS: The CIFs of EAC-specific survival at 1, 3, and 5 years after diagnosis were 60.9%, 37.1%, and 31.3%, respectively. Predictors for cancer-specific mortality for EAC comprised tumor grade, tumor extension, the involvement of lymph nodes, distant metastasis, surgery of primary site, insurance recode, and marital status. For overall mortality, it also included the predictor of age at diagnosis. The nomograms were well-calibrated and had good discriminative ability with concordance indexes (c-indexes) of 0.733, 0.728, and 0.728 for 1-, 3- and 5-year prognosis prediction of EAC-specific mortality respectively, and 0.726, 0.720, 0.719 for 1-, 3-, and 5-year prognosis prediction of overall mortality respectively. CONCLUSIONS: We proposed and validated the effective and convenient nomograms to predict cancer-specific mortality and the overall mortality for patients with EAC, which only require the basic information available in clinical practice.

Curcumin protects neural cells against ischemic injury in N2a cells and mouse brain with ischemic stroke.

Background and Purpose: Curcumin, a natural antioxidant isolated from Curcuma longa, has been reported to exert neuroprotective effect in animal models of ischemic stroke. However, the underlying mechanism is still not fully understood. The purpose of this study was to investigate the effect of curcumin treatment on neuronal apoptosis in the periinfarct cortex after cerebral ischemia/reperfusion (I/R) injury and in mouse N2a cells after oxygen-glucose deprivation/reoxygenation (OGD/R) injury and its underlying mechanism. Methods: The cerebral I/R injury was established by 1-hr middle cerebral artery occlusion (MCAO) and reperfusion in mice. Infarct volume was determined by TTC staining, and neurological score was evaluated by mNSS. Cell morphology in the ischemic boundary zone were detected by HE staining. The number and apoptotic rate of neurons in ischemic boundary zone were assayed by immunohistochemistry and TUNEL, respectively. Mouse neuroblastoma N2a cells were subjected to OGD/R. Cell viability was assessed with CCK-8. The mitochondrial membrane potential was measured using JC-1 staining. The expression of Bax, Bcl-2, and caspase-3 was detected using Western blotting. Besides, cellular distribution of Bax was determined by immunofluorescence assays. Results: Curcumin treatment reduced infarct volume, improved neurological function, alleviated the morphological damage of neurons, and increased neuronal survival rate after I/R injury in vivo. Moreover, curcumin treatment improved cell viability, reduced cell apoptosis, increased Bcl-2 protein levels while decreased Bax and caspase-3 expressions in mouse N2a cells after OGD/R injury. Besides, curcumin treatment inhibited Bax activation and maintained mitochondrial membrane integrity. Conclusion: Curcumin promotes neuron survival in vivo and in vitro to exert neuroprotective effects against ischemia injury. Moreover, our results for the first time demonstrated curcumin inhibited ischemia-induced mitochondrial apoptosis via restricting Bax activation, which may be one of the possible mechanisms underlying the neuroprotective effects of curcumin.

Curcumin mitigates cerebral vasospasm and early brain injury following subarachnoid hemorrhage via inhibiting cerebral inflammation.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH)-induced cerebral vasospasm and early brain injury is a fatal clinical syndrome. Cerebral vasospasm and early brain injury are associated with inflammatory response and oxidative stress. Whether curcumin, which plays important roles to regulate inflammatory cytokines and inhibit oxidative stress, inhibits SAH-induced inflammation and oxidative stress are largely unknown. METHODS: Adult male rats underwent autologous blood injection into prechiasmatic cistern to induce SAH. Curcumin (150 mg/kg) was administered at 0.5, 24 and 48 hr post-SAH. Mortality calculation and neurological outcomes as well as morphological vasospasm of anterior cerebral artery were studied. Superoxide dismutase, lipid peroxidation, and inflammatory cytokines (MCP-1 and TNF-α) expression in prefrontal region were quantified. Furthermore, p65 and phosphor-p65 were quantitatively analyzed. RESULTS: Curcumin remarkedly reduced mortality and ameliorated neurological deficits after SAH induction (p < .05); morphological results showed that cerebral vasospasm in curcumin-treated group was mitigated (p < .05). SAH-induced MCP-1 and TNF-α overexpression were inhibited in curcumin-treated group (p < .05). Importantly, phosphor-p65 was significantly inhibited after curcumin treatment (p < .05). CONCLUSIONS: Curcumin can inhibit SAH-induced inflammatory response via restricting NF-κB activation to alleviate cerebral vasospasm and early brain injury.

A microRNA expression profile for vascular invasion can predict overall survival in hepatocellular carcinoma.

BACKGROUND: The presence of vascular invasion (VI) in pathology specimens is a well-known unfavorable prognostic factor of hepatocellular carcinoma (HCC) recurrence and overall survival (OS). We investigated the vascular invasion related microRNA (miRNA) expression profiles and potential of prognostic value in HCC. METHODS: MiRNA and mRNA expression data for HCC were accessed from The Cancer Genome Atlas (TCGA). LASSO logistic regression models were used to develop a miRNA-based classifier for predicting VI. The predictive capability was accessed by area under receiver operating characteristics (AUC). Concordance index (C-index) and time-dependent receiver operating characteristic (td-ROC) were used to determine its prognostic value. We validated the predictive and prognostic accuracy of this classifier in an external independent cohort of 127 patients. Functionally relevant targets of miRNAs were determined using miRNA target prediction, experimental validation and correlation of miRNA and mRNA expression data. RESULTS: A 16-miRNA-based classifier was developed which identified VI accurately, with AUC of 0.731 and 0.727 in TCGA set and validation cohort, respectively. C-index and td-ROC showed that the classifier was able to stratify patients into risk groups strongly associated with OS. When stratified by tumor characteristics, the classifier was still a clinically and statistically significant prognostic model. The predictive and prognostic accuracy of the classifier was confirmed in validation cohort. Vascular invasion related miRNA/target pairs were identified by integrating expression patterns of predicted targets, which were validated in cell lines. CONCLUSIONS: A multi-miRNA-based classifier developed based on the presence of VI, which could effectively predict OS in HCC.

A MELD-based nomogram for predicting 3-month mortality of patients with acute-on-chronic hepatitis B liver failure.

BACKGROUND: Acute-on-chronic hepatitis B liver failure (ACHBLF) is associated with poor short-term prognosis. The aim of the present study was to construct and validate a model for end-stage liver disease (MELD)-based nomogram for the 3-month mortality estimation for patients with ACHBLF. METHODS: A total of 551 patients with ACHBLF were prospectively enrolled from 2 independent medical centers and divided into 2 cohorts of training and validation, respectively. The 3-month mortality was recorded as the outcome. The MELD-based nomogram was constructed to predict the 3-month mortality for ACHBLF using the training group of 335 patients and validated using an independent cohort of 216 patients. The predictive capability of MELD-based nomogram was compared with the MELD score system by calibration analysis, receiver operating characteristics (ROC) and decision curve analysis in both training cohort and validation cohort. RESULTS: Multivariate analysis suggested that age, serum sodium, and MELD score were independent prognostic indicators associated with the 3-month mortality for ACHBLF, and therefore used for developing the nomogram. In terms of calibration, the predicted survival by the MELD-based nomogram was found to be extremely in line with the observed 3-month mortality both in training cohort and validation cohort. Additionally, both ROC and decision curve analyses showed that the MELD-based nomogram was better than MELD, MELD-Na, MELDNa, and iMELD for ACHBLF prognosis prediction. The results were confirmed in the external cohort of validation. CONCLUSIONS: The MELD-based nomogram provided a user-friendly, accurate and reproducible tool for predicting 3-month mortality of patients with ACHBLF.

Cannabinoid receptors are involved in the protective effect of a novel curcumin derivative C66 against CCl4-induced liver fibrosis.

Liver fibrosis is one of the major causes of morbidity and mortality worldwide and lacks efficient therapy. Recent studies suggest the curcumin protects liver from fibrosis. However, curcumin itself is in low bioavailable concentration when administered orally, and the protective mechanism remains poorly understood. The current study aimed to investigate whether a more stable derivative of curcumin, C66, protects against CCl4-inudced liver fibrosis and examine the underlying mechanism involving cannabinoid receptor (CB receptor). At a dose lower than curcumin itself, C66 displayed a superior anti-fibrotic effect. C66 significantly reduced collagen deposition, pro-inflammatory cytokine expression, and liver enzyme activities. Mechanistic study revealed that C66 treatment decreased CCl4-induced cannabinoid receptor 1 (CB1 receptor) expression and increased cannabinoid receptor 2 (CB2 receptor) expression, along with an inhibition of JNK/NF-κB-mediated inflammatory signaling. In conclusion, this curcumin derivative attenuates liver fibrosis likely involving a CB/JNK/NF-κB-mediated pathway.

Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding.

Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced Treg cell population while increased TH17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of Treg and TH17 cells in the role of LGG-s application.

A Case Report and a Short Literature Review of Pulmonary Sequestration Showing Elevated Serum Levels of Carbohydrate Antigen 19-9.

Pulmonary sequestration is a type of bronchopulmonary malformation defined as an isolated portion of lung tissue with systemic arterial supply and no bronchial communication. Carbohydrate antigen 19-9 (CA19-9) has been used for diagnosis and follow-up of gastrointestinal tumors. The current study presents a rare case of intralobar pulmonary sequestration associated with the marked elevation of CA19-9. A 39-year-old female patient was admitted to our hospital due to acute liver injury with marked elevation of serum CA19-9 (3,051.1 µmol/mL), and was then diagnosed with intralobar pulmonary sequestration after examination and surgery. After the pulmonary resection, the serum CA19-9 levels decreased to normal ranges. We briefly reviewed the literature on elevated serum CA19-9 levels and pulmonary sequestration since 1988. We found that serum CA19-9 levels are increased not only in patients with digestive tract cancers but also in those with nonmalignant diseases such as pulmonary sequestration.

Postoperative hemorrhage in an elderly patient with a glioblastoma multiform and a calcified chronic subdural hematoma.

BACKGROUND: Cases with brain tumor and subdural hematoma are rare; surgical management of the elderly patients with a glioblastoma multiform (GBM) and a chronic subdural hematoma (CSDH) can be intractable. CASE DESCRIPTION: We report a 77-year-old patient, who had a left front lobe GBM and a giant, calcified, left frontoparietaloccipitotemporal CSDH. The patient recovered well from anesthesia after removal of the GBM and CSDH. However, the patient developed severe hemiplegia and aphasia because of the in-situ hemorrhage 1 day later. Laboratory tests indicated disseminated intravascular coagulation (DIC) leading to the postoperative hemorrhage. The patient was left with hemiparesis and alalia after the in-situ hematoma evacuation. CONCLUSIONS: We presume elderly patients have a higher incidence of postoperative hemorrhage in residual intracranial cavity owing to higher possibility to get DIC. A less aggressive surgical management could be a more appropriate choice.