Effect of hepatic artery reconstruction techniques on prognosis of liver transplantation / 器官移植

Objective To evaluate the effect of different techniques of hepatic artery reconstruction on postoperative hepatic artery complications and clinical prognosis in liver transplantation. Methods Clinical data of 140 liver transplant recipients were retrospectively analyzed. All recipients were divided into the conventional hepatic artery reconstruction group (n=123) and special hepatic artery reconstruction group (n=17) according to hepatic artery reconstruction methods. Intraoperative and postoperative clinical indexes, the incidence of postoperative hepatic artery complications and survival rate were compared between two groups. Results The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at postoperative 1 d, total bilirubin (TB) at postoperative 7 d and prothrombin time international normalized ratio (PT-INR) at postoperative 30 d in special hepatic artery reconstruction group were higher than those in conventional hepatic artery reconstruction group, and the differences were statistically significant (all P < 0.05). There were no significant differences in the operation time, anhepatic phase, intraoperative blood loss, intraoperative transfusion volume of red blood cells, cold or warm ischemia time, the length of intensive care unit (ICU) stay, the length of hospital stay and postoperative blood flow of liver allograft between two groups (all P > 0.05). In the conventional hepatic artery reconstruction group, 5 recipients developed hepatic artery complications, whereas no hepatic artery complications occurred in the special hepatic artery reconstruction group, with no significant difference between two groups (P > 0.05). In the special hepatic artery reconstruction group, the 1-, 3- and 5-year cumulative survival rates were equally 82.4%, compared with 85.0%, 78.9% and 75.6% in the conventional hepatic artery reconstruction group, respectively. There was no significant difference between two groups (all P > 0.05). Conclusions When hepatic artery variations and (or) lesions are detected in donors and recipients, use of special hepatic artery reconstruction may effectively restore the hepatic arterial blood flow of liver allograft after liver transplantation, and will not affect the incidence of hepatic artery complications and survival rate of the recipients following liver transplantation.

Changes in liver function test levels in HIV patients undergoing highly active antiretroviral therapy (HAART). Longitudinal study in Lima, Peru / Cambios en los valores de las pruebas de función hepática en pacientes con VIH en terapia antirretroviral de gran actividad (TARGA). Estudio longitudinal en Lima, Perú

Abstract Introduction: Estimating and monitoring changes in liver function tests is necessary to prevent the occurrence of chronic liver disease in HIV patients undergoing highly active antiretroviral therapy (HAART). Objective: To determine the variation liver profile test levels in HIV patients undergoing HAART. Materials and methods: Retrospective longitudinal study conducted in 100 HIV patients treated at the Hospital Nacional Hipólito Unanue, Lima, Peru, between 2015 and 2017. Patients in all stages of clinical infection under HAART and with liver function panel results for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total protein (TP) were included. Three follow-up liver function tests (every 3 months) were performed while undergoing HAART and participants were categorized as having normal or elevated levels for all liver markers. Differences between the samples analyzed were determined using the paired-samples T test, with a 95% confidence interval and a significance level of p<0.05. Results: Participants' mean age was 33±9.56 years and 67% were male. Mean serum AST, ALT and ALP values decreased between the first and the third measurement (p=0.021, p=0.076 and p=0.002, respectively). No significant differences in GGT and TP levels were observed between the three measurements, nor between patients with normal and elevated AST, ALT, ALP and TP values, but significant differences were observed for GGT (p=0.010). Conclusions: Variations in liver marker levels were observed in all participants, with a decreasing trend in AST, ALT and ALP between the early and late stages of HAART, implying that this therapy could play a role in liver tissue damage.

Resumen Introducción. Para prevenir el desarrollo de enfermedad hepática crónica en pacientes con VIH, durante la terapia antirretroviral de gran actividad (TARGA) se deben estimar y monitorear cambios en el perfil hepático. Objetivo. Determinar la variación de las concentraciones del perfil hepático en pacientes con VIH durante la TARGA. Materiales y métodos. Estudio retrospectivo longitudinal realizado en 100 pacientes con VIH atendidos en el Hospital Nacional Hipólito Unanue, Lima, Perú, entre 2015 y 2017. Se incluyeron pacientes en todos los estadios de infección clínica que estuvieran recibiendo TARGA y en los que se contara con resultados del perfil hepático para alanina aminotransferasa (ALT), aspartato aminotransferasa (AST), fosfatasa alcalina (FA), gammaglutamiltranspeptidasa (GGT) y proteínas totales (PT). Se realizaron tres análisis de control de la función hepática durante la TARGA (1 cada 3 meses) y los participantes se agruparon en niveles normales y elevados para todos los marcadores hepáticos. Las diferencias entre las muestras analizadas fueron determinadas mediante la prueba t-Student para muestras relacionadas, con un intervalo de confianza de 95% y un nivel de significancia de p<0.05. Resultados. La edad promedio fue de 33±9.56 años y el 67% fueron varones. Los valores séricos promedio de AST, ALT y FA disminuyeron entre la primera y la tercera medición (p=0.021, p=0.076 y p=0.002, respectivamente). No se observaron diferencias significativas en los niveles de GGT y PT entre las tres mediciones, ni entre los pacientes con valores normales y elevados para AST, ALT, FA y PT, pero sí para GGT (p=0.010). Conclusiones. Se observaron variaciones en los niveles de los marcadores hepáticos de todos los participantes, con una tendencia a la reducción en AST, ALT y FA entre las etapas iniciales y finales de la terapia, lo que implica que la TARGA podría ejercer un rol en el daño tisular hepático.

Factores asociados a esteatosis hepática no alcohólica en pacientes del área rural del cantón Chambo / Factors Associated with Nonalcoholic Hepatic Steatosis in Patients from the Rural Area of Chambo town

La hepatopatía crónica más prevalente en el mundo es la esteatosis hepática no alcohólica. Así, se realizó una investigación con el objetivo de determinar los factores asociados a esa patología en pacientes atendidos en el Centro de salud tipo B Chambo, Ecuador, durante 2020. Se realizó un estudio con enfoque cuantitativo, de tipo no experimental, correlacional y retrospectivo. Las historias clínicas seleccionadas aportaron los datos de las variables de interés. La media de la edad de los involucrados fue de 54,43 ± 8,10 años. El 60,38% tenía hipertensión arterial, el 52,83% diabetes mellitus, el 62,26% sobrepeso u obesidad y el 49,06% dislipidemia, determi-nando que estas comorbilidades tuvieron una relación significativa con la enfermedad objeto de estudio, la que resultó más incidente en edades mayores de 50 años. Las personas sedentarias o con bajos niveles de actividad física mostraron de ALT y AST.

The most prevalent chronic liver disease in the world is nonalcoholic fatty liver disease. Thus, research aimed to determine the factors associated with this pathology in patients treated at the Type B Chambo Health Center, Ecuador, during 2020. A study was carried out with a quantitati-ve, non-experimental, correlational, and retrospective approach. The selected medical records provided the information for the variables of interest. The mean age of the population was 54.43 ± 8.10 years of age. 60.38% had arterial hypertension, 52.83% diabetes mellitus, 62.26% overweight or obesity and 49.06% dyslipidemia. It was determined that these comorbidities had a significant relationship with the disease under study, which was more incident in ages older than 50. Sedentary people or those ones with low levels of physical activity showed ALT and AST.

Quantitative Assessment of Dentine Sialophosphoprotein, Aspartate Aminotransferase and Lactate Dehydrogenase in Gingival Crevicular Fluid of Teeth with Root Resorption

ABSTRACT@#Root resorption is a shortening of root dentine which occurs physiologically in deciduous teeth. The present study aimed to quantify dentine sialophosphoprotein (DSPP), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in gingival crevicular fluid (GCF) during the physiological process of root resorption of deciduous teeth. A cross-sectional study was conducted with 25 children aged between 4 and 10 years old. GCF was collected from the gingival sulcus using periopaper strips from the upper first deciduous molar (n = 45). The samples were divided equally into three groups, no resorption (R0), moderate resorption (RM) and severe resorption (RS), based on the existing radiographs taken. The GCF samples were then analysed using an enzyme-linked immunosorbent assay (ELISA) kit to determine the DSPP concentration levels and BioAssays System kit for AST and LDH. One-way ANOVA was used to determine the statistical differences between the means of the DSPP, AST and LDH concentration level in the three groups. A difference was considered significant when p < 0.05. High concentration levels of DSPP were significantly noted in RS (p < 0.05), compared to RM and R0. AST also portrayed significant high activity level (p < 0.05) similar to DSPP but LDH showed no significant changes between groups (p > 0.05). The high quantification of DSPP and AST levels in the severe and moderately resorbed roots indicated the potential use of this protein as a biomarker for detecting moderate-severe stages of root resorption.

A case report of macro-AST with isolated elevated aspartate aminotransferase in a child / 中华检验医学杂志

We need to consider the macro-AST when the elevated AST activity cannot be explained. A 3-year-old child was found to have an increase in serum AST activity, but no obvious abnormality be found ofter examination. The PEG precipitation assay showed that the activity was 98.7%, which was diagnosed as macro-AST.

The value of Fib4 and APRI in predicting liver failure after hepatectomy in patients with hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To evaluate the value of preoperative aspartate aminotransferaseto platelet ratio index (APRI) and fibrosis index 4 (Fib4) in predicting posthepatectomy liver failure (PHLF) of primary hepatocellular carcinoma.Methods:The data of 587 patients with hepatocellular carcinoma admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2014 to January 2020 were retrospectively collected and analyzed, including 412 males and 175 females, aged (56.8±11.2) years. Univariate and multivariate logistic regression were used to analyze the influencing factors of PHLF. The ability of Child-Pugh score, model for end-stage liver diseas (MELD) score, APRI and Fib4 to predict PHLF was evaluated through the receiver operating characteristic (ROC) curve of subjects.Results:Among 587 patients, 186 (31.7%) had liver failure after hepatectomy. In multivariate logistic regression analysis, APRI ( OR=2.660, 95% CI: 1.314-5.384, P=0.007) and Fib4 ( OR=1.322, 95% CI: 1.157-1.511, P<0.001) were risk factors for PHLF in patients with hepatocellular carcinoma. The higher the number, the greater the risk of PHLF. The predicted area under the ROC curve of PHLF in patients with hepatocellular carcinoma was Fib4(0.719)>APRI(0.686)>MELD score(0.618)>Child-Pugh score(0.565). Conclusion:APRI and Fib4 were risk factors of PHLF in patients with hepatocellular carcinoma. They predict the occurrence of PHLF better than Child-Pugh score and MELD score.

Relationship between the incidence of acute kidney injury and postoperative changes of coagulation function in adult recipients after liver transplantation / 器官移植

Objective To evaluate the effect of coagulation function changes on the incidence of acute kidney injury (AKI) after liver transplantation. Methods Clinical data of 245 liver transplant recipients who met the inclusion and exclusion criteria were retrospectively analyzed. According to the incidence of AKI after liver transplantation, all recipients were divided into the AKI group (n=99) and non-AKI group (n=146). The incidence of AKI after liver transplantation was summarized. Perioperative parameters of the recipients were collected. The risk factors of AKI after liver transplantation were assessed by univariate and multivariate analysis. Results Among 245 recipients undergoing liver transplantation, 99 cases developed AKI after operation with an incidence rate of 40.4%. Preoperative serum creatinine levels of the recipients and the in-hospital fatality were relatively high in the AKI group (all P < 0.05). Compared with the recipients in the non-AKI group, those in the AKI group presented with significantly higher liver function parameters within postoperative 24 h, significantly decreased levels of stage Ⅱ coagulation parameters including coagulation factorsⅤ, Ⅶ, Ⅸ, Ⅹ, Ⅻ and protein S, protein C and antithrombin Ⅲ, evidently elevated prothrombin time international normalized ratio (PT-INR), remarkably increased stage Ⅲ coagulation parameters including D-dimer and fibrin degradation product (FDP) levels and considerably decreased fibrinogen (FIB) level (all P < 0.05). Thrombelastogram showed that the R value was increased, the α angle was decreased and the coagulation time was prolonged in the AKI group (all P < 0.05). Logistic regression analysis demonstrated that the increased R value of postoperative thrombelastogram [odd ratio (OR) 1.116, 95% confidence interval (CI) 1.018-1.223, P=0.019], and decreased levels of antithrombin Ⅲ (OR 0.974, 95%CI 0.955-0.993, P=0.007) were the independent risk factors of incidence of AKI after liver transplantation. Conclusions The incidence of AKI after liver transplantation is high, which is associated with the coagulation function changes of the recipients. Decreased coagulation factor activity (increased R value) and declined antithrombin Ⅲ level are the independent risk factors of AKI in liver transplantat recipients.

Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.

Study on the diagnostic value of transient elastography, APRI and FIB-4 for liver fibrosis in children with non-alcoholic fatty liver disease / 中华肝脏病杂志

Objective: To evaluate the diagnostic value of transient elastography, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) for liver fibrosis in children with non-alcoholic fatty liver disease (NAFLD). Methods: A retrospective study was conducted on 100 cases of nonalcoholic fatty liver disease in Hunan Children's Hospital between August 2015 to October 2020 to collect liver tissue pathological and clinical data. The receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic value of liver stiffness measurement (LSM), APRI and FIB-4 in the diagnosis of different stages of liver fibrosis caused by NAFLD in children. Results: The area under the ROC curve (AUC) value of LSM, APRI and FIB-4 for diagnosing liver fibrosis (S≥1) were 0.701 [95% confidence interval (CI): 0.579 ~ 0.822, P = 0.011], 0.606 (95%CI: 0.436 ~ 0.775, P = 0.182), and 0.568 (95%CI: 0.397 ~ 0.740, P = 0.387), respectively. The best cut-off values were 6.65 kPa, 21.20, and 0.18, respectively. The AUCs value of LSM, APRI, and FIB-4 for diagnosing significant liver fibrosis (S≥ 2) were 0.660 (95% CI: 0.552 ~ 0.768, P = 0.006), 0.578 (95% CI: 0.464 ~ 0.691, P = 0.182) and 0.541 (95% CI: 0.427 ~ 0.655, P = 0.482), respectively. The best cut-off values were 7.35kpa, 24.78 and 0.22, respectively. The AUCs value of LSM, APRI and FIB-4 for the diagnosis of advanced liver fibrosis (S≥ 3) were 0.639 (95% CI: 0.446 ~ 0.832, P = 0.134), 0.613 (95% CI: 0.447 ~ 0.779, P = 0.223) and 0.587 (95% CI: 0.411 ~ 0.764, P = 0.346), respectively. The best cut-off values were 8.55kpa, 26.66 and 0.27, respectively. Conclusion: The transient elastography technique has a better diagnostic value than APRI and FIB-4 for liver fibrosis in children with NAFLD.

Prediction of impacts on liver enzymes from the exposure of low-dose medical radiations through artificial intelligence algorithms

SUMMARY OBJECTIVES: This study aimed to develop artificial intelligence and machine learning-based models to predict alterations in liver enzymes from the exposure of low annual average effective doses in radiology and nuclear medicine personnel of Institute of Nuclear Medicine and Oncology Hospital. METHODS: Ninety workers from the Radiology and Nuclear Medicine departments were included. A high-capacity thermoluminescent was used for annual average effective radiation dose measurements. The liver function tests were conducted for all subjects and controls. Three supervised learning models (multilayer precentron; logistic regression; and random forest) were applied and cross-validated to predict any alteration in liver enzymes. The t-test was applied to see if subjects and controls were significantly different in liver function tests. RESULTS: The annual average effective doses were in the range of 0.07-1.15 mSv. Alanine transaminase was 50% high and aspartate transaminase was 20% high in radiation workers. There existed a significant difference (p=0.0008) in Alanine-aminotransferase between radiation-exposed and radiation-unexposed workers. Random forest model achieved 90-96.6% accuracies in Alanine-aminotransferase and Aspartate-aminotransferase predictions. The second best classifier model was the Multilayer perceptron (65.5-80% accuracies). CONCLUSION: As there is a need of regular monitoring of hepatic function in radiation-exposed people, our artificial intelligence-based predicting model random forest is proved accurate in prediagnosing alterations in liver enzymes.

Application value of ultrasound elastography in evaluating liver elasticity of stable recipients at different stages after liver transplantation / 器官移植

Objective To explore the value of ultrasound elastography in the non-invasive monitoring of liver elasticity of stable recipients at different stages after liver transplantation. Methods Clinical data of 73 stable recipients after liver transplantation were collected. According to the time after liver transplantation, all patients were divided into the early group (n=25) and medium-to-long group (n=48). In addition, 38 healthy subjects were assigned into the control group. The ultrasound indexes and liver function indexes were statistically compared among each group. The ultrasound elastography indexes of liver and spleen were analyzed, and their correlation with liver function indexes was analyzed. Results Compared with the control group, the ultrasound indexes, alanine aminotransferase (ALT), γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) levels were significantly increased in the early group (all P < 0.05), and the ultrasound indexes in the medium-to-long group were significantly increased, whereas the GGT level was significantly decreased (all P < 0.05). Compared with the early group, the right oblique diameter of liver, ALT, GGT and ALP levels were significantly decreased in the medium-to-long group (all P < 0.05). Compared with the control group, the sound touch elastography (STE) and sound touch quantify (STQ) values of liver and STE value of spleen in the early group and medium-to-long group were significantly increased (all P < 0.05). Compared with the early group, the ultrasound elastography indexes of liver and spleen in the medium-to-long group were remarkably decreased (all P < 0.05). The ultrasound elastography indexes of liver were weakly correlated with the ALT, aspartate aminotransferase (AST) and GGT levels, significantly correlated with ALP level. The STE value of spleen was weakly correlated with the ALP level. The STE value of liver was significantly correlated with the STQ value of liver. The STE and STQ values of liver were weakly correlated with the STE value of spleen. Conclusions The characteristics of liver elasticity in stable recipients after liver transplantation are various among different stages. Persistent monitoring of liver elasticity may provide a novelnon-invasive monitoring method during follow-up after liver transplantation.

Synergetic delivery of triptolide and Ce6 with light-activatable liposomes for efficient hepatocellular carcinoma therapy

Hepatocellular carcinoma (HCC) has been known as the second common leading cancer worldwide, as it responds poorly to both chemotherapy and medication. Triptolide (TP), a diterpenoid triepoxide, is a promising treatment agent for its effective anticancer effect on multiple cancers including HCC. However, its clinical application has been limited owing to its severe systemic toxicities, low solubility, and fast elimination in the body. Therefore, to overcome the above obstacles, photo-activatable liposomes (LP) integrated with both photosensitizer Ce6 and chemotherapeutic drug TP (TP/Ce6-LP) was designed in the pursuit of controlled drug release and synergetic photodynamic therapy in HCC therapy. The TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention (EPR) effect. Under laser irradiation, the photosensitizer Ce6 generated reactive oxygen species (ROS) and further oxidized the unsaturated phospholipids. In this way, the liposomes were destroyed to release TP. TP/Ce6-LP with NIR laser irradiation (TP/Ce6-LP+L) showed the best anti-tumor effect both

Artemisinin and artemisinin derivatives as anti-fibrotic therapeutics

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects. Here we summarize literature describing anti-fibrotic effects of artemisinin compounds in

VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses

Self-assembled FeS-based cascade bioreactor with enhanced tumor penetration and synergistic treatments to trigger robust cancer immunotherapy

Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death (ICD) to provoke a robust immune response for metastasis control. Here, a self-assembled cascade bioreactor was developed to improve cancer treatment with enhanced tumor penetration and synergistic therapy of starvation, chemodynamic (CDT) and photothermal therapy. Ultrasmall FeS-GOx nanodots were synthesized with glucose oxidase (GOx) as template and induced by paclitaxel (PTX) to form self-assembling FeS-GOx@PTX (FGP)

3D disorganization and rearrangement of genome provide insights into pathogenesis of NAFLD by integrated Hi-C, Nanopore, and RNA sequencing

The three-dimensional (3D) conformation of chromatin is integral to the precise regulation of gene expression. The 3D genome and genomic variations in non-alcoholic fatty liver disease (NAFLD) are largely unknown, despite their key roles in cellular function and physiological processes. High-throughput chromosome conformation capture (Hi-C), Nanopore sequencing, and RNA-sequencing (RNA-seq) assays were performed on the liver of normal and NAFLD mice. A high-resolution 3D chromatin interaction map was generated to examine different 3D genome hierarchies including A/B compartments, topologically associated domains (TADs), and chromatin loops by Hi-C, and whole genome sequencing identifying structural variations (SVs) and copy number variations (CNVs) by Nanopore sequencing. We identified variations in thousands of regions across the genome with respect to 3D chromatin organization and genomic rearrangements, between normal and NAFLD mice, and revealed gene dysregulation frequently accompanied by these variations. Candidate target genes were identified in NAFLD, impacted by genetic rearrangements and spatial organization disruption. Our data provide a high-resolution 3D genome interaction resource for NAFLD investigations, revealed the relationship among genetic rearrangements, spatial organization disruption, and gene regulation, and identified candidate genes associated with these variations implicated in the pathogenesis of NAFLD. The newly findings offer insights into novel mechanisms of NAFLD pathogenesis and can provide a new conceptual framework for NAFLD therapy.

Pure photosensitizer-driven nanoassembly with core-matched PEGylation for imaging-guided photodynamic therapy

Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPa-PEG

Role of acoustic radiation force impulse elastography, aminotransferase to platelet ratio index and fibrotest for the assessment of significant fibrosis and cirrhosis in chronic liver disease

Background: Accurate grading of hepatic fibrosis is important for the application of appropriate intervening strategy. Liver biopsy is the golden standard of fibrotic grading, however wide clinical application is hindered by its inherent drawbacks. Biomechanical-based ultrasonic elastography has received mass attention. However, several clinical studies found that the sole application of ultrasonic elastography may bring evident errors in diagnosing hepatic fibrosis. It is suggested that a combination of ultrasonic elastography and serum liver functions tests holds the potential to overcome those disadvantages. Aims and objectives was to study the diagnostic accuracy of ultrasonography elastography, APRI, fibrotest for significant fibrosis and cirrhosis in patients with chronic liver disease and established the correlation between ARFI elastography, APRI, Fibrotest in grading of liver fibrosisMethods: Sixty three patients with chronic liver disease were studied.  Liver stiffness was evaluated with ARFI elastography. Histologic staging of liver fibrosis served as the reference standard except a very few cirrhotic patients who were graded as cirrhotic on the basis of clinical examination. The required APRI, Fibrotest parameters and relevant clinical history was recorded.  Fibrosis stage was assessed according to the METAVIR classification.Results: ARFI, APRI, and Fibrotest demonstrated a significant correlation with the histological stage. According to ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI. The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage that showed  significant concordance  i.e. 79.3% cases,  out of which 69.8% of total cases were correctly diagnosed on comparison with the gold standard. Fibrotest and ARFI elastography show significant concordance in grading of fibrosis i.e. 82.5%. Cases out of which 68.3% of total cases were correctly diagnosed on comparison with the gold standard.Conclusions: APRI, ARFI, and fibrotest are novel tools among non-invasive modalities to rule out significant fibrosis and cirrhosis in patients with chronic liver disease. ARFI with APRI and ARFI with fibrotest showed enhanced diagnostic accuracy than ARFI or APRI or fibrotest alone for significant liver fibrosis.

Predictors and Outcome of Severe Dengue Illness in Children.

Dengue fever has become a major public health concern during the last few years with an alarming increase in the incidence in 2017. The state of Kerala was one among the top of the list in India reported to have severe dengue infection. The two main districts in Kerala with high prevalence were Thiruvananthapuram and Palakkad, of which latter is the main referring area to our institution. This study was conducted to evaluate the clinical and demographic profile of children affected with dengue fever and determine the predictors of severity.METHODSThis is a hospital based prospective study done at the Department of Paediatrics, Government Medical College, Trissur, during the Monsoon season in 2017. Children diagnosed to have Dengue fever and confirmed by NS1 Ag test or IgM Elisa were included. Children were classified into 3 clinical groups and compared. Comparison was also made in 2 groups as dengue with warning signs and severe dengue as per WHO 2015 clinical guidelines, to find out the predictors of severity. Qualitative data was analysed and expressed in proportions and quantitative data in mean and standard deviation. Chi-square (χ2) test was used to evaluate the association between qualitative variables and ANOVA for quantitative variables. p value less than 0.05 was considered significant. SPSS 16.0 software was used for statistical analysis.RESULTSA total of 235 children were included. 77 children (32.9%) had mild dengue fever, 106 (45.29%) had DWS and 52 (22.22%) were having DSS). Mean age was 6.61± 3.497 years. 19 cases (8.2 %) were Infants below 1 year of age. Majority of children had normal nutritional status. Myalgia, tiredness, vomiting, diarrhoea, abdominal pain, flushing, bleeding, oedema, hypotension, were found to be the common clinical manifestations. Thrombocytopenia, elevated serum hepatic enzymes both SGOT and SGPT, abnormal renal function tests, low sodium, hypoalbuminemia, hypoglycaemia, abnormal radiological findings were found to be the predictors of severity. We had many cases of expanded dengue syndrome including 3 cases of Hemophagocytic lymphohistiocytosis (HLH). The mortality was 0.6%.CONCLUSIONSDengue fever can affect children irrespective of their age or nutritional status. Older children and male sex were found to be more affected. There are definite clinical and lab parameters which can predict the severity in Dengue fever. Though severe illness is associated with high morbidity early diagnosis and timely appropriate clinical management, correction of dehydration along with proper referral system can save the children. The mortality can be reduced to zero even in patients having expanded dengue syndrome and Dengue shock syndrome. None of the comorbidities had affected the outcome.