Normal Liver Research Articles

The applications of Ursodeoxycholic acid in infant with cholestasis: A retrospective cohort analysis

Biliary atresia is the predominant etiology of cholestasis in early infancy. Impairment of bile fluid excretion results in elevated bilirubin levels, causing a yellowing of the skin. Ursodeoxycholic acid is well-established to enhance liver function when taken promptly. The application of ursodeoxycholic acid for treating cholestasis in pediatric patients remains contentious. The objective of this study is to assess the impact of ursodeoxycholic acid treatment on liver biomarkers in infant with cholestasis. This was retrospective cohort study in infant with cholestasis who underwent ursodeoxycholic acid treatment for two weeks. Secondary data including aspartate aminotransferase, alanine aminotransferase, total bilirubin, and direct bilirubin were extracted from the medical records of the outpatient clinic in the Department of Child Health at Dr. Soetomo General Hospital, Indonesia (January 2020 - December 2023). The data was devided into two groups based on biopsy and examined utilizing SPSS version 23. This study included 64 participants. Statistics show an equal gender ratio. Ursodeoxycholic acid treatment in paediatric cholestasis patients can lower liver biomarker level. Levels of total bilirubin and direct bilirubin diminished in individuals both groups. Notable levels were recorded in individuals with normal biopsy outcomes (p=0.007 and p=0.012). Administration of ursodeoxycholic acid markedly elevated ALT levels in both the normal and abnormal liver biopsy outcome groups (p=0.031 and p=0.006). Ursodeoxycholic acid has been shown to be effective in improving liver function in infant with cholestasis. In order to avoid negative effects, the medication must be carefully administered to people who already have liver fibrosis.

Discovery of novel and highly potent dual-targeting PKMYT1/HDAC2 inhibitors for hepatocellular carcinoma through structure-based virtual screening and biological evaluation

Simultaneous inhibition of two or more pathways is playing a crucial role in the treatment of hepatocellular carcinoma with complex and diverse pathogenesis. However, there have been no reports of dual-targeting inhibitors for protein kinase membrane-associated tyrosine/threonine 1 (PKMYT1) and histone deacetylase 2 (HDAC2), which are critical targets for hepatocellular carcinoma treatment. Here, an integrated strategy of virtual screening was utilized to identify dual-targeting inhibitors for PKMYT1 and HDAC2. Notably, PKHD-5 has been identified as a potent inhibitor that selectively targets both PKMYT1 and HDAC2 with nanomolar affinity. Molecular dynamics have confirmed the strong binding stability of PKHD-5 with PKMYT1 and HDAC2. Importantly, it displayed a notably lower IC50 against the HepG2/MDR cell line, underscoring its potential to surmount drug resistance, while exhibiting minimal toxicity towards the normal liver cell line L02. Additionally, PKHD-5 has demonstrated significant antitumor proliferation effects without significant toxicity. In summary, the results suggest that PKHD-5 is a promising candidate for further preclinical studies of hepatocellular carcinoma therapy.

Therapeutic deep eutectic solvent with saponin, optimized through response surface methodology, exert potent in vivo antimicrobial effects against Pseudomonas aeruginosa.

Therapeutic deep eutectic solvents (THEDES) are a type of deep eutectics that can be used as active pharmaceutical ingredients (APIs) by enhancing the drug bioavailability, by increasing the solubility of APIs in aqueous solutions or by increasing their permeability through biological barriers. In this study, we demonstrate the utility of designer THEDES, based on Quillaja Saponin (SAP), a triterpene natural product to unravel the antimicrobial potential of such THEDES. THEDES were prepared by gently mixing and heating five different α- hydroxy acids- malic, citric, tartaric, glycolic, lactic acids and SAP with water as a third component in the THEDES. The antimicrobial assays were performed with the as-prepared SAP-THEDES and among the panel of bacterial strains, saponin-malic acid THEDES [SMA-THEDES] displayed potent activity in disassembling PA biofilms, demonstrating that the SMA-THEDES can serve as therapeutic antibacterial biomaterials. To further optimize, a Box-Behnken- response surface methodology (RSM) experimental design was done and at the optimum conditions of SAP (1.014m.mol), Malic acid (1.003m.mol), Water (0.117m.mol), SMA-THEDES exhibited maximum MIC of P. aeruginosa with the minimum absorbance at 590nm of 0.105. The effectiveness of SMA-THEDES as antibiofilm agents on P. aeruginosa with the mechanism studies have been explored. The colony count from the in vivo infection zebrafish model in the treatment group showed a decline of > 2 fold for SMA-THEDES. Toxicity studies did not reveal any abnormality in liver and brain enzyme levels. Liver morphology images show no severe cytological alterations when treated with SMA-THEDES and were almost similar to the normal liver.

Aging, ROS, and cellular senescence: a trilogy in the progression of liver fibrosis.

Ageing is an inevitable and multifaceted biological process that impacts a wide range of cellular and molecular mechanisms, leading to the development of various diseases, such as liver fibrosis. Liver fibrosis progresses to cirrhosis, which is an advanced form due to high amounts of extracellular matrix and restoration of normal liver structure with failure to repair damaged tissue and cells, marking the end of liver function and total liver failure, ultimately death. The most important factors are reactive oxygen species (ROS) and cellular senescence. Oxidative stress is defined as an impairment by ROS, which are by-products of the mitochondrial electron transport chain and other key molecular pathways that induce cell damage and can activate cellular senescence pathways. Cellular senescence is characterized by pro-inflammatory cytokines, growth factors, and proteases secreted by senescent cells, collectively known as the senescence-associated secretory phenotype (SASP). The presence of senescent cells, which disrupt tissue architecture and function and increase senescent cell production in liver tissues, contributes to fibrogenesis. Hepatic stellate cells (HSCs) are activated in response to chronic liver injury, oxidative stress, and senescence signals that drive excessive production and deposition of extracellular matrix. This review article aims to provide a comprehensive overview of the pathogenic role of ROS and cellular senescence in the aging liver and their contribution to fibrosis.

Cuproptosis, ferroptosis and PANoptosis in tumor immune microenvironment remodeling and immunotherapy: culprits or new hope.

Normal life requires cell division to produce new cells, but cell death is necessary to maintain balance. Dysregulation of cell death can lead to the survival and proliferation of abnormal cells, promoting tumor development. Unlike apoptosis, necrosis, and autophagy, the newly recognized forms of regulated cell death (RCD) cuproptosis, ferroptosis, and PANoptosis provide novel therapeutic strategies for tumor treatment. Increasing research indicates that the death of tumor and immune cells mediated by these newly discovered forms of cell death can regulate the tumor microenvironment (TME) and influence the effectiveness of tumor immunotherapy. This review primarily elucidates the molecular mechanisms of cuproptosis, ferroptosis, and PANoptosis and their complex effects on tumor cells and the TME. This review also summarizes the exploration of nanoparticle applications in tumor therapy based on in vivo and in vitro evidence derived from the induction or inhibition of these new RCD pathways.

Accuracy of International Guidelines in Identifying Normal Liver Histology in Chinese Patients With HBeAg-Positive Chronic HBV Infection.

We evaluated the diagnostic accuracy of various international guideline criteria for identifying HBeAg-positive chronic HBV infection patients with no significant liver disease. A total of 1108 HBeAg-positive CHB patients were retrospectively enrolled. The guidelines assessed included those from the European Association for the Study of the Liver (EASL) 2017, the American Association for the Study of the Liver Disease (AASLD) 2018, the Asian Pacific Association for the Study of the Liver (APASL) 2015 and the Chinese Society of Hepatology (CSH) 2022. The CSH criteria demonstrated a higher proportion of patients with G0-1 and S0-1 (82.9%) compared to the EASL (75.9%), AASLD (75.3%) and APASL groups (58.8%). Additionally, the CSH criteria exhibited a significantly higher predictive value (AUC 0.782, 95% CI 0.754-0.809) than the EASL (AUC 0.765, 95% CI 0.737-0.793), AASLD (AUC 0.749, 95% CI 0.720-0.778) and APASL (AUC 0.720, 95% CI 0.690-0.750) criteria for identifying G0-1 and S0-1. Adding quantitative HBsAg levels (> 104 IU/mL) to the EASL, AASLD and APASL criteria improved diagnostic performance. Consequently, the CSH guideline thresholds showed higher accuracy in identifying Chinese HBeAg-positive patients with no significant liver disease compared to EASL, AASLD and APASL criteria, emphasising the importance of considering quantitative HBsAg in the evaluation of HBeAg-positive chronic HBV infection.

HPB O06 - A computer tomography-based radiomics signature predicts overall survival following curative resection of colorectal liver metastasis: A multicentre, retrospective study

Abstract Background Colorectal cancer liver metastasis (CRLM) has a heterogeneous outcome and improved prognostic biomarkers are needed to aid patient-tailored management. Here, we assess the value of Computer Tomography (CT)-guided radiomics in the prognostication of post-resection CRLM using data from two large tertiary referral centres in the UK. Method Patient data was extracted from prospectively maintained databases of patients undergoing CRLM resection at two centres. CRLM and regions of interest from background normal liver were segmented. Radiomics features were extracted from portal venous phase CT images using open-source software. Feature selection techniques were applied. Machine learning models incorporating radiomic or clinical features, and their combination, were developed and assessed for mortality prediction at fixed time points. Cox proportional hazard regression was utilised for risk score generation to classify patients as high or low-risk for overall survival estimation. The models were evaluated on unseen testing data. Results Radiomics features (269) were generated from 959 metastases in 399 patients across the two sites. Models with combined clinical and radiomic features performed similarly to those with radiomic features alone, and often outperformed models with clinical features alone demonstrating good discrimination and risk prediction at 2 and 3 years. The computed radiomic scores allowed us to generate Kaplan–Meier curves which showed CRLM patients in the high-risk group had a lower overall survival vs the low-risk group(p<0.05). This risk-score independently predicted mortality in our multivariate Cox proportional-hazards model. Conclusion We demonstrate a robust combination of CT-based radiomics features can predict CRLM outcomes across two different hospital sites. Our radiomic risk-scores predicts overall survival and can prognosticate patients into high and low risk groups. These findings support the prognostic utility of CT-based radiomics in patients undergoing resection of CRLM and provide rationale for further investigation in a prospective, multi-centre setting.

HPB SO77 - Effects of Patient and Operative Variables on Isolation of Primary Human Hepatocytes

Abstract Background Isolation of human primary hepatocytes from tissue samples derived from therapeutic hepatectomy offers an important resource for a range of pharmacological and toxicology based experimental platforms, whilst simultaneously providing an opportunity to reduce the use of animal models. This study analysed the impact of a range of patient and operative derived variables on the yield and viability of isolated human primary hepatocytes. Method Excess hepatic tissue from resected liver parenchyma was sampled from consented patients undergoing major and minor hepatectomy for a range of oncological and non-oncological indications. Tissue dissociation and hepatocyte isolation was performed using a two-step collagenase perfusion procedure. Hepatocyte viability was calculated using the Trypan blue exclusion test while hepatocyte yield was calculated by the number of cells isolated divided by the tissue mass isolated from. Patient and operative variables were collected retrospectively from 25 patients in a prospectively maintained database. Results Samples from normal liver parenchyma achieved high hepatocyte viability and yields in all patients. Improved hepatoctye viability was associated with female sex, with a 2.9% increase in viability in samples from women (P<0.05). Patient age, BMI, operative indication, neo-adjuvant chemotherapy, as well as prolonged intra-operative Pringle time and blood loss did not significantly affect hepatocyte yield or viability, allowing use of primary human hepatocytes from a wide range of patients in a plethora of translational research experiments. Conclusion High levels of hepatocyte viability and yield are achievable across a broad range of patients, even in instances patients with high burdens of disease, prolonged Pringle time or higher levels of intra-operative blood loss. Tissue samples from consenting patients undergoing therapeutic liver resection provide an invaluable resource for various translational experimental platforms, including primary human hepatocytes. To date, more than 400 patients have donated tissue used in a range of basic science techniques, significantly reducing reliance on animal models.

Abstract 4122301: The Role of Hepatic CDS2 in Phosphatidylinositol Homeostasis and Lipid Metabolism

Background: Recent studies in both human genetics and mouse models have highlighted the significance of phosphatidylinositol (PI) in the progression of fatty liver disease (FLD). Despite this, the precise mechanisms underlying PI's role remain elusive. Aims: This study aimed to elucidate the involvement of PI in FLD by disrupting hepatic PI biosynthesis through modulation of CDP-diacylglycerol synthase 2 (CDS2) expression, the primary enzyme in PI biosynthesis (A). Methods: We generated liver-specific knockouts of CDS2 and SCAP (SREBP cleavage-activating protein) using adeno-associated virus (AAV) expressing sgRNA against each gene. Phospholipid species were analyzed and quantified by LC/MS. Results: CDS2 liver-specific knockout mice (B, C) exhibited a pronounced development of fatty liver, characterized by elevated triglyceride and cholesterol levels (C). Notably, liver PI levels were significantly reduced in CDS2 knockout mice (E), accompanied by dysregulated activation of sterol regulatory element-binding protein (SREBP) even during fasting conditions (F), leading to increased de novo lipogenesis. Intraperitoneal administration of exogenous PI effectively normalized SREBP cleavage (G), highlighting PI's critical role in SREBP regulation. Furthermore, simultaneous knockout of SCAP with CDS2 restored the normal liver phenotype, implicating SREBP activation as a central mechanism underlying fatty liver development in CDS2 knockout mice (H, I). Conclusion: Deletion of CDS2 in the liver reduced PI levels, subsequently inducing significant fatty liver due to dysregulated SREBP activation. This study underscores the importance of CDS2 in maintaining PI homeostasis, which in turn regulates SREBP activity and lipid metabolism. Our findings provide valuable insights into the pathogenesis of metabolic disorders and offer potential therapeutic strategies for targeting FLD.

MIMC-β: microdosimetric assessment method for internal exposure of β-emitters based on mesh-type cell cluster model

The method combining Monte Carlo (MC) simulation and mesh-type cell models provides a way to accurately assess the cellular dose induced byβ-emitters. Although this approach allows for a specific evaluation of various nuclides and cell type combinations, the associated time cost for obtaining results is relatively high. In this work, we propose a Microdosimetric assessment method for Internal exposure ofβ-emitters based on Mesh-type Cell cluster models (abbreviated as MIMC-β). This approach is applied to evaluate the dose in various types of cells (human bronchial epithelial cells, BEAS-2B; normal human liver cells, L-O2; and normal human small intestine epithelial cells, FHs74Int) exposed toβ-emitters. Furthermore, microdosimetric quantity based on the cell cluster model are employed to estimate the relative biological effectiveness (RBE) ofβ-emitters. The results indicate that this method can accurately and rapidly predict cellular doses caused by different types ofβ-emitters, significantly mitigating the efficiency challenges associated with directly employing MC to estimate the overall dose of the mesh-type cell cluster model. In comparison with results obtained from direct simulations of uniform administration ofβ- sources using PHITS for validation, the cellular cluster overallS-values obtained through MIMC-βshow discrepancies mostly below 5%, with the minimum deviation reaching 1.35%. Small sampling sizes within the cell nucleus led to larger average lineal energies. In comparison to C-14, the differences in cellular cluster average lineal energy for Cs-134, Cs-137, and I-131 are negligible, resulting in close numerical estimations of RBE based on lineal energy. The MIMC-βcan be extended to diverse cell types andβ-emitters. Additionally, the RBE assessment based on the cell cluster model offers valuable insights for predicting radiobiological damage resulting from internal exposure byβ-emitters. This method is expected to find applicability in various realistic scenarios, including radiation protection and radioligand therapy.

A new tumor-treating device OM-100 with low-frequency magnetic fields inhibits proliferation and metastasis in liver cancer.

This study aims to investigate a novel instrument OM-100 with low-frequency magnetic fields (LFMFs) for its potential applicability in the treatment of liver cancer. Liver cancer cell lines (HepG2 and Huh7) and normal liver cell line THLE-2 were exposed to OM-100 at LFMFs of 0, 10, 25, 50, and 100kHz for 2h in the morning, noon, and evening, respectively. The effects of LFMF on cell viability, apoptosis, migration, and invasion capabilities were examined. Additionally, impacts of LFMF on ROS production was assessed. In vivo studies were conducted to examine the safety profile of OM-100 and its effects on tumor growth. In vitro, OM-100 reduced the viability of liver cancer cells, increased cell apoptosis, and inhibited cell migration and invasion abilities in a frequency-dependent manner (P < 0.05). In vivo, OM-100significantly slowed down tumor growth and promoted apoptosis in liver tumors (P < 0.05). Moreover, OM-100 rarely affected the viability of normal liver cells, as well as the health of normal mice. Finally, we further found that OM-100 significantly increased the production of ROS in liver cancer cells (P < 0.05), a key factor in inducing autophagy, which is very important for the progression of liver cancer. Our findings reveal the safety of OM-100 and its frequency at 100kHz significantly inhibits liver cancer progression.

Expression and clinical significance of PIKFYVE gene in hepatocellular carcinoma analyzed based on TCGA database and experimental validation

Objective: To investigate the expression and clinical significance of human FYVE finger-containing phosphoinositide kinase (PIKFYVE) in hepatocellular carcinoma (HCC) on the basis of cancer genome atlas (The cancer genome atlas, TCGA) database analysis and clinical samples experimental validation. Methods: Based on the data information of 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumorous liver tissues) in the TCGA database, Cox regression analysis and Kaplan-Meier method were used to analyse the relationship between the PIKFYVE mRNA expression and the clinical characteristics, prognosis for survival of HCC patients. The relationship between the PIKFYVE gene and immune cell infiltration was examined by correlation analysis between the PIKFYVE gene and 24 immune cells. In addition, we analysed the correlation between the mRNA expression of PIKFYVE gene and RAC-alpha serine/threonine-protein kinase (AKT1), phosphatase and tensin homolog (PTEN), protein kinase C, alpha (PRKCA), inositol polyphosphate-5-phosphatase (INPP5D), phosphoinositide-3-kinase regulatory subunit 1(PIK3R1), Inositol Polyphosphate 4-phosphatase Type II (INPP4B) and phospholipase-C4 gene (PLCB4) in HCC tissues. Meanwhile, paraffin sections of highly differentiated, moderately differentiated, poorly differentiated, and nontumorous liver tissue in the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University were collected, each of which was 30 cases, and the histopathological observation was carried out by HE staining, and the expression levels of PIKFYVE and Ki67 proteins were verified by immunohistochemistry in each clinical sample. Results: The expression level of PIKFYVE gene in HCC tumours was significantly higher than that in normal liver tissues (P=0.000 2, P<0.01), and the overall survival of patients in the low PIKFYVE expression group was significantly longer than that in the high expression group (HR=1.57, 95%CI: 1.10～2.25, P=0.014). The results of Univariate Cox regression analysis showed that there was an effect of TNM stage, pathological stage, tumour status and residual tumour on Overall survival (OS) (P<0.05), and the expression level of PIKFYVE had an effect on OS survival (P<0.05); the PIKFYVE prognostic risk model score ratio was HR=1.533 (1.077-2.181, P=0.018). Multivariate Cox regression analysis showed a PIKFYVE prognostic risk model score ratio HR=1.481 (0.886-2.476, P=0.134) and an area under the Receiver Operating Characteristic curve of 0.640, which was greater than 0.5, suggesting that the PIKFYVE prognostic risk model has a predictive value in survival prediction. Correlation analysis showed that the expression level of PIKFYVE was highly correlated with immune cell infiltration and TP53 (P<0.01). The immunohistochemistry staining results showed that the expression of PIKFYVE in HCC tissues was significantly higher than that of nontumorous tissues (P<0.05), and there was a negative correlation with the degree of differentiation. Conclusion: PIKFYVE, as an independent risk factor for HCC, is expected to be developed as a clinical diagnostic biomarker for HCC, which will provide a reference for new drugs for the treatment of HCC.

Head-to-head study of [18F]FAPI-04 PET/CT and [18F]FDG PET/CT for non-invasive assessment of liver cancer and its immunohistochemical markers.

To compare the performance of [18F]FDG and [18F]FAPI-04 in PET/CT evaluation for liver cancer lesions, with a further exploration of the associations between PET semiquantitative data and immunohistochemical markers to liver cancer. Patients with suspected malignant liver lesions (MLL) underwent [18F]FDG and [18F]FAPI-04 PET/CT scanning. Liver lesions were visually classified as positive or negative based on their uptake level exceeding that of adjacent normal liver tissue. SUVmax and tumor-to-background ratio (TBR) were recorded for semi-quantitative analysis. Sensitivity, specificity and accuracy of each tracer were determined using pathological findings as the gold standard. Furthermore, immunohistochemical analysis provided the molecular characteristics of all MLLs. Comprehensive analysis explored correlations between these molecular markers and PET semiquantitative parameters (SUVmax andTBR) to identify potential associations. The study enrolled 44 patients, with 39 confirmed cases of MLL, comprising 28 hepatocellular carcinomas (HCC) and 11 intrahepatic cholangiocarcinomas (ICC). For MLL detection, [18F]FAPI-04 and [18F]FDG exhibited sensitivities of 84.6% (33/39) and 76.9% (30/39), specificitiesy of 60% (3/5) and 100%(5/5), and accuracy of 81.8% (36/44) and 79.5%(35/44). Across all liver lesions, [18F]FAPI-04 significantly surpassed [18F]FDG in SUVmax(10.54 ± 6.72 VS. 7.68 ± 6.79) and TBR(4.35 ± 3.78 Vs. 3.17 ± 3.05). Notably, [18F]FAPI-04 displayed markebly elevated SUVmax in benign liver lesions (BLLs) (P = 0.032), HCCs (P = 0.005), and ICCs (P = 0.011). Lesions with hepatocyte negativity (P = 0.023), CD34 negativity(P = 0.044), and high Ki67 expression (> 30%) (P = 0.001) had higher SUVmax on [18F]FAPI-04. Additionally, ARG-1-negative lesions demonstrated higher TBR on [18F]FAPI-04 than ARG-1-positive lesions(P = 0.018). No significant SUVmax/TBR differences were observed with [18F]FDG based on these markers. A linear relationship was identified between Ki67 scores and SUVmax of [18F]FAPI-04 (R = 0.603, P < 0.001). [18F]FAPI-04 exhibits superior performance over [18F]FDG in PET/CT evaluation of liver cancer, characterized by increased sensitivity and SUVmax/TBR. Significant correlations with molecular markers, including Ki67, suggest [18F]FAPI-04's potential for characterizing liver cancer subtypes and assessing tumor proliferation. However, further research is required to validate these findings and their clinical significance. NCT05485792, Registered 01 August 2022.

Cytokines and Madness: A Unifying Hypothesis of Schizophrenia Involving Interleukin-22

Schizophrenia is a severe neuropsychiatric illness of uncertain etiopathogenesis in which antipsychotic drugs can attenuate the symptoms, but patients rarely return to the premorbid level of functioning. In fact, with each relapse, people living with schizophrenia progress toward disability and cognitive impairment. Moreover, our patients desire to live normal lives, to manage their daily affairs independently, date, get married, and raise and support a family. Those of us who work daily with schizophrenia patients know that these objectives are rarely met despite the novel and allegedly improved dopamine blockers. We hypothesize that poor outcomes in schizophrenia reflect the gray matter volume reduction, which continues despite antipsychotic treatment. We hypothesize further that increased gut barrier permeability, due to dysfunctional aryl hydrocarbon receptor (AhR), downregulates the gut barrier protectors, brain-derived neurotrophic factor (BDNF), and interleukin-22 (IL-22), facilitating microbial translocation into the systemic circulation, eventually reaching the brain. Recombinant human IL-22 could ameliorate the outcome of schizophrenia by limiting bacterial translocation and by initiating tissue repair. This short review examines the signal transducer and transcription-three (STAT3)/AhR axis and downregulation of IL-22 and BDNF with subsequent increase in gut barrier permeability. Based on the hypothesis presented here, we discuss alternative schizophrenia interventions, including AhR antagonists, mitochondrial transplant, membrane lipid replacement, and recombinant human IL-22.

Detection and quantification of human immunodeficiency virus-1 (HIV-1) total nucleic acids in wastewater settled solids from two California communities.

Human immunodeficiency virus (HIV)-1 has infected nearly 100 million people since it emerged in the 1980s. Antiretroviral therapy prevents transmission of HIV and also allows infected individuals to live healthy lives with normal life expectancy. Consequently, identifying unrecognized cases of HIV is of paramount importance. Since wastewater represents a composite biological sample from a community, it may provide valuable information on HIV-1 prevalence that can be used to inform HIV testing and outreach.

A Study On The Effectiveness Of Cow's Milk Along With Arogyavardhini Vati (An Ayurvedic Formulation) In The Management Of Ascites- A Case Study

Ascites is the accumulation of peritoneal fluid in the abdominal cavity. Among all the causes of ascites, liver cirrhosis is one of the commonest cause. .Liver cirrhosis is a chronic degenerative disease characterized by replacement of normal liver tissue fibrosis that disrupts the normal liver function., which is complicated by ascites. Mild to moderate ascites is treated by salt restriction and diuretic therapy. Tense ascites is treated by paracentesis, followed by albumin infusion and diuretic therapy. Ascites due to liver cirrhosis , a life threatening condition is incurable due to its fibrotic nature .So, there is always a search for an alternative treatment like Ayurveda for its management. This paper highlights the effectiveness of using ‘only milk diet’ and a potent Ayurvedic formulation, Arogyavardhini vati for the management of ascites

Research on the Impact of Parenting Styles on Internet Addiction in Primary School Students

Abstract: With the rapid development of mobile phones and smartwatches, many primary school students have become increasingly dependent on the internet, to the extent that it affects their normal lives. Parental upbringing significantly influences children's behavior, as a warm family environment can reduce internet dependency, while an overly strict and highly controlling one can increase the amount of time primary school students spend on the internet. This study investigated the impact of parenting styles on Internet addiction in adolescents. The sample comprised 71 elementary school students, including 34 females and 37 males. A personal information form, "The Revised Chinese Internet Addiction Scale (CIAS-R)," and "The 21-item Chinese version of the s-EMBU" were used in the data gathering process. Regression analysis, simple correlation, F-test, and t-test methods were applied in data analysis. According to the findings, internet addiction is favorably connected with perceived poor parenting styles and negatively correlated with perceived positive parenting styles. Furthermore, there are gender differences in the prevalence of internet addiction among teenagers, with male teens being more likely than female teens to experience problematic online addiction.

Subjective and objective effects of anxiety and fatigue on social function in patients with enterostomy and their family caregivers.

Many patients with enterostomy and their family caregivers experience severe anxiety and fatigue, which affects their participation in normal social activities and family life, resulting in impaired social function. The purpose of this study was to understand the status of social function of patients with enterostomy and their family caregivers;at the same time to analyze the subjective and objective effects of anxiety and fatigue on their social functions. The self-made general information questionnaire, WHO Social Disability rating Scale, Miao Yu's Multidimensional Fatigue Scale-20 and Zung et al. 's Self-rating Anxiety Scale were used to investigate the general situation, social function, fatigue and anxiety of enterostomy patients and their family caregivers who came to the hospital for treatment from March 28, 2023 to November 30, 2023. SPSS27.0 was used to complete the statistical analysis of the data, and AMOS26.0 was used to establish the structural equation model to complete the subject and object effect analysis. A total of 260 pairs of enterostomy patients and their family caregivers were included in this study. The social function scores of enterostomy patients and their family caregivers were (8.80±3.44) and (6.44±3.60). The anxiety scores were (37.81±7.60) and (34.73±7.50). The fatigue scores were (63.35±12.80) and (51.21±12.38).The results of the subject-object effect analysis reported the subject effect: the anxiety of patients with enterostomy had a significant positive impact on the degree of social dysfunction (β = 0.154, P = 0.015); The fatigue of patients with enterostomy had a significant positive effect on the degree of social dysfunction (β = 0.132, P = 0.034). The anxiety of family caregivers had a significant positive effect on the degree of social dysfunction (β = 0.161, P = 0.023). The fatigue of family caregivers had a significant positive effect on the degree of social dysfunction (β = 0.201, P = 0.005). In terms of object effects: only the fatigue of family caregivers had a significant positive impact on the degree of social dysfunction of enterostomy patients (β = 0.224, P < 0.001), and other ways had no object effects. Patients with enterostomy and their family caregivers have serious social function defects. Clinical medical staff should take care of them as a whole in order to better return to family and society after surgery.

Studying the association between single nucleotide polymorphisms of metabolizing enzymes and the therapeutic serum levels of calcineurin inhibitors in Egyptian liver transplant patients

BackgroundMany clinical variables might impact the pharmacokinetics of calcineurin inhibitors (CIs). Different alleles of cytochromes P450 (CYP)3A4/5 and drug transporter P-glycoprotein are the main variables. Other variables include relocated type, treatment duration after transplantation, age, sex, dietary consumption, medications used and renal or hepatic impairment. Tacrolimus and cyclosporine are two main CIs extensively used in organ transplantation. Both drugs are metabolized by CYP3A4 and CYP3A5 isoforms, and single-nucleotide polymorphisms in these genes have been displayed to influence CIs pharmacokinetics. Another important gene is the pregnane X receptor (PXR), which manages the statement of a variety of genes including CYP3A4 genes. PXR has a clinical significance in CIs metabolism. The liver is the essential site for CIs metabolism. A decreased clearance with a prolonged CIs half-life was occurred in patients with impaired liver compared with patients with normal liver function. The presence of different genetic and clinical factors that may affect calcineurin inhibitors trough levels will consequently affect their immunosuppressant effect after liver transplantation.PurposeThis study aims to determine the effect of different genetic polymorphisms in CYP3A4 1B rs2740574 and PXR A7635G rs6785049 and other clinical factors that may affect calcineurin inhibitors pharmacokinetics after liver transplantation.ResultsThe presence of T allele in CYP3A4 gene was associated with elevated DATLs with P values of 0.00, 0.00, 0.007 and 0.00 after tacrolimus doses 4, 30, 60 and 90, respectively. Regarding PXR gene, the presence of G allele was associated with elevated DATLs in cyclosporine. About 432 correlations were tested in both drugs. In CYP3A4 genotype CC, male sex was associated with elevated DATLs interpreted by strong positive correlations and statistically significant difference in all DATLs, except DATL 60 (P value 0.374). No strong association was found between low hemoglobin levels and DATLs in almost all the follow-up periods. There were many positive relations between increased total and direct bilirubin and increased DATLs.ConclusionsStudying the various genetics and clinical factors that may affect calcineurin inhibitors serum concentrations is very essential for successful treatment plans after organ transplantation. These different factors may interact with each other and these complicated interactions may complicate the patient’s conditions post-transplantation. Considering all these complicated interactions is very crucial in monitoring treatment plans, especially in the presence of other comorbidities or chronic diseases. More studies with large number of patients should be conducted to explore more consequences of these interacting variables of treatment plans of these patients and all studied parameters in this study should be considered while monitoring patients after transplantation.

Causal relationship between gout and liver cancer: A Mendelian randomization and transcriptome analysis.

Gout is an inflammatory arthritis resulting from urate crystal deposition, now recognized as part of metabolic syndrome. Hyperuricemia, a hallmark of gout, is associated with various health complications, including liver cancer. Observational studies indicate a link between gout and increased cancer incidence. However, the causal relationship between gout and hepatocellular carcinoma remains uncertain. This study utilizes Mendelian randomization (MR) to explore this connection, minimizing confounding factors commonly present in observational studies. Genome-wide association study data for gout and liver cancer were sourced from the UK Biobank. We selected single nucleotide polymorphisms that are strongly associated with gout and liver cancer as instrumental variables for the analysis. We conducted 2-sample MR analysis using multiple MR methods (MR-Egger, weighted median, inverse variance weighting, and weighted mode) to evaluate causality. Co-localization and transcriptomic analyses were employed to identify target genes and assess their expression in hepatocellular carcinoma tissues. The 2-sample MR analysis indicated a significant causal relationship between gout and heightened liver cancer risk (P_IVW = .014). Co-localization analysis identified phosphatidylethanolamine N-methyltransferase (PEMT) as a crucial gene associated with gout (pH4 = 0.990). Transcriptomic data showed that PEMT expression was significantly higher in normal liver tissues compared to malignant samples (P < .001), and higher PEMT levels correlated with improved survival outcomes (P = .045). Immunohistochemical analysis revealed lower PEMT expression in hepatocellular carcinoma from patients with concurrent gout compared to those without (P < .05). The results indicate that gout increases the risk of hepatocellular carcinoma, with PEMT potentially playing a key role. Although this study focused on European populations, indicating a need for further research in diverse groups, the results emphasize the potential for liver cancer screening in newly diagnosed gout patients. Understanding the relationship between these conditions may inform future clinical practices and cancer prevention strategies.