A new prediction model for acute kidney injury following liver transplantation using grafts from donors after cardiac death.

Acute kidney injury (AKI) is a major complication following liver transplantation (LT), which utilizes grafts from donors after cardiac death (DCD). We developed a machine-learning-based model to predict AKI, using data from 894 LT recipients (January 2015-March 2021), split into training and testing sets. Five machine learning algorithms were employed to construct the prediction models using 17 clinical variables. The performance of the models was assessed by the area under the receiver operating characteristic curve (AUC), accuracy, F1-score, sensitivity and specificity. The best-performing model was further validated in an independent cohort of 195 LT recipients who received DCD grafts between April 2021 and December 2021. The Shapley additive explanations method was utilized to elucidate the predictions and identify the most crucial features. The gradient boosting machine (GBM) model demonstrated the highest AUC (0.76, 95% CI: 0.70-0.82), F1-score (0.73, 95% CI: 0.66-0.79) and sensitivity (0.74, 95% CI: 0.66-0.80) in the testing set and a comparable AUC (0.75, 95% CI: 0.67-0.81) in the validation set. The GBM model identified high preoperative indirect bilirubin, low intraoperative urine output, prolonged anesthesia duration, low preoperative platelet count and graft steatosis graded NASH Clinical Research Network 1 and above as the top five important features for predicting AKI following LT using DCD grafts. The GBM model is a reliable and interpretable tool for predicting AKI in recipients of LT using DCD grafts. This model can assist clinicians in identifying patients at high risk and providing timely interventions to prevent or mitigate AKI.

Longitudinal changes in sarcopenia was associated with survival among cirrhotic patients.

Background: Sarcopenia is common in patients with liver cirrhosis and is an independent predictor of multiple clinical outcomes. Most studies to date have used a static assessment of sarcopenia. However, there is very limited data evaluating the temporal course of muscle area in cirrhosis. To bridge this gap in clinical studies, we performed a longitudinal analysis to evaluate the impact of changes in sarcopenia for cirrhotic patients. Methods: Adult patients with clinically diagnosed liver cirrhosis who underwent at least 2 abdominal computed tomography (CT) scans in the hospital were enrolled. The interval between the two abdominal scans was 6 ± 1 months. Patients were categorized into persistent non-sarcopenia, new-onset sarcopenia, sarcopenia to non-sarcopenia, and persistent sarcopenia based on changes in sarcopenia. Kaplan-Meier method and Log-rank tests were used to separately compare unadjusted survival curves by different statuses of sarcopenia. Cox regression analysis was performed to assess the associations between different states of sarcopenia and overall mortality. The association between persistent non-sarcopenia and new-onset sarcopenia was analyzed by multivariate logistic regression analysis. Results: A total of 307 patients were included for analysis. At the second assessment, 10.10% (31/307) patients were new-onset sarcopenia, 27.69% (85/307) with persistent sarcopenia status, while 13.03% (40/307) patients with sarcopenia developed non-sarcopenia and 49.19% (151/307) with persistent non-sarcopenia status. The overall survival rate was significantly lower in the persistent sarcopenia and new-onset sarcopenia than in the non-sarcopenia group and sarcopenia to non-sarcopenia group (p < 0.001). Persistent sarcopenia (HR 5.799, 95%CI 1.563-21.521, p = 0.009) and new onset sarcopenia (HR 5.205, 95%CI 1.482-18.282, p = 0.010) were identified as poor prognostic factors for cirrhotic patients. The etiology of cirrhosis and the initial skeletal muscle mass were independent risk factors for new-onset sarcopenia. Conclusion: Sarcopenia is a dynamically changing process in patients with cirrhosis. Persistent and new-onset sarcopenia were independently and robustly associated with overall survival.

Analysis of fluid force and flow fields during gliding in swimming using smoothed particle hydrodynamics method.

Gliding is a crucial phase in swimming, yet the understanding of fluid force and flow fields during gliding remains incomplete. This study analyzes gliding through Computational Fluid Dynamics simulations. Specifically, a numerical model based on the Smoothed Particle Hydrodynamics (SPH) method for flow-object interactions is established. Fluid motion is governed by continuity, Navier-Stokes, state, and displacement equations. Modified dynamic boundary particles are used to implement solid boundaries, and steady and uniform flows are generated with inflow and outflow conditions. The reliability of the SPH model is validated by replicating a documented laboratory experiment on a circular cylinder advancing steadily beneath a free surface. Reasonable agreement is observed between the numerical and experimental drag force and lift force. After the validation, the SPH model is employed to analyze the passive drag, vertical force, and pitching moment acting on a streamlined gliding 2D swimmer model as well as the surrounding velocity and vorticity fields, spanning gliding velocities from 1 m/s to 2.5 m/s, submergence depths from 0.2 m to 1 m, and attack angles from -10° to 10°. The results indicate that with the increasing gliding velocity, passive drag and pitching moment increase whereas vertical force decreases. The wake flow and free surface demonstrate signs of instability. Conversely, as the submergence depth increases, there is a decrease in passive drag and pitching moment, accompanied by an increase in vertical force. The undulation of the free surface and its interference in flow fields diminish. With the increase in the attack angle, passive drag and vertical force decrease whereas pitching moment increases, along with the alteration in wake direction and the increasing complexity of the free surface. These outcomes offer valuable insights into gliding dynamics, furnishing swimmers with a scientific basis for selecting appropriate submergence depth and attack angle.

Prevalence and clinical impact of sarcopenia in liver transplant recipients: A meta-analysis.

BACKGROUND: The prevalence of sarcopenia in patients undergoing liver transplantation (LT) remains to be determined partly because of different diagnostic criteria. Sarcopenia has recently been recognized as a new prognostic factor for predicting outcomes in LT candidates. AIM: To estimate the prevalence of sarcopenia and evaluate its clinical effect on LT candidates. METHODS: This systematic search was conducted in PubMed, Web of Science, Embase, and Cochrane Library for original English-language articles that investigated the prevalence and influence of sarcopenia in patients undergoing LT from database inception to November 30, 2022. Cohort studies of the definition of sarcopenia that estimate sarcopenia prevalence and evaluate its effect on clinical outcomes and the risk of mortality were included. RESULTS: Twenty-five studies involving 7760 patients undergoing LT were included. The pooled prevalence of sarcopenia in patients undergoing LT was 40.7% [95% confidence intervals (95%CI): 32.1-49.6]. The 1-, 3-, and 5-year cumulative probabilities of post-LT survival in patients with preoperative sarcopenia were all lower than those without sarcopenia (P < 0.05). Sarcopenia was associated with an increased risk of post-LT mortality in patients undergoing LT (adjusted hazard ratio: 1.58; 95%CI: 1.21-2.07). Patients with preoperative sarcopenia had a longer intensive care unit stay, a high risk ratio of sepsis, and serious post-LT complications than those without sarcopenia. CONCLUSION: Sarcopenia is prevalent in a substantial proportion of patients undergoing LT and is strongly and independently associated with higher a risk of mortality risk.

LONP1 ameliorates liver injury and improves gluconeogenesis dysfunction in acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe liver disease with complex pathogenesis. Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis. Accumulating evidence suggests that glucose metabolic disturbance, especially gluconeogenesis dysfunction, plays a critical role in the disease progression of ACLF. Lon protease-1 (LONP1) is a novel mediator of energy and glucose metabolism. However, whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown. METHODS: In this study, we collected liver tissues from ACLF patients, established an ACLF mouse model with carbon tetrachloride (CCl 4 ), lipopolysaccharide (LPS), and D-galactose (D-gal), and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model. LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation. Liver histopathology, biochemical index, mitochondrial morphology, cell viability and apoptosis, and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF. RESULTS: We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues. Furthermore, LONP1 overexpression remarkably attenuated liver injury, which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in ACLF mice. Moreover, mitochondrial morphology was improved upon overexpression of LONP1. Meanwhile, the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression. Similarly, the hepatoprotective effect was also observed in the hepatocyte injury model, as evidenced by improved cell viability, reduced cell apoptosis, and improved gluconeogenesis level and activity, while LONP1 knockdown worsened liver injury and gluconeogenesis disorders. CONCLUSION: We demonstrated that gluconeogenesis dysfunction exists in ACLF, and LONP1 could ameliorate liver injury and improve gluconeogenic dysfunction, which would provide a promising therapeutic target for patients with ACLF.

An effective framework for predicting drug-drug interactions based on molecular substructures and knowledge graph neural network.

Drug-drug interactions (DDIs) play a central role in drug research, as the simultaneous administration of multiple drugs can have harmful or beneficial effects. Harmful interactions lead to adverse reactions, some of which can be life-threatening, while beneficial interactions can promote efficacy. Therefore, it is crucial for physicians, patients, and the research community to identify potential DDIs. Although many AI-based techniques have been proposed for predicting DDIs, most existing computational models primarily focus on integrating multiple data sources or combining popular embedding methods. Researchers often overlook the valuable information within the molecular structure of drugs or only consider the structural information of drugs, neglecting the relationship or topological information between drugs and other biological objects. In this study, we propose MSKG-DDI - a two-component framework that incorporates the Drug Chemical Structure Graph-based component and the Drug Knowledge Graph-based component to capture multimodal characteristics of drugs. Subsequently, a multimodal fusion neural layer is utilized to explore the complementarity between multimodal representations of drugs. Extensive experiments were conducted using two real-world datasets, and the results demonstrate that MSKG-DDI outperforms other state-of-the-art models in binary-class, multi-class, and multi-label prediction tasks under both transductive and inductive settings. Furthermore, the ablation analysis further confirms the practical usefulness of MSKG-DDI.

Application of Global Leadership Initiative on Malnutrition criteria in patients with liver cirrhosis.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients. METHODS: This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes. RESULTS: The optimal cut-off values of L3-SMI were 39.50 cm 2 /m 2 for male patients and 33.06 cm 2 /m 2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis ( Wald = 6.347, P  = 0.012). CONCLUSIONS: This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.

A viologen-based Cd(II) coordination polymer as a multifunctional platform for photochromism, chemochromism and a broad range of fluorescence pH sensing.

A multi-responsive Cd(II) coordination polymer (1) has been constructed by introducing a viologen derivative as both the framework backbone and ligand side pendant. Notably, compound 1 exhibits intriguing properties, including photochromism, methanol-assisted photochromism and chemochromism to ammonia. Furthermore, compound 1 also displays fluorescence pH sensing ability in a wide pH range.

Protection against cancer therapy-induced cardiovascular injury by planed-derived polyphenols and nanomaterials.

Cancer therapy-induced heart injury is a significant concern for cancer patients undergoing chemotherapy, radiotherapy, immunotherapy, and also targeted molecular therapy. The use of these treatments can lead to oxidative stress and cardiomyocyte damage in the heart, which can result in heart failure and other cardiac complications. Experimental studies have revealed that chemotherapy drugs such as doxorubicin and cyclophosphamide can cause severe side effects such as cardiac fibrosis, electrophysiological remodeling, chronic oxidative stress and inflammation, etc., which may increase risk of cardiac disorders and attacks for patients that underwent chemotherapy. Similar consequences may also be observed for patients that undergo radiotherapy for left breast or lung malignancies. Polyphenols, a group of natural compounds with antioxidant and anti-inflammatory properties, have shown the potential in protecting against cancer therapy-induced heart injury. These compounds have been found to reduce oxidative stress, necrosis and apoptosis in the heart, thereby preserving cardiac function. In recent years, nanoparticles loaded with polyphenols have also provided for the delivery of these compounds and increasing their efficacy in different organs. These nanoparticles can improve the bioavailability and efficacy of polyphenols while minimizing their toxicity. This review article summarizes the current understanding of the protective effects of polyphenols and nanoparticles loaded with polyphenols against cancer therapy-induced heart injury. The article discusses the mechanisms by which polyphenols protect the heart, including antioxidant and anti-inflammation abilities. The article also highlights the potential benefits of using nanoparticles for the delivery of polyphenols.

Elevated C-reactive protein mediates the liver-brain axis: a preliminary study.

BACKGROUND: Chronic liver diseases of all etiologies exist along a spectrum with varying degrees of hepatic fibrosis. Despite accumulating evidence implying associations between liver fibrosis and cognitive functioning, there is limited research exploring the underlying neurobiological factors and the possible mediating role of inflammation on the liver-brain axis. METHODS: Using data from the UK Biobank, we examined the cross-sectional association of liver fibrosis (as measured by Fibrosis-4 score) with cognitive functioning and regional grey matter volumes (GMVs) while adjusting for numerous covariates and multiple comparisons. We further performed post-hoc preliminary analysis to investigate the mediating effect of C-reactive protein (CRP) on the association between liver fibrosis and both cognitive functioning and GMVs. FINDINGS: We analysed behaviour from up to 447,626 participants (N ranged from 45,055 to 447,533 per specific cognitive metric) 37 years and older. 38,244 participants (age range 44-82 years) had GMV data collected at a median 9-year follow-up. Liver fibrosis showed significant associations with cognitive performance in reasoning, working memory, visual memory, prospective memory, executive function, and processing speed. Subgroup analysis indicated larger effects sizes for symbol digital substitution but smaller effect sizes for trail making in middle-aged people than their old counterparts. Neuroimaging analyses revealed significant associations between liver fibrosis and reduced regional GMVs, primarily in the hippocampus, thalamus, ventral striatum, parahippocampal gyrus, brain stem, and cerebellum. CRP levels were significantly higher in adults with advanced liver fibrosis than those without, indicating an elevated systemic inflammation. Moreover, the serum CRP significantly mediated the effect of liver fibrosis on most cognitive measures and regional GMVs in the hippocampus and brain stem. INTERPRETATION: This study provides a well-powered characterization of associations between liver fibrosis, cognitive impairment, and grey matter atrophy. It also highlights the possibly mediating role of systemic inflammation on the liver-brain axis. Early surveillance and prevention of liver diseases may reduce cognitive decline and brain GMV loss. FUNDING: National Science Foundation, and National Institutes of Health.

Temporal variations of 7Be and 210Pb activity concentrations in the atmospheric aerosols during 2018-2019 in Beijing, China and their correlations with meteorological parameters.

In order to establish a regional database on natural radioactivity, a series of measurements of 713 atmospheric aerosol samples collected on filters over a two-year period (2018-2019) in center of Beijing, northeastern China have been performed to analyze 7Be and 210Pb activity concentrations. The mean activity concentrations of 7Be and 210Pb were found to be 7.10 ± 2.44 mBq m-3 and 2.93 ± 1.52 mBq m-3, respectively. Both the radionuclides exhibited strong seasonal variations, with maximum concentration of 7Be occurring in the spring and that of 210Pb in the winter. The concentration of both the radionuclides was minimum in the rainy summer. Higher 7Be concentration in the spring was mainly caused by the stratosphere to troposphere exchange. Higher 210Pb concentration during winter was maybe attributed to the combustion processes in heating systems and the ingression of continental air masses resulted from winds originating from northwest. The dependence of the activity concentrations of 7Be and 210Pb with meteorological parameters such as rainfall, temperature, and humidity was studied through linear correlation analysis. Statistically significant negative correlations were observed between 7Be and 210Pb activity concentrations with rainfall, respectively, which suggested that the removal mechanisms of these two radionuclides were similar. Lead-210 showed statistically significant correlations with temperature, humidity and PM10. A comparison of the data obtained in the present study for Beijing with the northern hemisphere literature values of 7Be and 210Pb in the atmospheric aerosols showed that the values were smaller than the ones observed in the present study. Overall, the study provides an improved understanding of the temporal variability and correlation of 7Be and 210Pb concentrations in the atmosphere in center of Beijing, northeastern China.

The effects and safety of anticoagulation or antiplatelet therapy following TIPS in cirrhotic patients with portal hypertension: A meta-analysis.

Introduction: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective way to improve portal hypertension, however, the role of anticoagulation or antiplatelet therapy following TIPS remains controversial. We conducted this study to evaluate the efficacy and safety of anticoagulation or antiplatelet therapy following TIPS. Methods: A literature search was conducted on anticoagulation or antiplatelet therapy after TIPS using Pubmed, Web of Science, EMBASE, and Cochrane. The retrieval period was from the earliest accessible date in the database to 31 October 2022. We collected information on the incidence of stent dysfunction, bleeding, hepatic encephalopathy, the new occurrence of portal vein thrombosis, and the survival rate. Stata was analyzed in RevMan. Results: 1. Four studies received anticoagulation or antiplatelet therapy after TIPS without control groups. According to the single-group rate meta-analysis, stent dysfunction occurred at 27% [95% CI (0.19, 0.38)], bleeding occurred at 21% [95% CI (0.14, 0.29)], new portal vein thrombosis occurred at 17% [(95%CI(0.04.0.71)], hepatic encephalopathy occurred at 47% [95%CI (0.34, 0.63)], and death occurred at 31% [95% CI (0.22, 0.42)]. 2. Eight studies, including 1025 patients, compared anticoagulation and antiplatelet therapy after TIPS to TIPS alone. In terms of stent dysfunction, bleeding, and hepatic encephalopathy, there were no significant differences between the two groups. The use of anticoagulation or antiplatelet therapy may result in a significant decrease in the incidence of new portal vein thrombosis and mortality over 1 year. Discussion: Anticoagulant or antiplatelet therapy may not improve the patency rate of TIPS, but may effectively prevent new portal vein thrombosis after TIPS. Following TIPS, the use of anticoagulants or antiplatelet drugs does not lead to an increase in bleeding or death.

Preparation of a Cellulosic Photosensitive Hydrogel for Tubular Tissue Engineering.

Since the concept of tissue engineering was proposed, biocompatible hydrogel materials have attracted the attention of researchers. With the help of three-dimensional (3D) printing technology, precise shaping of hydrogels can be realized. In this paper, we synthesized a cellulosic photosensitive acrylamide (AM)/N,N-methylenebisacrylamide (MBA) hydrogel. With the high-efficiency water-soluble photoinitiator TPO@Tw developed by our research group, the efficient photocuring cross-linking process of the hydrogel can be realized under 405 nm visible light. In consideration of the viscosity, curing mass, curing depth, and break distance of the hydrogel, we screened out hydroxypropyl cellulose (HPC) as the preferred tackifier of the material. The addition of HPC greatly improved the mechanical properties of the hydrogel. The compressive modulus of the optimal sample AM-HPC-5 increased by 709.2% and the tensile strength increased by 76.7% compared with the blank control group. By adding a PEGDA shell to the surface of the material, the water retention capacity of the hydrogel was effectively improved. The water loss rate was greatly reduced. The 3D wooden-pile structure model was printed by a DIW 3D printer. Further, through coaxial extrusion, the microtubule structure that may be applied in tissue engineering was obtained. Cell experiment results showed high biocompatibility of the hydrogel. NIH 3T3 cells could adhere and grow on the surface of microtubules.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Global stabilization via output feedback for a class of uncertainty nonlinear systems with time-varying delay and zero dynamics.

This paper proposes a new control strategy to deal with three different types of uncertainties for a class of time-varying delay nonlinear systems. Quite different from related celebrated works, the considered systems allow the existence of parameter uncertainties in the output function and nonlinearities, dynamic uncertainties of the unmeasurable state, and continuous external disturbances, which invokes the motivation of the paper. The objective is to construct a continuous output feedback controller by utilizing a new restructured integral function and the double-domination method. The novelty control design is the capability of tackling zero-dynamic and unknown output function simultaneously, thereby guaranteeing the state convergence of the closed-loop system. Finally, the proposed scheme is applied to a practical example and a numerical one simultaneously to demonstrate the effectiveness and the superiority.

P-element-Induced Wimpy-Testis-Like Protein 1 Regulates the Activation of Pancreatic Stellate Cells Through the PI3K/AKT/mTOR Signaling Pathway.

AIM: Pancreatic fibrosis is the main pathological characteristic of chronic pancreatitis (CP) and pancreatic cancer. Pancreatic stellate cells (PSCs) play a critical role in pancreatic fibrosis. Any targets that may have an impact on the activation of PSCs could become potential treatment candidates for CP and pancreatic cancer. Our goal was to investigate the effect of P-element-induced wimpy-testis (PIWI) protein 1 (PIWIL1) on PSC activation. METHODS: Lentivirus-based RNA interference (RNAi) and overexpression vector construction were used to knock down and over-express the PIWIL1 protein. Immunocytofluorescent staining, western blotting, wound healing assay, transwell assay, and phalloidin staining were used to investigate the effects of PIWIL1 on the secretion of extracellular matrix components (EMC), actin cytoskeleton, and on the invasion and migration abilities of primary PSCs isolated from C57BL/6 mice. Moreover, pancreatic fibrosis was induced by L-arginine in C57BL/6 mice. The expression of PIWIL1 and collagen deposition in vivo were tested by western blotting and Sirius red staining. RESULTS: Expression levels of collagen I, collagen III, and α-smooth muscle actin were significantly decreased in the LV-PIWIL1 group. Compared with the si-PIWIL1 group, significant differences were observed in the expression of desmin, p-PI3K, p-AKT, and p-mTOR in the LV-PIWIL1 group. Furthermore, PIWIL1 suppressed the PSCs' invasion and migration abilities. In a rescue experiment, the PI3K/AKT/mTOR signaling pathway was found to be the underlying mechanism in PSCs activation mediated by PIWIL1. CONCLUSIONS: Our findings suggest that PIWIL1 inhibits the activation of PSCs via the PI3K/AKT/mTOR signaling pathway. PIWIL1 is a potential therapeutic target for pancreatic fibrosis.

Late evening snack and oral amino acid capsules improved respiratory quotient and Fischer ratio in patients with alcoholic liver cirrhosis.

INTRODUCTION AND OBJECTIVES: Appropriate nutritional support may improve energy metabolism in alcoholic liver cirrhosis (ALC) patients. We explored the effect of a late evening snack (LES) and oral amino acid (OAA) capsules on energy metabolism and the Fischer ratio in ALC. PATIENTS AND METHODS: Ninety-one ALC patients were enrolled and randomly divided into three groups: 31 patients in the LES and OAA group, 32 in the LES group, and 28 controls. Respiratory quotient (RQ), carbohydrate oxidation rate (CHO%), fat oxidation rate (FAT%), serum isoleucine and the Fischer ratio were measured at baseline and at months 1, 3, and 6 of follow-up. RESULTS: The RQ in the LES and OAA group was 0.79 ± 0.06, 0.80 ± 0.04, 0.82 ± 0.04, and 0.82 ± 0.04 at baseline and at months 1, 3, and 6 of follow-up, respectively. These values were significantly higher than those in the LES group (P < 0.05). The RQ in the LES group was significantly higher than that in the control group at month 1 and month 6 (P < 0.05). CHO% in the LES and OAA group was significantly increased and FAT% was significantly decreased at month 3 of follow-up (P < 0.05). In the LES and OAA group, serum isoleucine and the Fischer ratio were markedly increased compared with the LES group and control group (P < 0.05). CONCLUSIONS: LES can significantly increase the RQ in ALC. LES and OAA were more effective than LES alone in improving serum isoleucine and the Fischer ratio.

Efficacy and Safety Analysis of Piperacillin Tazobactam in Combination With High Frequency Chest Wall Oscillation in Patients With COPD Coupled With Pneumonia.

Context: Chronic obstructive pulmonary disease (COPD) is a common, chronic inflammatory disease of the airway, and acute exacerbation of COPD (AE-COPD) refers to the manifestations of inflammation in the lungs that appear within a short period of time. Some patients contract pneumonia, and they can be prone to recurrent attacks of AE-COPD combined with pneumonia. The efficacy of conventional treatments isn't generally satisfactory. Objective: The study intended to investigate the effectiveness and safety of piperacillin tazobactam in combination with the use of high-frequency chest-wall oscillation (HFCWO) to produce expectoration for the treatment of pneumonia in patients with AE-COPD and to provide a reference for clinical treatment. Design: The research team designed a prospective, randomized controlled trial. Setting: The study took place at the Sixth Hospital of Wuhan of the Affiliated Hospital of Jianghan University in Wuhan, China. Participants: Participants were 92 patients who had been admitted to the hospital between January 2020 and November 2021 with AE-COPD combined with pneumonia. Intervention: Using the random number table method, the research team randomly assigned participants to one of two groups, an intervention group or a control group, each with 46 participants. The control group received conventional treatment with oxygen, antibiotics, antispasmodics, antiasthmatic drugs, and phlegmolytic drugs as well as HFCWO for sputum removal. In addition to those treatments, the intervention group received piperacillin tazobactam. Outcome measures: The research team measured the treatment's efficacy at one day postintervention. At baseline and at one day postintervention, the study also measured pulmonary function, laboratory indexes, and blood-gas-analysis indexes. In addition, the research team identified the time of disappearance of clinical symptoms, including the disappearance of cough, sputum, dyspnea, and pulmonary rales; calculated the length of hospital stay, and evaluated the treatment's safety. Results: Postintervention, the intervention group's clinical efficacy was significantly higher than that of the control group (P < .05), and the group's cough, coughing of sputum, dyspnea, disappearance time of pulmonary rales, and hospitalization times were all significantly lower than those in the control group (P < .05). The FEV1, FVC, FEV1% and FEV1/FVC levels were higher in both groups postintervention than at baseline and were significantly higher in the intervention group than in the control group (P < .05). Postintervention, the levels of IL-2, IL-10, TNF-α, CRP and PCT were lower in both groups than at baseline, and the intervention group's levels were significantly lower than those in the control group (P < .05). Postintervention, the PaCO2 level decreased and PaO2 and SaO2 levels increased in both groups compared to baseline; the intervention group's PaCO2 level was lower and PaO2 and SaO2 levels were higher than those in the control group. During the treatment, no adverse reactions occurred in the control group, and one participant had a decreased appetite in the intervention group; the incidence of adverse reactions in that group was 2.17% (1/46). That participant received no special treatment, and the condition improved after stopping the drug. Conclusion: Piperacillin tazobactam combined with HFCWO for sputum evacuation can effectively treat patients with pneumonia in acute exacerbation of COPD, with high safety. The treatment is worthy of clinical application.

Dysregulated hepatic lipid metabolism and gut microbiota associated with early-stage NAFLD in ASPP2-deficiency mice.

Background: Growing evidence indicates that lipid metabolism disorders and gut microbiota dysbiosis were related to the progression of non-alcoholic fatty liver disease (NAFLD). Apoptosis-stimulating p53 protein 2 (ASPP2) has been reported to protect against hepatocyte injury by regulating the lipid metabolism, but the mechanisms remain largely unknown. In this study, we investigate the effect of ASPP2 deficiency on NAFLD, lipid metabolism and gut microbiota using ASPP2 globally heterozygous knockout (ASPP2+/-) mice. Methods: ASPP2+/- Balb/c mice were fed with methionine and choline deficient diet for 3, 10 and 40 day to induce an early and later-stage of NAFLD, respectively. Fresh fecal samples were collected and followed by 16S rRNA sequencing. HPLC-MRM relative quantification analysis was used to identify changes in hepatic lipid profiles. The expression level of innate immunity-, lipid metabolism- and intestinal permeability-related genes were determined. A spearman's rank correlation analysis was performed to identify possible correlation between hepatic medium and long-chain fatty acid and gut microbiota in ASPP2-deficiency mice. Results: Compared with the WT control, ASPP2-deficiency mice developed moderate steatosis at day 10 and severe steatosis at day 40. The levels of hepatic long chain omega-3 fatty acid, eicosapentaenoic (EPA, 20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3), were decreased at day 10 and increased at day 40 in ASPP+/- mice. Fecal microbiota analysis showed significantly increased alpha and beta diversity, as well as the composition of gut microbiota at the phylum, class, order, family, genus, species levels in ASPP2+/- mice. Moreover, ASPP-deficiency mice exhibited impaired intestinal barrier function, reduced expression of genes associated with chemical barrier (REG3B, REG3G, Lysozyme and IAP), and increased expression of innate immune components (TLR4 and TLR2). Furthermore, correlation analysis between gut microbiota and fatty acids revealed that EPA was significantly negatively correlated with Bifidobacterium family. Conclusion: Our findings suggested that ASPP2-deficiency promotes the progression of NAFLD, alterations in fatty acid metabolism and gut microbiota dysbiosis. The long chain fatty acid EPA was significantly negatively correlated with Bifidobacterial abundance, which is a specific feature of NAFLD in ASPP2-deficiency mice. Totally, the results provide evidence for a mechanism of ASPP2 on dysregulation of fatty acid metabolism and gut microbiota dysbiosis.