Ferritinophagy: A new idea for liver diseases regulated by ferroptosis.

BACKGROUND: The discovery of regulatory cell death has led to a breakthrough in the therapeutic field. Various forms of cell death, such as necrosis, apoptosis, pyroptosis, autophagy, and ferroptosis, play an important role in the development of liver diseases. In general, more than one form of cell death pathways is responsible for the disease state. Therefore, it is particularly important to study the regulation and interaction of various cell death forms in liver diseases. DATA SOURCES: We performed a PubMed search up to November 2022 with the following keywords: ferritinophagy, ferroptosis, and liver disease. We also used terms such as signal path, inducer, and inhibitor to supplement the query results. RESULTS: This review summarized the basic characteristics of ferritinophagy and ferroptosis and the regulation of ferroptosis by ferritinophagy and reviewed the key targets and treatment strategies of ferroptosis in different liver diseases. CONCLUSIONS: Ferritinophagy is a potential therapeutic target in ferroptosis-related liver diseases.

The association between psychological resilience and hair cortisol concentration in adults: A systematic review and meta-analysis.

BACKGROUND: Resilience measures are typically based on subjective self-assessment, which is prone to bias. Objective biological/physiological measures of resilience are therefore needed. Hair cortisol concentration is a particularly promising candidate as a biomarker for resilience. METHODS: We conducted a meta-analytic review from inception to April 2023 in PubMed, EMBASE, Cochrane Library, and Psych Info databases. All data were analyzed using a random-effects model. RESULTS: Eight studies were identified that included a total of 1,064 adults. The random effects model demonstrated that resilience and hair cortisol concentration were inversely correlated (r = -0.18, 95% confidence interval [CI] = -0.27 to -0.09) with substantial heterogeneity (I2 = 54.2%, p = 0.03). The inverse association was stronger in those who were age 40 years or younger compared to those who were over 40 years. The correlation coefficients between psychological resilience and hair cortisol concentration among adults assessed by different resilience measures were r = -0.29 (95% CI = -0.49 to -0.08) for the CD-RISC-10; r = -0.21 (95% CI = -0.31 to -0.11) for the CDRISC- 25, and r = -0.08 (95% CI = -0.22 to 0.06) for the BRS. Six of eight studies examined the connection between resilience and perceived stress, where the weighted mean correlation coefficient was r = -0.45 (95% CI = -0.56 to -0.33), with considerable heterogeneity (I2 = 76.2%, p = 0.001). CONCLUSIONS: There is a negative association between psychological resilience and hair cortisol concentration based on these eight studies. Additional research, particularly prospective studies, is needed to determine whether hair cortisol concentration can be used as a biomarker for psychological resilience.

Knockout of UBE2S inhibits the proliferation of gastric cancer cells and induces apoptosis by FAS-mediated death receptor pathway.

Ubiquitin binding enzyme E2S (UBE2S) is a member of ubiquitin binding enzyme family involved in a variety of biological functions, including cell cycle regulation, apoptosis, and regulation of the ubiquitination of proteins, which are closely correlated with the development of various tumors. However, its role in gastric cancer (GC) remains unknown. In this study, we found that UBE2S was upregulated in GC tissues and cells. Further, its high expression positively correlated with the tumor stage and indicated a poor prognosis. Knockout of UBE2S by CRISPR/Cas9-mediated strategy suppressed the growth of GC in vitro and in vivo. Moreover, RNA-Seq-based transcriptome analysis and tandem mass tag (TMT)-based quantitative proteomics analysis was performed for exploring the underlying mechanism. The multi-omics and verification results showed that UBE2S knockout-induced apoptosis and proliferation inhibition of GC cells was related to upregulation of FAS and the activation of the FAS-mediated apoptotic pathway. Moreover, a negative correlation between UBE2S and FAS expression was observed in GC tissue samples. Finally, the ubiquitination assay confirmed that knockout of UBE2S might activate endogenous FAS by inhibiting ubiquitination and degradation of p53 in GC cells. Collectively, UBE2S is expected to be a novel prognostic biomarker and potential therapeutic target for GC.

Efficacy and safety of alfosbuvir plus daclatasvir in Chinese patients with hepatitis C virus genotypes 1, 2, 3, and 6 infection: An open-label, phase 2 study.

Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. Our previous studies indicated that alfosbuvir monotherapy was well-tolerated and druggable in healthy subjects and HCV-infected patients. Here, we evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV genotype 1, 2, 3 or 6. In this open-label study, patients with chronic HCV infection were randomly assigned with a 1:1:1 ratio to receive 12 weeks of daclatasvir 60 mg plus alfosbuvir at a dose of 400, 600 or 800 mg (Cohort A, B or C) daily. Randomization was stratified by HCV genotype and the presence or absence of cirrhosis at screening. The primary endpoint was a sustained virologic response 12 weeks after the end of treatment (SVR12). A total of 124 patients were enrolled in the study, all of whom were available for post-treatment week 12 assessments. SVR12 was achieved in 92.7% (38/41), 95.2% (40/42) and 100% (41/41) of patients in Cohort A, B and C respectively. The most common adverse events were hepatic steatosis, upper respiratory tract infection, hypercholesterolaemia, hypertriglyceridaemia, blood bilirubin increased, and total bile acids increased. There were no discontinuations due to adverse events, and no treatment-related serious adverse events were reported. Once-daily oral administration of alfosbuvir plus daclatasvir were highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3 or 6, suggesting this regimen could be a promising drug candidate for HCV treatment irrespective of genotype. (ClinicalTrials.gov number, NCT04070235).

Diagnostic Value of FibroTouch and Non-invasive Fibrosis Indexes in Hepatic Fibrosis with Different Aetiologies.

BACKGROUND: Liver biopsy is the gold standard for staging liver fibrosis, but it has numerous drawbacks, mainly associated with bleeding and bile fistula risks. A number of non-invasive techniques have been investigated, but they all have their own disadvantages. To avoid the risks mentioned above and to improve the diagnostic value, we still need to search for a more accurate non-invasive method to evaluate the degree of liver fibrosis. AIM: This study aimed to evaluate the diagnostic performance of FibroTouch versus other non-invasive fibrosis indexes in hepatic fibrosis of different aetiologies. METHODS: This study retrospectively enrolled 227 patients with chronic hepatic liver disease admitted to the first hospital of Lanzhou University from 2017 to 2020. Liver biopsy was performed in all of the patients, and their biochemical indicators were all tested. Non-invasive indexes including the fibrosis index based on four factors (FIB-4), the aminotransferase-to-platelet ratio index (APRI), and the gamma-glutamyl transpeptidase-to-platelet ratio index (GPRI) were all calculated. Transient elastography was performed using FibroTouch. RESULTS: The correlation between FibroTouch and the pathology of liver fibrosis was significantly higher than that between the non-invasive fibrosis indexes and the biopsy results (r = 0.771, p < 0.05). The area under the receiver operating curve (AUC) of FibroTouch was significantly higher than that of FIB-4, APRI, and GPRI for the diagnosis of significant fibrosis (≥ S2 fibrosis stage), advanced fibrosis (≥ S3 fibrosis stage), and cirrhosis (= S4 fibrosis stage) (p < 0.05). The patients were grouped according to different aetiologies. The diagnostic value of FibroTouch had much higher credibility in different fibrosis stages for different causes compared with other non-invasive indexes. The AUC of FibroTouch showed both higher specificity and higher sensitivity than FIB-4, APRI, and GPRI for different liver fibrosis stages with different aetiologies. CONCLUSIONS: FibroTouch demonstrates the highest diagnostic value for liver fibrosis and cirrhosis among non-invasive methods, showing better results than FIB-4, APRI, and GPRI, and surpassed only by liver biopsy. FibroTouch is reliable in assessing liver fibrosis with different aetiologies.

Role of annexin A family in tumorigenesis and chemoresistance of gastric cancer.

Gastric cancer (GC) is one of the most common cancer types and the fourth leading cause of cancer-related mortality among all malignant tumors worldwide. Due to insidious onset and lack of reliable early diagnostic markers, most GC patients are at an advanced stage at the time of diagnosis. Annexin is an evolutionally-conserved Ca2+-dependent phospholipid-binding protein superfamily, including five members (A, B, C, D, and E). Annexins in the cells of vertebrates comprised the annexin A family, consisting of 12 members in humans. The biological functions of annexin A are Ca2+-signal transduction, vesicle transport, cell proliferation, cell division, cell apoptosis, signal transduction, anti-inflammatory, proangiogenesis, and anticoagulation, most of which overlap with the basic characteristics of tumors. Accumulating evidence indicated that members of the annexin A family are correlated with tumorigenesis and chemoresistance and can be used as potential tumor prognostic factors and targets for biological therapy. Thus, the current review focused on the role and relative mechanisms of the annexin A family in GC.

Development and validation of a radiomics signature as a non-invasive complementary predictor of gastroesophageal varices and high-risk varices in compensated advanced chronic liver disease: A multicenter study.

BACKGROUND AND AIM: Gastroesophageal varices (GEV) present in compensated advanced chronic liver disease (cACLD) and can develop into high-risk varices (HRV). The gold standard for diagnosing GEV is esophagogastroduodenoscopy (EGD). However, EGD is invasive and less tolerant. This study aimed to develop and validate radiomics signatures based on noncontrast-enhanced computed tomography (CT) images for non-invasive diagnosis of GEV and HRV in patients with cACLD. METHODS: The multicenter trial enrolled 161 patients with cACLD from six university hospitals in China between January 2015 and September 2019, who underwent both EGD and noncontrast-enhanced CT examination within 14 days prior to the endoscopy. Two radiomics signatures, termed rGEV and rHRV, respectively, were built based on CT images in a training cohort of 129 patients and validated in a prospective validation cohort of 32 patients (ClinicalTrials. gov identifier: NCT03749954). RESULTS: In the training cohort, both rGEV and rHRV exhibited high discriminative abilities on determining the existence of GEV and HRV with the area under receiver operating characteristic curve (AUC) of 0.941 (95% confidence interval [CI] 0.904-0.978) and 0.836 (95% CI 0.766-0.905), respectively. In validation cohort, rGEV and rHRV showed high discriminative abilities with AUCs of 0.871 (95% CI 0.739-1.000) and 0.831 (95% CI 0.685-0.978), respectively. CONCLUSIONS: This study demonstrated that rGEV and rHRV could serve as the satisfying auxiliary parameters for detection of GEV and HRV with good diagnostic performance.

The effectiveness of the laid-back position on lactation-related nipple problems and comfort: a meta-analysis.

BACKGROUND: The importance of breastfeeding for maternal and child health is agreed upon worldwide. However, lactation-related nipple problems are common and are important factors affecting breastfeeding. Multiple studies recommended laid-back breastfeeding, but they are of various levels of quality, and the results are inconclusive. METHODS: We systematically searched the following twelve databases from inception to January 28,2020: Cochrane Library, EMBASE, Medline, Ovid, PubMed, Web of Science, CINAHL, Scopus, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), WanFang, and VIP. All studies regarding laid-back breastfeeding or biological nurturing were considered, regardless of whether they were randomized controlled trials. Two trained investigators independently evaluated the quality of the selected articles and screened the data. All the data were analysed separately using Review Manager Version 5.3 and STATA/SE Version 15.1. RESULTS: A total of 12 studies involving 1936 groups of postpartum women and their newborns were included. The results of the meta-analysis showed that nipple pain (RR = 0.24; 95% CI 0.14, 0.40; p < 0.00001), nipple trauma (RR = 0.47; 95% CI 0.29, 0.75; p = 0.002) and correct latching position (RR = 1.22; 95% CI 1.11, 1.33; p < 0.0001) in the experimental groups were all better than those of the control groups, and the differences were statistically significant (p < 0.05), which indicates that the laid-back position has a positive effect on maternal breastfeeding. However, the results of position comfort showed that there was no statistical significance between the two groups (ES = 0.09; 95% CI -0.63, 0.81; p = 0.798). CONCLUSION: Compared with traditional breastfeeding positions, the laid-back position has been proven to be related to a decreased incidence of nipple pain and nipple trauma and is seemingly conducive to the use of the correct latching position. It is suggested that the laid-back position is helpful in solving lactation-related nipple problems and can be recommended as a position for breastfeeding. However, no significant difference in position comfort was found between the two groups based on the current evidence, and further studies are still needed to validate these results due to the limitations of the included studies.

Effect of kinesio taping on low back pain during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Low back pain during pregnancy affects the normal daily activities of pregnant women to a certain extent. Current studies have shown that Kinesio Taping (KT) may be a treatment for low back pain during pregnancy, but there is still a lack of key evidence. The purpose of this study is to evaluate the efficacy and safety of KT in the treatment of low back pain during pregnancy. METHODS: PubMed, Web of Science, The Cochrane Library, Scopus, Embase, Wanfang Data, CNKI, and VIP databases were searched to collect randomized controlled trials (RCTs) of the efficacy of KT intervention on low back pain in women during pregnancy. The retrieval time limit is from the establishment of the database to April 2021. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.3 software. RESULTS: A total of 7 RCTs were included, including 444 patients. Meta-analysis results showed that: Compared with the control group, KT intervention could significantly improve low back pain and dysfunction, VAS score (- 1.62, 95%CI - 2.08 to - 1.16, P < 0.00001, I2 = 77%), RMDQ score (- 1.00, 95%CI - 1.54 to - 0.46, P = 0.0003, I2 = 80%); The results of the meta-analysis of the subgroup showed that compared with the control group, the KT intervention was less than or equal to 1 week, and the waist pain and dysfunction were improved, with statistically significant differences. The difference in the improvement of low back pain was statistically significant after KT intervention for more than 1 week, but there was no statistically significant difference in RMDQ score (- 1.25, 95%CI - 2.66 to 0.15, P = 0.08, I2 =77%). Compared with the control group, KT intervention improved low back pain in the second and third trimesters, and the difference was statistically significant. CONCLUSION: KT has a positive effect on the improvement of low back pain during pregnancy, KT intervention can significantly improve pregnant women's low back pain and dysfunction problems, improve the quality of life. It is suggested that future research should focus on the prevention and treatment of low back pain during pregnancy to provide more research data for improving women's health.

Translation and Validation of TRANSITION-Q for Chinese Pediatric Cancer Survivors.

PURPOSE: Cancer survivorship starts at diagnosis. Transition readiness is an important indicator for pediatric cancer survivors to move from pediatric to adult medical care. Appropriate measurement of transition readiness can facilitate better cancer survivorship. This study aimed to translate and validate of the English version of the TRANSITION-Q into Chinese. DESIGN AND METHODS: The translation followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) best-practice guidelines for the translation and cultural adaptation of patient-reported outcome measures (PROM). A cross- psychometric testing on reliability and validity were conducted from a convenient sample of Chinese adolescent cancer survivors aged 10-19 years. RESULTS: Two hundred seventy-one pediatric cancer patients were recruited for the psychometric validation. The 14-item Chinese TRANSITION-Q demonstrated adequate reliability. In exploratory factorial analyses and confirmatory factor analysis, a two-factor structure emerged with a variance of 54.78%, demonstrating construct validity. Convergent validity test showed TRANSITION-Q score was significantly positively correlated with self-efficacy (r = -0.84, p = 0.002). The known-group validity demonstrated the older group (age ≥14 years) had a significantly higher mean TRANSITION-Q score than the younger group (age < 14 years) (p = 0.04). CONCLUSION: The Chinese version of the TRANSITION-Q is reliable and valid and can be used in Chinese research and clinical settings. IMPLICATIONS FOR PRACTICE: This scale can be used in Chinese clinical and research settings to investigate understanding of transition readiness in Chinese pediatric cancer survivors.

An illumination of the ICN's core competencies in disaster nursing version 2.0: Advanced nursing response to COVID-19 outbreak in China.

AIM: This study aims to report on the actions and incident management of the advanced practice nurses of a disaster operation team who were deployed in response to the COVID-19 outbreak, and to explore how it illustrated the Core Competencies in Disaster Nursing Version 2.0 delineated by the International Council of Nurses in 2019. METHODS: This is a descriptive study. The participants (responders) communicated and reported their actions in the operation with headquarter on a popular social media platform in China (WeChat), established specifically for the three-rescue teams. RESULTS: The response approach of advanced nurses to COVID-19 encompassed six of the eight domains of the competencies outlined in ICN CCDN V2.0, namely on preparation and planning, communication, incident management systems, safety and security, assessment and intervention. CONCLUSIONS: The response teams of advanced practice nurses in this study clearly demonstrated their competencies in disaster rescue, which fulfilled most of the core competencies set forth by the ICN. IMPLICATIONS FOR NURSING MANAGEMENT: The findings of this study contributed to understand the roles played by advanced practice nurses and nurse managers in disaster management and how these relate to the competencies set forth by the ICN.

Whole-Liver Apparent Diffusion Coefficient Histogram Analysis for the Diagnosis and Staging of Liver Fibrosis.

BACKGROUND: Conventional diffusion-weighted imaging is limited in the quantitative evaluation of liver fibrosis, and whole-liver apparent diffusion coefficient (ADC) histogram analysis might contribute to the diagnosis and staging of liver fibrosis. PURPOSE: To explore the value of whole-liver ADC histogram parameters in the diagnosis and staging of liver fibrosis. STUDY TYPE: Retrospective. POPULATION: Twenty individuals with no liver disease and 86 patients with liver fibrosis, including 30 with chronic viral hepatitis, 29 with autoimmune hepatitis, and 27 with unexplained liver fibrosis patients. FIELD STRENGTH/SEQUENCE: 3.0T/T1 -weighted, T2 -weighted, and diffusion-weighted images. ASSESSMENT: A region of interest (ROI) was drawn in each slice of the diffusion-weighted images. Whole-liver histogram parameters were obtained with dedicated software by accumulating all ROIs. The effectiveness of the parameters in differentiating stage 1 or greater (≥F1), stage 2 or greater (≥F2), and stage 3 or greater (≥F3) liver fibrosis was assessed. STATISTICAL TESTS: Mann-Whitney U-test and receiver operating characteristic curve analysis. RESULTS: Kurtosis, entropy, skewness, mode, and 90th and 75th percentiles exhibited significant differences among the pathological fibrosis stages (P < 0.05). Kurtosis was found to be the most meaningful parameter in differentiating fibrosis stages of the viral hepatitis, autoimmune hepatitis, and unexplained liver fibrosis group (area under the curve) (AUC = 0.793, 0.771, 0.798, respectively). In the combined liver fibrosis group, kurtosis achieved the highest AUC (0.801; 95% confidence interval [CI]: 0.702-0.900; sensitivity: 0.750; specificity: 0.850; positive likelihood ratio: 4.953; negative likelihood ratio: 0.302; positive predictive value: 0.946; negative predictive value: 0.486), with a cutoff value of 1.817, in differentiating fibrosis stage ≥F1. DATA CONCLUSION: Kurtosis, entropy, skewness, mode, and 90th and 75th percentiles may contribute to the diagnosis and staging of liver fibrosis, especially kurtosis. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1745-1754.

Weighted gene coexpression network analysis reveals hub genes involved in cholangiocarcinoma progression and prognosis.

AIM: Cholangiocarcinoma (CCA) is a highly malignant tumor found in the bile duct epithelial cells, and the second most common primary tumor of the liver. However, the pivotal roles of molecular biomarkers in oncogenesis of CCA are unclear. Therefore, we aim to explore the underlying mechanisms of progression and screen for novel prognostic biomarkers and treatment targets. METHOD: The data of mRNA sequencing and clinical information of CCA patients in The Cancer Genome Atlas was analyzed by weighted gene coexpression network analysis (WGCNA). Modules and clinical traits were constructed according to Pearson's correlation analysis, and Gene Ontology and pathway enrichment analysis were applied. Hub genes of these modules were screened by intramodule analysis; Cytoscape with Search Tool for the Retrieval of Interacting Genes was utilized to visualize protein-protein interaction of these modules; hub genes of these modules were validated afterwards. Furthermore, the significance of these genes was confirmed by survival analysis. RESULTS: Genes MRPS18A, CST1, and SCP2 were identified as candidate genes in the module, which was associated with clinical traits including pathological stage, histological grade, and liver function and which also affected overall survival of CCA patients. Nineteen hub genes were analyzed together and were associated with progression and prognosis of CCA. Survival analyses found that several of the multiple genes could serve as biomarkers to stratify CCA patients into low- and high-risk groups. CONCLUSION: These candidate genes could be involved in progression of CCA, which could serve as novel prognostic markers and treatment targets. Moreover, most of them were first reported in CCA and deserve further research.

[Distribution of HCV genotypes in Chinese Han population with chronic hepatitis C].

OBJECTIVE: To investigate the distribution of HCV genotypes in Chinese Han population with chronic hepatitis C (CHC). METHODS: This randomized multicenter study included 1 014 CHC patients from 28 hospitals in different regions of China. SPSS 20.0 was applied to analyze the relationship among region, HCV genotype, gender and the replication level of HCV-RNA. RESULTS: HCV 1 genotype (56.80%) was the most common genotype. The majority of CHC patients were of genotype 1, 2, 3, 6 in the order of frequency, except those in southwestern, southern and central China. HCV 1, 2, 3, 6 genotypes were most common among male patients in southern China; among female patients in northern China; among male patients in northern and northwestern China and among male patients in northwestern China, respectively (all P <0.05). There was no statistical significance between different genders in other regions. The high viral load was more common than the low viral load among HCV 1, 2, 3, 6 genotype-infected patients. CONCLUSION: There are different distributions of HCV genotypes among the different regions. In addition, HCV genotypes are correlated with gender and HCV-RNA load.

Macrophage Perspectives in Liver Diseases: Programmed Death, Related Biomarkers, and Targeted Therapy.

Macrophages, as important immune cells of the organism, are involved in maintaining intrahepatic microenvironmental homeostasis and can undergo rapid phenotypic changes in the injured or recovering liver. In recent years, the crucial role of macrophage-programmed cell death in the development and regression of liver diseases has become a research hotspot. Moreover, macrophage-targeted therapeutic strategies are emerging in both preclinical and clinical studies. Given the macrophages' vital role in complex organismal environments, there is tremendous academic interest in developing novel therapeutic strategies that target these cells. This review provides an overview of the characteristics and interactions between macrophage polarization, programmed cell death, related biomarkers, and macrophage-targeted therapies. It aims to deepen the understanding of macrophage immunomodulation and molecular mechanisms and to provide a basis for the treatment of macrophage-associated liver diseases.

Comparison of perioperative outcomes of selective arterial clipping guided by near-infrared fluorescence imaging using indocyanine green versus undergoing standard robotic-assisted partial nephrectomy: a systematic review and meta-analysis.

BACKGROUND: This study employs a meta-analytic approach to investigate the impact of robotic-assisted partial nephrectomy, with and without near-infrared fluorescence imaging (NIRF-RAPN vs S-RAPN), on patients' perioperative outcomes and postoperative changes in renal function. MATERIALS AND METHODS: The authors conducted a comprehensive and rigorous systematic review and cumulative meta-analysis of primary outcomes following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), AMSTAR (Assessing the Methodological Quality of Systematic Reviews) Guidelines, and Risk-of-Bias Tool (RoB2). To ensure a thorough search, the authors systematically searched five major databases, including Medline, PubMed, Cochrane Library, Scopus, and Web of Science, from databases' inception to April 2023. RESULTS: No significant differences were found between the two groups in terms of age ( P =0.19), right side ( P =0.54), BMI ( P =0.39), complexity score ( P =0.89), tumor size ( P =0.88), operating time ( P =0.39), estimated blood loss ( P =0.47), length of stay ( P =0.87), complications ( P =0.20), transfusion ( P =0.36), and positive margins ( P =0.38). However, it is noteworthy that the NIRF-RAPN group exhibited significant reductions in warm ischemia time ( P =0.001), the percentage change in estimated glomerular filtration rate at discharge ( P =0.01) compared to the S-RAPN group. CONCLUSION: This meta-analysis provides evidence that the group undergoing NIRF-RAPN showed a statistically significant protective effect on the estimated glomerular filtration rate (eGFR).

Naringin from Ganshuang granule inhibits inflammatory to relieve liver fibrosis through TGF-ß-Smad signaling pathway.

OBJECTIVE: The present study aims to investigate the specific protective effects and underlying mechanisms of Ganshuang granule (GSG) on dimethylnitrosamine (DMN)-induced hepatic fibrosis in rat models. METHODS: Hepatic fibrosis was experimentally evoked in rats by DMN administration, and varying dosages of GSG were employed as an intervention. Hepatocellular damage was assessed by measuring serum levels of aminotransferase and bilirubin, accompanied by histopathological examinations of hepatic tissue. The hepatic concentrations of platelet-derived growth factor (PDGF) and transforming growth factor-ß1 (TGF-ß1) were quantitated via enzyme-linked immunosorbent assay (ELISA). The expression of α-smooth muscle actin (α-SMA) within hepatic tissue was evaluated using immunohistochemical techniques. The levels of hepatic interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and a spectrum of interleukins (IL-2, IL-4, IL-6, IL-10) were quantified by quantitative real-time PCR (qRT-PCR). Additionally, hepatic stellate cells (HSCs) were cultured in vitro and exposed to TNF-α in the presence of naringin, a principal component of GSG. The gene expression levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metallopeptidase-1 (MMP-1) in these cells were also quantified by qRT-PCR. Proliferative activity of HSCs was evaluated by the Cell Counting Kit-8 assay. Finally, alterations in Smad protein expression were analyzed through Western blotting. RESULTS: Administration of GSG in rats with fibrosis resulted in reduced levels of serum aminotransferases and bilirubin, along with alleviation of histopathological liver injury. Furthermore, the fibrosis rats treated with GSG exhibited significant downregulation of hepatic TGF-ß1, PDGF, and TNF-α levels. Additionally, GSG treatment led to increased mRNA levels of IFN-γ, IL-2, and IL-4, as well as decreased expression of α-SMA in the liver. Furthermore, treatment with naringin, a pivotal extract of GSG, resulted in elevated expression of MMP-1 and decreased levels of TIMP-1 in TNF-α-stimulated HSCs when compared to the control group. Additionally, naringin administration led to a reduction in Smad expression within the HSCs. CONCLUSION: GSG has the potential to mitigate fibrosis induced by DMN in rat models through the regulation of inflammatory and fibrosis factors. Notably, naringin, the primary extract of GSG, may exert a pivotal role in modulating the TGF-ß-Smad signaling pathway.

Investigation of the application of Enhanced Recovery After Surgery (ERAS) in elderly patients undergoing surgery for kidney stones.

OBJECTIVE: To investigate the efficacy and application of Enhanced Recovery After Surgery (ERAS) in elderly patients undergoing surgery for kidney stones. METHODS: Clinical data of 104 elderly patients who underwent kidney stone surgery at West China Hospital, Sichuan University from January 2020 to December 2022 were retrospectively analyzed in this study. The patients were divided into two groups according to different nursing plans. Among them, 52 patients in the control group received conventional nursing, and 52 patients in the study group received ERAS mode nursing. Postoperative recovery, anxiety, complications, stress response and quality of life were compared between the two groups. RESULTS: The time to recovery of postoperative rehabilitation indices in the research group was significantly shorter compared to the control group (P < 0.05). The research group also exhibited a significantly lower incidence of complications such as hematuria, abdominal pain, vomiting, chills, fever, and hypotension (all P < 0.05). Before the initiation of nursing care, there were no significant differences in the State Anxiety Inventory (SAI) and Trait Anxiety Inventory (TAI) scores between the two groups (both P > 0.05). However, after nursing care, the research group exhibited lower SAI and TAI scores compared to the control group (all P < 0.05). Similarly, there was no significant difference in the General Quality of Life Inventory-74 (GQOLI-74) scores in any dimension between the two groups before nursing care (P > 0.05), but the research group showcased higher scores in every dimension after nursing care (P < 0.05). The levels of Heme Oxygenase-1 (HO-1), Endothelin-1 (ET-1), Adrenocorticotropic Hormone (ACTH), and Cortisol (Cor) were significantly lower in the research group after nursing care (all P < 0.05). The acknowledgment and approval scores of nursing care in the research group were higher than those in the control group (P < 0.05). CONCLUSION: The application of ERAS in elderly patients with kidney stones undergoing transurethral ureteral holmium laser lithotripsy is efficacious in mitigating stress reactions, enhancing quality of life and reducing perioperative anxiety, minimizing the incidence of complications, and promoting overall patient recovery.

Predictors of portal vein thrombosis after splenectomy in patients with cirrhosis.

BACKGROUND: Portal vein thrombosis (PVT) is a commonthsn complication after splenectomy in patients with cirrhosis. However, the predictors of postoperative PVT are not known. AIM: To investigate the predictors of PVT after splenectomy in patient with cirrhosis. METHODS: A total of 45 patients with cirrhosis who underwent splenectomy were consecutively enrolled from January 2017 to December 2018. The incidence of PVT at 1 months, 3 months, and 12 months after splenectomy in patients with cirrhosis was observed. The hematological indicators, biochemical and coagulation parameters, and imaging features were recorded at baseline and at each observation point. The univariable, multivariable, receiver operating characteristic curve and time-dependent curve analyses were performed. RESULTS: The cumulative incidence of PVT was 40.0%, 46.6%, and 48.9% at 1 months, 3 months, and 12 months after splenectomy. Multivariable analysis showed that portal vein diameter (PVD) ≥ 14.5 mm and monthsdel end-stage liver disease (MELD) score > 10 were independent predictors of PVT at 1 months, 3 months, and 12 months after splenectomy (P < 0.05). Time-dependent curve showed that the cumulative incidence of PVT was significantly different between patients with MELD score ≤ 10 and > 10 (P < 0.05). In addition, the cumulative incidence of PVT in the PVD ≥ 14.5 mm group was significantly higher than that in the PVD < 14.5 mm group (P < 0.05). CONCLUSION: Wider PVD and MELD score > 10 were independent predictors of PVT at 1 months, 3 months, and 12 months after splenectomy in patient with cirrhosis.

[Association of hepatitis C virus genotype with glycolipid iron metabolism in Gansu Han population].

OBJECTIVE: To investigate the association of hepatitis C virus (HCV) genotype with glycolipids iron metabolism in Gansu Han population. METHODS: The genotypes of HCV 1b type and 2a type were detected in Gansu Han HCV carriers. The Glu, Insulin, CHOL, TG, UIBC, TRF, TIBC, SF, Serum Iron, AST, ALT, TBil, IBil, DBil, ALP, GGT were measured and compared between patients with different HCV genotypes. RESULTS: There were 84 cases with HCV1b type and 136 cases with 2a type. There were significant differences in TG, ALT, TRF, TIBC between 1b type and 2a type genotype HCV carriers. CONCLUSION: The 2a type HCV carriers may be more inclined to develop hyperlipidemia and liver damage, and 1b type HCV carriers are likely to have iron metabolism defect.