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AIMS: To explore rare and difficult cases of undifferentiated embryonal sarcoma of the liver (UESL) in children in a single centre, summarize the diagnosis and treatment experience and analyse the role of a computer-assisted surgery system (Hisense CAS), thus providing a new global vision and three-dimensional perspective. METHODS: We retrospectively collected the clinical data including the diagnoses and treatment processes, of children with UESL confirmed by histopathological examination in our hospital from January 2009 to December 2020. The relationship between the tumour volume and important blood vessels and between the liver volume and tumour volume, as well as other three-dimensional characteristics in the reconstructed three-dimensional model were analysed using Hisense CAS. The findings from this analysis can be used to aid in surgical decision-making and preoperative planning. RESULTS: Four children-3 girls and 1 boy-with UESL were included in the study. The age at onset ranged from 6 to 8 years. All four children presented with symptoms of abdominal discomfort, and abdominal masses were detected during physical examination. Owing to the wishes of their parents and the possibility that the disease was benign, all four children underwent one-stage radical surgery. For patient 1, a three-dimensional reconstruction was created during the initial diagnosis, which made accurate evaluation and planning of the preoperative procedure challenging. In patient 2, the tumour was located in the middle lobe of the liver and involved the first and second hepatic hilum. For patient 3, the pathological diagnosis of the tumour after surgery was challenging, but eventually, the diagnosis was confirmed through histochemistry and consultation with higher-level hospitals. Patient 4 had a giant tumour, which had a preoperative simulated future liver remnant volume (FLV) that was 21.0% of the total volume of the liver and tumour (TLTV). According to the standard liver volume (SLV) for children, the FLV was 77.0% of the SLV, making surgery feasible. All four children underwent complete resection, and only patient 4 experienced recurrence below the diaphragm 19 months after surgery. Currently, the 3-year overall survival rate is 100%, and the 3-year event-free survival rate is 75%. CONCLUSION: UESL in children is rare, and the key to diagnosis and treatment is complete surgical resection. Through individualized three-dimensional surgical planning, accurate and complete resection of difficult and complex UESL in children can be achieved, leading to a favourable prognosis.
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Liver Neoplasms , Neoplasms, Germ Cell and Embryonal , Sarcoma , Humans , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Male , Female , Child , Retrospective Studies , Sarcoma/surgery , Sarcoma/pathology , Sarcoma/diagnosis , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/surgery , Neoplasms, Germ Cell and Embryonal/diagnosis , Prognosis , Imaging, Three-Dimensional , Surgery, Computer-Assisted/methods , Hepatectomy/methods , Follow-Up Studies , Tomography, X-Ray ComputedABSTRACT
Toward the development of a sustainable utilization strategy for adsorption materials, a starch-based adsorbent starch-chitosan-tannic acid (St-CTS-TA) with a three-dimensional (3D) structure was fabricated in water via electrostatic and hydrogen bonding reactions between St, CTS, and TA without using toxic reducing agents or special instruments. St-CTS-TA demonstrated a high specific surface area of 37 m2/g as well as a mesoporous/macroporous distribution ranging from 30 to 80 nm, which enhanced the mass transfer of adsorbate and the exposure of catechol groups in TA. The Langmuir isotherm adsorption model revealed that the highest adsorption capacities of St-CTS-TA for Fe3+ and Co2+ were 1678.2 and 944.8 mg/g, respectively. Surprisingly, the specific surface area of St-CTS-TA increased from 37 to 87 and 42 m2/g after Fe3+ and Co2+ adsorption, respectively, and the resulting St-CTS-TA-Fe and St-CTS-TA-Co could continuously adsorb basic fuchsin (BF) and rhodamine B (RhB). The adsorption capacities of St-CTS-TA-Fe and St-CTS-TA-Co for BF/RhB were found to be 1854.79/401.19 mg/g and 2229.77/537.49 mg/g, respectively, based on the Langmuir isotherm adsorption model.
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Chitosan , Nanostructures , Starch , Adsorption , Starch/chemistry , Nanostructures/chemistry , Chitosan/chemistry , Water Pollutants, Chemical/chemistry , Water Purification/methods , Porosity , RhodaminesABSTRACT
Cell sheet technology has emerged as a novel scaffold-free approach for cell-based therapies in regenerative medicine. Techniques for harvesting cell sheets are essential to preserve the integrity of living cell sheets. This review provides an overview of fundamental technologies to fabricate cell sheets and recent advances in cell sheet-based tissue engineering. In addition to the commonly used temperature-responsive systems, we introduce alternative approaches, such as ROS-induced, magnetic-controlled, and light-induced cell sheet technologies. Moreover, we discuss the modification of the cell sheet to improve its function, including stacking, genetic modification, and vascularization. With the significant advances in cell sheet technology, cell sheets have been widely applied in various tissues and organs, including but not limited to the lung, cornea, cartilage, periodontium, heart, and liver. This review further describes both the preclinical and clinical applications of cell sheets. We believe that the progress in cell sheet technology would further propel its biomedical applications.
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Type 2 innate lymphoid cells were found to be members of the innate immune cell family, which is involved in innate and adaptive immunity to resist the invasion of foreign antigens and induce allergic reactions caused by allergens. The advancement of ILC2 research has pointed out that ILC2s have a high degree of diversity, challenging the notion of their homogeneity as a cellular population. An increasing number of studies indicate that ILC2 is a cell population with tissue specificity which can be induced by the tissue microenvironment. In addition, crosstalk between tissues can change ILC2 functions of migration and activation. Here, we emphasize that ILC2 undergoes adaptive changes under the regulation of the tissue microenvironment and distant tissues, thereby coordinating the organization's operation. In addition, ILC2 alterations induced by the tissue microenvironment are not limited to the ILC2 cell population, and ILC2 can also transdifferentiate into another class of ILC cell population (ILC1 or ILC3). In this review, we summarized the tissue-specific effects of ILC2 by tissue microenvironment and focused on the function of ILC2 in inter-tissue crosstalk. Lastly, we discussed the transdifferentiations of ILC2 caused by the abnormal change in tissue environment.
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Physical exercise has beneficial effect on anxiety disorders, but the underlying molecular mechanism remains largely unknown. Here, it is demonstrated that physical exercise can downregulate the S-nitrosylation of gephyrin (SNO-gephyrin) in the basolateral amygdala (BLA) to exert anxiolytic effects. It is found that the level of SNO-gephyrin is significantly increased in the BLA of high-anxiety rats and a downregulation of SNO-gephyrin at cysteines 212 and 284 produced anxiolytic effect. Mechanistically, inhibition of SNO-gephyrin by either Cys212 or Cys284 mutations increased the surface expression of GABAAR γ2 and the subsequent GABAergic neurotransmission, exerting anxiolytic effect in male rats. On the other side, overexpression of neuronal nitric oxide synthase in the BLA abolished the anxiolytic-like effects of physical exercise. This study reveals a key role of downregulating SNO-gephyrin in the anxiolytic effects of physical exercise, providing a new explanation for protein post-translational modifications in the brain after exercise.
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A pot experiment was conducted to investigate the combined effects of different nitrogen fertilizer levels (5, 25, and 45 kg of pure nitrogen per 667 m²) and biochar concentrations (0, 0.7, 1.4, and 2.1%) on the growth, yield, and fruit quality of pepper. The findings indicated that a combination of 25 kg/667 m2 of nitrogen and either 0.7% or 1.4% biochar significantly enhanced plant growth, yield, and fruit quality. Specifically, the N2 treatment (25 kg of pure nitrogen per 667 m²) increased substrate porosity, alkali-hydrolyzed nitrogen content, and available phosphorus content. It also boosted root activity and superoxide dismutase activity in pepper leaves, resulting in increased yield and better fruit quality. Furthermore, the proper addition of biochar (0.7-1.4% by weight) enhanced the physical and chemical properties of the substrate, including increased chlorophyll content and enzyme activity in plants, thereby leading to improved overall plant growth, yield, and fruit quality.
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Sjögren's syndrome (SS) is an autoimmune disease in which the salivary glands (SGs) and the lacrimal glands (LGs) are affected by lymphocytic infiltration and inflammation. It has been reported that interferon-α (IFN-α) released by plasmacytoid dendritic cells (pDCs) contribute to the pathology of SS, and ART has been shown to effectively ameliorates SS. Despite the current research endeavors, the mechanism of how ART works in the treatment of SS remains to be fully elucidated. Whether ART can treat SS by inhibiting IFN-α remains unclear. This hypothesis was tested both in vivo and in vitro settings during the study. The SS model mice, which were treated with ART, showed amelioration in symptoms related to dryness. RNA-seq analysis revealed strong anti-IFN-α signaling response upon ART treatment. Additional in vitro studies provided further confirmation that the application of ART inhibits the MyD88 protein expression and the nuclear translocation of IRF7. This suggests that the intervention of ART in the TLR-MyD88-IRF7 pathway plays a role in the therapeutic approach for SS. In summary, this study highlighted the therapeutic potential of ART in SS and ART inhibited the IFN-α signaling in pDCs via the TLR-MyD88-IRF7 pathway.
Subject(s)
Artesunate , Dendritic Cells , Interferon Regulatory Factor-7 , Interferon-alpha , Mice, Inbred C57BL , Myeloid Differentiation Factor 88 , Signal Transduction , Sjogren's Syndrome , Animals , Sjogren's Syndrome/drug therapy , Sjogren's Syndrome/metabolism , Dendritic Cells/drug effects , Dendritic Cells/metabolism , Myeloid Differentiation Factor 88/metabolism , Interferon-alpha/metabolism , Interferon-alpha/pharmacology , Signal Transduction/drug effects , Interferon Regulatory Factor-7/metabolism , Mice , Artesunate/pharmacology , Artesunate/therapeutic use , Toll-Like Receptors/metabolism , Female , Disease Models, AnimalABSTRACT
Gold nanoclusters exhibiting concomitant photothermy (PT) and photoluminescence (PL) under near-infrared (NIR) light irradiation are rarely reported, and some fundamental issues remain unresolved for such materials. Herein, we concurrently synthesized two novel rod-shaped Au nanoclusters, Au52(PET)32 and Au66(PET)38 (PET = 2-phenylethanethiolate), and precisely revealed that their kernels were 4 × 4 × 6 and 5 × 4 × 6 face-centered cubic (fcc) structures, respectively, based on the numbers of Au layers in the [100], [010], and [001] directions. Following the structural growth mode from Au52(PET)32 to Au66(PET)38, we predicted six more novel nanoclusters. The concurrent synthesis provides rational comparison of the two nanoclusters on the stability, absorption, emission and photothermy, and reveals the aspect ratio-related properties. An interesting finding is that the two nanoclusters exhibit concomitant PT and PL under 785â nm light irradiation, and the PT and PL are in balance, which was explained by the qualitative evaluation of the radiative and non-radiative rates. The ligand effects on PT and PL were also investigated.
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Phosphatidylserine (PS) is an important lipid signaling required for plant growth regulation and salt stress adaptation. However, how PS positively regulate plant salt tolerance is still largely unknown. In this study, IbPSS1-overexpressed sweetpotato plants that exhibited overproduction of PS was employed to explore the mechanisms underlying the PS stimulation of plant salt tolerance. The results revealed that the IbPSS1-overexpressed sweetpotato accumulated less Na+ in the stem and leaf tissues compared with the wild type plants. Proteomic profile of roots showed that lignin synthesis-related proteins over-accumulated in IbPSS1-overexpressed sweetpotato. Correspondingly, the lignin content was enhanced but the influx of Na + into the stele was significantly blocked in IbPSS1-overexpressed sweetpotato. The results further revealed that ethylene synthesis and signaling related genes were upregulated in IbPSS1-overexpressed sweetpotato. Ethylene imaging experiment revealed the enhancement of ethylene mainly localized in the root stele. Inhibition of ethylene synthesis completely reversed the PS-overproduction induced lignin synthesis and Na+ influx pattern in stele tissues. Taken together, our findings demonstrate a mechanism by which PS regulates ethylene signaling and lignin synthesis in the root stele, thus helping sweetpotato plants to block the loading of Na+ into the xylem and to minimize the accumulation of Na+ in the shoots.
Subject(s)
Ethylenes , Ipomoea batatas , Lignin , Plant Proteins , Plant Roots , Salt Tolerance , Signal Transduction , Ethylenes/metabolism , Ethylenes/biosynthesis , Lignin/metabolism , Lignin/biosynthesis , Ipomoea batatas/genetics , Ipomoea batatas/metabolism , Plant Roots/metabolism , Plant Roots/genetics , Salt Tolerance/genetics , Plant Proteins/metabolism , Plant Proteins/genetics , Gene Expression Regulation, Plant , Plants, Genetically Modified , Phosphatidylserines/metabolism , Sodium/metabolismABSTRACT
BACKGROUND: Long noncoding RNAs (lncRNAs) participate in diseases, especially tumorigenesis, including gastric cancer (GC). Although lncRNAs in GC tissues have been extensively studied in previous research, the possible significance of circulating lncRNAs in diagnosing GC is still unknown. OBJECTIVE: The present work investigated lncRNAs ZFPM2-AS1 and XIST with high expression in GC tissues proved as potential plasma biomarkers from 20 early GC cases, 100 GC cases, and 90 normal subjects. METHODS: The possible correlation between ZFPM2-AS1 and XIST expression levels was analyzed with general characteristics and clinicopathological features. The performance in diagnosis was assessed according to receiver operating characteristic (ROC) analysis. RESULTS: According to the results, XIST and ZFPM2-AS1 expression remarkably increased within GC plasma relative to normal subjects (P< 0.01); besides, lncRNA XIST expression after surgery had a tendency of downregulation compared with preoperative levels (P< 0.05). Moreover, the area under ROC curve (AUC) values were 0.62 for ZFPM2-AS1 and 0.68 for XIST, while the pooled AUC value of CA-724 and two lncRNAs was 0.751. CONCLUSION: Circulating lncRNAs ZFPM2-AS1 and XIST can serve as the candidate plasma biomarkers used to diagnose GC.
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BACKGROUND: The management of hepatoblastoma (HB) becomes challenging when the tumor remains in close proximity to the major liver vasculature (PMV) even after a full course of neoadjuvant chemotherapy (NAC). In such cases, extreme liver resection can be considered a potential option. AIM: To explore whether computer-assisted three-dimensional individualized extreme liver resection is safe and feasible for children with HB who still have PMV after a full course of NAC. METHODS: We retrospectively collected data from children with HB who underwent surgical resection at our center from June 2013 to June 2023. We then analyzed the detailed clinical and three-dimensional characteristics of children with HB who still had PMV after a full course of NAC. RESULTS: Sixty-seven children diagnosed with HB underwent surgical resection. The age at diagnosis was 21.4 ± 18.8 months, and 40 boys and 27 girls were included. Fifty-nine (88.1%) patients had a single tumor, 39 (58.2%) of which was located in the right lobe of the liver. A total of 47 patients (70.1%) had PRE-TEXT III or IV. Thirty-nine patients (58.2%) underwent delayed resection. After a full course of NAC, 16 patients still had close PMV (within 1 cm in two patients, touching in 11 patients, compressing in four patients, and showing tumor thrombus in three patients). There were 6 patients of tumors in the middle lobe of the liver, and four of those patients exhibited liver anatomy variations. These 16 children underwent extreme liver resection after comprehensive preoperative evaluation. Intraoperative procedures were performed according to the preoperative plan, and the operations were successfully performed. Currently, the 3-year event-free survival of 67 children with HB is 88%. Among the 16 children who underwent extreme liver resection, three experienced recurrence, and one died due to multiple metastases. CONCLUSION: Extreme liver resection for HB that is still in close PMV after a full course of NAC is both safe and feasible. This approach not only reduces the necessity for liver transplantation but also results in a favorable prognosis. Individualized three-dimensional surgical planning is beneficial for accurate and complete resection of HB, particularly for assessing vascular involvement, remnant liver volume and anatomical variations.
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Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiple etiological factors. Immune disorder contributes to SLE development and is an important clinical manifestation of SLE patients. Immune dysfunction is characterized by abnormal of B cells, T cells, monocyte-macrophages and dendritic cells (DCs), in both quantity and quality. Adenosine is a critical factor for human immune homeostasis, which acts as an immunosuppressive signal and can prevent the hyperactivity of human immune system. Adenosine levels are significant decreased in serum from SLE patients. Adenosine level is regulated by the CD39, CD73 and adenosine deaminase (ADA). CD39/CD73/ADA catalyzed the cascade enzymatic reaction, which contained the adenosine generation and degradation. Adenosine affects the function of various immune cells via bind to the adenosine receptors, which are expressed on the cell surface. This review aims to export the changes of immune cells and adenosine signal pathway in SLE, as well as the effect of adenosine signal pathway in SLE development.
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For a long time, human activities have been prohibited in ecologically protected areas in the Ebinur Lake Wetland National Nature Reserve (ELWNNR). The implementation of total closure is one of the main methods for ecological protection. For arid zones, there is a lack of in-depth research on whether this measure contributes to ecological restoration in the reserve. The Normalized Difference Vegetation Index (NDVI) is considered to be the best indicator for ecological monitoring and has a key role to play in assessing the ecological impacts of total closure. In this study, we used Sentinel-2, Landsat-8, and Moderate Resolution Imaging Spectroradiometer (MODIS) remote sensing data to select optimal data and utilized Sen slope estimation, Mann-Kendall statistical tests, and the geographical detector model to quantitatively analyze the normalized difference vegetation index (NDVI) dynamics and its driving factors. Results were as follows: (1) The vegetation distribution of the Ebinur Lake Wetland National Nature Reserve (ELWNNR) had obvious spatial heterogeneity, showing low distribution in the middle and high distribution in the surroundings. The correlation coefficients of Landsat-8 and MODIS, Sentinel-2 and MODIS, and Sentinel-2 and Landsat-8 were 0.952, 0.842, and 0.861, respectively. The NDVI calculated from MODIS remote sensing data was higher than the value calculated by Landsat-8 and Sentinel-2 remote sensing images, and Landsat-8 remote sensing data were the most suitable data. (2) NDVI indicated more degraded areas on the whole, but the ecological recovery was obvious in the localized areas where anthropogenic closure was implemented. The ecological environment change was the result of the joint action of man and nature. Man-made intervention will change the local ecological environment, but the overall ecological environment change was still dominated by natural environmental factors. (3) Factors affecting the distribution of NDVI in descending order were as follows: precipitation > evapotranspiration > land use type > elevation > vegetation type > soil type > soil erosion > slope > temperature > slope direction. Precipitation was the main driver of vegetation change in ELWNNR. The synergistic effect of the factors showed two-factor enhancement and nonlinear enhancement, and the combined effect of the driving factors would increase the influence on NDVI.
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BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing year by year and has become one of the leading causes of end-stage liver disease worldwide. Triggering Receptor Expressed on Myeloid Cells 2 (Trem2) has been confirmed to play an essential role in the progression of MASLD, but its specific mechanism still needs to be clarified. This study aims to explore the role and mechanism of Trem2 in MASLD. METHODS: Human liver tissues were obtained from patients with MASLD and controls. Myeloid-specific knockout mice (Trem2mKO) and myeloid-specific overexpression mice (Trem2TdT) were fed a high-fat diet, either AMLN or CDAHFD, to establish the MASLD model. Relevant signaling molecules were assessed through lipidomics and RNA-seq analyses after that. RESULTS: Trem2 is upregulated in human MASLD/MASH-associated macrophages and is associated with hepatic steatosis and inflammation progression. Hepatic steatosis and inflammatory responses are exacerbated with the knockout of myeloid Trem2 in MASLD mice, while mice overexpressing Trem2 exhibit the opposite phenomenon. Mechanistically, Trem2mKO can aggravate macrophage pyroptosis through the PI3K/AKT signaling pathway and amplify the resulting inflammatory response. At the same time, Trem2 promotes the inflammation resolution phenotype transformation of macrophages through TGFß1, thereby promoting tissue repair. CONCLUSIONS: Myeloid Trem2 ameliorates the progression of Metabolic dysfunction-associated steatotic liver disease by regulating macrophage pyroptosis and inflammation resolution. We believe targeting myeloid Trem2 could represent a potential avenue for treating MASLD.
Subject(s)
Disease Progression , Fatty Liver , Inflammation , Macrophages , Membrane Glycoproteins , Pyroptosis , Receptors, Immunologic , Animals , Humans , Male , Mice , Fatty Liver/metabolism , Fatty Liver/pathology , Fatty Liver/genetics , Inflammation/metabolism , Inflammation/pathology , Liver/metabolism , Liver/pathology , Macrophages/metabolism , Membrane Glycoproteins/metabolism , Membrane Glycoproteins/genetics , Metabolic Diseases/metabolism , Metabolic Diseases/pathology , Metabolic Diseases/genetics , Mice, Inbred C57BL , Mice, Knockout , Pyroptosis/physiology , Receptors, Immunologic/metabolism , Receptors, Immunologic/geneticsABSTRACT
To reduce the cost of healthcare expenditures in China, the government has developed a centralised volume-based procurement (CVBP) policy for medicines and medical consumables. Based on tracking the development history of centralised procurement in China, this study explores China's CVBP model. By comparing the centralised procurement models and healthcare expenditure data among China, the United States (U.S), the United Kingdom (UK), and Singapore, we find that China still faces many challenges in implementing the CVBP policy. The main challenges are as follows. First, the policy cannot be guaranteed the effectiveness of implementation without a well-coordinated regulatory mechanism. Second, the CVBP rules and quality evaluation standards are imperfect. Third, the interests of healthcare companies cannot be guaranteed. Fourth, the policy affects the benefits of medical institutions, and the government has not built a compensation mechanism for medical institutions. Fifth, it poses a challenge to the operational capacity and innovation level of Chinese companies. Therefore, this paper posits a three-stage strategy and nine measures that could benefit China's progress in implementing the CVBP policy.
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BACKGROUND: According to epidemiological studies, particulate matter 2.5 (PM2.5) is a significant contributor to cardiovascular disease (CVD). However, making causal inferences is difficult due to the methodological constraints of observational studies. In this study, we used two-sample Mendelian randomization (MR) to examine the causal relationship between PM 2.5 and the risk of CVD. METHODS: Genome-wide association study (GWAS) statistics for PM2.5 and CVD were collected from the FinnGen and UK Biobanks. Mendelian randomization analyses were applied to explore the causal effects of PM2.5 on CVD by selecting single-nucleotide polymorphisms(SNP) as instrumental variables. RESULTS: The results revealed that a causal effect was observed between PM2.5 and coronary artery disease(IVW: OR 2.06, 95% CI 1.35, 3.14), and hypertension(IVW: OR 1.07, 95% CI 1.03, 1.12). On the contrary, no causal effect was observed between PM2.5 and myocardial infarction(IVW: OR 0.73, 95% CI 0.44, 1.22), heart failure(IVW: OR 1.54, 95% CI 0.96, 2.47), atrial fibrillation(IVW: OR 1.03, 95% CI 0.71, 1.48), and ischemic stroke (IS)(IVW: OR 0.98, 95% CI 0.54, 1.77). CONCLUSION: We discovered that there is a causal link between PM2.5 and coronary artery disease and hypertension in the European population, using MR methods. Our discovery may have the significance of public hygiene to improve the understanding of air quality and CVD risk.
Subject(s)
Cardiovascular Diseases , Coronary Artery Disease , Hypertension , Humans , Cardiovascular Diseases/etiology , Cardiovascular Diseases/genetics , Coronary Artery Disease/etiology , Coronary Artery Disease/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Particulate Matter/adverse effectsABSTRACT
This study is to explore the proportion of significant liver histopathology in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients with normal alanine aminotransferase (ALT) and investigate noninvasive indicators for predicting significant liver histopathology. A total of 201 HBeAg-negative chronic HBV-infected patients with normal ALT who underwent liver biopsy were involved in this study. Significant liver histological changes were defined as necroinflammation grade ≥2 (G ≥ 2) and/or fibrosis stage ≥2 (S ≥ 2). The results showed that 42.3% (85/201) and 45.8% (92/201) of the HBeAg-negative patients with normal ALT have significant liver necroinflammation (G ≥ 2) and fibrosis (S ≥ 2), respectively. High normal ALT (>22 U/L), high level of serum HBV DNA (>3.42 log IU/mL), and low level of prealbumin (PA) (<170 mg/L) were independent predictors for significant liver necroinflammation, and the predictive value of the combined indicators was 0.750 (P < 0.001), while high normal ALT (>24 U/L) and high level of FIB-4 (>1.53) were independent predictors for significant liver fibrosis, and the predictive value of the combined indicators was 0.740 (P < 0.001). In conclusion, more than 40% of HBeAg-negative patients with normal ALT have significant liver histopathology and require immediate antiviral treatment. ALT, PA, HBV DNA, and FIB-4 can independently predict significant liver inflammation and fibrosis for HBeAg-negative patients with normal ALT. Lowering the treatment threshold of ALT may benefit the HBeAg-negative chronic HBV-infected patients. IMPORTANCE: Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients with normal alanine aminotransferase (ALT) were supposed to have a low risk of progression to cirrhosis or hepatocellular carcinoma, and it was recommended to regularly follow up or undergo liver biopsy to assess liver histopathology according to the major international guidelines. However, this study indicates that a considerable number of HBeAg-negative chronic HBV-infected patients with normal ALT have significant liver histopathology and require immediate antiviral treatment. Besides, several clinical commonly used noninvasive indicators were found that can be used to predict significant liver histopathology; thereby liver biopsy might be avoided for HBeAg-negative chronic HBV-infected patients with normal ALT.
Subject(s)
Hepatitis B, Chronic , Humans , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , Hepatitis B e Antigens/therapeutic use , Alanine Transaminase , DNA, Viral , Liver Cirrhosis/diagnosis , Liver Cirrhosis/pathology , Fibrosis , Biomarkers , Antiviral Agents/therapeutic useABSTRACT
Typhoons can bring substantial casualties and economic ramifications, and effective prevention strategies necessitate a comprehensive risk assessment. Nevertheless, existing studies on its comprehensive risk assessment are characterized by coarse spatial scales, limited incorporation of geographic big data, and rarely considering disaster mitigation capacity. To address these problems, this study combined multi-source geographic big data to develop the Comprehensive Risk Assessment Model (CRAM). The model integrated 17 indicators from 4 categories of factors, including exposure, vulnerability, hazard, and mitigation capacity. A subjective-objective combination weighting method was introduced to generate the indicator weights, and comprehensive risk index of typhoon disasters was calculated for 987 counties along China's coastal regions. Results revealed a pronounced spatial heterogeneity of the comprehensive typhoon risk, which exhibited an overall decreasing trend from the southeast coastal areas toward the northwest inland territories. 61.7 % of the counties exhibited a medium-to-high level of comprehensive risk, and counties with very-high risks are predominantly concentrated in the Shandong Peninsula, Yangtze River Delta, Hokkien Golden Triangle, Greater Bay Area, Leizhou Peninsula, and Hainan Province, mainly due to high exposure and hazard factors. The correlation coefficient between the risk assessment results and typhoon-induced direct economic losses reached 0.702, indicating the effectiveness and reliability of the CRAM. Meanwhile, indicators from intrinsic attributes of typhoons and geographic big data had pronounced importance, and regional mitigation capacity should be improved. Our proposed method can help to scientifically understand spatial patterns of comprehensive risk and mitigate the effects of typhoon disasters in China's coastal regions.
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BACKGROUND: Diabetes retinopathy (DR) is one of the most common microvascular consequences of diabetes, and the economic burden is increasing. Our aim is to decipher the relevant mechanisms of immune-related gene features in DR and explore biomarkers targeting DR. Provide a basis for the treatment and prevention of DR. METHOD: The immune infiltration enrichment score of DR patients was evaluated from the single- cell RNA sequencing dataset, and the samples were divided into low immune subgroups and high immune subgroups based on this result. Through weighted gene correlation network analysis, differentially expressed genes (DEGs) between two subgroups were identified and crossed with genes with the strongest immune association, resulting in significant key genes. Then divide the DR individuals into two immune related differentially expressed gene (IDEG) clusters, A and B. Submit cross DEGs between two clusters through Gene Set Enrichment Analysis (GSEA) to further explore their functions. A protein-protein interaction (PPI) network of IDEG was established to further identify central genes associated with DR. Use the discovered central genes to predict the regulatory network involved in the pathogenesis of DR. Then, the role of the identified hub gene in the pathogenesis of DR was further studied through in vitro experiments. RESULT: We found that the immune scores of DR and control groups were different, and 27 IDEGs were found in the DR subgroup. Compared with cluster A, the proportion of cytotoxic lymphocytes, B lineage, monocyte lineage, and fibroblasts in DR patients in cluster B is significantly enriched. GSEA indicates that these genes are associated with T cell activation, regulation of immune response processes, lymphocyte-mediated immunity, TNF signaling pathway, and other signaling pathways. The PPI network subsequently identified 10 hub genes in DR, including SIGLEC10, RGS10, PENK, FGD2, LILRA6, CIITA, EGR2, SIGLEC7, LILRB1, and CD300LB. The upstream regulatory network and lncRNA miRNA mRNA ceRNA network of these hub genes were ultimately constructed. The discovery and identification of these genes will provide biomarkers for targeted prediction and treatment of DR. CONCLUSION: By integrating bioinformatics analysis and in vitro experiments, we have identified a set of central genes, indicating that these genes can serve as potential biomarkers for DR, which may be promising targets for future DR immunotherapy interventions.
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BACKGROUND: Nephroblastoma, also known as Wilms' tumor (WT), is an embryonic malignant tumor and one of the most common malignant tumors in the abdominal region of children. The exact role and underlying mechanisms of aquaporin-1 (AQP1) in the occurrence and development of nephroblastoma remain unclear. METHODS: After overexpression of AQP1, cell proliferation was assessed using the CCK-8 proliferation assay and EdU staining. Flow cytometry was employed to assess cell apoptosis, and Western blotting (WB) analysis was conducted to validate the expression of relevant protein markers. mRNA sequencing (mRNA-Seq) was performed on WT cells overexpressing AQP1 to predict and characterize the associated mechanisms. Transmission electron microscopy was utilized to observe changes in the ultrastructure of WT cells undergoing apoptosis and pyroptosis following AQP1 overexpression. Functional in vivo validation was conducted through animal experiments. RESULTS: We validated that overexpression of AQP1 inhibited cell proliferation and promoted cell apoptosis and pyroptosis both in vitro and in vivo. mRNA-Seq analysis of WT cells with AQP1 overexpression suggested that these effects might be mediated through the inhibition of the JAK-STAT signaling pathway. Additionally, we discovered that overexpression of AQP1 activated the classical pyroptosis signaling pathway dependent on caspase-1, thereby promoting pyroptosis in WT. CONCLUSION: These findings highlight the important functional role of AQP1 in the pathobiology of nephroblastoma, providing novel insights into the development of this disease. Moreover, these results offer new perspectives on the potential therapeutic targeting of AQP1 as a treatment strategy for nephroblastoma.