Progress and hotspot of diet or exercise therapy in the treatment of non-alcoholic fatty liver disease.

Introduction: The primary treatment for non-alcoholic fatty liver disease (NAFLD) is modifying lifestyle through dietary or exercise interventions. In recent decades, it has received increasing attention. However, the lack of bibliometric analysis has posed a challenge for researchers seeking to understand the overall trends in this field. Methods: As of February 3rd, 2024, 876 articles on treating NAFLD through diet or exercise therapy from 2013 to 2023 had been retrieved. Two software tools, VOSviewer and CiteSpace, were utilized to analyze the growth of publications, countries, institutions, authors, journals, citations, and keywords. Additionally, the keywords with strong citation burstiness were identified to determine the changes and future trends of research hotspots in this field. Results: China had the highest number of articles, followed by the United States and South Korea. Yonsei University and Nutrients were the institutions and journals with the most significant contributions. Professor Younossi Zobair M, from the United States, is the most prolific author in this field. Through analyzing the keywords, three research hotspots were identified: research on the pathogenesis of NAFLD, research on the treatment modalities of NAFLD, and research on the risk factors and diagnosis methods of NAFLD. In recent years, the research emphasis in this field has changed, suggesting that future research will focus on two frontier keywords: "oxidative stress" and "aerobic capacity." Conclusion: In the past eleven years, the attention in this field was still rising, and the authors, journals, countries and so on had formed a considerable cooperative relationship. There were also many highly influential and productive researchers in this field. It is speculated that new research will continue around "aerobic exercise" and "oxidative stress" in the future.

Effects of Ganjianglingzhu Decoction on Lean Non-Alcoholic Fatty Liver Disease in Mice Based on Untargeted Metabolomics.

Non-alcoholic fatty liver disease (NAFLD) is usually associated with obesity. However, it is crucial to recognize that NAFLD can also occur in lean individuals, which is frequently overlooked. Without an approved pharmacological therapy for lean NAFLD, we aimed to investigate whether the Ganjianglingzhu (GJLZ) decoction, a representative traditional Chinese medicine (TCM), protects against lean NAFLD and explore the potential mechanism underlying these protective effects. The mouse model of lean NAFLD was established with a methionine-choline-deficient (MCD) diet in male C57BL/6 mice to be compared with the control group fed the methionine-choline-sufficient (MCS) diet. After four weeks, physiological saline, a low dose of GJLZ decoction (GL), or a high dose of GJLZ decoction (GH) was administered daily by gavage to the MCD group; the MCS group was given physiological saline by gavage. Untargeted metabolomics techniques were used to explore further the potential mechanism of the effects of GJLZ on lean NAFLD. Different doses of GJLZ decoction were able to ameliorate steatosis, inflammation, fibrosis, and oxidative stress in the liver; GL performed a better effect on lean NAFLD. In addition, 78 candidate differential metabolites were screened and identified. Combined with metabolite pathway enrichment analysis, GL was capable of regulating the glucose and lipid metabolite pathway in lean NAFLD and regulating the glycerophospholipid metabolism by altering the levels of sn-3-O-(geranylgeranyl)glycerol 1-phosphate and lysoPC(P-18:0/0:0). GJLZ may protect against the development of lean NAFLD by regulating glucose and lipid metabolism, inhibiting the levels of sn-3-O-(geranylgeranyl)glycerol 1-phosphate and lysoPC(P-18:0/0:0) in glycerophospholipid metabolism.

Tc-99m-MIBI SPECT/CT imaging to diagnose secondary hyperparathyroidism after parathyroid forearm transplantation.

This article report a 40-year-old male patient who underwent total thyroidectomy and forearm auto-transplantation in another hospital for secondary hyperparathyroidism. After 4 years of follow-up, the level of parathyroid hormone continued to increase, and ultrasound showed nodules in the neck and right forearm, which were considered to be of parathyroid origin. Technetium 99m sestamibi single photon emission computed tomography and computed tomography (Tc-99m-MIBI SPECT/CT) imaging showed increased radioactive uptake in the submuscular soft tissue nodule of the right medial forearm, maximum standardized uptake value (SUVmax) is 0.98, which was identified as transplanted functioning parathyroid tissue. No parathyroid imaging activity was found in the neck. The patient then underwent partial removal of ectopic parathyroid tissue from the right forearm. Pathological examination confirmed parathyroid tissue, and removal was followed by a rapid decline in serum parathyroid hormone levels.

Advancing Alzheimer's research: Radiomics visualization of the default mode network in cerebral perfusion imaging.

OBJECTIVE: Alzheimer's disease, an irreversible neurological condition, demands timely diagnosis for effective clinical intervention. This study employs radiomics analysis to assess image features in default mode network cerebral perfusion imaging among individuals with cognitive impairment. METHODS: A radiomics analysis of cerebral perfusion imaging was conducted on 117 patients with cognitive impairment. They were divided into training and validation sets in a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest were employed to select and model image features, followed by logistic regression analysis of LASSO and Random Forest results. Diagnostic performance was assessed by calculating the area under the curve (AUC). RESULTS: In the training set, LASSO achieved AUC of 0.978, Random Forest had an AUC of 0.933. In the validation set, LASSO had AUC of 0.859, Random Forest had AUC of 0.986. By conducting Logistic Regression analysis in combination with LASSO and Random Forest, we identified a total of five radiomics features, with four related to morphology and one to textural features, originating from the medial prefrontal cortex and middle temporal gyrus. In the training set, Logistic Regression achieved AUC of 0.911, while in the validation set, it attained AUC of 0.925. CONCLUSION: The medial prefrontal cortex and middle temporal gyrus are the two brain regions within the default mode network that hold the highest significance for Alzheimer's disease diagnosis. Radiomics analysis contributes to the clinical assessment of Alzheimer's disease by delving into image data to extract deeper layers of information.

Intestinal microbiota and metabolome perturbations in ischemic and idiopathic dilated cardiomyopathy.

BACKGROUND: Various clinical similarities are present in ischemic (ICM) and idiopathic dilated cardiomyopathy (IDCM), leading to ambiguity on some occasions. Previous studies have reported that intestinal microbiota appeared dysbiosis in ICM, whether implicating in the IDCM remains unclear. The aim of this study was to assess the alterations in intestinal microbiota and fecal metabolites in ICM and IDCM. METHODS: ICM (n = 20), IDCM (n = 22), and healthy controls (HC, n = 20) were enrolled in this study. Stool samples were collected for 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Both ICM and IDCM exhibited reduced alpha diversity and altered microbial community structure compared to HC. At the genus level, nine taxa including Blautia, [Ruminococcus]_torques_group, Christensenellaceae_R-7_group, UCG-002, Corynebacterium, Oceanobacillus, Gracilibacillus, Klebsiella and Citrobacter was specific to ICM, whereas one taxa Alistipes uniquely altered in IDCM. Likewise, these changes were accompanied by significant metabolic differences. Further differential analysis displayed that 18 and 14 specific metabolites uniquely changed in ICM and IDCM, respectively. The heatmap was generated to display the association between genera and metabolites. Receiver operating characteristic curve (ROC) analysis confirmed the predictive value of the distinct microbial-metabolite features in disease status. The results showed that microbial (area under curve, AUC = 0.95) and metabolic signatures (AUC = 0.84) were effective in discriminating ICM from HC. Based on the specific microbial and metabolic features, the patients with IDCM could be separated from HC with an AUC of 0.80 and 0.87, respectively. Furthermore, the gut microbial genus (AUC = 0.88) and metabolite model (AUC = 0.89) were comparable in predicting IDCM from ICM. Especially, the combination of fecal microbial-metabolic features improved the ability to differentiate IDCM from ICM with an AUC of 0.96. CONCLUSION: Our findings highlighted the alterations of gut microbiota and metabolites in different types of cardiomyopathies, providing insights into the pathophysiological mechanisms of myocardial diseases. Moreover, multi-omics analysis of fecal samples holds promise as a non-invasive tool for distinguishing disease status.

Lactobacillus induced by irbesartan on spontaneously hypertensive rat contribute to its antihypertensive effect.

OBJECTIVE: Hypertension is linked to gut dysbiosis. Here, the impact of the angiotensin receptor antagonist irbesartan on the gut microbiota of spontaneously hypertensive rats (SHR) were investigated. In addition, we assessed their contribution to its antihypertensive effect. METHODS: Eight-week-old Wistar-Kyoto (WKY) rats and SHR were administered irbesartan for 8 weeks. Fecal microbiota transplantation (FMT) was performed from SHR treated with irbesartan or untreated SHR to recipient untreated SHR. The preventive effect of Lactobacillus on hypertension in SHR was evaluated. Blood pressure (BP) was calculated using a tail-sleeve sphygmomanometer. To better assess the composition of the gut microbiota, the V3-V4 region of the 16S rRNA gene was amplified while short-chain fatty acids (SCFAs) in feces were tested by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). RESULTS: Irbesartan restored gut dysbiosis, increased the abundance of Lactobacillus , and improved anti-inflammatory ability, antioxidative ability, intestinal integrity, and intestinal inflammation in SHR. The microbiota in SHR-treated irbesartan could reduce BP and improve antioxidative ability and gut integrity in SHR. Lactobacillus johnsonii ( L. johnsonii ) and Lactobacillus reuteri ( L. reuteri ) reduced BP, restored gut dysbiosis and improved anti-inflammatory ability, antioxidative ability, intestinal integrity in SHR. Most notably, irbesartan, L. johnsonii , and L. reuteri can significantly increase SCFA content in SHR feces. CONCLUSION: The current study demonstrated that irbesartan treatment ameliorated gut dysbiosis in SHR. Irbesartan induced alterations in gut microbiota, with increased prevalence of Lactobacillus .

Effect of mesenchymal stem cell therapy in animal models of allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: Allergic rhinitis (AR) is a worldwide problem that affects people of all ages, impairing patients' physical and mental health and causing great social expenditure. Animal studies have suggested the potential efficacy of mesenchymal stem cell (MSC) therapy in treating AR. Our meta-analysis was performed to evaluate the effect of MSC therapy in animal models of AR by pooling animal studies. METHODS: The search was executed in PubMed, Embase, Web of Science, OVID, and the Cochrane Library for relevant studies up to February 2023. The applicable data were extracted from the eligible studies, and the risk of bias was assessed for each study. The meta-analysis was conducted using Review Manager (version 5.4.1) and Stata (version 15.1). RESULTS: A total of 12 studies were included in the final analysis. Compared to the model control group, the MSC therapy group presented lower frequency of sneezing [(Standardized mean difference (SMD) -1.87, 95% CI -2.30 to -1.43)], nasal scratching (SMD -1.41, 95% CI -1.83 to -0.99), and overall nasal symptoms (SMD -1.88, 95% CI -3.22 to -0.54). There were also remarkable reductions after transplantation with MSCs in the levels of total immunoglobulin E (IgE) (SMD -1.25, 95% CI -1.72 to -0.79), allergen-specific IgE (SMD -1.79, 95% CI -2.25 to -1.32), and allergen-specific immunoglobulin G1 (SMD -1.29, 95% CI -2.03) in serum, as well as the count of eosinophils (EOS) in nasal mucosa (SMD -3.48, 95% CI -4.48 to -2.49). In terms of cytokines, MSC therapy significantly decreased both protein and mRNA levels of T helper cell 2 (Th2)-related cytokines, including interleukin (IL)-4, IL-5, IL-10, and IL-13. CONCLUSION: MSC therapy has the potential to be an effective clinical treatment for AR patients by attenuating Th2 immune responses, reducing secretion of IgE and nasal infiltration of EOS, and consequently alleviating nasal symptoms.

A bidirectional link between metabolic syndrome and elevation in alanine aminotransferase in elderly female: a longitudinal community study.

Pre-obesity, as a significant risk factor for the progression of metabolic syndrome (MS), has become a prevalent public health threat globally. In this three-year longitudinal study of pre-obese women at baseline, the goal was to clarify the female-specific bidirectional relationship between the risk of MS and blood alanine aminotransferase. In this manuscript, the MS score was determined using the following equation: MS score = 2*waist/height + fasting glucose/5.6 + TG/1.7 + SBP/130-HDL/1.02 for men and 1.28 for women, which is highly related to the risk of MS. With 2,338 participants, a hierarchical nonlinear model with random effects was utilized to analyze the temporal trends of serum characteristics from 2017 to 2019. A bivariate cross-lagged panel model (CLPM) was employed to estimate the structural relations of frequently measured variables at three different time points to determine the directionality of the relationship between the risk of MS and serum characteristics. MassARRAY Analyzer 4 platforms were used to evaluate and genotype candidate SNPs. In this study, the MS score only rose with age in females; it was positively correlated with serum alanine aminotransferase (ALT) in females; the CLPM revealed that the MS score in 2017 predicted ALT in 2018 (ß = 0.066, p < 0.001); and ALT in 2018 predicted an MS score in 2019 (ß = 0.037, p < 0.050); both relationships were seen in females. Additionally, the MS score in elderly females with NAFLD was related to the rs295 in the lipoprotein lipase (LPL) gene (p = 0.042). Our work showed that there may be female-specific causal correlations between elevated ALT and risk of MS and that the polymorphism rs295 in LPL may serve as a marker for the prognosis of MS. The genetic roles of rs295 in the LPL gene in the onset of MS and the development of ALT in the elderly Chinese Han population are thus provided by this, offering one potential mechanism.

Corrigendum: Effect of 131 I with and without artificial liver support system in patients with Graves' disease and severe liver dysfunction: A retrospective study.

[This corrects the article DOI: 10.3389/fendo.2022.1034374.].

Poly (lactic-co-glycolic acid)-encapsulated iodine-131 nanoparticles fabricated with rhTSH induce apoptosis and immobilization of thyroid cancer cells.

Background: Aggressive thyroid carcinoma (ATC) usually loses radioiodine avidity to iodine-131 (131I) due to the downregulation of sodium/iodide symporter (NIS). The expression of thyroid stimulating hormone receptor (TSHR) is more persistent than NIS and the administration of recombinant human thyroid stimulating hormone (rhTSH) promotes de novo NIS synthesis. Hence, exploring methods integrating 131I with rhTSH might be a feasible therapeutic strategy for selective delivery of 131I into thyroid cancer to fortify the effect of radioiodine ablation. Methods: The 131I, poly (lactic-co-glycolic acid) (PLGA) and rhTSH were used to synthesize of the 131I-PLGA-rhTSH nanoparticles. The characteristics of the 131I-PLGA-rhTSH nanoparticles was determined using a light microscopy, scanning electron microscopy (SEM), autoradiography and immunofluorescence (IF) staining. The diameter of the 131I-PLGA-rhTSH nanoparticles was measured with a Mastersizer 3000, and the encapsulation efficiency (EF) of 131I in 131I-PLGA-rhTSH nanoparticles and the radioactivity of a single nanoparticle were determined. Then, the mouse tumor xenograft model was established, and the biodistribution and effect of 131I-PLGA-rhTSH nanoparticles on apoptosis of thyroid cance cells were investigated in vivo. Thereafter, the role of 131I-PLGA-rhTSH nanoparticles in cell viability using cell counting kit-8 and lactate dehydrogenase (LDH) release assays. Subsequently, the underlying mechanism of 131I-PLGA-rhTSH nanoparticles in reducing cell viability was assessed using immunostaining, boyden invasion assays and phalloidin staining. Results: Our results showed that the method of developing nanoparticles-encapsulated 131I using poly (lactic-co-glycolic acid) (PLGA) and modified with rhTSH (131I-PLGA-rhTSH), was a feasible avenue for the integration of 131I and rhTSH. Meanwhile, the encapsulation efficiency (EF) of 131I-PLGA-rhTSH nanoparticles was approximately 60%, and the radioactivity of a single nanoparticle was about 1.1×10-2 Bq. Meanwhile, the 131I-PLGA-rhTSH nanoparticles were selectively delivered into, gradually enriched and slowly downregulated in xenograft tumor after the administration of 131I-PLGA-rhTSH nanoparticles through tail vein in mouse tumor xenograft model. Thereafter, the tumor weight was significantly reduced after the administration of 131I-PLGA-rhTSH nanoparticles. Subsequently, the application of 131I-PLGA-rhTSH nanoparticles facilitated apoptosis and attenuated immobilization via inhibiting F-actin assembling of FTC-133 cells. Conclusion: The present study develops a suitable approach integrating 131I and rhTSH, and this strategy is a feasible regimen enhancing the effect of radioiodine ablation for the treatment of thyroid cancer.

Anti-malarial artesunate ameliorates atherosclerosis by modulating arterial inflammatory responses via inhibiting the NF-κB-NLRP3 inflammasome pathway.

Introduction: Chronic inflammation plays a critical role in the pathogenesis of atherosclerosis (AS), and involves a complex interplay between blood components, macrophages, and arterial wall. Therefore, it is valuable in the development of targeted therapies to treat AS. Methods: AS rat model was induced by atherogenic diet plus with lipopolysaccharide (LPS) and then treated by anti-malarial artesunate (Art), a succinate derivative of artemisinin. The arterial morphology was observed after Oil red O, hematoxylin-eosin, and Masson's staining. The arterial protein level was detected by immunohistochemistry or immunofluorescence. The expression level of mRNA was determined by PCR array or real-time PCR. Results: Herein, we showed that Art possessed a dose-dependently protective effect on AS rats. In detail, Art showed a comparable inhibitory effect on arterial plaque and serum lipids compared to those of rosuvastatin (RS), and further showed a better inhibition on arterial lipid deposition and arterial remodeling comprised of arterial wall thicken and vascular collagen deposition, than those of RS. The improvement of Art on AS rats was related to inhibit arterial macrophage recruitment, and inhibit nuclear factor κB (NF-κB)-related excessive arterial inflammatory responses. Critically, Art showed significant inhibition on the NLRP3 inflammasome activation in both arterial wall and arterial macrophages, by down-regulating the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and apoptosis associated speckle-like protein containing CARD (ASC), leading to less production of the NLRP3 inflammasome-derived caspase-1, interleukin-1ß (IL-1ß), IL-18, and subsequent transforming growth factor ß1 (TGF-ß1) in AS rats. Conclusion: We propose that Art is an anti-AS agent acts through modulating the arterial inflammatory responses via inhibiting the NF-κB - NLRP3 inflammasome pathway.

Antibiotics-Induced Depletion of Rat Microbiota Induces Changes in the Expression of Host Drug-Processing Genes and Pharmacokinetic Behaviors of CYPs Probe Drugs.

The metabolism of exogenous substances is affected by the gut microbiota, and the relationship between them has become a hot topic. However, the mechanisms by which the microbiota regulates drug metabolism have not been clearly defined. This study characterizes the expression profiles of host drug-processing genes (DPGs) in antibiotics-treated rats by using an unbias quantitative RNA-sequencing method and investigates the effects of antibiotics-induced depletion of rat microbiota on the pharmacokinetic behaviors of cytochrome P450s (CYPs) probe drugs, and bile acids metabolism by ultra-performance liquid chromatography-tandem mass spectrometry. Our results show that antibiotics treatments altered the mRNA expressions of 112 DPGs in the liver and jejunum of rats. The mRNA levels of CYP2A1, CYP2C11, CYP2C13, CYP2D, CYP2E1, and CYP3A of CYP family members were significantly downregulated in antibiotics-treated rats. Furthermore, antibiotics treatments also resulted in a significant decrease in the protein expressions and enzyme activities of CYP3A1 and CYP2E1 in rat liver. Pharmacokinetic results showed that, except for tolbutamide, antibiotics treatments significantly altered the pharmacokinetic behaviors of phenacetin, omeprazole, metoprolol, chlorzoxazone, and midazolam. In conclusion, the presence of stable, complex, and diverse gut microbiota plays a significant role in regulating the expression of host DPGs, which could contribute to some individual differences in pharmacokinetics. SIGNIFICANCE STATEMENT: This study investigated how the depletion of rat microbiota by antibiotics treatments influences the expression profiles of host DPGs and the pharmacokinetic behaviors of CYPs probe drugs. Combined with previous studies in germ-free mice, this study will improve the understanding of the role of gut microbiota in drug metabolism and contribute to the understanding of individual differences in the pharmacokinetics of some drugs.

CH4 and CO2 emissions in water networks of rice cultivation regions.

Rice cultivation regions have a high density of open water networks to meet the requirements of rice growth and production. These open water networks have a significant risk of carbon (C) emissions due to agricultural production, but the C emissions from these waters are not clearly recorded in previous studies. Therefore, this study aimed to explore the pattern and internal mechanism of methane (CH4) and carbon dioxide (CO2) emissions from multiple types of waters (i.e., river, fish pond, reservoir, and ditch) in a typical rice cultivation region in southwestern China. The annual CH4 and CO2 fluxes were higher in the downstream river (2.79-94.89 and 39.39-1699.98 mg m-2 h-1) and ditch (8.80-74.99 and 123.43-542.65 mg m-2 h-1, respectively) and lower in the reservoir (-0.67 to 3.45 and -239.15 to 141.50 mg m-2 h-1) (P < 0.05). The monthly trends of CH4 and CO2 fluxes from the middle river and ditch were driven by interactive reactions of rice cultivation practices and precipitation. In contrast, the emission patterns of CH4 and CO2 from the lower river, upper river, and fish pond were mainly driven by domestic sewage discharge, precipitation, and aquaculture practices, respectively. This study suggested that river and ditch were more sensitive to C emissions than other waters, and the rice production period was the critical period for controlling C emission. Although rice paddy soils yield more cumulative emissions of CH4, water networks in rice cultivation regions were possible hotspots for C emissions due to the higher emission intensities, which were largely overlooked before. Thus, it is necessary to refine and promote practices to better mitigate C emissions from waters in rice cultivation regions in the future.

Effect of 131I with and without artificial liver support system in patients with Graves' disease and severe liver dysfunction: A retrospective study.

Objective: Treatment decision-making in Graves' disease (GD) with severe liver dysfunction (LD) is a clinical challenge. This research was carried out to evaluate the effect of radioiodine (131I) with or without an artificial liver support system (ALSS) in GD patients with severe LD. Methods: In total, 45 patients diagnosed with GD and severe LD were enrolled and allocated to two groups: patients treated with 131I alone (n=30) (Group A)and patients by a combination of 131I and ALSS (n=15)(Group B). Liver function, thyroid hormone concentrations, therapeutic efficacy, and the cost of treatment were compared between the two groups. Results: Thyroid hormone concentrations were lower 2 weeks after 131I treatment, but no deterioration in liver function was identified. There was no statistically significant difference in the treatment efficacy between the two groups. The hospital stay, total cost, and daily cost were lower in patients treated with 131I alone than in those treated with 131I and an ALSS (p<0.05). Conclusion: The key point of treating GD patients with severe LD is to control the GD.131I is recommended as an effective and safe and should be applied as soon as possible once the diagnosis is clarified; however, when used in combination with an ALSS, there was no substantial improvement in therapeutic efficacy.

Analysis of factors influencing the clinical outcome after surgery and 131I therapy in patients with moderate-risk thyroid papillary carcinoma.

Purpose: Generally, the prognosis for papillary thyroid cancer (PTC) is favorable. However, the moderate risk involved warrants further evaluation. Hence, we investigated the clinical outcomes in patients with moderate-risk PTC following surgery and the first 131I therapy, as well as the relevant factors that influence the therapeutic efficacy. Methods: Retrospective analyses of 175 patients with medium-risk PTC who visited the Second Affiliated Hospital of Chongqing Medical University from September 2017 to April 2019 were conducted. In according with the 2015 American Thyroid Association (ATA) guideline treatment response evaluation system, the patients were categorized into the following groups: excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), and structurally incomplete response (SIR), of which IDR, BIR, and SIR were collectively referred to as the NER group. To compare the general clinical features between the 2 groups of patients, 2 independent samples t-tests, χ2 test, and Mann-Whitney U-test were performed, followed by multivariate logistic regression analyses. With reference to the receiver operating characteristic (ROC) curve, the predicted value of ps-Tg to ER was evaluated, and the best cut-off value was determined. The subgroups with BRAFV600E test results were analyzed by χ2 test only. Results: The treatment responses of 123 patients were ER, while those of 52 patients were NER. The differences in the maximum tumor diameter (U = 2495.50), the amount of metastatic lymph nodes (U = 2313.50), the size of metastatic lymph node (U = 2113.50), the metastatic lymph node ratio (U = 2111.50), metastatic lymph node location (χ2 = 9.20), and ps-Tg level (U = 1011.00) were statistically significant. Multivariate regression analysis revealed that ps-Tg (OR = 1.209, 95% CI: 1.120-1.305) was an independent variable affecting ER. The cut-off value of ps-Tg for predicting ER was 6.915 ug/L, while its sensitivity and specificity were 69.2% and 89.4%, respectively. Conclusions: Patients with smaller tumor size, fewer lymph nodes, lower metastatic lymph node ratio, metastatic lymph nodes in the central region, smaller lymph node size, and ps-Tg <6.915 ug/L demonstrated better therapeutic effects after the initial treatment.

The Chinese Herbal Formula Huoxiang Zhengqi Dropping Pills Prevents Acute Intestinal Injury Induced by Heatstroke by Increasing the Expression of Claudin-3 in Rats.

Intestinal injury has been regarded as an important causative factor for systemic inflammation during heatstroke, and maintaining intestinal integrity has been a potential target for the prevention of HS. Huoxiang Zhengqi Dropping Pills (HZPD) is a modern preparation of Huoxiang Zhengqi and widely used to prevent HS. The present study aims to explore the protective effect of HZDP on intestinal injury during heatstroke and analyze its potential pharmacodynamic basis. Male rats in the control and HS groups were given normal saline, and those in the HZDP groups were given HZDP (0.23, 0.46, and 0.92 g/kg) before induction of HS. Serum contents of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intestinal fatty acid-binding protein (iFABP), and diamine oxidase (DAO) were determined using ELISA. Histopathology of intestinal injury was observed following H&E staining. The expression of claudin-3 was determined using western blot, immunohistochemistry, and immunofluorescence techniques. Moreover, network pharmacological tools were used to analyze the potential pharmacodynamic basis and the mechanism of HZDP. Treatment with HZDP significantly prolonged the time to reach Tc. Compared with the control group, the contents of TNF-α, IL-6, iFABP, and DAO in HS rats increased markedly. HZDP treatments reduced these levels significantly, and the effects in the middle dose group (0.46 g/kg) were most obvious. HZDP also attenuated intestinal injury and significantly reversed the decrease in claudin-3 expression. Bioinformatics analysis suggested that 35 active ingredients and 128 target genes of HZDP were screened from TCMSP and 93 target genes intersected with heatstroke target genes, which were considered potential therapeutic targets. TNF-α and IL-6 were the main inflammatory target genes of HZDP correlated with HS. These results indicated that HZDP effectively protected intestinal barrier function and prevented acute intestinal injury by increasing the expression of claudin-3 in rats, eventually improving heat resistance.

Cardiomyocytic FoxP3 is involved in Parkin-mediated mitophagy during cardiac remodeling and the regulatory role of triptolide.

Rationale: Forkhead/winged helix transcriptional factor P3 (FoxP3) is a well-studied transcription factor that maintains the activity of T cells, but whether cardiomyocytic FoxP3 participates in cardiac remodeling (CR) remains unclear. The present study was to investigate the role of cardiomyocytic FoxP3 in CR from the perspective of mitophagy. Methods: CR was induced by angiotensin II (AngII) in vitro, or by isoproterenol (Iso) in vivo using male C57 mice or FoxP3DTR mice. Histological changes were observed by hematoxylin-eosin and Masson staining. Molecular changes were detected by immunohistochemistry, immunofluorescence, immunoblotting, and real-time PCR. Mitophagy was shaped by transmission electron microscopy and co-localization. The mRNA expression was operated by siRNA or adeno associated virus (AAV). Molecular interactions were detected by co-localization, immunoprecipitation (IP), and chromatin IP. Results: The expression and nuclear translocation of cardiomyocytic FoxP3 were downregulated in CR, while they were upregulated after triptolide (TP) treatment. In left ventricle (LV) remodeling in mice, autophagy was activated continuously in the myocardium, and TP significantly attenuated it. AngII induced massive mitophagy characterized by the activation of autophagy regulatory protein 5 (Atg5)-dependent autophagic flux. Critically, Parkin was identified as the main adaptor mediated myocardial mitophagy and was responsible for the effect of TP. Moreover, FoxP3 was responsible for the downregulation of Parkin and inhibited AngII-induced cardiac mitophagy. We found that mitophagy increased significantly and the inhibition of TP treatment reversed completely in FoxP3-deficient LVs. Mechanistically, FoxP3 interacted with a motif located downstream of the activating transcription 4 (ATF4)-binding motif involved in the promoter of Parkin and hijacked free nuclear ATF4 to decrease Parkin mRNA expression in CR. Conclusion: Cardiomyocytic FoxP3 could negatively regulate Parkin-mediated mitophagy in CR, and restoring cardiomyocytic FoxP3 activity provided a cardioprotective strategy by inhibiting excessive cardiac mitophagy.

The Role of Gut Microbiota in Hypertension Pathogenesis and the Efficacy of Antihypertensive Drugs.

PURPOSE OF HEADING: To review the relationship between intestinal microbes and hypertension and its impact on the efficacy of antihypertensive drugs, and help to address some of these knowledge gaps. RECENT FINDINGS: Hypertension is associated with cardiovascular diseases and is the most important modifiable risk factor for all-cause morbidity and mortality worldwide. The pathogenesis of hypertension is complex, including factors such as dietary, environmental and genetics. Recently, the studies have shown that the gut microbiota influences the occurrence and development of hypertension through a variety of ways, including affecting the production of short-chain fatty acids, dysfunction of the brain-gut axis, and changes in serotonin content that cause the imbalance of vagus and sympathetic nerve output associated with hypertension. However, patients with hypertension typically take antihypertensive drugs orally on a long-term basis, and most antihypertensive drugs are absorbed by the gastrointestinal tract. Studies have shown that the pharmacokinetics and metabolism of antihypertensive drugs may be influenced by microbiota, or antihypertensive drugs act directly on the intestinal flora to exert efficacy, including regulation of intestinal microbial metabolism, intestinal inflammation, and intestinal sympathetic nervous system disorders. The intestinal flora can affect the pharmacokinetics and metabolism of antihypertensive drugs in the rats, and intestinal microbiota also can be the target "organ" by antihypertensive drugs.

Dual Role of Triptolide in Interrupting the NLRP3 Inflammasome Pathway to Attenuate Cardiac Fibrosis.

In a previous paper, we reported that triptolide (TP), a commonly used immunomodulator, could attenuate cardiac hypertrophy. This present study aimed to further explore the inhibition of cardiac fibrosis by TP and the possible mechanism from the perspective of the NOD-like receptor protein 3 (NLRP3) inflammasome. Hematoxylin-eosin and Masson's staining, immunohistochemistry, and immunofluorescence were performed to observe cardiac fibrotic changes in mice and mouse cardiac fibroblasts (CFs). The Western blot, colocalization, and immunoprecipitation were applied to detect protein expression and interactions. Results suggested that TP dose-dependently inhibited cardiac fibrosis induced by isoproterenol and collagen production of CFs induced by angiotensin II. TP exhibited an antifibrotic effect via inhibiting activation of the NLRP3 inflammasome, which sequentially decreased IL-1ß maturation, myeloid differentiation factor 88 (MyD88)-related phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase 1/2 (ERK1/2), and TGF-ß1/Smad signaling, and ultimately resulted in less collagen production. Moreover, TP showed no antifibrotic effect in Nlrp3-knockout CFs. Notably, TP inhibited the expression of NLRP3 and apoptosis-associated speck-like proteins containing a caspase recruitment domain (ASC) as well as inflammasome assembly, by interrupting the NLRP3-ASC interaction to inhibit inflammasome activation. Finally, TP indeed inhibited the NLRP3-TGFß1-Smad pathway in vivo. Conclusively, TP was found to play a dual role in interrupting the activation of the NLRP3 inflammasome to attenuate cardiac fibrosis.