Effect of long snake moxibustion on gut microbiota of patients with ankylosing spondylitis.

OBJECTIVE: To study the effect of long snake moxibustion intervention on gut microbiota of patients with ankylosing spondylitis (AS) by 16S rDNA sequencing technology. METHODS: 30 AS patients and 30 healthy volunteers were recruited and treated with long snake moxibustion once a week for 12 weeks. AS patients were divided into pre-treatment and post-treatment groups. VAS, BASDAI and BASFI scores of AS patients before and after treatment were collected. 16S rDNA high-throughput sequencing technology was used to analyze the characteristics and differences of gut microbiota in AS patients before and after treatment and in healthy volunteers. RESULTS: VAS, BASDAI and BASFI scores of AS patients after long snake moxibustion treatment were lower than those of pre-treatment group (P<0.05). The results of gut microbiota Alpha diversity showed that ace and chao1 index of the post-treatment group were higher than those of the healthy group (P<0.05), but there was no statistical significance in ace and chao1 index between the pre-treatment group and the post-treatment group (P>0.05). Beta diversity analysis showed that mild classification aggregation occurred between the healthy group and the pre-treatment group , but did not reach a significant level, and there was no significant difference between the the pre-treatment group and the post-treatment group. The results of species abundance showed that, at the phylum level, compared with the healthy group, the relative abundance of Firmicutes and Proteobacteria decreased in the pre-treatment group, while the relative abundance of Bacteroidetes and Actinobacteria increased. Compared with the pre-treatment group, the relative abundance of Firmicutes increased and the relative abundance of Actinobacteria decreased in the post-treatment group, but there were no statistically significant differences in the above changes (P>0.05). At the genus level, compared with the healthy group, the relative abundances of Subdoligranulum in the pre-treatment group were increased (P<0.05), while the relative abundances of Bifidobacterium and Streptococcus were decreased (P<0.05). Compared with the pre-treatment group, the relative abundance of Romboutsia in the post-treatment group was increased (P<0.05). CONCLUSION: Long snake moxibustion can obviously improve the clinical symptoms of AS patients. The possible mechanism of action is related to regulating the abundance of gut microbiota, increasing beneficial bacteria and restoring the homeostasis of gut microorganisms.

Downregulation of LOX Overexpression Promotes Retinal Ganglion Cells Survival in an Acute Ocular Hypertension Model.

PURPOSE: To investigate the effect of reducing Lysyl oxidase (LOX) overexpression on retinal ganglion cells (RGCs) apoptosis in an acute ocular hypertension (AOH) rat model. METHODS: AOH rat model was performed by anterior chamber perfusion and either received an intravitreal injection with ß-aminopropionitrile (BAPN) or normal saline. After 2wk, Quantification of survival RGCs in the retina was performed using Retrograde FluoroGold labeling. The mRNA expression levels of LOX, LOXL1-4, collagen 1a1 (Col1a1), collagen 3a1 (Col3a1), collagen4a1 (Col4a1), elastin (Eln), fibronectin1 (Fbn1), fibronectin4 (Fbn4) were determined by RT-qPCR. LOX expression was determined by Western blot (WB) analysis and immunohistochemistry. The RNA expression of LOX, Eln and Col1a1 in RGCs retrograde-labeled with 1,1'-dioctadecyl-3,3,3',3' tetra-methylindocarbocyanine perchlorate(DiI)that selected through FACS sorting were determined by RT-qPCR analysis. Changes of the retinal function were detected by Electroretinogram (ERG) analysis. RESULTS: Results showed that significant LOX overexpression and loss of RGCs related to IOP exposure in AOH retinas. PCR analysis indicated significant increased mRNA level of Col1a1, Col3al and Eln in AOH retinas. Significant increase mRNA expression of LOX, Col1a1 and Eln in the RGCs were observed in AOH group compared with CON group. AOH rats injected with BAPN showed a significant decrease in LOX expression, reduced the loss of RGCs and retinal function damage. CONCLUSIONS: The results demonstrated that changes of LOX and specific ECM components in retina were correlated with AOH. Findings from this study indicated that preventing LOX over-expression may be protective against RGCs loss and retinal function damage in AOH animal model.

BHBA attenuates endoplasmic reticulum stress-dependent neuroinflammation via the gut-brain axis in a mouse model of heat stress.

BACKGROUND: Heat stress (HS) commonly occurs as a severe pathological response when the body's sensible temperature exceeds its thermoregulatory capacity, leading to the development of chronic brain inflammation, known as neuroinflammation. Emerging evidence suggests that HS leads to the disruption of the gut microbiota, whereas abnormalities in the gut microbiota have been demonstrated to affect neuroinflammation. However, the mechanisms underlying the effects of HS on neuroinflammation are poorly studied. Meanwhile, effective interventions have been unclear. ß-Hydroxybutyric acid (BHBA) has been found to have neuroprotective and anti-inflammatory properties in previous studies. This study aims to explore the modulatory effects of BHBA on neuroinflammation induced by HS and elucidate the underlying molecular mechanisms. METHODS: An in vivo and in vitro model of HS was constructed under the precondition of BHBA pretreatment. The modulatory effects of BHBA on HS-induced neuroinflammation were explored and the underlying molecular mechanisms were elucidated by flow cytometry, WB, qPCR, immunofluorescence staining, DCFH-DA fluorescent probe assay, and 16S rRNA gene sequencing of colonic contents. RESULTS: Heat stress was found to cause gut microbiota disruption in HS mouse models, and TM7 and [Previotella] spp. may be the best potential biomarkers for assessing the occurrence of HS. Fecal microbiota transplantation associated with BHBA effectively reversed the disruption of gut microbiota in HS mice. Moreover, BHBA may inhibit microglia hyperactivation, suppress neuroinflammation (TNF-α, IL-1ß, and IL-6), and reduce the expression of cortical endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP) mainly through its modulatory effects on the gut microbiota (TM7, Lactobacillus spp., Ruminalococcus spp., and Prevotella spp.). In vitro experiments revealed that BHBA (1 mM) raised the expression of the ERS marker GRP78, enhanced cellular activity, and increased the generation of reactive oxygen species (ROS) and anti-inflammatory cytokines (IL-10), while also inhibiting HS-induced apoptosis, ROS production, and excessive release of inflammatory cytokines (TNF-α and IL-1ß) in mouse BV2 cells. CONCLUSION: ß-Hydroxybutyric acid may be an effective agent for preventing neuroinflammation in HS mice, possibly due to its ability to inhibit ERS and subsequent microglia neuroinflammation via the gut-brain axis. These findings lay the groundwork for future research and development of BHBA as a preventive drug for HS and provide fresh insights into techniques for treating neurological illnesses by modifying the gut microbiota.

Controllable self-cleaning FET self-assembled RNA-cleaving DNAzyme based DNA nanotree for culture-free Staphylococcus aureus detection.

Staphylococcus aureus (SA) poses a serious risk to human and animal health, necessitating a low-cost and high-performance analytical platform for point-of-care diagnostics. Cellulose paper-based field-effect transistors (FETs) with RNA-cleaving DNAzymes (RCDs) can fulfill the low-cost requirements, however, its high hydrophilicity and lipophilicity hinder biochemical modification and result in low sensitivity, poor mechanical stability and poor fouling performance. Herein, we proposed a controllable self-cleaning FET to simplify biochemical modification and improve mechanical stability and antifouling performance. Then, we constructed an RCD-based DNA nanotree to significantly enhance the sensitivity for SA detection. For controllable self-cleaning FET, 1 H,1 H,2 H,2 H-perfluorodecyltrimethoxysilane based-polymeric nanoparticles were synthesized to decorate cellulose paper and whole carbon nanofilm wires. O2 plasma was applied to regulate to reduce fluorocarbon chain density, and then control the hydrophobic-oleophobic property in sensitive areas. Because negatively charged DNA affected the sensitivity of semiconducting FETs, three Y-shaped branches with low-cost were designed and applied to synthesize an RCD-based DNA-Nanotree based on similar DNA-origami technology, which further improved the sensitivity. The trunk of DNA-Nanotree was composed of RCD, and the canopy was self-assembled using multiple Y-shaped branches. The controllable self-cleaning FET biosensor was applied for SA detection without cultivation, which had a wide linear range from 1 to 105 CFU/mL and could detect a low value of 1 CFU/mL.

Role of Cardiolipin in regulating and treating atherosclerotic cardiovascular diseases.

Cardiovascular diseases, mainly caused by atherosclerosis, are the leading causes of morbidity and mortality worldwide. Despite the discrepancies in clinical manifestations between different abnormalities, atherosclerosis shares similar pathophysiological processes, such as mitochondrial dysfunction. Cardiolipin (CL) is a conserved mitochondria-specific lipid that contributes to the cristae structure of the inner mitochondrial membrane (IMM). Alterations in the CL, including oxidative modification, reduced quantity, and abnormal localization, contribute to the onset and progression of atherosclerosis. In this review, we summarize the knowledge that CL is involved in the pathogenesis of atherosclerosis. On the one hand, CL and its oxidative modification promote the progression of atherosclerosis via several mechanisms, including oxidative stress, apoptosis, and inflammation in response to stress. On the other hand, CL externalizes to the outer mitochondrial membrane (OMM) and acts as the pivotal "eat-me" signal in mitophagy, removing dysfunctional mitochondria and safeguarding against the progression of atherosclerosis. Given the imbalance between proatherogenic and antiatherogenic effects, we provide our understanding of the roles of the CL and its oxidative modification in atherosclerotic cardiovascular diseases, in addition to potential therapeutic strategies aimed at restoring the CL. Briefly, CL is far more than a structural IMM lipid; broader significances of the evolutionarily conserved lipid need to be explored.

An Ensemble Learning Approach Based on TabNet and Machine Learning Models for Cheating Detection in Educational Tests.

The pervasive issue of cheating in educational tests has emerged as a paramount concern within the realm of education, prompting scholars to explore diverse methodologies for identifying potential transgressors. While machine learning models have been extensively investigated for this purpose, the untapped potential of TabNet, an intricate deep neural network model, remains uncharted territory. Within this study, a comprehensive evaluation and comparison of 12 base models (naive Bayes, linear discriminant analysis, Gaussian process, support vector machine, decision tree, random forest, Extreme Gradient Boosting (XGBoost), AdaBoost, logistic regression, k-nearest neighbors, multilayer perceptron, and TabNet) was undertaken to scrutinize their predictive capabilities. The area under the receiver operating characteristic curve (AUC) was employed as the performance metric for evaluation. Impressively, the findings underscored the supremacy of TabNet (AUC = 0.85) over its counterparts, signifying the profound aptitude of deep neural network models in tackling tabular tasks, such as the detection of academic dishonesty. Encouraged by these outcomes, we proceeded to synergistically amalgamate the two most efficacious models, TabNet (AUC = 0.85) and AdaBoost (AUC = 0.81), resulting in the creation of an ensemble model christened TabNet-AdaBoost (AUC = 0.92). The emergence of this novel hybrid approach exhibited considerable potential in research endeavors within this domain. Importantly, our investigation has unveiled fresh insights into the utilization of deep neural network models for the purpose of identifying cheating in educational tests.

Endothelial cell specific molecule 1 promotes epithelial-mesenchymal transition of cervical cancer via the E-box binding homeobox 1.

OBJECTIVE: To investigate the mechanism of endothelial cell specific molecule 1 (ESM1) promoting cervical cancer cell proliferation and EMT characteristics through zinc finger E-box binding homeobox 1 (ZEB1)/EMT pathway. METHODS: The correlation between ESM1 expression and prognosis of cervical cancer patients was analyzed by bioinformatics. SiHa, HeLa cell lines and corresponding control cell lines with stable ESM1 expression were obtained. Cell proliferation ability was detected by CCK-8 assay. The invasion and migration ability of Hela and SiHa cells were detected by Transwell assay and scratch closure assay. Expressions of EMT-related markers E-cadherin and Vimentin were detected by real-time PCR. The ability of silenced ESM1 to tumor formation in vivo was detected by tumor formation in nude mice. The effects of aloe-emodin on inhibit ESM1 expression and its inhibitory effect on cervical cancer cells in vitro and in vivo were analyzed by the same method. RESULTS: ESM1 was highly expressed in cervical cancer, and the high expression of ESM1 was associated with poor prognosis of cervical cancer patients. CCK-8 results showed that the proliferation, invasion and migration of Hela and SiHa cells were significantly reduced after siRNA interfered with ESM1 expression. Overexpression of ESM1 promoted the proliferation and migration of cervical cancer cells. Mechanism studies have shown that the oncogenic effect of ESM1 is realized through the ZEB1/PI3K/AKT pathway. High throughput drug screening found that aloe-emodin can target ESM1. Inhibitory effect of aloe emodin on ESM1/ZEB1/EMT signaling pathway and cervical cancer cells. CONCLUSION: The silencing of ESM1 expression may inhibit the proliferation, invasion, metastasis and epithelial-mesenchymal transformation of cervical cancer cells by inhibiting ZEB1/PI3K/AKT. Aloe-emodin is a potential treatment for cervical cancer, which can play an anti-tumor role by inhibiting ESM1/ZEB1.

The association between TLR2/4 and clinical outcome in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Toll-like receptors (TLRs) are involved in innate immunity and inflammatory responses in various diseases. Our study aimed to investigate the association between the levels of soluble TLR4 (sTLR4) and soluble TLR2 (sTLR2) and clinical outcomes following intracerebral hemorrhage (ICH). METHODS: Patients admitted to department of Neurology with acute ICH were included. Plasma levels of sTLR4 and sTLR2 after ICH were measured by enzyme-linked immunosorbent assay. Poor clinical outcome was defined as a modified Rankin score (mRS) of 3-6 at 3-month and 12-month after onset. RESULTS: All 207 patients with ICH and 100 non-stroke controls were included in our analysis. The mean sTLR4 level was 4.53±1.51 ng/ml and mean sTLR2 level was 3.65±0.72 ng/ml. There was significant trend towards worse clinical outcomes with increasing sTLR4 and sTLR2 terciles at 3 and 12 months. According to receiver operating curve (ROC), the sTLR4 was reliable predictor for poor clinical outcome at 3 months (ROC=0.75) and 12 months (ROC=0.74). The sTLR2 was less reliable predictor for poor clinical outcome at 3 months (ROC=0.64) and 12 months (ROC=0.65). The level of sTLR4 was an independent predictor of poor clinical outcome at 12-month (OR 1.24, 95 % CI 1.16-1.80; P=0.019). CONCLUSIONS: The sTLR4 quantification may provide accurate prognostic information after ICH.

HMGB1/TLR4 axis promotes pyroptosis after ICH by activating the NLRP3 inflammasome.

BACKGROUND: We previously reported that the HMGB1/TLR4 axis promoted inflammation during the acute phase of intracerebral hemorrhage. Given that this phase is known to involve neuronal pyroptosis and neuroinflammation, here we explore whether HMGB1/TLR signaling activate inflammasome and pyroptosis after intracerebral hemorrhage. METHODS: Autologous blood was injected into Sprague-Dawley rats to induce intracerebral hemorrhage. Neurological deficits were assessed using a modified neurological severity score. These expression and localization of NLRP1 and NLRP3 inflammasomes, as well as the levels of pyroptosis and pyroptosis-associated proteins were assessed using Western blot or immunocytochemistry. These experiments were repeated in animals that received treatment with short interfering RNAs against NLRP1 or NLRP3, with HMGB1 inhibitor ethyl pyruvate or TLR4 inhibitor TAK-242. RESULTS: Intracerebral hemorrhage upregulated NLRP1 and NLRP3 in the ipsilateral striatum and increased the proportions of these cells that were pyroptosis-positive. Additionally, the levels of caspase protein family (e.g., pro-caspase-1 and caspase-1), apoptosis-associated speck-like protein (ASC), pro-interleukin-1ß (IL-1ß), and IL-1ß were also elevated. These effects on pyroptosis and associated neurological deficit, were partially reversed by knockdown of NLRP1 or NLRP3, or by inhibition of HMGB1 or TLR4. Inhibition of HMGB1 or TLR4 resulted in the downregulation NLRP3 but not NLRP1. CONCLUSIONS: The HMGB1/TLR4 signaling may activate the NLRP3 inflammasome during the acute phase of intracerebral hemorrhage, resulting in the inflammatory process known as pyroptosis. These insights suggest potential therapeutic targets for the mitigation tissue injury and associated neurological deficits following hemorrhagic stroke.

A thermosensitive luminescence halloysite-based nanocomposite enabling encryptable thermal printing.

In situ formation of carbon dots on halloysite nanotubes is demonstrated by treating polyacrylamide-grafted halloysite nanotubes with polycarboxylic acid without the recourse to extremely high temperatures or solvents. Thermosensitive luminescence and phosphorescence properties are carefully investigated. The polyacrylamide-grafted halloysite nanotubes are further processed as composite films for encryptable thermal printing.

NIPT-PG: empowering non-invasive prenatal testing to learn from population genomics through an incremental pan-genomic approach.

Non-invasive prenatal testing (NIPT) is a quite popular approach for detecting fetal genomic aneuploidies. However, due to the limitations on sequencing read length and coverage, NIPT suffers a bottleneck on further improving performance and conducting earlier detection. The errors mainly come from reference biases and population polymorphism. To break this bottleneck, we proposed NIPT-PG, which enables the NIPT algorithm to learn from population data. A pan-genome model is introduced to incorporate variant and polymorphic loci information from tested population. Subsequently, we proposed a sequence-to-graph alignment method, which considers the read mis-match rates during the mapping process, and an indexing method using hash indexing and adjacency lists to accelerate the read alignment process. Finally, by integrating multi-source aligned read and polymorphic sites across the pan-genome, NIPT-PG obtains a more accurate z-score, thereby improving the accuracy of chromosomal aneuploidy detection. We tested NIPT-PG on two simulated datasets and 745 real-world cell-free DNA sequencing data sets from pregnant women. Results demonstrate that NIPT-PG outperforms the standard z-score test. Furthermore, combining experimental and theoretical analyses, we demonstrate the probably approximately correct learnability of NIPT-PG. In summary, NIPT-PG provides a new perspective for fetal chromosomal aneuploidies detection. NIPT-PG may have broad applications in clinical testing, and its detection results can serve as a reference for false positive samples approaching the critical threshold.

Recognition of apnea and hypopnea by non-contact optical fiber mattress and its application in the diagnosis of obstructive sleep apnea hypopnea syndrome: a retrospective study.

Objectives: This study sought to evaluate the diagnostic value of a non-contact optical fiber mattress for apnea and hypopnea and compare it with traditional polysomnography (PSG) in adult obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: To determine the value of a non-contact optical fiber mattress for apnea and hypopnea, six healthy people and six OSAHS patients were selected from Tongji Hospital to design a program to identify apnea or hypopnea. A total of 108 patients who received polysomnography for drowsiness, snoring or other suspected OSAHS symptoms. All 108 patients were monitored with both the non-contact optical fiber mattress and PSG were collected. Results: Six healthy controls and six patients with OSAHS were included. The mean apnea of the six healthy controls was 1.22 times/h, and the mean hypopnea of the six healthy controls was 2 times/h. Of the six patients with OSAHS, the mean apnea was 12.63 times/h, and the mean hypopnea was 19.25 times/h. The non-contact optical fiber mattress results showed that the mean apnea of the control group was 3.17 times/h and the mean hypopnea of the control group was 3.83 times/h, while the mean apnea of the OSAHS group was 11.95 times/h and the mean hypopnea of the OSAHS group was 17.77 times/h. The apnea index of the non-contact optical fiber mattress was positively correlated with the apnea index of the PSG (P < 0.05, r = 0.835), and the hypopnea index of the non-contact optical fiber mattress was also positively correlated with the hypopnea index of the PSG (P < 0.05, r = 0.959). The non-contact optical fiber mattress had high accuracy (area under curve, AUC = 0.889), specificity (83.4%) and sensitivity (83.3%) for the diagnosis of apnea. The non-contact fiber-optic mattress also had high accuracy (AUC = 0.944), specificity (83.4%) and sensitivity (100%) for the diagnosis of hypopnea. Among the 108 patients enrolled, there was no significant difference between the non-contact optical fiber mattress and the polysomnography monitor in total recording time, apnea hypopnea index (AHI), average heart rate, tachycardia index, bradycardia index, longest time of apnea, average time of apnea, longest time of hypopnea, average time of hypopnea, percentage of total apnea time in total sleep time and percentage of total hypopnea time in total sleep time. The AHI value of the non-contact optical fiber mattress was positively correlated with the AHI value of the PSG (P < 0.05, r = 0.713). The specificity and sensitivity of the non-contact optical fiber mattress AHI in the diagnosis of OSAHS were 95% and 93%, with a high OSAHS diagnostic accuracy (AUC = 0.984). Conclusion: The efficacy of the non-contact optical fiber mattress for OSAHS monitoring was not significantly different than PSG monitoring. The specificity of the non-contact optical mattress for diagnosing OSAHS was 95% and its sensitivity was 93%, with a high OSAHS diagnostic accuracy.

Trigonelline hydrochloride attenuates silica-induced pulmonary fibrosis by orchestrating fibroblast to myofibroblast differentiation.

BACKGROUND: Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it's unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear. METHODS: To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions. RESULTS: In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO2-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO2 group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-ß/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts. CONCLUSION: In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis.

Capmatinib is an effective treatment for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy.

BACKGROUND: Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGG and are associated with devastating morbidity and mortality. METHODS: To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion IHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy. RESULTS: Capmatinib showed superior brain pharmacokinetic properties and greater in vitro and in vivo efficacy than cabozantinib or crizotinib in both models. The PDOX models recapitulated the poor efficacy of cabozantinib experienced by the patient. In contrast, capmatinib extended survival and induced long-term progression-free survival when combined with radiotherapy in two complementary mouse models. Capmatinib treatment increased radiation-induced DNA double-strand breaks and delayed their repair. CONCLUSIONS: We comprehensively investigated the combination of MET inhibition and radiotherapy as a novel treatment option for MET-driven pHGG. Our seminal preclinical data package includes pharmacokinetic characterization, recapitulation of clinical outcomes, coinciding results from multiple complementing in vivo studies, and insights into molecular mechanism underlying increased efficacy. Taken together, we demonstrate the groundbreaking efficacy of capmatinib and radiation as a highly promising concept for future clinical trials.

Effects of Saponins on Lipid Metabolism: The Gut-Liver Axis Plays a Key Role.

Unhealthy lifestyles (high-fat diet, smoking, alcohol consumption, too little exercise, etc.) in the current society are prone to cause lipid metabolism disorders affecting the health of the organism and inducing the occurrence of diseases. Saponins, as biologically active substances present in plants, have lipid-lowering, inflammation-reducing, and anti-atherosclerotic effects. Saponins are thought to be involved in the regulation of lipid metabolism in the body; it suppresses the appetite and, thus, reduces energy intake by modulating pro-opiomelanocortin/Cocaine amphetamine regulated transcript (POMC/CART) neurons and neuropeptide Y/agouti-related peptide (NPY/AGRP) neurons in the hypothalamus, the appetite control center. Saponins directly activate the AMP-activated protein kinase (AMPK) signaling pathway and related transcriptional regulators such as peroxisome-proliferator-activated-receptors (PPAR), CCAAT/enhancer-binding proteins (C/EBP), and sterol-regulatory element binding proteins (SREBP) increase fatty acid oxidation and inhibit lipid synthesis. It also modulates gut-liver interactions to improve lipid metabolism by regulating gut microbes and their metabolites and derivatives-short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine (TMA), lipopolysaccharide (LPS), et al. This paper reviews the positive effects of different saponins on lipid metabolism disorders, suggesting that the gut-liver axis plays a crucial role in improving lipid metabolism processes and may be used as a therapeutic target to provide new strategies for treating lipid metabolism disorders.

Evaluating the spatial accessibility and spatial layout optimization of HIV/AIDS healthcare services in Shandong Province, China.

Improving access to HIV/AIDS healthcare services is of great concern to government and policymakers striving to strengthen overall public health. How to reasonably allocate HIV/AIDS healthcare resources and maximize the equality of access to healthcare services across subdistrict areas has become an urgent problem to be solved. However, there is limited research on this topic in China. It is necessary to evaluate spatial accessibility to improve the accessibility and equity of HIV/AIDS healthcare services. In this study, the improved multi-modal two-step floating catchment area (2SFCA) and inverted 2SFCA (i2SFCA) methods are used to measure the spatial accessibility of HIV/AIDS healthcare services and the crowdedness of the healthcare sites in Shandong Province, China. Then, the theoretical supply and the optimal spatial distribution of resources are calculated and visualized by minimizing the accessibility gaps between demand locations. This study showed that the spatial accessibility of HIV/AIDS service resources in Shandong Province was concentrated and unevenly distributed, and the accessibility scores in the marginal areas of prefecture-level cities were significantly lower than those in other areas. Regions with a large number of doctors had significantly higher levels of spatial accessibility. The ART accessibility scores in the southwest of Shandong Province were higher than those in other regions. As the travel friction coefficient increased, the accessibility scores formed an approximately circular cluster distribution centered on the healthcare sites in geographical distribution. More ART drugs needed to be supplied in marginal areas and more doctors were needed to work on HIV/AIDS in urban areas to address the spatial distribution imbalance of HIV/AIDS healthcare services. This study profoundly analyzed the spatial accessibility of HIV/AIDS healthcare services and provided essential references for decision-makers. In addition, it gives a significant exploration for achieving the goal of equal access to HIV/AIDS healthcare services in the future.

Evaluating eight indicators for identifying metabolic syndrome in Chinese and American adolescents.

BACKGROUND: Early intervention and diagnosis of Metabolic Syndrome (MetS) are crucial for preventing adult cardiovascular disease. However, the optimal indicator for identifying MetS in adolescent remains controversial. METHODS: In total,1408 Chinese adolescents and 3550 American adolescents aged 12-17 years were included. MetS was defined according to the modified version for adolescents based on Adult Treatment Panel III (NCEP-ATP III) criteria. Areas under the curve (AUC) and corresponding 95% confidence interval (95% CI) of 8 anthropometric/metabolic indexes, such as waist circumference (WC), body mass index (BMI), a body shape index (ABSI), waist triglyceride index (WTI), were calculated to illustrate their ability to differentiate MetS. Sensitivity analysis using the other MetS criteria was performed. RESULTS: Under the modified NCEP-ATP III criteria, WTI had the best discriminating ability in overall adolescents, with AUC of 0.922 (95% CI: 0.900-0.945) in Chinese and 0.959 (95% CI: 0.949-0.969) in American. In contrast, ABSI had the lowest AUCs. Results of sensitivity analysis were generally consistent for the whole Chinese and American population, with the AUC for WC being the highest under some criteria, but it was not statistically different from that of WTI. CONCLUSIONS: WTI had relatively high discriminatory power for MetS detection in Chinese and American adolescents, but the performance of ABSI was poor. IMPACT: While many studies have compared the discriminatory power of some anthropometric indicators for MetS, there are few focused on pediatrics. The current study is the first to compare the discriminating ability of anthropometric/metabolic indicators (WC, BMI, TMI, ABSI, WHtR, VAI, WTI, and TyG) for MetS in adolescents. WTI remains the optimal indicator in screening for MetS in adolescents. WC was also a simple and reliable indicator when screening for MetS in adolescents, but the performance of ABSI was poor. This study provides a theoretical basis for the early identification of MetS in adolescents by adopting effective indicators.

Evaluating the use of three-dimensional reconstruction visualization technology for precise laparoscopic resection in gastroesophageal junction cancer.

BACKGROUND: Laparoscopic gastrectomy for esophagogastric junction (EGJ) carcinoma enables the removal of the carcinoma at the junction between the stomach and esophagus while preserving the gastric function, thereby providing patients with better treatment outcomes and quality of life. Nonetheless, this surgical technique also presents some challenges and limitations. Therefore, three-dimensional reconstruction visualization technology (3D RVT) has been introduced into the procedure, providing doctors with more comprehensive and intuitive anatomical information that helps with surgical planning, navigation, and outcome evaluation. AIM: To discuss the application and advantages of 3D RVT in precise laparoscopic resection of EGJ carcinomas. METHODS: Data were obtained from the electronic or paper-based medical records at The First Affiliated Hospital of Hebei North University from January 2020 to June 2022. A total of 120 patients diagnosed with EGJ carcinoma were included in the study. Of these, 68 underwent laparoscopic resection after computed tomography (CT)-enhanced scanning and were categorized into the 2D group, whereas 52 underwent laparoscopic resection after CT-enhanced scanning and 3D RVT and were categorized into the 3D group. This study had two outcome measures: the deviation between tumor-related factors (such as maximum tumor diameter and infiltration length) in 3D RVT and clinical reality, and surgical outcome indicators (such as operative time, intraoperative blood loss, number of lymph node dissections, R0 resection rate, postoperative hospital stay, postoperative gas discharge time, drainage tube removal time, and related complications) between the 2D and 3D groups. RESULTS: Among patients included in the 3D group, 27 had a maximum tumor diameter of less than 3 cm, whereas 25 had a diameter of 3 cm or more. In actual surgical observations, 24 had a diameter of less than 3 cm, whereas 28 had a diameter of 3 cm or more. The findings were consistent between the two methods (χ2 = 0.346, P = 0.556), with a kappa consistency coefficient of 0.808. With respect to infiltration length, in the 3D group, 23 patients had a length of less than 5 cm, whereas 29 had a length of 5 cm or more. In actual surgical observations, 20 cases had a length of less than 5 cm, whereas 32 had a length of 5 cm or more. The findings were consistent between the two methods (χ2 = 0.357, P = 0.550), with a kappa consistency coefficient of 0.486. Pearson correlation analysis showed that the maximum tumor diameter and infiltration length measured using 3D RVT were positively correlated with clinical observations during surgery (r = 0.814 and 0.490, both P < 0.05). The 3D group had a shorter operative time (157.02 ± 8.38 vs 183.16 ± 23.87), less intraoperative blood loss (83.65 ± 14.22 vs 110.94 ± 22.05), and higher number of lymph node dissections (28.98 ± 2.82 vs 23.56 ± 2.77) and R0 resection rate (80.77% vs 61.64%) than the 2D group. Furthermore, the 3D group had shorter hospital stay [8 (8, 9) vs 13 (14, 16)], time to gas passage [3 (3, 4) vs 4 (5, 5)], and drainage tube removal time [4 (4, 5) vs 6 (6, 7)] than the 2D group. The complication rate was lower in the 3D group (11.54%) than in the 2D group (26.47%) (χ2 = 4.106, P < 0.05). CONCLUSION: Using 3D RVT, doctors can gain a more comprehensive and intuitive understanding of the anatomy and related lesions of EGJ carcinomas, thus enabling more accurate surgical planning.

Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine.

Against the backdrop of rapid social economy and scientific and technological development, intelligent medical technology expanded based on the Internet plays a crucial role in the innovation and development of the modern medical industry. Intelligent medical technology has completely changed the fixed medical methods of the past, and it can solve the isolated defects between various unit systems, greatly improving the overall informatization level of hospitals. This article analyzed the clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome (NDS) in intelligent medicine. Dyspepsia can cause palpitations, vomiting, abdominal distension, dizziness, and other symptoms so that it can cause discomfort and pain in the middle or around the epigastric region. Therefore, it is necessary to make a correct diagnosis of neurodyspepsia in order to reduce the discomfort of patients. Intelligent medical technology is of great significance in improving patients' symptoms. This study sets up a control group and an experimental group for the experiment. The control group used conventional medication technology, while the experimental group used intelligent medical technology to analyze the patient samples taken. By comparing the factors that affect patients with NDS, it was found that the physical function score of the experimental group was 6.3% lower than that of the control group. Intelligent medical technology has high diagnostic efficiency and can achieve rapid diagnosis of NDS, meeting the clinical diagnosis and prevention requirements of NDS.

Lactobacillus-derived protoporphyrin IX and SCFAs regulate the fiber size via glucose metabolism in the skeletal muscle of chickens.

The gut microbiota contributes to skeletal muscle energy metabolism and is an indirect factor affecting meat quality. However, the role of specific gut microbes in energy metabolism and fiber size of skeletal muscle in chickens remains largely unknown. In this study, we first performed cecal microbiota transplantation from Chinese indigenous Jingyuan chickens (JY) to Arbor Acres chickens (AA), to determine the effects of microbiota on skeletal muscle fiber and energy metabolism. Then, we used metagenomics, gas chromatography, and metabolomics analysis to identify functional microbes. Finally, we validated the role of these functional microbes in regulating the fiber size via glucose metabolism in the skeletal muscle of chickens through feeding experiments. The results showed that the skeletal muscle characteristics of AA after microbiota transplantation tended to be consistent with that of JY, as the fiber diameter was significantly increased, and glucose metabolism level was significantly enhanced in the pectoralis muscle. L. plantarum, L. ingluviei, L. salivarius, and their mixture could increase the production of the microbial metabolites protoporphyrin IX and short-chain fatty acids, therefore increasing the expression levels of genes related to the oxidative fiber type (MyHC SM and MyHC FRM), mitochondrial function (Tfam and CoxVa), and glucose metabolism (PFK, PK, PDH, IDH, and SDH), thereby increasing the fiber diameter and density. These three Lactobacillus species could be promising probiotics to improve the meat quality of chicken.IMPORTANCEThis study revealed that the L. plantarum, L. ingluviei, and L. salivarius could enhance the production of protoporphyrin IX and short-chain fatty acids in the cecum of chickens, improving glucose metabolism, and finally cause the increase in fiber diameter and density of skeletal muscle. These three microbes could be potential probiotic candidates to regulate glucose metabolism in skeletal muscle to improve the meat quality of chicken in broiler production.