Transcutaneous auricular vagus nerve stimulation as a novel therapy connecting the central and peripheral systems: a review.

Currently, clinical practice and scientific research mostly revolve around a single disease or system, but the single disease-oriented diagnostic and therapeutic paradigm needs to be revised. This review describes how transcutaneous auricular vagus nerve stimulation (taVNS), a novel noninvasive neuromodulation approach, connects the central and peripheral systems of the body. Through stimulation of the widely distributed vagus nerve from the head to the abdominal cavity, this therapy can improve and treat central system disorders, peripheral system disorders, and central-peripheral comorbidities caused by autonomic dysfunction. In the past, research on taVNS has focused on the treatment of central system disorders by modulating this brain nerve. As the vagus nerve innervates the heart, lungs, liver, pancreas, gastrointestinal tract, spleen and other peripheral organs, taVNS could have an overall modulatory effect on the region of the body where the vagus nerve is widespread. Based on this physiological basis, we summarize the existing evidence of the taVNS ability to regulate cardiac function, adiposity, glucose levels, gastrointestinal function, and immune function, among others, to treat peripheral system diseases, and complex diseases with central and peripheral comorbidities. This review shows the successful examples and research progress of taVNS using peripheral neuromodulation mechanisms from more perspectives, demonstrating the expanded scope and value of taVNS to provide new ideas and approaches for holistic therapy from both central and peripheral perspectives.

Electroencephalography-based biological and functional characteristics of spinal cord injury patients with neuropathic pain and numbness.

Objectives: To identify potential treatment targets for spinal cord injury (SCI)-related neuropathic pain (NP) by analysing the differences in electroencephalogram (EEG) and brain network connections among SCI patients with NP or numbness. Participants and methods: The EEG signals during rest, as well as left- and right-hand and feet motor imagination (MI), were recorded. The power spectral density (PSD) of the θ (4-8 Hz), α (8-12 Hz), and ß (13-30 Hz) bands was calculated by applying Continuous Wavelet Transform (CWT) and Modified S-transform (MST) to the data. We used 21 electrodes as network nodes and performed statistical measurements of the phase synchronisation between two brain regions using a phase-locking value, which captures nonlinear phase synchronisation. Results: The specificity of the MST algorithm was higher than that of the CWT. Widespread non-lateralised event-related synchronization was observed in both groups during the left- and right-hand MI. The PWP (patients with pain) group had lower θ and α bands PSD values in multiple channels of regions including the frontal, premotor, motor, and temporal regions compared with the PWN (patients with numbness) group (all p < 0.05), but higher ß band PSD values in multiple channels of regions including the frontal, premotor, motor, and parietal region compared with the PWN group (all p < 0.05). During left-hand and feet MI, in the lower frequency bands (θ and α bands), the brain network connections of the PWP group were significantly weaker than the PWN group except for the frontal region. Conversely, in the higher frequency bands (ß band), the brain network connections of the PWP group were significantly stronger in all regions than the PWN group. Conclusion: The differences in the power of EEG and network connectivity in the frontal, premotor, motor, and temporal regions are potential biological and functional characteristics that can be used to distinguish NP from numbness. The differences in brain network connections between the two groups suggest that the distinct mechanisms for pain and numbness.

Transcutaneous vagus nerve stimulation modulates depression-like phenotype induced by high-fat diet via P2X7R/NLRP3/IL-1ß in the prefrontal cortex.

BACKGROUND: Depression is a common psychiatric disorder in diabetic patients. Depressive mood associated with obesity/metabolic disorders is related to the inflammatory response caused by long-term consumption of high-fat diets, but its molecular mechanism is unclear. In this study, we investigated whether the antidepressant effect of transcutaneous auricular vagus nerve stimulation (taVNS) in high-fat diet rats works through the P2X7R/NLRP3/IL-1ß pathway. METHODS: We first used 16S rRNA gene sequencing analysis and LC-MS metabolomics assays in Zucker diabetic fatty (ZDF) rats with long-term high-fat diet (Purina #5008) induced significant depression-like behaviors. Next, the forced swimming test (FST) and open field test (OFT) were measured to evaluate the antidepressive effect of taVNS. Immunofluorescence and western blotting (WB) were used to measure the microglia state and the expression of P2X7R, NLRP3, and IL-1ß in PFC. RESULTS: Purina#5008 diet induced significant depression-like behaviors in ZDF rats and was closely related to purine and inflammatory metabolites. Consecutive taVNS increased plasma insulin concentration, reduced glycated hemoglobin and glucagon content in ZDF rats, significantly improved the depressive-like phenotype in ZDF rats through reducing the microglia activity, and increased the expression of P2X7R, NLRP3, and IL-1ß in the prefrontal cortex (PFC). CONCLUSION: The P2X7R/NLRP3/IL-1ß signaling pathway may play an important role in the antidepressant-like behavior of taVNS, which provides a promising mechanism for taVNS clinical treatment of diabetes combined with depression.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

Metabolic Regulation-Mediated Reversion of the Tumor Immunosuppressive Microenvironment for Potentiating Cooperative Metabolic Therapy and Immunotherapy.

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.

Optimal decision-making in relieving global high temperature-related disease burden by data-driven simulation.

The rapid acceleration of global warming has led to an increased burden of high temperature-related diseases (HTDs), highlighting the need for advanced evidence-based management strategies. We have developed a conceptual framework aimed at alleviating the global burden of HTDs, grounded in the One Health concept. This framework refines the impact pathway and establishes systematic data-driven models to inform the adoption of evidence-based decision-making, tailored to distinct contexts. We collected extensive national-level data from authoritative public databases for the years 2010-2019. The burdens of five categories of disease causes - cardiovascular diseases, infectious respiratory diseases, injuries, metabolic diseases, and non-infectious respiratory diseases - were designated as intermediate outcome variables. The cumulative burden of these five categories, referred to as the total HTD burden, was the final outcome variable. We evaluated the predictive performance of eight models and subsequently introduced twelve intervention measures, allowing us to explore optimal decision-making strategies and assess their corresponding contributions. Our model selection results demonstrated the superior performance of the Graph Neural Network (GNN) model across various metrics. Utilizing simulations driven by the GNN model, we identified a set of optimal intervention strategies for reducing disease burden, specifically tailored to the seven major regions: East Asia and Pacific, Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa. Sectoral mitigation and adaptation measures, acting upon our categories of Infrastructure & Community, Ecosystem Resilience, and Health System Capacity, exhibited particularly strong performance for various regions and diseases. Seven out of twelve interventions were included in the optimal intervention package for each region, including raising low-carbon energy use, increasing energy intensity, improving livestock feed, expanding basic health care delivery coverage, enhancing health financing, addressing air pollution, and improving road infrastructure. The outcome of this study is a global decision-making tool, offering a systematic methodology for policymakers to develop targeted intervention strategies to address the increasingly severe challenge of HTDs in the context of global warming.

The effect of age, sex, and eastern cooperative oncology group performance status on the efficacy and safety of immune checkpoint inhibitors in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The effect of age, sex, and eastern cooperative oncology group performance status (ECOG PS) on the efficacy and safety of immune checkpoint inhibitor (ICI) therapy among hepatocellular carcinoma (HCC) patients remains elusive. Thus, a meta-analysis was conducted to evaluate whether such effects exist. RESEARCH DESIGN AND METHODS: Eligible studies in PubMed, Embase, and Cochrane Library databases were retrieved. RESULTS: One-hundred-and-eleven studies involving 14,768 HCC patients were included. The findings indicated that the ECOG PS didn't have a significant effect on the ORR and PFS in ICI-treated HCC patients (higher ECOG PS vs. lower ECOG PS: ORR: OR = 0.78, 95%CI = 0.55-1.10; PFS: HR = 1.15, 95%CI = 0.97-1.35), while those patients with a higher ECOG PS may have a worse OS (HR = 1.52, 95% CI = 1.26-1.84). There is no significant evidence of the effect of age (older vs. younger) or sex (males vs. females) on the efficacy of ICI therapy in HCC. CONCLUSION: ICI therapy in HCC should not be restricted strictly to certain patients in age or sex categories, while HCC patients with higher ECOG PS may require closer medication or follow-up strategy during ICI therapy. PROSPERO REGISTRATION: CRD42024518407.

The integrated bioinformatic analysis identifies immune microenvironment-related potential biomarkers for patients with gestational diabetes mellitus.

Background: Gestational diabetes mellitus (GDM), a transient disease, may lead to short- or long-term adverse influences on maternal and fetal health. Therefore, its potential functions, mechanisms and related molecular biomarkers must be comprehended for the control, diagnosis and treatment of GDM. Methods: The differentially expressed genes (DEGs) were identified using GSE49524 and GSE87295 associated with GDM from the Gene Expression Omnibus database, followed by function enrichment analysis, protein-protein interactions network construction, hub DEGs mining, diagnostic value evaluation and immune infiltration analysis. Finally, hub DEGs, the strongest related to immune infiltration, were screened as immune-related biomarkers. Results: A hundred and seven DEGs were identified between patients with GDM and healthy individuals. Six hub genes with high diagnostic values, including ALDH1A1, BMP4, EFNB2, MME, PLAUR and SLIT2, were identified. Among these, two immune-related genes (PLAUR and SLIT2) with the highest absolute correlation coefficient were considered immune-related biomarkers in GDM. Conclusion: Our study provides a comprehensive analysis of GDM, which would provide a foundation for the development of diagnosis and treatment of GDM.

Femtosecond Laser Fabrication of Three-Dimensional Bubble-Propelled Microrotors for Multicomponent Mechanical Transmission.

Inspired by the reverse thrust generated by fuel injection, micromachines that are self-propelled by bubble ejection are developed, such as microrods, microtubes, and microspheres. However, controlling bubble ejection sites to build micromachines with programmable actuation and further enabling mechanical transmission remain challenging. Here, bubble-propelled mechanical microsystems are constructed by proposing a multimaterial femtosecond laser processing method, consisting of direct laser writing and selective laser metal reduction. The polymer frame of the microsystems is first printed, followed by the deposition of catalytic platinum into the desired local site of the microsystems by laser reduction. With this method, a variety of designable microrotors with selective bubble ejection sites are realized, which enable excellent mechanical transmission systems composed of single and multiple mechanical components, including a coupler, a crank slider, and a crank rocker system. We believe the presented bubble-propelled mechanical microsystems could be extended to applications in microrobotics, microfluidics, and microsensors.

Insect-Scale Biped Robots Based on Asymmetrical Friction Effect Induced by Magnetic Torque.

Multimodal and controllable locomotion in complex terrain is of great importance for practical applications of insect-scale robots. Robust locomotion plays a particularly critical role. In this study, a locomotion mechanism for magnetic robots based on asymmetrical friction effect induced by magnetic torque is revealed and defined. The defined mechanism overcomes the design constraints imposed by both robot and substrate structures, enabling the realization of multimodal locomotion on complex terrains. Drawing inspiration from human walking and running locomotion, a biped robot based on the mechanism is proposed, which not only exhibits rapid locomotion across substrates with varying friction coefficients but also achieves precise locomotion along patterned trajectories through programmed controlling. Furthermore, apart from its exceptional locomotive capabilities, the biped robot demonstrates remarkable robustness in terms of load-carrying and weight-bearing performance. The presented locomotion and mechanism herein introduce a novel concept for designing magnetic robots while offering extensive possibilities for practical applications in insect-scale robotics.

DNAJA1­knockout alleviates heat stroke­induced endothelial barrier disruption via improving thermal tolerance and suppressing the MLCK­MLC signaling pathway.

Endothelial barrier disruption plays a key role in the pathophysiology of heat stroke (HS). Knockout of DNAJA1 (DNAJA1­KO) is thought to be protective against HS based on a genome­wide CRISPR­Cas9 screen experiment. The present study aimed to illustrate the function of DNAJA1­KO against HS in human umbilical vein endothelial cells. DNAJA1­KO cells were infected using a lentivirus to investigate the role of DNAJA1­KO in HS­induced endothelial barrier disruption. It was shown that DNAJA1­KO could ameliorate decreased cell viability and increased cell injury, according to the results of Cell Counting Kit­8 and lactate dehydrogenase assays. Moreover, HS­induced endothelial cell apoptosis was inhibited by DNAJA1­KO, as indicated by Annexin V­FITC/PI staining and cleaved­caspase­3 expression using flow cytometry and western blotting, respectively. Furthermore, the endothelial barrier function, as measured by transepithelial electrical resistance and FITC­Dextran, was sustained during HS. DNAJA1­KO was not found to have a significant effect on the expression and distribution of cell junction proteins under normal conditions without HS. However, DNAJA1­KO could effectively protect the HS­induced decrease in the expression and distribution of cell junction proteins, including zonula occludens­1, claudin­5, junctional adhesion molecule A and occludin. A total of 4,394 proteins were identified using proteomic analysis, of which 102 differentially expressed proteins (DEPs) were activated in HS­induced wild­type cells and inhibited by DNAJA1­KO. DEPs were investigated by enrichment analysis, which demonstrated significant enrichment in the 'calcium signaling pathway' and associations with vascular­barrier regulation. Furthermore, the 'myosin light­chain kinase (MLCK)­MLC signaling pathway' was proven to be activated by HS and inhibited by DNAJA1­KO, as expected. Moreover, DNAJA1­KO mice and a HS mouse model were established to demonstrate the protective effects on endothelial barrier in vivo. In conclusion, the results of the present study suggested that DNAJA1­KO alleviates HS­induced endothelial barrier disruption by improving thermal tolerance and suppressing the MLCK­MLC signaling pathway.

Association between ambient particulate matter exposure and mitochondrial DNA copy number: A systematic review and meta-analysis.

BACKGROUND: Ambient particulate matter (PM) has been recognized as inducing oxidative stress, which could contribute to mitochondrial damage and dysfunction. However, studies investigating the association between ambient PM and mitochondria, particularly mitochondrial DNA copy number (mtDNA-CN), have yielded inconsistent results. METHODS: We conducted comprehensive literature searches to identify observational studies published before July 17, 2023, examining the association between ambient PM exposure and mtDNA-CN. Meta-analysis using random effects model was employed to calculate the pooled effect estimates for general individual exposures, as well as for prenatal exposure with specific trimester. Additionally, the quality and level of evidence for each exposure-outcome pair was evaluated. RESULTS: A total of 10 studies were included in the systematic review and meta-analysis. The results indicated that general individual exposure to PM2.5 (ß = -0.084, 95 % CI: -0.521, 0.353; I2 = 93 %) and PM10 (ß = 0.035, 95 % CI: -0.129, 0.199; I2 = 95 %) did not significantly affect mtDNA-CN. Prenatal exposure to PM2.5 (ß = 0.023, 95 % CI: -0.087, 0.133; I2 = 0 %) and PM10 (ß = 0.006, 95 % CI: -0.135; 0.147; I2 = 51 %) were also not significantly associated with mtDNA-CN in offspring. The level of evidence for each tested exposure-outcome pair was assessed as "inadequate." CONCLUSIONS: The findings of this systematic review and meta-analysis indicate that there is an "inadequate" strength of evidence for the association between general individual or prenatal exposure to ambient PM and mtDNA-CN. Future research necessitates studies with more rigorous design, enhanced control of confounding factors, and improved measures of exposure to substantiate our findings.

Economic burden attributable to hospital-acquired infections among tumor patients from a large regional cancer center in Southern China.

BACKGROUND: To evaluate the economic loss of hospital-acquired infections (HAIs) among tumor patients so as to help policymakers to allocate health care resources and address the issue. METHODS: We conducted a retrospective, 1:1 matched case-control study in a large region cancer hospital between January 1 and December 31, 2022. The economic burden was estimated as the median of the 1:1 pair differences of various hospitalization fees and hospital length of stay (LOS). RESULTS: In this study of 329 matched pairs, the patients with HAIs incurred higher hospitalization cost (ie, $16,927) and experienced longer hospital LOS (ie, 22 days), compared to the non-HAI groups. The extra hospitalization cost and the prolonged hospital LOS caused by HAIs were $4,919 and 9 days, respectively. Accordingly, the direct nonmedical economic loss attributable to HAI was approximately $478 to 835 per case. Furthermore, the increment of hospitalization costs varied by sites of infection, types of tumors, and stratum of age. CONCLUSIONS: HAIs lead to the increment of direct economic burden and hospital LOS in tumor patients. Our findings highlight the importance of implementing effective infection control measures in hospitals to reduce the financial burden on tumor patients.

Corrigendum: Untreated depression and anxiety in patients with common skin diseases: a cross-sectional study in China.

[This corrects the article DOI: 10.3389/fpsyg.2023.1150998.].

Retrospective analysis of antimicrobial resistance in bacterial pathogens from pet rabbits in Hong Kong, 2019-2022.

Antimicrobial resistance (AMR) is a growing threat to human and animal health. Data are limited on the prevalence of resistant bacteria in pet rabbits. Therefore, we aimed to identify prevalent bacterial infections and AMR profiles among pet rabbits in Hong Kong (HK). Our search of the CityU Veterinary Diagnostic Laboratory (VDL) database found 301 cases of pet rabbits submitted for bacteriologic and antimicrobial susceptibility testing by veterinarians at 20 exotic veterinary clinics across HK between 2019 and 2022. The rabbits were of 8 different breeds and had a median age of 6.5 y, with 54.8% males, 40.2% females, and 5% unspecified. Of the 301 samples received, 168 (55.8%) had positive bacterial growth; 125 (74.4%) had single bacterial isolates, and 43 (25.6%) had mixed cultures. Cultures included Enterococcus faecalis (21.3%) as the most frequently isolated gram-positive bacterium, followed by Streptococcus intermedius (12.5%), and Staphylococcus aureus (11.3%). The most frequently isolated gram-negative bacteria were Pseudomonas aeruginosa (18.1%), followed by Escherichia coli (8.3%), Pasteurella multocida (6.9%), and Klebsiella pneumoniae (4.2%). Approximately 83% of the isolates had acquired resistance to at least one antimicrobial agent, and 49.4% were multidrug-resistant. The isolated bacteria had high levels of resistance to penicillin (69.8%), clindamycin (47.4%), and doxycycline (46.9%). Our findings highlight the high levels of AMR in bacteria isolated from pet rabbit clinical samples in HK; many of these bacteria are zoonotic and pose a public health threat.

Effects of water fluoridation on early embryonic development of zebrafish.

Fluoride has strong electronegativity and exposes diversely in nature. Water fluoridation is the most pervasive form of occurrence, representing a significant threat to human health. In this study, we investigate the morphometric and physiological alterations triggered by fluoride stimulation during the embryogenesis of zebrafish and reveal its putative effects of stage- and/or dose-dependent. Fluoride exhibits potent biological activity and can be extensively absorbed by the yolk sac, exerting significant effects on the development of multiple organs. This is primarily manifested as restricted nutrient utilization and elevated levels of lipid peroxidation, further leading to the accumulation of superoxide in the yolk sac, liver, and intestines. Moreover, pericardial edema exerts pressure on the brain and eye development, resulting in spinal curvature and reduced body length. Besides, acute fluoride exposure with varying concentrations has led to diverse teratogenic outcomes. A low dose of water fluoridation tends to induce abnormal development of the embryonic yolk sac, while vascular malformation is widely observed in all fluoride-treated groups. The effect of fluoride exposure on blood circulation is universally present, even in zebrafish larvae that do not exhibit obvious deformities. Their swimming behavior is also affected by water fluoridation, resulting in reduced activity and delayed reactions. In conclusion, this study provides valuable insights into the monitoring of environmental quality related to water fluoridation and disease prevention.

Research on the dentification of Panax ginseng and Panax quinquefolium using catalysed hairpin assembly technology.

INTRODUCTION: Panax ginseng and Panax quinquefolium are traditional Chinese herb medicines and similar in morphology and some chemical components but differ in drug properties, so they cannot be mixed. However, the processed products of them are often sold in the form of slices, powder, and capsules, which are difficult to identify by traditional morphological methods. Furthermore, an accurate evaluation of P. ginseng, P. quinquefolium and the processed products have not been conducted. OBJECTIVE: This study aimed to establish a catalysed hairpin assembly (CHA) identification method for authenticating products made from P. ginseng and P. quinquefolium based on single nucleotide polymorphism (SNP) differences. METHOD: By analysing the differences of SNP in internal transcribed spacer 2 (ITS2) in P. ginseng and P. quinquefolium to design CHA-specific hairpins. Establish a sensitive and efficient CHA method that can identify P. ginseng and P. quinquefolium, use the sequencing technology to verify the accuracy of this method in identifying Panax products, and compare this method with high-resolution melting (HRM). RESULTS: The reaction conditions of CHA were as follows: the ratio of forward and reverse primers, 20:1; hairpin concentration, 5 ng/µL. Compared with capillary electrophoresis, this method had good specificity and the limit of detection was 0.5 ng/µL. The result of Panax product identification with CHA method were coincidence with that of the sequencing method; the positive rate of CHA reaction was 100%. CONCLUSION: This research presents an effective identification method for authenticating P. ginseng and P. quinquefolium products, which is helpful to improve the quality of Panax products.

Effect of Different Postures on Intraocular Pressure in Open-Angle Glaucoma.

INTRODUCTION: This study aims to investigate the pattern of intraocular pressure (IOP) changes in different postures among patients with open-angle glaucoma (OAG). METHODS: A observational study was conducted on a total of 74 patients with OAG (148 eyes). IOP measurements were taken in a variety of positions, including supine, left lateral decubitus, right lateral decubitus, head tilted downwards position with immediate head-up (transient head tilted downwards), seated, seated with head tilted downwards, standing, and walking. Each position was held for 5 min before measurement. In all positions, the patient maintains both eyes looking forward and remains alert. In the head tilted downwards position, the angle of head tilt with respect to the sagittal plane was 30°. RESULTS: The overall trend of IOP changes showed a significant decrease with an increase in the position height (r = 0.037, p < 0.001). The IOP was significantly higher in the supine, left lateral decubitus, right lateral decubitus, and head tilted downwards positions than in the seated position (p < 0.001). Compared with the seated position with eyes at primary gaze, IOP decreased significantly when standing (p = 0.008) or walking (p < 0.001). The IOP in the left lateral decubitus and right lateral decubitus was significantly higher than in the supine position (p = 0.008, p = 0.001, respectively). The IOP decreased significantly during walking compared with standing (p < 0.001). CONCLUSIONS: The magnitude of IOP strongly correlates with the body position during IOP measurement. The head tilted downwards, supine, left lateral decubitus, and right lateral decubitus positions result in a higher IOP than IOP at the seated position. Patients with OAG can potentially reduce IOP fluctuations by adjusting their daily postures.

Association of Estimated Glucose Disposal Rate With the Stenosis Severity of Coronary Artery Disease： A Cross-sectional Study / 中山大学学报(医学科学版)

ObjectiveTo investigate the association between estimated glucose disposal rate （eGDR） and the severity of coronary heart disease. MethodsWe conducted a hospital-based cross-sectional study that included 1258 patients （mean age： 62（53-68） years） who underwent coronary angiography for suspected coronary artery disease （53.9% were male）. Insulin resistance level （IR） was calculated according to eGDR formula： eGDR = 21.158 - （0.09 × WC） - （3.407 × hypertension） - （0.551 × HbA1c） ［hypertension （yes = 1 / no = 0）， HbA1c = HbA1c （%）］. Subjects were grouped according to the eGDR quantile. CAD severity was determined by the number of narrowed vessels： no-obstructive CAD group （all coronary stenosis were<50%， n=704）， Single-vessel CAD group （only one involved major coronary artery stenosis≥50%， n=205）， Multi-vessel CAD group （two or more involved major coronary arteries stenosis≥50%， n=349）； Multivariate logistic regression model was used to analyze the association between eGDR and CAD severity. The linear relationship between eGDR and CAD in the whole range of eGDR was analyzed using restricted cubic spline. Subgroup analyses were used to assess the association between eGDR and CAD severity in different diabetic states. Receiver operating characteristic （ROC） curve analysis were used to evaluate the value of eGDR in improving CAD recognition. ResultsA decrease in the eGDR index was significantly associated with an increased risk of CAD severity （OR： 2.79； 95%CI： 1.72~4.55； P<0.001）. In multivariate logistic regression models， individuals with the lowest quantile of eGDR （T1） were 2.79 times more likely to develop multi-vessel CAD than those with the highest quantile of eGDR （T3） （OR： 2.79； 95%CI： 1.72~4.55； P<0.001）. Multivariate restricted cubic spline analysis showed that eGDR was negatively associated with CAD and multi-vessel CAD （P-nonlinear>0.05）. In non-diabetic patients， compared with the reference group （T3）， the T1 group had a significantly increased risk of CAD （OR： 1.42； 95% CI： 1.00~2.01； P<0.05） and multi-vessel CAD （OR： 1.86； 95%CI： 1.21~2.86； P<0.05）. No statistical association was found between eGDR and CAD in diabetic patients. In ROC curve analysis， when eGDR was added to traditional model for CAD， significant improvements were observed in the model's recognition of CAD and multi-vessel CAD. ConclusionOur study shows eGDR levels are inversely associated with CAD and CAD severity. eGDR， as a non-insulin measure to assess IR， could be a valuable indicator of CAD severity for population.

Effect of Atractylodis Macrocephalae Rhizoma on Short-chain Fatty Acids and Intestinal Barrier in Mice with Slow-transit Constipation / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Atractylodis Macrocephalae Rhizoma（AMR） in the treatment of slow-transmission constipation（STC） by observing the effects of AMR on short-chain fatty acids and intestinal barries in STC mice. MethodForty-eight male KM mice were randomly divided into blank group， model group， AMR low-， medium-， high-dose groups（2.5， 5， 10 g·kg-1） and mosapride group（2.5 mg·kg-1）. Except for the blank group， all groups were gavaged with loperamide suspension（5 mg·kg-1） twice daily for 14 d to construct the STC mouse model. At the same time， each drug administration group was given the corresponding drug by gavage for consecutive 14 d， the blank and model groups were gavaged with equal volume of distilled water. The effects of the treatment of AMR on body mass， defecation frequency， fecal water content and intestinal propulsion rate of mice were observed， the pathological changes of mouse colon were observed by hematoxylin-eosin（HE） staining and periodic acid-Schiff（PAS） staining， the levels of gastrin（GAS） and motilin（MTL） in serum were detected by enzyme-linked immunosorbent assay（ELISA）， gas chromatography-mass spectrometry（GC-MS） was used to detect the contents of short-chain fatty acids（SCFAs） in mouse feces， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to determine the mRNA and protein expression levels of zonula occludens-1（ZO-1）， Occludin， and Claudin-1 in the colon of mice. ResultCompared with the blank group， the body mass， defecation frequency， fecal water content and intestinal propulsion rate of mice in the model group were significantly decreased（P<0.05， P<0.01）， the arrangement of colonic tissues was disordered， and the number of goblet cells was reduced， the levels of GAS and MTL in serum were significantly decreased（P<0.01）， and the levels of SCFAs in the feces were on a decreasing trend， with the contents of acetic acid， propionic acid， butyric acid， isobutyric acid and valeric acid were significantly decreased（P<0.05， P<0.01）， the mRNA and protein expression levels of ZO-1， Occludin and Claudin-1 in the colonic tissues were significantly decreased（P<0.01）. The above results suggested that STC mouse model was successfully constructed. Compared with the model group， the body mass， defecation frequency， fecal water content and intestinal propulsion rate of mice in AMP administration groups all increased significantly（P<0.05， P<0.01）， the mucosal layer of the colonic tissues was structurally intact without obvious damage， and the number of goblet cells increased， serum levels of GAS and MTL were significantly increased（P<0.01）， the contents of SCFAs in the feces were all on a rising trend， with the contents of acetic， propionic， butyric and isobutyric acids rising significantly（P<0.05， P<0.01）， the mRNA and protein expression levels of ZO-1， Occludin and Claudin-1 in the colonic tissues were significantly increased（P<0.05， P<0.01）. ConclusionAMR is able to improve the constipation symptoms in STC mice， and its mechanism may be related to increasing the contents of SCFAs in the intestine as well as promoting the mRNA and protein expression levels of ZO-1， Occludin and Claudin-1 in the colon.