New advances of adiponectin in regulating obesity and related metabolic syndromes

Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.

Percutaneous Coronary Intervention in Acute Coronary Syndromes at the Mother-Child University Hospital Luxembourg in Bamako

Introduction: Acute coronary syndromes (ACS) are a diagnostic and therapeutic emergency. Objective: Studying the feasibility, difficulties and results of coronary angioplasty in acute coronary syndromes at the Luxembourg Mother-Child University Hospital in Bamako. Patients and Methods: Cross-sectional, descriptive study with prospective recruitment over 18 months from September 2020 to February 2022. All patients aged at least 18 years old admitted for SCA and having undergone PCI during the study period were included. Result: We collected 249 patients for SCA, of whom 160 underwent angioplasty, either an angioplasty/SCA ratio of 0.64. The average age of the patients was 59.54 ± 11.62 with extremes of 32 and 92 years. The age group of 45 to 65 years was the most representative. The predominance was male, sex ratio of 2.4. The main cardiovascular risk factors were high blood pressure (58.23%) and diabetes (45.78%). Persistent ST-segment elevation on the electrocardiogram was present in 71.48%. The treatment time was more than 12 hours after the first medical contact in 95.5%. The approach was radial in 96.5% of cases. Coronarography was pathological in 91.16% of our patients. The lesions were tri-truncular in 34.13% with the anterior inter ventricular as culprit artery in 72% of cases. The majority of patients (64%) had undergone angioplasty with implantation of an active stent. Angioplasty was performed successfully in 98% and per procedural mortality was 1.87%. Only 6.45% of ACS with ST elevation benefited from primary angioplasty. Conclusion: Percutaneous coronary intervention is performed routinely in our center with satisfactory results. Difficulties exist, related to the diagnostic delay of ACS and the high cost of angioplasty.

The Distribution Pattern of Traditional Chinese Medicine Syndromes in Patients with Hyperlipidemia

Objective: Hyperlipidemia is a representative nutritional metabolic disease in clinic, which is easy to induce atherosclerotic cardiovascular and cerebrovascular diseases, with complex classification. Traditional Chinese Medicine (TCM) syndrome aims to reflect the characteristics of diseases and is the basic principle of TCM treatment of diseases. This study aimed to summarize the distribution pattern of TCM syndromes in patients with hyperlipidemia. Methods: The frequency, characteristics and distribution of all TCM syndromes of 1012 patients with hyperlipidemia were analyzed. Results: The main disease types determined by frequency of 1012 patients included hypertriglyceridemia combined with hypo high-density lipoprotein cholesterolemia (19.76%), hypo high-density lipoprotein cholesterolemia (18.58%), hypercholesterolemia (16.50%), mixed hyperlipidemia (16.40%), and hypertriglyceridemia (15.12%). The distribution of TCM syndromes, in order of frequency, was as follows: Qi-deficiency and blood stasis syndrome (23.52%), liver depression and spleen deficiency (9.88%), syndrome of qi stagnation and blood stasis (9.29%), phlegm stasis syndrome (7.41%), and syndrome of yang deficiency of spleen and kidney (6.92%). Conclusion: Qi-deficiency and blood stasis syndrome and liver depression and spleen deficiency are the most common TCM syndromes in patients with hyperlipidemia.

Progress of Triglyceride Glucose Index in Lesion Severity and Prognosis of Acute Coronary Syndromes

Background: In response to the escalating burden of cardiovascular diseases (CVDs) worldwide, exacerbated by lifestyle changes and socioeconomic shifts, acute coronary syndromes (ACS) stand out as a leading cause of morbidity and mortality. The pivotal role of insulin resistance in the pathogenesis of atherosclerosis, independent of traditional risk factors, has garnered significant interest. Objective: This review aims to synthesize the recent advancements in the utilization of the triglyceride glucose index (TyG index) as a biomarker for assessing the severity and predicting the prognosis of ACS lesions. Methods: A systematic search was conducted across PubMed, Embase, and Scopus databases, incorporating keywords such as “triglyceride glucose index”, “TyG index”, “acute coronary syndrome”, “cardiovascular disease”, “insulin resistance”, “coronary artery calcification”, “SYNTAX score”, “Gensini score”, and “major adverse cardiac events”. Studies were included from the inception of each database up to July 2024. Selection criteria encompassed observational studies, case-control studies, and randomized controlled trials, with a particular emphasis on evaluating the diagnostic and prognostic value of the TyG index in patients with acute coronary syndromes. Ultimately, 46 publications met the inclusion criteria. Data extraction and quality assessment were performed in accordance with established guidelines. Results: Evidence suggests that the TyG index, reflecting insulin resistance, blood glucose, and lipid levels, is significantly associated with lesion severity in ACS, including coronary artery calcification, SYNTAX score, and Gensini score. Moreover, it demonstrates predictive power for major adverse cardiovascular events, underscoring its potential as a valuable tool in clinical decision-making. Conclusion: The review highlights the emerging role of the TyG index in the assessment and prognosis of ACS, advocating for its incorporation into clinical practice as a complement to existing diagnostic modalities. However, the establishment of standardized reference ranges and further validation across diverse populations are warranted to refine its applicability in personalized medicine. The interdisciplinary approach is essential to advance our understanding of the complex interplay between insulin resistance and cardiovascular disease, paving the way for the development of more effective prevention and treatment strategies.

A Systematic Review of Cannabidiol Effects in Coronary Syndromes: Challenges to Clinical Translation

Background: Myocardial ischemia in addition to other several cardiac syndromes represent a pathological proinflammatory state alongside a complex cellular microenvironment that can be modified by using cannabinoids. Cannabidiol (CBD), a non-psychoactive compound of cannabis has been recently proposed as an immudomodulatory and cardioprotective drug. Objectives: In this systematic review we sought to clarify and summarize the clinical and preclinical evidence of potential benefit of the use of CBD in coronary syndromes. Methods: We conducted a systematic search and review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Review of Animal Data from Experimental Studies (CAMARADES) guidelines, in the electronic database from PubMed, Web of Science and Scopus up to April 2022 using predefined search terms. Pre-specified exclusion and inclusion criteria were considered, finally 11 articles were chosen to be included for this peer review. Results: Currently there are no good-quality clinical trials with the use of CBD in acute or chronic coronary syndromes. A total of 11 preclinical studies where prescreened and 5 demonstrated reproducible positive cardiovascular outcomes on in-vivo models treated with CBD. Mechanisms of CBD cardioprotection observed: 1) reduction in oxidative stress and inflammation, 2) activation of adenosine receptors and 3) increased expression of angiotensin type 2-receptor. Experimental models included ischemia/reperfusion injury, myocardial infarction, arrhythmias, and metabolic syndrome-like conditions. Conclusion: No clinical recommendation can be issued with the current evidence, on the use of CBD in acute and chronic coronary syndromes. Based on preclinical evidence, we considered there is enough evidence to propose the development of well-designed clinical trials that include CBD in the management of coronary syndromes.

An overview on CV2/CRMP5 antibody-associated paraneoplastic neurological syndromes

Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis.Patients with this syndrome produce multiple antibodies,each targeting a different antigen and causing different symptoms and signs.The CV2/collapsin response mediator protein 5(CRMP5)antibody is a major antibody of this type.It damages the nervous system,which often manifests as limbic encephalitis,chorea,ocular manifestation,cerebellar ataxia,myelopathy,and peripheral neuropathy.Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome,and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis.However,because of the low incidence of this disease,few repo rts and no reviews have been published about it so far.This article intends to review the research on CV2/CRMP5antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease.Additionally,this review discusses the curre nt challenges that this disease poses,and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrom e,including CV2/CRMP5-associated paraneoplastic neurological syndrome,in recent years.

Hereditary polyposis syndromes remain a challenging disease entity:Old dilemmas and new insights

In this editorial we present an overview and insights of the management of hereditary polyposis syndromes.The primary focus was on familial adenomatous polyposis,juvenile polyposis syndrome and Peutz-Jegher syndrome.Genetic testing has become increasingly available and is easier than ever to integrate into clinical practice.Furthermore,several genes have been added to the expanding list of genes associated with hereditary polyposis syndromes,allowing for precise diagnostics and tailored follow-up.Endoscopic evaluation of patients with hereditary polyposis syndromes is paramount in the surveillance strategies.Current endoscopic procedures include both diagnostic procedures and surveillance as well as therapeutic interventions.Recommendations for endoscopic procedures in the upper and lower gastrointestinal canal were described.Surgery is still a key component in the management of patients with hereditary polyposis syndromes.The increased cancer risk in these patients often render prophylactic procedures or intended curative procedures in the case of cancer development.Surgical interventions in the upper and lower gastrointestinal canal were described with relevant considerations.Development of chemopreventive medications is ongoing.Few drugs have been investigated,including nonsteroidal anti-inflammatory drugs.It has been demonstrated that cyclooxygenase-2 inhibitors may lower the number of polyps.Other medications are currently under investigation,but none have,to date,consistently been able to prevent development of disease.

Root structure syndromes of four families of monocots in the Middle Urals

The present article tests the following general assumption:plant taxa with different specializations towards mycorrhizal interactions should have different root syndromes.Roots of 61 species common in boreal zone were studied:16 species of Poaceae,24 species of Cyperaceae,14 species of Orchidaceae,and 7 species of Iridaceae.Using a fixed material of 5 individuals of each species,the following was determined:number of orders of branching roots;transverse dimensions of root,stele and cortex;number of primary xylem vessels and exodermis layers;length of root hairs;abundance of mycorrhiza.Species of each family had well-defined syndromes.Roots of Orchidaceae and Iridaceae were thick with a large stele and developed exodermis.Orchidaceae had no branching roots and had long root hairs.In Iridaceae,roots were branched,and root hairs were short.Roots of Poaceae and Cyperaceae were thin with a relatively thin stele.Root hairs were short in Poaceae and long in Cyperaceae.Our finding that root syndromes of four families of monocots differed is a new and unexpected discovery.The high specificity of root syndromes in Cyperaceae,Iridaceae,Poaceae,and Orchidaceae indicates that species of these families use different strategies to obtain water and soil nutrients.

Methylation Characteristics of Perivisceral Fat Gene in Obese Rats with Phlegm-dampness Syndrome and the Effect of Wen Dan Decoction

Objective To observe the characteristics of gene methylation in obese rats with phlegm-dampness syndrome induced by the high-fat diet, and to study the effect of Wen Dan Decoction on gene methylation after the intervention. Methods Methylation sites of genes were detected by the MeDIP-seq method. Bioinformatics method was used to analyze the gene methylation characteristics of obesity with phlegmdampness syndrome and the effect of Wen Dan Decoction. Results (1) There were 3 242 methylation differential loci in dietinduced obesity with phlegm-dampness syndrome, of which 1 243 were down-regulated and 1 999 were up-regulated, involving 1 579 differential genes. GO analysis showed that "offactory receptor activity" and others were enriched. The possible signal pathways involved were "Olfactory transduction""Tuberculosis""Systemic lupus erythematosus" and "Ribosome".(2) After the intervention of Wen Dan Decoction in obesity with phlegmdampness syndrome, 4 046 different methylation loci were obtained, including 1 067 down-regulated loci and 2 979 up-regulated loci, involving 2 068 genes. GO analysis showed that "offactory receptor activity" and others were enriched. These genes involved seven signaling pathways, such as "Metabolic pathways".(3) Between diet-induced obesity with phlegm-dampness syndrome and Wen Dan Decoction intervening obesity with the phlegm-dampness syndrome, 582 common genes of methylation differential genes were obtained. After the intervention of Wen Dan Decoction, the number of GO enrichment items was more than that of obesity with phlegm-dampness syndrome, and even the same GO enrichment items involved more genes. Conclusions The phlegm-dampness syndrome of obesityinduced by diet had the characteristics of gene methylation changes, and the intervention of Wen Dan Decoction could also affect the status of gene methylation. The genes affected by Wen Dan Decoction were closely related to the methylation gene of phlegm-dampness syndrome of obesity-induced by diet but covered a wider range.

Hepatocardiorenal syndrome in liver cirrhosis:Recognition of a new entity?

Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context.In the absence of established heart disease,cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease.It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities.Despite the clinical description of these potential cardiac-related complications of the liver,the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS.Yet from a physiological sense,temporality(prior onset)of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients.In this review,we discuss current concepts surrounding how the heart may influence the development and progression of HRS,and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting.The temporality of heart and kidney dysfunction in HRS will be discussed.For a subgroup of patients who receive portosystemic shunting,the dynamics of cardiorenal interactions following treatment is reviewed.Continued research to determine the unknowns in this topic is anticipated,hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.

Tricuspid mass-curious case of Li-Fraumeni syndrome: A case report

BACKGROUND Li-Fraumeni syndrome(LFS)is a rare autosomal dominant cancer-predisposing syndrome,which can manifest as a polymorphic spectrum of malignancies.LFS is associated with an early onset in life,with the majority of cases occurring prior to the age of 46.Notwithstanding the infrequency of primary cardiac tumors,it behooves clinicians to remain vigilant in considering the differential diagnosis of such tumors in LFS patients who present with a cardiac mass.This is due to the markedly elevated risk for malignancy in this particular population,far surpassing that of the general populace.CASE SUMMARY Herein,we present a case of a 30-year-old female with LFS who was found to have a tricuspid valve leaflet mass.CONCLUSION This case exemplifies valuable learning points in the diagnostic approach for this exceptionally rare patient population.

Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.

Body composition and metabolic syndrome in patients with type 1 diabetes

BACKGROUND In recent years,the prevalence of obesity and metabolic syndrome in type 1 diabetes(T1DM)patients has gradually increased.Insulin resistance in T1DM deserves attention.It is necessary to clarify the relationship between body composition,metabolic syndrome and insulin resistance in T1DM to guide clinical treatment and intervention.AIM To assess body composition(BC)in T1DM patients and evaluate the relationship between BC,metabolic syndrome(MS),and insulin resistance in these indi-viduals.METHODS A total of 101 subjects with T1DM,aged 10 years or older,and with a disease duration of over 1 year were included.Bioelectrical impedance analysis using the Tsinghua-Tongfang BC Analyzer BCA-1B was employed to measure various BC parameters.Clinical and laboratory data were collected,and insulin resistance was calculated using the estimated glucose disposal rate(eGDR).RESULTS MS was diagnosed in 16/101 patients(15.84%),overweight in 16/101 patients(15.84%),obesity in 4/101(3.96%),hypertension in 34/101(33.66%%)and dyslip-idemia in 16/101 patients(15.84%).Visceral fat index(VFI)and trunk fat mass were significantly and negatively correlated with eGDR(both P<0.001).Female patients exhibited higher body fat percentage and visceral fat ratio compared to male patients.Binary logistic regression analysis revealed that significant factors for MS included eGDR[P=0.017,odds ratio(OR)=0.109],VFI(P=0.030,OR=3.529),and a family history of diabetes(P=0.004,OR=0.228).Significant factors for hypertension included eGDR(P<0.001,OR=0.488)and skeletal muscle mass(P=0.003,OR=1.111).Significant factors for dyslipidemia included trunk fat mass(P=0.033,OR=1.202)and eGDR(P=0.037,OR=0.708).CONCLUSION Visceral fat was found to be a superior predictor of MS compared to conventional measures such as body mass index and waist-to-hip ratio in Chinese individuals with T1DM.BC analysis,specifically identifying visceral fat(trunk fat),may play an important role in identifying the increased risk of MS in non-obese patients with T1DM.

Epidemiological, Clinical and Angiographic Profile of Chronic Coronary Syndromes in the Catheterization Room. Single-Centre Study Carried Out in the Cardiology Department of the Chu Aristide Le Dantec in Dakar (Senegal)

Background: Ischaemic heart disease is the cause of 7.4 million deaths per year. Their prevention is based on the management of cardiovascular risk factors, but also on the early detection and management of chronic coronary syndromes (CCS), for which few data are available in Africa. The main objective of our study was to determine the factors related to significative coronary artery disease in patients undergoing coronarography for suspected chronic coronary syndrome (CCS). Methodology: We conducted a retrospective descriptive and analytical study over 2 years (from January, 1st, 2018 to December 31st, 2019) in the Cardiology Department of the University Hospital Aristide Le DANTEC in Dakar. All patients admitted for coronary angiography for suspected chronic coronary syndrome were included. Results: One hundred and fifty-two patients were included with a mean age of 60.79 ± 9.73 years, the most represented age group was 60 - 69 years. Advanced age was the most frequent risk factor (77.63%) followed by sedentary lifestyle (56.58%) and hypertension (41.45%). Diabetes was present in 17.1% of cases. A history of angioplasty was found in 1.97% of patients. Typical pain was found in 71.05% of cases, atypical pain in 19.74% and exertional dyspnoea in 2.63%. The pre-test probability was intermediate in 67.1% of cases, low in 25% and high in 7.9%. Significative coronary lesion was found in 52.63% of the patients, while coronary angiography was normal in the remaining cases. Tritroncular status was observed in 37.50%, it was bitroncular in 26.25% and monotroncular in 36.25% of cases. Factors associated with significative coronary artery disease were age (p = 0.0001), diabetes (p = 0.006), previous angioplasty (p = 0.023), previous myocardial infarction (p = 0.018), typical angina (p = 0.001), intermediate pretest probability (p = 0.001). Low pretest probability was significantly correlated with the absence of a coronary lesion with a p = 0.001. Conclusion: Our study shows that screening for chronic coronary disease should be done especially in diabetics, elderly subjects and those with previous angioplasty taking into account symptoms and pretest probability to avoid unnecessary invasive procedures.

Causal role of immune cells in obstructive sleep apnea hypopnea syndrome:Mendelian randomization study

BACKGROUND Despite being one of the most prevalent sleep disorders,obstructive sleep apnea hypoventilation syndrome(OSAHS)has limited information on its immunologic foundation.The immunological underpinnings of certain major psychiatric diseases have been uncovered in recent years thanks to the extensive use of genome-wide association studies(GWAS)and genotyping techniques using highdensity genetic markers(e.g.,SNP or CNVs).But this tactic hasn't yet been applied to OSAHS.Using a Mendelian randomization analysis,we analyzed the causal link between immune cells and the illness in order to comprehend the immunological bases of OSAHS.AIM To investigate the immune cells'association with OSAHS via genetic methods,guiding future clinical research.METHODS A comprehensive two-sample mendelian randomization study was conducted to investigate the causal relationship between immune cell characteristics and OSAHS.Summary statistics for each immune cell feature were obtained from the GWAS catalog.Information on 731 immune cell properties,such as morphologic parameters,median fluorescence intensity,absolute cellular,and relative cellular,was compiled using publicly available genetic databases.The results'robustness,heterogeneity,and horizontal pleiotropy were confirmed using extensive sensitivity examination.RESULTS Following false discovery rate(FDR)correction,no statistically significant effect of OSAHS on immunophenotypes was observed.However,two lymphocyte subsets were found to have a significant association with the risk of OSAHS:Basophil%CD33dim HLA DR-CD66b-(OR=1.03,95%CI=1.01-1.03,P<0.001);CD38 on IgD+CD24-B cell(OR=1.04,95%CI=1.02-1.04,P=0.019).CONCLUSION This study shows a strong link between immune cells and OSAHS through a gene approach,thus offering direction for potential future medical research.

Chitin-glucan improves important pathophysiological features of irritable bowel syndrome

BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic gains.Chitin-glucan(CG)is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority.To provide an alternative approach to managing patients with IBS,we performed preclinical molecular,cellular,and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS.AIM To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular models.METHODS Visceral pain was recorded through colorectal distension(CRD)in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS[15 milligrams(mg)/kilogram(kg)]in 33 Sprague-Dawley rats.Intracolonic pressure was regularly assessed during the 9 wk-experiment(weeks 0,3,5,and 7)in animals receiving CG(n=14)at a human equivalent dose(HED)of 1.5 g/d or 3.0 g/d and compared to negative control(tap water,n=11)and positive control(phloroglucinol at 1.5 g/d HED,n=8)groups.The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate(DSS)administered in their drinking water during 14 d.HT-29 cells under basal conditions and after stimulation with lipopolysaccharide(LPS)were treated with CG to evaluate changes in pathways related to analgesia μ-opioid receptor(MOR),cannabinoid receptor 2(CB2),peroxisome proliferator-activated receptor alpha,inflammation[interleukin(IL)-10,IL-1b,and IL-8]and barrier function[mucin 2-5AC,claudin-2,zonula occludens(ZO)-1,ZO-2]using the real-time PCR method.Molecular modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations.Data were expressed as the mean±SEM.RESULTS Daily CG orally-administered to rats or mice was well tolerated without including diarrhea,visceral hypersensitivity,or inflammation,as evaluated at histological and molecular levels.In a model of CRD,CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14%after 2 wk of administration(P<0.01)and reduced inflammation intensity by 50%,resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis.To better reproduce the characteristics of visceral pain in patients with IBS,we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity.CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20%five weeks after colitis induction(P<0.01).When the CG dosage was increased to 3.0 g/d HED,this analgesic effect surpassed that of the spasmolytic agent phloroglucinol,manifesting more rapidly within 3 wk and leading to a 50%inhibition of pain perception(P<0.0001).The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved,at least in part,a significant induction of MOR,CB2 receptor,and IL-10,as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8.CG also significantly upregulated barrier-related genes including muc5AC,claudin-2,and ZO-2.Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids,sequestering gram-negative LPS and gram-positive LTA bacterial toxins,as well as PLM in fungi at the lowesr energy conformations.CONCLUSION CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products,suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBSlike symptoms.

Prognostic significance of identification of traditional Chinese medicine syndromes in colorectal cancer

Background:Traditional Chinese medicine(TCM)syndrome is the basic unit of TCM treatment,which help clinicians assess the disease progression and treatment preoperative of tumor patients.However,the prognostic significance of TCM syndrome is still unclear.This study aims to detect the differences in overall survival between different TCM syndrome and further develop a new nomogram with TCM syndrome for predicting overall survival in colorectal cancer.Methods:A total of 324 patients with colorectal cancer were enrolled and categorized into three groups based on TCM syndrome:deficiency,excess,and deficiency-excess.The prognosis of colorectal cancer patients with different TCM syndromes was evaluated using Kaplan-Meier analysis and Cox regression analysis.Results:The proportion of advanced stage and lymph metastasis in the patients with deficiency syndrome was higher,and the overall survival was shorter than other syndromes.Meanwhile,the TCM syndrome(P<0.001),tumor invasion depth(P<0.001),lymph metastasis(P=0.018),organic metastasis(P=0.005)and tumor node metastasis(TNM)stage(P=0.029)were the independent prognostic factor.Then,a new nomogram with TCM syndrome was established and assessed.324 colorectal cancer patients were randomly divided into training(n=215)and validation cohorts(n=109).A nomogram incorporating preoperative TCM syndrome,gender,age,T,N,and M status was developed,which had good discrimination and calibration.Conclusion:Taken together,our results indicated that TCM syndrome could assess the prognosis of colorectal cancer.The nomogram incorporating TCM syndromes and tumor information is helpful for risk stratification and prognostic predictions in colorectal cancer preoperatively.

Predictive value of bilirubin and serum γ-glutamyltranspeptidase levels in type-2 diabetes mellitus patients with acute coronary syndrome

BACKGROUND Cardiovascular disease is a major complication of diabetes mellitus(DM).Type-2 DM(T2DM)is associated with an increased risk of cardiovascular events and mortality,while serum biomarkers may facilitate the prediction of these outcomes.Early differential diagnosis of T2DM complicated with acute coronary syndrome(ACS)plays an important role in controlling disease progression and improving safety.AIM To investigate the correlation of serum bilirubin andγ-glutamyltranspeptidase(γ-GGT)with major adverse cardiovascular events(MACEs)in T2DM patients with ACS.METHODS The clinical data of inpatients from January 2022 to December 2022 were analyzed retrospectively.According to different conditions,they were divided into the T2DM complicated with ACS group(T2DM+ACS,n=96),simple T2DM group(T2DM,n=85),and simple ACS group(ACS,n=90).The clinical data and laboratory indices were compared among the three groups,and the correlations of serum total bilirubin(TBIL)levels and serumγ-GGT levels with other indices were discussed.T2DM+ACS patients received a 90-day follow-up after discharge and were divided into event(n=15)and nonevent(n=81)groups according to the occurrence of MACEs;Univariate and multivariate analyses were further used to screen the independent influencing factors of MACEs in patients.RESULTS The T2DM+ACS group showed higherγ-GGT,total cholesterol,low-density lipoprotein cholesterol(LDL-C)and glycosylated hemoglobin(HbA1c)and lower TBIL and high-density lipoprotein cholesterol levels than the T2DM and ACS groups(P<0.05).Based on univariate analysis,the event and nonevent groups were significantly different in age(t=3.3612,P=0.0011),TBIL level(t=3.0742,P=0.0028),γ-GGT level(t=2.6887,P=0.0085),LDL-C level(t=2.0816,P=0.0401),HbA1c level(t=2.7862,P=0.0065)and left ventricular ejection fraction(LEVF)levels(t=3.2047,P=0.0018).Multivariate logistic regression analysis further identified that TBIL level and LEVF level were protective factor for MACEs,and age andγ-GGT level were risk factors(P<0.05).CONCLUSION Serum TBIL levels are decreased andγ-GGT levels are increased in T2DM+ACS patients,and the two indices are significantly negatively correlated.TBIL andγ-GGT are independent influencing factors for MACEs in such patients.

Clinical efficacy and mechanism study of mid-frequency anti-snoring device in treating moderate obstructive sleep apnea-hypopnea syndrome

BACKGROUND Obstructive sleep apnea-hypopnea syndrome(OSAHS)is primarily caused by airway obstruction due to narrowing and blockage in the nasal and nasopha-ryngeal,oropharyngeal,soft palate,and tongue base areas.The mid-frequency anti-snoring device is a new technology based on sublingual nerve stimulation.Its principle is to improve the degree of oropharyngeal airway stenosis in OSAHS patients under mid-frequency wave stimulation.Nevertheless,there is a lack of clinical application and imaging evidence.METHODS We selected 50 patients diagnosed with moderate OSAHS in our hospital between July 2022 and August 2023.They underwent a 4-wk treatment regimen involving the mid-frequency anti-snoring device during nighttime sleep.Following the treatment,we monitored and assessed the sleep apnea quality of life index and Epworth Sleepiness Scale scores.Additionally,we performed computed tomo-graphy scans of the oropharynx in the awake state,during snoring,and while using the mid-frequency anti-snoring device.Cross-sectional area measurements in different states were taken at the narrowest airway point in the soft palate posterior and retrolingual areas.RESULTS Compared to pretreatment measurements,patients exhibited a significant reduction in the apnea-hypopnea index,the percentage of time with oxygen saturation below 90%,snoring frequency,and the duration of the most prolonged apnea event.The lowest oxygen saturation showed a notable increase,and both sleep apnea quality of life index and Epworth Sleepiness Scale scores improved.Oropharyngeal computed tomography scans revealed that in OSAHS patients cross-sectional areas of the oropharyngeal airway in the soft palate posterior area and retrolingual area decreased during snoring compared to the awake state.Conversely,during mid-frequency anti-snoring device treatment,these areas increased compared to snoring.CONCLUSION The mid-frequency anti-snoring device demonstrates the potential to enhance various sleep parameters in patients with moderate OSAHS,thereby improving their quality of life and reducing daytime sleepiness.These therapeutic effects are attributed to the device’s ability to ameliorate the narrowing of the oropharynx in OSAHS patients.

Hereditary cancer syndromes

Hereditary cancer syndromes(HCSs)are arguably the most frequent category of Mendelian genetic diseases,as at least 2%of presumably healthy subjects carry highly-penetrant tumor-predisposing pathogenic variants(PVs).Hereditary breast-ovarian cancer and Lynch syndrome make the highest contribution to cancer morbidity;in addition,there are several dozen less frequent types of familial tumors.The development of the majority albeit not all hereditary malignancies involves two-hit mechanism,i.e.the somatic inactivation of the remaining copy of the affected gene.Earlier studies on cancer families suggested nearly fatal penetrance for the majority of HCS genes;however,population-based investigations and especially large-scale next-generation sequencing data sets demonstrate that the presence of some highly-penetrant PVs is often compatible with healthy status.Hereditary cancer research initially focused mainly on cancer detection and prevention.Recent studies identified multiple HCS-specific drug vulnerabilities,which translated into the development of highly efficient therapeutic options.