Cancer is a leading cause of death worldwide. Cancer treatments by chemotherapeutic agents, surgery, and radiation have not been highly effective in reducing the incidence of cancers and increasing the survival rate o...Cancer is a leading cause of death worldwide. Cancer treatments by chemotherapeutic agents, surgery, and radiation have not been highly effective in reducing the incidence of cancers and increasing the survival rate of cancer patients. In recent years, plant-derived compounds have attracted considerable attention as alternative cancer remedies for enhancing cancer prevention and treatment because of their low toxicities, low costs, and low side effects. Ellagic acid(EA) is a natural phenolic constituent. Recent in vitro and in vivo experiments have revealed that EA elicits anticarcinogenic effects by inhibiting tumor cell proliferation, inducing apoptosis, breaking DNA binding to carcinogens, blocking virus infection, and disturbing inflammation, angiogenesis, and drug-resistance processes required for tumor growth and metastasis. This review enumerates the anticarcinogenic actions and mechanisms of EA. It also discusses future directions on the applications of EA.展开更多
Chloroquine(CQ)and hydroxychloroquine(HCQ),originally developed as anti-malarial drugs,have found a new purpose in treating various autoimmune dis-eases due to their immunomodulatory properties.These drugs work throug...Chloroquine(CQ)and hydroxychloroquine(HCQ),originally developed as anti-malarial drugs,have found a new purpose in treating various autoimmune dis-eases due to their immunomodulatory properties.These drugs work through mu-ltiple mechanisms,including inhibiting Toll-like receptor signaling,suppressing antigen presentation,and modulating autophagy.This review article provides a comprehensive analysis of the immunomodulatory effects of CQ and HCQ in several autoimmune diseases such as systemic lupus erythematosus,rheumatoid arthritis,systemic sclerosis,and others.We delve into the intricate mechanisms of action,highlighting the key immune cells involved and discussing the clinical implications of these drugs in managing autoimmune conditions.Our review covers the latest research and clinical trials,offering a comprehensive under-standing of the therapeutic potential of CQ and HCQ in autoimmune diseases.We also discuss the challenges and controversies surrounding the use of these drugs,such as their long-term side effects and the need for personalized treatment approaches.By synthesizing current knowledge and identifying areas for future research,this review aims to provide a valuable resource for healthcare profes-sionals and researchers involved in the management of autoimmune diseases.展开更多
Human temporal bone specimens are used in experiments to measure the sound transfer function of the middle ear.This standard method for the development of middle ear implants requires temporal bones that possess appro...Human temporal bone specimens are used in experiments to measure the sound transfer function of the middle ear.This standard method for the development of middle ear implants requires temporal bones that possess appropriate mechanical properties and structural stability and are free from pathological conditions.A laser Doppler vibrometer is commonly employed to measure the vibration of the stapes footplate.These experiments are typically conducted in the middle ear by leaving the inner ear intact,exposing the stapes footplate through the tympanic cavity,and directing the laser beam onto the footplate.However,previous studies have shown that the influence of inner ear impedance on the middle ear transfer function cannot be ignored,and any surgical manipulation may cause a change in inner ear pressure,resulting in instability in the middle ear transfer function.Therefore,this study aims to eliminate the influence of the inner ear and to establish a new experimental method in human temporal bone specimens that is more suitable for the study of sound conduction in middle ear implants.As a result,a range for middle ear transfer function was developed,which serves as a reference for assessing the conformity of temporal bone specimens to experimental standards,and the stability of this range was demonstrated under experimental conditions.展开更多
In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing i...In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing is complex and involves a coordinated series of biological events,including inflammation,cell proliferation,and tissue remodeling.The innate immune system is important in the early stages of wound repair,with inflammation being a crucial initial phase in tissue rege-neration.However,the inflammatory response should be regulated,as excessive or dysregulated inflammation can impair healing.Platelet concentrates,specifi-cally PRF,have originated as promising tools to optimize the tissue repair process.PRF is a second-generation platelet concentrate,and the release of growth factors(GFs)plays a determining role in several aspects of wound healing,including promoting cell proliferation,stimulating angiogenesis,and modulating inflam-mation.PRF forms a fibrin matrix that entraps platelets and GFs.This structure allows for their sustained release over time,which is believed to provide a more favorable microenvironment for tissue repair.Recent research by Sá-Oliveira et al has provided valuable evidence supporting the efficacy of PRF in promoting wound healing.Their study,conducted on an animal model,demonstrated that PRF-based dressings were more effective in accelerating wound closure in the early stages of the healing process,enhancing tissue repair,and modulating the inflammatory response.We explore how PRF's unique properties contribute to a more controlled and effective healing process.By examining these findings,we aim to highlight PRF's potential as a promising therapeutic strategy for improved wound management.展开更多
This editorial highlights the critical role of viral RNA signatures encapsulated within circulating exosomes as a potential missing link in the early diagnosis of gastrointestinal(GI)cancers.Current diagnostic methods...This editorial highlights the critical role of viral RNA signatures encapsulated within circulating exosomes as a potential missing link in the early diagnosis of gastrointestinal(GI)cancers.Current diagnostic methods for virus-associated GI malignancies often fall short in detecting infections at subclinical or pre-cancerous stages.We propose that viral RNA-loaded exosomes,by offering stable,specific,and non-invasive biomarkers,can bridge this gap and revolutionize early de-tection compared to conventional approaches.As highlighted by Zhang et al in their recent review,viral infections,such as hepatitis B and C viruses,Epstein-Barr virus,and human papillomavirus,are well-established contributors to the pathogenesis of various GI malignancies.However,current diagnostic methods often underperform in detecting these infections at subclinical or pre-cancerous stages.We highlight the shared points between virology,exosome biology,and oncology,reinforcing the importance of viral RNA-loaded exosomes as a“missing link”in the early detection of virus-associated GI cancers.We also discuss current challenges,translational opportunities,and the requirements for clinical vali-dation of these promising biomarkers.展开更多
Alcohol-associated liver disease(ALD)is a major global health concern,contributing to liver injury,morbidity,and mortality.Elafibranor(EFN),a dual peroxisome proliferator-activated receptorα/δagonist,has shown promi...Alcohol-associated liver disease(ALD)is a major global health concern,contributing to liver injury,morbidity,and mortality.Elafibranor(EFN),a dual peroxisome proliferator-activated receptorα/δagonist,has shown promise as a therapeutic candidate in preclinical studies.EFN reduces liver fibrosis by inhibiting lipid accumulation,apoptosis,and inflammatory pathways(LPS/TLR4/NF-κB),while enhancing autophagy and antioxidant responses.It also improves intestinal barrier function and modulates gut microbiota,reducing endotoxin-producing bacteria and increasing beneficial species.By strengthening the intestinal barrier and suppressing pro-inflammatory mediators like tumor necrosis factor-alpha and interleukin-6,EFN mitigates hepatic stellate cell activation and fibrogenic signaling.Macrophages play a central role in ALD progression,and EFN’s ability to modulate macrophage activity further highlights its anti-inflammatory properties.This review emphasizes EFN’s dual-targeted approach,addressing both hepatic and intestinal dysfunctions,distinguishing it from conventional ALD treatments.While preclinical results are promising,EFN remains under clinical investigation,with ongoing trials evaluating its safety and efficacy.Future research should focus on elucidating EFN’s molecular mechanisms and advancing its clinical application to establish its therapeutic potential in human populations.EFN represents a novel,comprehensive strategy for ALD management,targeting both liver and gut pathologies.展开更多
Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic p...Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients.Twenty infertile males with VC and twenty-three age-matched healthy controls(HCs)were recruited from Peking Union Medical College Hospital(Beijing,China)between October 2019 and April 2021.Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry.Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs.The top enriched pathways among these significantly different metabolites are protein digestion and absorption,aminoacyl-transfer RNA(tRNA)biosynthesis,and biosynthesis of amino acids.Different key lipid species,including triglyceride(TG),diacylglycerol(DG),ceramides(Cer),and phosphatidylserine(PS),varied betweenVC and HC groups.The distinct metabolites and lipids were moderately correlated.DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility(area under the curve[AUC]=0.893),positively correlating with sperm count,concentration,and motility.Furthermore,DL-3-phenyllactic acid is the only metabolite shared by all four comparisons(VC vs HC,VC-induced oligoasthenospermia[OAS]vs VC-induced asthenospermia[AS],OAS vs HC,and AS vs HC).DL-3-phenyllactic acid significantly decreased in OAS than AS.Metabolite-targeting gene analysis revealed carbonic anhydrase 9(CA9)might be the strongest candidate associated with the onset and severity of VC.The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs.DL-3-phenyllactic acid could be a promising biomarker.展开更多
Aspergillus species produce aflatoxins and raise concerns about food safety in departmental stores and manufacturing mills.To address the risks posed by aflatoxins,and to advise the public on the highest quality rice ...Aspergillus species produce aflatoxins and raise concerns about food safety in departmental stores and manufacturing mills.To address the risks posed by aflatoxins,and to advise the public on the highest quality rice that serves as a nutritious food source,an inquiry following the guidelines outlined in both local and international standards of food safety for the presence of aflatoxins is an essential requirement.Therefore,16 white rice samples were selected randomly from low/high socio-economic departmental stores from 16 different localities.Grind powdered rice filtrate was extracted using chloroform.The filtrate applied on TLC plates and the amount of aflatoxin and moisture contents were determined.In the non-infected rice,moisture content was low(9.08%)whereas high[13.65%>12%(standard>value)]in infected ones.Four out of 8 samples of low-quality rice were contaminated with AFB_(1) and AFB_(2)(ranging from 22.2 to 29.3μg/kg).All the samples except one(22.3μg/kg)from high-quality rice were certified fit despite the contamination with AFB_(1).Furthermore,phylogenetic analysis showed Aspergillus flavus from unfit low(Long grain brown and Brown basmati)and high-quality(Basmati-198)rice whereas A.parasiticus from unfit low-quality Medium-grain brown rice.The presented research proves that the detection of fungi and aflatoxins in rice grains poses a huge risk to the health of consumers.Therefore,it is necessary to check the rice grains before distribution.展开更多
BACKGROUND The persistent burden of cardiovascular(CV)disease in the United States requires innovative and cost-effective prognostic markers that can be relied upon.AIM To provide insights into how adiponectin can pre...BACKGROUND The persistent burden of cardiovascular(CV)disease in the United States requires innovative and cost-effective prognostic markers that can be relied upon.AIM To provide insights into how adiponectin can predict all-cause mortality and major adverse CV events(MACE)in patients with coronary artery disease(CAD)and to determine the prognostic value of adiponectin in predicting all-cause mortality and MACE in patients with stable CAD.METHODS We conducted a systematic search on PubMed,Scopus,and Google Scholar to find relevant studies published through June 2023 evaluating the long-term prognostic role of adiponectin in patients with stable CAD.Using a random effects model with 95%CI,we estimated the odds ratio(OR)while assessing heterogeneity through I^(2)statistics.To ensure robustness,we performed a sensitivity analysis using the leave-one-out approach.RESULTS After screening,we included five prospective studies involving 3225 patients who were followed up for a median duration of 3.8 years.Within the study population,prevalent risk factors included hypertension,diabetes,hyperlipidemia,and smoking.The commonly prescribed medications were angiotensin-converting enzyme inhibitors,beta blockers,and statins.The combined adjusted OR for all-cause mortality was found to be 2.51(95%CI:1.36–4.62),showing heterogeneity(I^(2)=65.51%,P=0.03).On the other hand,the combined adjusted OR for MACE was determined to be 1.04(95%CI:1.02–1.06)with no significant heterogeneity observed(I^(2)=0%,P=0.68).Through a sensitivity analysis,it was discovered that none of the studies significantly impacted the overall results of the meta-analysis,thus indicating their robustness.CONCLUSION Higher levels of adiponectin were found to be associated with an increased risk of long-term mortality and MACE in patients with CAD,which highlights its potential as a cost-effective marker for risk assessment and guiding treatment strategies.Further research on the role of adiponectin could greatly influence decision-making and resource allocation in CV care.展开更多
OBJECTIVE:To investigate the optimal timing and underlying mechanism of electroacupuncture(EA)at Baihui(GV 20)and Dazhui(GV 14)for improved long-term functional recovery after focal cerebral ischemia in a photothrombo...OBJECTIVE:To investigate the optimal timing and underlying mechanism of electroacupuncture(EA)at Baihui(GV 20)and Dazhui(GV 14)for improved long-term functional recovery after focal cerebral ischemia in a photothrombotic stroke mouse model.METHODS:Totally 50 adult male C57 BL/6 J mice were assigned into 5 groups:(a)the control group,sham-operated mice(n=10);(b)the vehicle group,focal cerebral ischemia induction without EA(n=10);(c)the acute EA group,mice received EA immediately post-ischemia,followed by once-daily treatments for 7 consecutive days(n=10);(d)the subacute EA group,mice received EA 4 days post-ischemia,followed by once-daily treatments for 7 consecutive days(n=10);(e)the delayed EA group.EA stimulation(2 Hz,2 V for 20 min)was applied to acupuncture points(acupoints),Baihui(GV 20)and Dazhui(GV 14),once a day for 7 consecutive days beginning immediately(acute treatment),4 d(subacute treatment)and 10 d(delayed treatment)after focal cerebral ischemia in C57 BL/6 J mice.Behavioral assessments were conducted 21 and 28 d post-ischemia and histopathological analyses were performed 28 days post-ischemia.RESULTS:The subacute EA treatment at Baihui(GV20)and Dazhui(GV 14)significantly improved functional recovery compared to the vehicle group 28 d after ischemic brain injury,although brain atrophy was not reduced.The number of Neu N+and Neu N+/Brd U+cells as well as GFAP intensity in the ipsilateral cortex were significantly increased in the subacute group compared to the vehicle group 28 d post-ischemia.We concluded that EA stimulation 4 d post-ischemia(subacute treatment)enhanced neurogenesis and astrogliosis,likely contributing to long-term functional recovery following focal cerebral ischemia.CONCLUSION:Our findings suggest that the timing of the EA therapy at Baihui(GV 20)and Dazhui(GV 14)determines the therapeutic effects in mice with focal cerebral ischemia induced by photothrombotic occlusion.展开更多
Pulmonary hypertension(PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure(PAP) and pulmonary vascular resistance(PVR), finally leading to right heart failure and de...Pulmonary hypertension(PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure(PAP) and pulmonary vascular resistance(PVR), finally leading to right heart failure and death. The pathogenesis of this arteriopathy remains unclear, leaving it impossible to target pulmonary vascular remodeling and reverse the deterioration of right ventricular(RV) function. Different animal models have been designed to reflect the complex mechanistic origins and pathology of PH, roughly divided into 4 categories according to the modeling methods: noninvasive models in vivo, invasive models in vivo, gene editing models, and multi-means joint modeling. Though each model shares some molecular and pathological changes with different classes of human PH, in most cases the molecular etiology of human PH is poorly known. The appropriate use of classic and novel PH animal models is essential for the hunt of molecular targets to reverse severe phenotypes.展开更多
Digestive endoscopy is currently the main diagnostic procedure for investigation of the digestive tract when a digestive disease is suspected.The use of computers and electronic medical records for the management of e...Digestive endoscopy is currently the main diagnostic procedure for investigation of the digestive tract when a digestive disease is suspected.The use of computers and electronic medical records for the management of endoscopic data are an important key to improving endoscopy unit efficiency and productivity.This technology supports optimal program operation,monitoring and evaluation colorectal cancer screening.This article is a comprehensive survey of endoscopic electronic medical records and information systems.Computerized clinical records have the capability of identifying patients due for screening and to calculate baseline rates of colorectal cancer screening by patient characteristics and by primary care physician and practice group.This paper describes data flow in the endoscopy unit,the minimum data set of colorectal cancer and key features of endoscopic electronic medical record.In addition,the researchers state standards in different aspects,especially terminology standards and interoperability standards for image and text.展开更多
The gut-brain axis is a bidirectional communication system that exists between the brain and gut. Several studies claimed that some types of headaches are associated with various gastrointestinal(GI) disorders.In Pers...The gut-brain axis is a bidirectional communication system that exists between the brain and gut. Several studies claimed that some types of headaches are associated with various gastrointestinal(GI) disorders.In Persian medicine(PM), physicians believed that gastric disturbances could stimulate headache and introduced some herbs for boosting gastric function as a therapeutic remedy for headache. Here we review the current evidence for the gastroprotective and antiheadache effects of herbs used in PM.Herbs used for their gastrotonic effects in PM were identified from selected Persian medical and pharmaceutical textbooks. Pub Med, Scopus and Google Scholar were used to search for contemporary scientific evidence relating to the gastric and neurologic effects of these plants. A total of 24 plants were recorded from the selected sources included in this review, most of which belonged to the Rosaceae family.Phyllanthus emblica, Zingiber officinale, Boswellias errata, Punica granatum and Hypericum perforatum had the most recent studies related to GI disorder and headache, while current research about quince, rose,apple, hawthorn and pear was limited. Reducing Helicobacter pylori growth, gastritis, erosion of the stomach lining, hemorrhage and perforation, improving gastric mucosal resistance, antisecretary, antiulcer,antipyretic, analgesic, sedative, anxiolytic, anti-inflammatory, anticonvulsant, neuroprotective and antioxidant effects as well as improvement in memory scores were some of the gastrotonic and neuroprotective mechanisms described in the current research. These results confirmed that medicinal plants prescribed in PM may improve headache in patients through the management of GI abnormalities.However, further studies are recommended to investigate the efficacy and safety of the mentioned medicinal plants.展开更多
This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used fo...This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used for diabetes management,and its potential cardioprotective effects in a diabetic mouse model.They suggested teneligliptin administration may reverse established markers of DCM,including cardiac hypertrophy and compromised function.It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice.Macrophages play crucial roles in DCM pathogenesis.Chronic hyperglycemia disturbs the balance between pro-inflammatory(M1)and antiinflammatory(M2)macrophages,favoring a pro-inflammatory state contributing to heart damage.Here,we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment.These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome.Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.展开更多
Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19,especially those with pre-existing cardiovascular diseases(CVDs)and diabetes....Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19,especially those with pre-existing cardiovascular diseases(CVDs)and diabetes.Methods This multicenter retrospective cohort study included all patients who were hospitalized due to COVID-19 from 21 hospitals in Hubei province,China between December 31,2019 and April 21,2020.Patients who were aged<18 or≥85 years old,in pregnancy,with acute lethal organ injury(e.g.,acute myocardial infarction,severe acute pancreatitis,acute stroke),hypothyroidism,malignant diseases,severe malnutrition,and those with normal lipid profile under lipid-lowering medicines(e.g,statin,niacin,fenofibrate,gemfibrozil,and ezetimibe)were excluded.Propensity score matching(PSM)analysis at 1:1 ratio was performed to minimize baseline differences between patient groups of hyperlipidemia and non-hyperlipidemia.PSM analyses with the same strategies were further conducted for the parameters of hyperlipidemia in patients with increased triglyceride(TG),increased low・density lipoprotein cholesterol(LDL-C),and decreased high-density lipoprotein cholesterol(HDL-C).Mixed-effect Cox model analysis was performed to investigate the associations of the 28-days all-cause deaths of COVID-19 patients with hyperlipidemia and the abnormalities of lipid parameters.The results were verified in male,female patients,and in patients with pre-existing CVDs and type 2 diabetes.Results Of 1094S inpatients confirmed as COVID-19,there were 9822 inpatients included in the study,comprising 3513(35.8%)cases without hyperlipidemia and 6309(64.2%)cases with hyperlipidemia.Based on a mixed-effect Cox model after PSM at 1:1 ratio,hyperlipidemia was not associated with increased or decreased 28-day all-cause death[adjusted hazard ratio(HR),1.17(95%C/,0.95-1.44),P二0.151].Wb found that the parameters of hyperlipidemia were not associated with the risk of 28-day all-cause mortality[adjusted HR,1.23(95%CI,0.98-1.55),P=0.075 in TG increase group;0.78(95%CI,0.57-1.07),P=0.123 in LDL-C increase group;and 1.12(95%CI,0.9-1.39),P=0.299 in HDL-C decrease group,respectively].Hyperlipidemia was also not significantly associated with the increased mortality of COVID-19 in patients accompanied with CVDs or type 2 diabetes,and in both male and female cohorts.Conclusion Our study support that the imbalanced lipid profile is not significantly associated with the 28-day all-cause mortality of COVID-19 patients,even in those accompanied with CVDs or diabetes.Similar results were also obtained in subgroup analyses of abnormal lipid parameters.Therefore,hyperlipidemia might be not a major causative factor for poor outcome of COVID-19,which provides guidance for the intervention of inpatients during the epidemic of COVID-19.展开更多
BACKGROUND Dipeptidyl peptidase-4(DPP4)is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects.Recent structural analyses indicated a potential tight interaction ...BACKGROUND Dipeptidyl peptidase-4(DPP4)is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects.Recent structural analyses indicated a potential tight interaction between DPP4 and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),raising a promising hypothesis that DPP4 inhibitor(DPP4i)drugs might be an optimal strategy for treating coronavirus disease 2019(COVID-19)among patients with diabetes.However,there has been no direct clinical evidence illuminating the associations between DPP4i use and COVID-19 outcomes.AIM To illuminate the associations between DPP4i usage and the adverse outcomes of COVID-19.METHODS We conducted a multicenter,retrospective analysis including 2563 patients with type 2 diabetes who were hospitalized due to COVID-19 at 16 hospitals in Hubei Province,China.After excluding ineligible individuals,142 patients who received DPP4i drugs and 1115 patients who received non-DPP4i oral anti-diabetic drugs were included in the subsequent analysis.We performed a strict propensity score matching(PSM)analysis where age,sex,comorbidities,number of oral hypoglycemic agents,heart rate,blood pressure,pulse oxygen saturation(SpO2)<95%,CT diagnosed bilateral lung lesions,laboratory indicators,and proportion of insulin usage were matched.Finally,111 participants treated with DPP4i drugs were successfully matched to 333 non-DPP4i users.Then,a linear logistic model and mixed-effect Cox model were applied to analyze the associations between inhospital DPP4i use and adverse outcomes of COVID-19.RESULTS After rigorous matching and further adjustments for imbalanced variables in the linear logistic model and Cox adjusted model,we found that there was no significant association between in-hospital DPP4i use(DPP4i group)and 28-d allcause mortality(adjusted hazard ratio=0.44,95%CI:0.09-2.11,P=0.31).Likewise,the incidences and risks of secondary outcomes,including septic shock,acute respiratory distress syndrome,or acute organ(kidney,liver,and cardiac)injuries,were also comparable between the DPP4i and non-DPP4i groups.The performance of DPP4i agents in achieving glucose control(e.g.,the median level of fasting blood glucose and random blood glucose)and inflammatory regulation was approximately equivalent in the DPP4i and non-DPP4i groups.Furthermore,we did not observe substantial side effects such as uncontrolled glycemia or acidosis due to DPP4i application relative to the use of non-DPP4i agents in the study cohort.CONCLUSION Our findings demonstrated that DPP4i use is not significantly associated with poor outcomes of COVID-19 or other adverse effects of anti-diabetic treatment.The data support the continuation of DPP4i agents for diabetes management in the setting of COVID-19.展开更多
Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One k...Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One key player in this process is the Aryl Hydrocarbon Receptor(AhR),which influences multiple cellular processes,including proliferation,differentiation,metabolism,and immune regulation.Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis,epithelial-mesenchymal transition,and immune escape.Targeting AhR signaling is a potential therapeutic approach for ESCC,with AhR ligands showing efficacy in preclinical studies.Additionally,modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention.This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.展开更多
Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats.Methods:Asiaticoside(50 and...Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats.Methods:Asiaticoside(50 and 100 mg/kg body weight)was administered to STZ-NAD-induced diabetic rats for 45 days,and its effects on hyperglycaemic,carbohydrate metabolic,and insulin signaling pathway markers were examined.Results:Asiaticoside increased insulin production,lowered blood glucose levels,and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities.Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity.Furthermore,asiaticoside upregulated the mRNA expressions of IRS-1,IRS-2,and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal.Conclusions:Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis,gluconeogenesis,and insulin signaling pathways.展开更多
Anxiety is among the most common disorders affecting a great number of people. Different neurotransmitter systems, such as GABAergic system, play an important role in emergence of anxiety-related behaviors. In this st...Anxiety is among the most common disorders affecting a great number of people. Different neurotransmitter systems, such as GABAergic system, play an important role in emergence of anxiety-related behaviors. In this study, we have investigated the effect of Citrus aurantium L. essential oil on anxiety and its interaction with GABAergic pathways. Male mice were assigned into control, sham, and experimental groups. Intraperitoneal injection of Citrus aurantium L. essential oil was applied at doses of 0.5, 2.5, and 5 percent for 5 days. Diazepam (0.1 mg/kg) was injected on the fifth day, thirty minutes before applying Citrus aurantium L. essential oil. The anxiety-related behavior of mice was then assessed using elevated plus-maze test. In groups receiving Citrus aurantium L. essential oil at doses of 2.5 and 5 percent, the percent time spent in the open arms increased significantly (P Citrus aurantium L. essential oil resulted in increasing in the number of entries to the open arms and the percent time spent in the open arms (P Citrus aurantium L. essential oil can reduce anxiety-related behaviors in male mice thah may act via GABAergic system.展开更多
基金supported in part by grants from The National Science and Technology Foundation for Rural Development in China during the "12th Five-Year-Plan" (Grant No. 2011BAD33B02)The National Natural Science Foundation of China (Grant No. 81300323)
文摘Cancer is a leading cause of death worldwide. Cancer treatments by chemotherapeutic agents, surgery, and radiation have not been highly effective in reducing the incidence of cancers and increasing the survival rate of cancer patients. In recent years, plant-derived compounds have attracted considerable attention as alternative cancer remedies for enhancing cancer prevention and treatment because of their low toxicities, low costs, and low side effects. Ellagic acid(EA) is a natural phenolic constituent. Recent in vitro and in vivo experiments have revealed that EA elicits anticarcinogenic effects by inhibiting tumor cell proliferation, inducing apoptosis, breaking DNA binding to carcinogens, blocking virus infection, and disturbing inflammation, angiogenesis, and drug-resistance processes required for tumor growth and metastasis. This review enumerates the anticarcinogenic actions and mechanisms of EA. It also discusses future directions on the applications of EA.
基金Supported by the Oman Ministry of Higher Education,Research,and Innovation,No.BFP/RGP/HSS/24/015.
文摘Chloroquine(CQ)and hydroxychloroquine(HCQ),originally developed as anti-malarial drugs,have found a new purpose in treating various autoimmune dis-eases due to their immunomodulatory properties.These drugs work through mu-ltiple mechanisms,including inhibiting Toll-like receptor signaling,suppressing antigen presentation,and modulating autophagy.This review article provides a comprehensive analysis of the immunomodulatory effects of CQ and HCQ in several autoimmune diseases such as systemic lupus erythematosus,rheumatoid arthritis,systemic sclerosis,and others.We delve into the intricate mechanisms of action,highlighting the key immune cells involved and discussing the clinical implications of these drugs in managing autoimmune conditions.Our review covers the latest research and clinical trials,offering a comprehensive under-standing of the therapeutic potential of CQ and HCQ in autoimmune diseases.We also discuss the challenges and controversies surrounding the use of these drugs,such as their long-term side effects and the need for personalized treatment approaches.By synthesizing current knowledge and identifying areas for future research,this review aims to provide a valuable resource for healthcare profes-sionals and researchers involved in the management of autoimmune diseases.
文摘Human temporal bone specimens are used in experiments to measure the sound transfer function of the middle ear.This standard method for the development of middle ear implants requires temporal bones that possess appropriate mechanical properties and structural stability and are free from pathological conditions.A laser Doppler vibrometer is commonly employed to measure the vibration of the stapes footplate.These experiments are typically conducted in the middle ear by leaving the inner ear intact,exposing the stapes footplate through the tympanic cavity,and directing the laser beam onto the footplate.However,previous studies have shown that the influence of inner ear impedance on the middle ear transfer function cannot be ignored,and any surgical manipulation may cause a change in inner ear pressure,resulting in instability in the middle ear transfer function.Therefore,this study aims to eliminate the influence of the inner ear and to establish a new experimental method in human temporal bone specimens that is more suitable for the study of sound conduction in middle ear implants.As a result,a range for middle ear transfer function was developed,which serves as a reference for assessing the conformity of temporal bone specimens to experimental standards,and the stability of this range was demonstrated under experimental conditions.
基金Supported by The Oman Ministry of Higher Education,Research,and Innovation,No.BFP/RGP/HSS/24/015.
文摘In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing is complex and involves a coordinated series of biological events,including inflammation,cell proliferation,and tissue remodeling.The innate immune system is important in the early stages of wound repair,with inflammation being a crucial initial phase in tissue rege-neration.However,the inflammatory response should be regulated,as excessive or dysregulated inflammation can impair healing.Platelet concentrates,specifi-cally PRF,have originated as promising tools to optimize the tissue repair process.PRF is a second-generation platelet concentrate,and the release of growth factors(GFs)plays a determining role in several aspects of wound healing,including promoting cell proliferation,stimulating angiogenesis,and modulating inflam-mation.PRF forms a fibrin matrix that entraps platelets and GFs.This structure allows for their sustained release over time,which is believed to provide a more favorable microenvironment for tissue repair.Recent research by Sá-Oliveira et al has provided valuable evidence supporting the efficacy of PRF in promoting wound healing.Their study,conducted on an animal model,demonstrated that PRF-based dressings were more effective in accelerating wound closure in the early stages of the healing process,enhancing tissue repair,and modulating the inflammatory response.We explore how PRF's unique properties contribute to a more controlled and effective healing process.By examining these findings,we aim to highlight PRF's potential as a promising therapeutic strategy for improved wound management.
基金Supported by the Oman Ministry of Higher Education,Research,and Innovation,No.BFP/RGP/HSS/24/015.
文摘This editorial highlights the critical role of viral RNA signatures encapsulated within circulating exosomes as a potential missing link in the early diagnosis of gastrointestinal(GI)cancers.Current diagnostic methods for virus-associated GI malignancies often fall short in detecting infections at subclinical or pre-cancerous stages.We propose that viral RNA-loaded exosomes,by offering stable,specific,and non-invasive biomarkers,can bridge this gap and revolutionize early de-tection compared to conventional approaches.As highlighted by Zhang et al in their recent review,viral infections,such as hepatitis B and C viruses,Epstein-Barr virus,and human papillomavirus,are well-established contributors to the pathogenesis of various GI malignancies.However,current diagnostic methods often underperform in detecting these infections at subclinical or pre-cancerous stages.We highlight the shared points between virology,exosome biology,and oncology,reinforcing the importance of viral RNA-loaded exosomes as a“missing link”in the early detection of virus-associated GI cancers.We also discuss current challenges,translational opportunities,and the requirements for clinical vali-dation of these promising biomarkers.
文摘Alcohol-associated liver disease(ALD)is a major global health concern,contributing to liver injury,morbidity,and mortality.Elafibranor(EFN),a dual peroxisome proliferator-activated receptorα/δagonist,has shown promise as a therapeutic candidate in preclinical studies.EFN reduces liver fibrosis by inhibiting lipid accumulation,apoptosis,and inflammatory pathways(LPS/TLR4/NF-κB),while enhancing autophagy and antioxidant responses.It also improves intestinal barrier function and modulates gut microbiota,reducing endotoxin-producing bacteria and increasing beneficial species.By strengthening the intestinal barrier and suppressing pro-inflammatory mediators like tumor necrosis factor-alpha and interleukin-6,EFN mitigates hepatic stellate cell activation and fibrogenic signaling.Macrophages play a central role in ALD progression,and EFN’s ability to modulate macrophage activity further highlights its anti-inflammatory properties.This review emphasizes EFN’s dual-targeted approach,addressing both hepatic and intestinal dysfunctions,distinguishing it from conventional ALD treatments.While preclinical results are promising,EFN remains under clinical investigation,with ongoing trials evaluating its safety and efficacy.Future research should focus on elucidating EFN’s molecular mechanisms and advancing its clinical application to establish its therapeutic potential in human populations.EFN represents a novel,comprehensive strategy for ALD management,targeting both liver and gut pathologies.
基金supported by the National Key Research and Development Program of China(No.2018YFE0207300)Beijing Natural Science Foundation(No.M23008)+1 种基金the National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-124)the National High Level Hospital Clinical Research Funding(No.2022-PUMCH-A-057)。
文摘Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients.Twenty infertile males with VC and twenty-three age-matched healthy controls(HCs)were recruited from Peking Union Medical College Hospital(Beijing,China)between October 2019 and April 2021.Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry.Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs.The top enriched pathways among these significantly different metabolites are protein digestion and absorption,aminoacyl-transfer RNA(tRNA)biosynthesis,and biosynthesis of amino acids.Different key lipid species,including triglyceride(TG),diacylglycerol(DG),ceramides(Cer),and phosphatidylserine(PS),varied betweenVC and HC groups.The distinct metabolites and lipids were moderately correlated.DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility(area under the curve[AUC]=0.893),positively correlating with sperm count,concentration,and motility.Furthermore,DL-3-phenyllactic acid is the only metabolite shared by all four comparisons(VC vs HC,VC-induced oligoasthenospermia[OAS]vs VC-induced asthenospermia[AS],OAS vs HC,and AS vs HC).DL-3-phenyllactic acid significantly decreased in OAS than AS.Metabolite-targeting gene analysis revealed carbonic anhydrase 9(CA9)might be the strongest candidate associated with the onset and severity of VC.The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs.DL-3-phenyllactic acid could be a promising biomarker.
基金supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project Number(PNURSP2025R317),Princess Nourah bintAbdulrahman University,Riyadh,Saudi Arabia.
文摘Aspergillus species produce aflatoxins and raise concerns about food safety in departmental stores and manufacturing mills.To address the risks posed by aflatoxins,and to advise the public on the highest quality rice that serves as a nutritious food source,an inquiry following the guidelines outlined in both local and international standards of food safety for the presence of aflatoxins is an essential requirement.Therefore,16 white rice samples were selected randomly from low/high socio-economic departmental stores from 16 different localities.Grind powdered rice filtrate was extracted using chloroform.The filtrate applied on TLC plates and the amount of aflatoxin and moisture contents were determined.In the non-infected rice,moisture content was low(9.08%)whereas high[13.65%>12%(standard>value)]in infected ones.Four out of 8 samples of low-quality rice were contaminated with AFB_(1) and AFB_(2)(ranging from 22.2 to 29.3μg/kg).All the samples except one(22.3μg/kg)from high-quality rice were certified fit despite the contamination with AFB_(1).Furthermore,phylogenetic analysis showed Aspergillus flavus from unfit low(Long grain brown and Brown basmati)and high-quality(Basmati-198)rice whereas A.parasiticus from unfit low-quality Medium-grain brown rice.The presented research proves that the detection of fungi and aflatoxins in rice grains poses a huge risk to the health of consumers.Therefore,it is necessary to check the rice grains before distribution.
文摘BACKGROUND The persistent burden of cardiovascular(CV)disease in the United States requires innovative and cost-effective prognostic markers that can be relied upon.AIM To provide insights into how adiponectin can predict all-cause mortality and major adverse CV events(MACE)in patients with coronary artery disease(CAD)and to determine the prognostic value of adiponectin in predicting all-cause mortality and MACE in patients with stable CAD.METHODS We conducted a systematic search on PubMed,Scopus,and Google Scholar to find relevant studies published through June 2023 evaluating the long-term prognostic role of adiponectin in patients with stable CAD.Using a random effects model with 95%CI,we estimated the odds ratio(OR)while assessing heterogeneity through I^(2)statistics.To ensure robustness,we performed a sensitivity analysis using the leave-one-out approach.RESULTS After screening,we included five prospective studies involving 3225 patients who were followed up for a median duration of 3.8 years.Within the study population,prevalent risk factors included hypertension,diabetes,hyperlipidemia,and smoking.The commonly prescribed medications were angiotensin-converting enzyme inhibitors,beta blockers,and statins.The combined adjusted OR for all-cause mortality was found to be 2.51(95%CI:1.36–4.62),showing heterogeneity(I^(2)=65.51%,P=0.03).On the other hand,the combined adjusted OR for MACE was determined to be 1.04(95%CI:1.02–1.06)with no significant heterogeneity observed(I^(2)=0%,P=0.68).Through a sensitivity analysis,it was discovered that none of the studies significantly impacted the overall results of the meta-analysis,thus indicating their robustness.CONCLUSION Higher levels of adiponectin were found to be associated with an increased risk of long-term mortality and MACE in patients with CAD,which highlights its potential as a cost-effective marker for risk assessment and guiding treatment strategies.Further research on the role of adiponectin could greatly influence decision-making and resource allocation in CV care.
基金Supported by a 2-Year Research Grant of Pusan National University
文摘OBJECTIVE:To investigate the optimal timing and underlying mechanism of electroacupuncture(EA)at Baihui(GV 20)and Dazhui(GV 14)for improved long-term functional recovery after focal cerebral ischemia in a photothrombotic stroke mouse model.METHODS:Totally 50 adult male C57 BL/6 J mice were assigned into 5 groups:(a)the control group,sham-operated mice(n=10);(b)the vehicle group,focal cerebral ischemia induction without EA(n=10);(c)the acute EA group,mice received EA immediately post-ischemia,followed by once-daily treatments for 7 consecutive days(n=10);(d)the subacute EA group,mice received EA 4 days post-ischemia,followed by once-daily treatments for 7 consecutive days(n=10);(e)the delayed EA group.EA stimulation(2 Hz,2 V for 20 min)was applied to acupuncture points(acupoints),Baihui(GV 20)and Dazhui(GV 14),once a day for 7 consecutive days beginning immediately(acute treatment),4 d(subacute treatment)and 10 d(delayed treatment)after focal cerebral ischemia in C57 BL/6 J mice.Behavioral assessments were conducted 21 and 28 d post-ischemia and histopathological analyses were performed 28 days post-ischemia.RESULTS:The subacute EA treatment at Baihui(GV20)and Dazhui(GV 14)significantly improved functional recovery compared to the vehicle group 28 d after ischemic brain injury,although brain atrophy was not reduced.The number of Neu N+and Neu N+/Brd U+cells as well as GFAP intensity in the ipsilateral cortex were significantly increased in the subacute group compared to the vehicle group 28 d post-ischemia.We concluded that EA stimulation 4 d post-ischemia(subacute treatment)enhanced neurogenesis and astrogliosis,likely contributing to long-term functional recovery following focal cerebral ischemia.CONCLUSION:Our findings suggest that the timing of the EA therapy at Baihui(GV 20)and Dazhui(GV 14)determines the therapeutic effects in mice with focal cerebral ischemia induced by photothrombotic occlusion.
基金CAMS Innovation Fund for Medical Sciences (CIFMS):2021-I2M-1-018。
文摘Pulmonary hypertension(PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure(PAP) and pulmonary vascular resistance(PVR), finally leading to right heart failure and death. The pathogenesis of this arteriopathy remains unclear, leaving it impossible to target pulmonary vascular remodeling and reverse the deterioration of right ventricular(RV) function. Different animal models have been designed to reflect the complex mechanistic origins and pathology of PH, roughly divided into 4 categories according to the modeling methods: noninvasive models in vivo, invasive models in vivo, gene editing models, and multi-means joint modeling. Though each model shares some molecular and pathological changes with different classes of human PH, in most cases the molecular etiology of human PH is poorly known. The appropriate use of classic and novel PH animal models is essential for the hunt of molecular targets to reverse severe phenotypes.
文摘Digestive endoscopy is currently the main diagnostic procedure for investigation of the digestive tract when a digestive disease is suspected.The use of computers and electronic medical records for the management of endoscopic data are an important key to improving endoscopy unit efficiency and productivity.This technology supports optimal program operation,monitoring and evaluation colorectal cancer screening.This article is a comprehensive survey of endoscopic electronic medical records and information systems.Computerized clinical records have the capability of identifying patients due for screening and to calculate baseline rates of colorectal cancer screening by patient characteristics and by primary care physician and practice group.This paper describes data flow in the endoscopy unit,the minimum data set of colorectal cancer and key features of endoscopic electronic medical record.In addition,the researchers state standards in different aspects,especially terminology standards and interoperability standards for image and text.
文摘The gut-brain axis is a bidirectional communication system that exists between the brain and gut. Several studies claimed that some types of headaches are associated with various gastrointestinal(GI) disorders.In Persian medicine(PM), physicians believed that gastric disturbances could stimulate headache and introduced some herbs for boosting gastric function as a therapeutic remedy for headache. Here we review the current evidence for the gastroprotective and antiheadache effects of herbs used in PM.Herbs used for their gastrotonic effects in PM were identified from selected Persian medical and pharmaceutical textbooks. Pub Med, Scopus and Google Scholar were used to search for contemporary scientific evidence relating to the gastric and neurologic effects of these plants. A total of 24 plants were recorded from the selected sources included in this review, most of which belonged to the Rosaceae family.Phyllanthus emblica, Zingiber officinale, Boswellias errata, Punica granatum and Hypericum perforatum had the most recent studies related to GI disorder and headache, while current research about quince, rose,apple, hawthorn and pear was limited. Reducing Helicobacter pylori growth, gastritis, erosion of the stomach lining, hemorrhage and perforation, improving gastric mucosal resistance, antisecretary, antiulcer,antipyretic, analgesic, sedative, anxiolytic, anti-inflammatory, anticonvulsant, neuroprotective and antioxidant effects as well as improvement in memory scores were some of the gastrotonic and neuroprotective mechanisms described in the current research. These results confirmed that medicinal plants prescribed in PM may improve headache in patients through the management of GI abnormalities.However, further studies are recommended to investigate the efficacy and safety of the mentioned medicinal plants.
文摘This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used for diabetes management,and its potential cardioprotective effects in a diabetic mouse model.They suggested teneligliptin administration may reverse established markers of DCM,including cardiac hypertrophy and compromised function.It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice.Macrophages play crucial roles in DCM pathogenesis.Chronic hyperglycemia disturbs the balance between pro-inflammatory(M1)and antiinflammatory(M2)macrophages,favoring a pro-inflammatory state contributing to heart damage.Here,we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment.These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome.Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.
基金National Key R&D Program of China(2016YFF0101500)the National Natural Science Foundation of China(81970364,81770053).
文摘Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19,especially those with pre-existing cardiovascular diseases(CVDs)and diabetes.Methods This multicenter retrospective cohort study included all patients who were hospitalized due to COVID-19 from 21 hospitals in Hubei province,China between December 31,2019 and April 21,2020.Patients who were aged<18 or≥85 years old,in pregnancy,with acute lethal organ injury(e.g.,acute myocardial infarction,severe acute pancreatitis,acute stroke),hypothyroidism,malignant diseases,severe malnutrition,and those with normal lipid profile under lipid-lowering medicines(e.g,statin,niacin,fenofibrate,gemfibrozil,and ezetimibe)were excluded.Propensity score matching(PSM)analysis at 1:1 ratio was performed to minimize baseline differences between patient groups of hyperlipidemia and non-hyperlipidemia.PSM analyses with the same strategies were further conducted for the parameters of hyperlipidemia in patients with increased triglyceride(TG),increased low・density lipoprotein cholesterol(LDL-C),and decreased high-density lipoprotein cholesterol(HDL-C).Mixed-effect Cox model analysis was performed to investigate the associations of the 28-days all-cause deaths of COVID-19 patients with hyperlipidemia and the abnormalities of lipid parameters.The results were verified in male,female patients,and in patients with pre-existing CVDs and type 2 diabetes.Results Of 1094S inpatients confirmed as COVID-19,there were 9822 inpatients included in the study,comprising 3513(35.8%)cases without hyperlipidemia and 6309(64.2%)cases with hyperlipidemia.Based on a mixed-effect Cox model after PSM at 1:1 ratio,hyperlipidemia was not associated with increased or decreased 28-day all-cause death[adjusted hazard ratio(HR),1.17(95%C/,0.95-1.44),P二0.151].Wb found that the parameters of hyperlipidemia were not associated with the risk of 28-day all-cause mortality[adjusted HR,1.23(95%CI,0.98-1.55),P=0.075 in TG increase group;0.78(95%CI,0.57-1.07),P=0.123 in LDL-C increase group;and 1.12(95%CI,0.9-1.39),P=0.299 in HDL-C decrease group,respectively].Hyperlipidemia was also not significantly associated with the increased mortality of COVID-19 in patients accompanied with CVDs or type 2 diabetes,and in both male and female cohorts.Conclusion Our study support that the imbalanced lipid profile is not significantly associated with the 28-day all-cause mortality of COVID-19 patients,even in those accompanied with CVDs or diabetes.Similar results were also obtained in subgroup analyses of abnormal lipid parameters.Therefore,hyperlipidemia might be not a major causative factor for poor outcome of COVID-19,which provides guidance for the intervention of inpatients during the epidemic of COVID-19.
基金Supported by National Key R&D Program of China,No.2019YFC2004702 and No.2020YFC0845500the National Natural Science Foundation of China,No.81970070 and No.81970011the Hubei Science and Technology Support Project,No.2019BFC582 and No.2018BEC473.
文摘BACKGROUND Dipeptidyl peptidase-4(DPP4)is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects.Recent structural analyses indicated a potential tight interaction between DPP4 and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),raising a promising hypothesis that DPP4 inhibitor(DPP4i)drugs might be an optimal strategy for treating coronavirus disease 2019(COVID-19)among patients with diabetes.However,there has been no direct clinical evidence illuminating the associations between DPP4i use and COVID-19 outcomes.AIM To illuminate the associations between DPP4i usage and the adverse outcomes of COVID-19.METHODS We conducted a multicenter,retrospective analysis including 2563 patients with type 2 diabetes who were hospitalized due to COVID-19 at 16 hospitals in Hubei Province,China.After excluding ineligible individuals,142 patients who received DPP4i drugs and 1115 patients who received non-DPP4i oral anti-diabetic drugs were included in the subsequent analysis.We performed a strict propensity score matching(PSM)analysis where age,sex,comorbidities,number of oral hypoglycemic agents,heart rate,blood pressure,pulse oxygen saturation(SpO2)<95%,CT diagnosed bilateral lung lesions,laboratory indicators,and proportion of insulin usage were matched.Finally,111 participants treated with DPP4i drugs were successfully matched to 333 non-DPP4i users.Then,a linear logistic model and mixed-effect Cox model were applied to analyze the associations between inhospital DPP4i use and adverse outcomes of COVID-19.RESULTS After rigorous matching and further adjustments for imbalanced variables in the linear logistic model and Cox adjusted model,we found that there was no significant association between in-hospital DPP4i use(DPP4i group)and 28-d allcause mortality(adjusted hazard ratio=0.44,95%CI:0.09-2.11,P=0.31).Likewise,the incidences and risks of secondary outcomes,including septic shock,acute respiratory distress syndrome,or acute organ(kidney,liver,and cardiac)injuries,were also comparable between the DPP4i and non-DPP4i groups.The performance of DPP4i agents in achieving glucose control(e.g.,the median level of fasting blood glucose and random blood glucose)and inflammatory regulation was approximately equivalent in the DPP4i and non-DPP4i groups.Furthermore,we did not observe substantial side effects such as uncontrolled glycemia or acidosis due to DPP4i application relative to the use of non-DPP4i agents in the study cohort.CONCLUSION Our findings demonstrated that DPP4i use is not significantly associated with poor outcomes of COVID-19 or other adverse effects of anti-diabetic treatment.The data support the continuation of DPP4i agents for diabetes management in the setting of COVID-19.
文摘Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One key player in this process is the Aryl Hydrocarbon Receptor(AhR),which influences multiple cellular processes,including proliferation,differentiation,metabolism,and immune regulation.Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis,epithelial-mesenchymal transition,and immune escape.Targeting AhR signaling is a potential therapeutic approach for ESCC,with AhR ligands showing efficacy in preclinical studies.Additionally,modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention.This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.
文摘Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats.Methods:Asiaticoside(50 and 100 mg/kg body weight)was administered to STZ-NAD-induced diabetic rats for 45 days,and its effects on hyperglycaemic,carbohydrate metabolic,and insulin signaling pathway markers were examined.Results:Asiaticoside increased insulin production,lowered blood glucose levels,and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities.Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity.Furthermore,asiaticoside upregulated the mRNA expressions of IRS-1,IRS-2,and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal.Conclusions:Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis,gluconeogenesis,and insulin signaling pathways.
文摘Anxiety is among the most common disorders affecting a great number of people. Different neurotransmitter systems, such as GABAergic system, play an important role in emergence of anxiety-related behaviors. In this study, we have investigated the effect of Citrus aurantium L. essential oil on anxiety and its interaction with GABAergic pathways. Male mice were assigned into control, sham, and experimental groups. Intraperitoneal injection of Citrus aurantium L. essential oil was applied at doses of 0.5, 2.5, and 5 percent for 5 days. Diazepam (0.1 mg/kg) was injected on the fifth day, thirty minutes before applying Citrus aurantium L. essential oil. The anxiety-related behavior of mice was then assessed using elevated plus-maze test. In groups receiving Citrus aurantium L. essential oil at doses of 2.5 and 5 percent, the percent time spent in the open arms increased significantly (P Citrus aurantium L. essential oil resulted in increasing in the number of entries to the open arms and the percent time spent in the open arms (P Citrus aurantium L. essential oil can reduce anxiety-related behaviors in male mice thah may act via GABAergic system.
