Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

AIM To study the effects of Jiaotai Pills and their single composition drugs on high-fat diet-induced hypothalamic inflammation in obese mice.METHODS C57BL/6J mice were randomly divided into the normal group(15 mice)and the high-fat group(75 mice).The mice given 12 weeks of high-fat diet feeding were further randomly divided into the model group,the Jiaotai Pills group,the Coptis chinensis group,the Cinnamomum cassia group and the positive metformin group,with 15 mice in each group.After 6 weeks of administration,the mice had their body weight and fasting blood glucose(FBG)levels detected;their hypothalamic expressions of IL-1β,IL-6,TNF-α and Socs3 mRNA detected by RT-qPCR;their hypothalamic expressions of TLR4,MyD88,IKKβ and activated NF-κB protein detected by Western blot;their hypothalamic expressions of Iba1 and GFAP detected by immunohistochemistry;and their ultrastructural changes of nerve tissues observed using transmission electron microscopy(TEM).RESULTS Compared with the model group,each drug group displayed decreased hypothalamic expressions of IL-1β,IL-6,TNF-α and Socs3 mRNA(P＜0.01),and improved number and morphology of nerve cells revealed by TEM.The groups intervened with Jiaotai Pills,or Coptis chinensis,or metformin shared decreased body weight and FBG levels(P＜0.05);decreased protein expressions of TLR4,MyD88,IKKβ and p-NF-κB(P＜0.05);and decreased number of hypothalamic astrocytes and microglia(P＜0.05).Additionally,decreased p-NF-κB protein expression was observed in the Cinnamomum cassia group(P＜0.05).CONCLUSION Jiaotai Pills and their single composition drugs can improve high-fat diet-induced hypothalamic inflammation in obese mice.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnor-malities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms under-lying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Uti-lizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expres-sion QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4 110,NControls=13 569),we imple-mented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Associa-tion Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD patho-genesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate＜0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were asso-ciated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were asso-ciated with CJD at the transcriptional level.

Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnor-malities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms under-lying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Uti-lizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expres-sion QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4 110,NControls=13 569),we imple-mented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Associa-tion Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD patho-genesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate＜0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were asso-ciated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were asso-ciated with CJD at the transcriptional level.

The theory of "turbid pathogen harming the clarity" was proposed by YE Tianshi in his book Wenre Lun, which can be applied to clear orifices diseases such as ear, eye, nose, and mouth. Based on the location and characteristics of vitreous opacity, as well as its understanding by medical professionals throughout history, this article points out that the core pathogenesis of vitreous opacity is "turbid pathogen harming the clarity" and the obstruction of the spirit light, and the basic pathogenesis is: unfavorable liver and gallbladder conditions, damp heat accumulation and turbidity; imbalance of middle jiao, qi deficiency leading to turbidity; kidney failure with yang deficiency, stagnant water and fluids; and stagnation entering the collaterals for an extended time, causing blockage and turbidity. And based on the pathogenesis of "turbid pathogen harming the clarity" , corresponding treatment principles are proposed: soothing liver and promoting bile flow, clearing heat and eliminating turbidity; cultivating soil to produce gold, enhancing clarity and reducing turbidity; tonifying kidney and promoting yang, warming and dispelling turbid pathogens; and removing blood stasis and activating collaterals, dispelling turbidity and unblocking the orifices. Based on the theory of "turbid pathogen harming the clarity" , this article summarizes the pathogenesis and treatment of vitreous opacity, in order to provide new ideas for traditional Chinese medicine treatment of this disease.

Objective To summarize the clinical efficacy of robotic-assisted left thoracic small-incision minimally invasive direct coronary artery bypass grafting(MIDCAB).Methods A retrospective analysis was conducted on the procedures and treatment outcomes of robotic-assisted MIDCAB in the Army Medical Center of PLA from October 2016 to June 2023.Baseline clinical information,MIDCAB-related data,perioperative conditions and data during follow-up were collected and analyzed.Results There were 23 patients subjected,including 21 males and 2 females,with a mean age of 58.17±7.49 years,and a body mass index(BMI)of 23.99±3.25 kg/m2.All of them experienced angina pectoris,and 1 had a history of myocardial infarction,1 had dilated cardiomyopathy,2 patients had chronic obstructive pulmonary disease(COPD),and 10 had a history of percutaneous coronary intervention(PCI).Robotic-assisted MIDCAB procedure was successfully completed.No internal mammary artery injury or transformation of the procedure occurred in these cases,and excellent bridging vessel flow was achieved after anastomosis of the internal mammary artery to left anterior descending branch.The incision length in the left chest was 8(8,8)cm,the operation time was 380(300,465)min,the intraoperative bleeding volume was 300(100,400)mL,the length of ICU stay was 3(2,3)d,the amount of thoracic drainage was 780(525,1 040)mL,and the postoperative length from surgery to discharge was 11.17±2.38 d.No mortality was observed during or within 30 d of hospitalization,and 1 patient was readmitted due to pericardial effusion within 30 d,and was discharged after symptomatic treatment including pericardiocentesis and drainage.No deaths,major adverse cardiovascular and cerebrovascular events(MACCE),or re-revascularization occurred in all patients during outpatient and telephone follow-up.Conclusion Robotic-assisted internal mammary artery dissection is a delicate and safe technique,and coronary artery bypass grafting in minimally invasive small-incision off-pump is effective,safe and feasible,with satisfactory short-and mid-term outcomes.The technique is suitable for minimally invasive coronary artery disease surgery and is worthy of popularization and application.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.

Objective:To investigate the influence of different ratios of contrast agent(CA)to saline on image quality of coronary computed tomography angiography(CCTA)in dual-flow injection technique.Methods:A prospective study included 102 patients who were clinically diagnosed as suspected coronary heart disease(CHD)to undergo CCTA scan at Beijing Friendship Hospital,Capital Medical University,between March 2024 and October 2024.Ultimately,90 patients were enrolled,who adopted CA injection protocol of dual-flow injection technique.Patients were randomly divided into three groups using a random number table,with 30 patients in each group.The different ratios of CA to saline were adopted,which were respectively Group A(1:9),Group B(2:8),and Group C(3:7).For the reconstructed images,the computed tomography(CT)values of heart-related anatomical structures,which included superior vena cava,right atrium,right ventricle,left atrium,left ventricle,interventricular septum and each segment of the coronary artery,were measured respectively.At the same time,two radiologists,who possessed over 10 years of diagnostic experience of CCTA examination,conducted subjective evaluations for image quality.For the cases of disagreement,the consensus between them was reached through discussion.Results:In three groups,the total CA doses were respectively(42.75±5.22)ml,(47.08±5.83)ml and(50.64±6.29)ml,and the differences of that among the three groups was statistically significant(F=13.964,P<0.05).The differences of CT values of superior vena cava,right atrium,right ventricle,left atrium,left ventricle and aorta among three groups were significant(F=29.141,24.194,39.308,9.643,8.178,6.881,P<0.05).There were significant differences in the CT values of the proximal,mid,and distal segments of the left anterior descending(LAD),and the proximal and mid segments of the left circumflex(LCx)and right coronary artery(RCA)among three groups(F=7.114,9.106,3.851,6.075,4.025,7.349,5.756,P<0.05).However,there was not statistically significant difference was found among the three groups in the CT value of the distal segments of the LCx and RCA(P>0.05).There were significant differences in the subjective scores for the superior vena cava,right atrium and right ventricle among the three groups(H=8.939,29.105,32.180,P<0.05).The number of cases with 3-4 points at the superior vena cava,right atrium and right ventricle were respectively 25(83.3%),29(96.7%)and 30(100%)in group B,there was no case with 1 point.In addition,the imaging quality of right heart in group B was better than that in group A and C.There were no significant differences at left atrium,left ventricle,and each segment of coronary artery among three groups(P>0.05).Conclusion:For patients with clinically non-extreme body weight,the selection of the ratio(2:8)of CA to saline can effectively show relevantly anatomic structures of heart,and coronary artery vessels,including the right heart system,which belongs to the optimal solution.