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.

Hematologic malignancies,such as lymphoma,myeloma,and myeloid neoplasms,can occur in extramedullary tissues.Traditional histopathological morphology and immunohistochemical staining have lim-itations,including time-consuming specimen processing,prolonged reporting cycles,and relatively low sensi-tivity in cases of limited cell numbers.Flow cytometry offers significant advantages in detecting tissue sam-ples,such as rapid processing,shorter reporting cycles,and high accuracy and sensitivity,making it an effective complement to histopathological and immunohistochemical methods.However,the application of flow cytome-try in tissue sample detection currently lacks standardized protocols for sample collection and preservation,single-cell suspension preparation,antibody panel design for limited samples,data analysis,and result repor-ting.To promote the standardized application of flow cytometry in detecting hematologic tumor cells in tissue samples,the Cell Analysis Professional Committee of the Chinese Society of Biotechnology organized experts to develop the Chinese Expert Consensus on Flow Cytometry for Detecting Hematologic Tumor Cells in Tis-sue Samples(hereinafter referred to as the Consensus).This Consensus elaborates on the technical aspects of flow cytometry for tissue sample detection,covering sample processing,antibody panel design,data analysis,reporting content,and quality management.It particularly emphasizes recommended antibody panels and data analysis methods for flow cytometry when tissue sample cell counts are low.This article aims to interpret the key points of the Consensus to facilitate its better application in clinical practice.

Objective To study the effect of notoginsenoside R2(NGR2)on palmitic acid(PA)-induced lipotoxicity in H9c2 cardiomyocytes.Methods The H9c2 cells were divided into control group,model group and experimental-L,-H groups.The control group was treated with 10％bovine serum albumin(BSA);the model group was treated with 250 μmol·L-1 PA to establish the lipotoxicity model;the experimental-L,-H groups were treated with 50,100 μmol·L-1 NGR2 and 250 μmol·L-1 PA.The accumulation of cellular lipid droplets was observed by oil red O staining and Bodipy staining;the mRNA expression levels of fatty acid synthase(FASN),stearoyl coenzyme A desaturase 1(SCD1)were detected by real time quantitative polymerase chain reaction;the protein expression levels of FASN and SCD1 were detected by Western blot.Results The absorbance of lipid droplet quantification after oil red O staining in the control group,the model group,the experimental-L,-H groups were 0.12±0.03,0.19±0.02,0.14±0.05 and 0.11±0.03;the relative fluorescence intensity quantified by Bodipy staining were(100.00±15.83)％,(249.65±6.44)％,(160.88±17.34)％and(136.84±4.83)％;FASN mRNA expression levels were 1.00±0.07,1.33±0.13,1.21±0.16 and 1.05±0.09;SCD1 mRNA expression levels were 1.00±0.04,1.26±0.07,1.24±0.15 and 1.02±0.09;the expression levels of FASN protein were 1.00±0.00,1.03±0.02,1.01±0.06 and 0.92±0.08;the expression levels of SCD1 protein were 1.00±0.00,1.08±0.08,0.98±0.15 and 0.87±0.18.In the above indicators,there were statistically significant differences between model group and control group,between experimental-H group and model group(P＜0.05,P＜0.01);there were significant differences in oil red O staining and Bodipy staining quantification of experimental-L group and model group(P＜0.05,P＜0.01).Conclusion NGR2 may reduce lipid accumulation and alleviate lipotoxicity in PA-induced H9c2 cardiomyocytes by decreasing the mRNA and protein expression of FASN and SCD1.

Polypeptide drugs have attracted much attention in the field of drug research and development due to their wide range of indications,especially in pharmaceutical R&D of new drugs with endocrine related indications such as diabetes and osteoporosis.With the advancement of peptide synthesis and delivery technologies,the research and application of peptide drugs have made significant breakthroughs.However,the R&D and nonclinical safety assessment of peptide drugs still face many challenges,and there are no specific guidelines for the nonclinical safety evaluation of this class of drugs domestically or abroad.This article focuses on the field of endocrine indications.By analyzing the nonclinical studies of approved peptide drugs,and considering the current R&D status and specific regulatory requirements,this paper proposes considerations on the nonclinical safety assessment of peptide drugs,including the selection of relevant animal species,key study contents,specific considerations for peptides containing non-natural amino acids,etc.The aims are to provide references for optimizing and improving the nonclinical safety evaluation of peptide drugs.

To investigate the existence of tick-borne pathogens infection of rodents at the border of China and the Demo-cratic People's Republic of Korea(DPRK).PCR was used to detect the spotted fever group rickettsiae(SFGR)ompA gene,Ehrlichia chaffeensis(Ec)and Anaplasma phagocytophilum(Ap)16S rRNA,Candidatus Neoehrlichia mikurensis(CNm)groEL gene,Bartonella(Ba)rpoB gene,and Francisella tularensis(Ft)fopA gene in rodents samples collected from Ji'an of Jilin province and Kuandian of Liaoning Province.The positivity rates of 132 wild rats spleen samples,SFGR,Ec,Ap,CNm,Ba,and Ft were 9.85％,12.88％,5.30％,3.79％,51.52％,and 6.06％,respectively,with statistical differences in in-fection rates(x2=149.236,P=0.000).The infection rate of Ba was the highest in wild rats in this area.There was no signifi-cant difference in the infection rate of SFGR,Ec,Ap,CNm,and Ft among different rats species,but there were significant differences in the infection rate of Ba(x2=13.36,P=0.010).The infection rate of Apodemus agrarius was the highest.A-mong 132 wild rats specimens,the coinfection rate of the two pathogens was 15.9％(21/132),with Ba as the main species(15/132),and two cases of coinfection with three pathogens were detected.The infection of six tick-borne pathogens is common in wild rats at the China/DPRK border.Co-infection of two or three pathogens indicates a risk of multiple tick-borne pathogens and mixed natural foci of multiple tick-borne infec-tious diseases.

This study was aimed at investigating the pathogenic and molecular characteristics of Klebsiella pneumoniae(KP)in fecal samples of diarrhea cases in a district of Beijing.Fecal samples from diarrhea cases in an outpatient department in a district of Beijing from 2018 to 2021 were collected,and used for isolation and culture of KP.The KP strains isolated strains were subjected to drug resistance phenotype testing and whole-genome sequencing.Multilocus sequence typing and whole-genome phyletic evolution analysis were performed on the sequencing results.The cases'epidemiological and clinical characteristics were analyzed.From 2018 to 2021,1 103 fecal samples were collected and detected.The total detection rate of KP was 10.43％(115/1 103),and the infection rate of KP mixed with other diarrhea-causing pathogens was 42.61％(49/115).The positivity rate was slightly high(12.47％,61/489)a-mong females and was highest in young adults 16-45 years of age.Small peaks were observed in January,April to May,and August to September.The gastrointestinal symptoms in cases were mainly nausea and watery stool,and the suspicious food was unknown.Ampicillin,tetracycline,and sulfafurazole were the top three antibiotics to which these 115 KP strains showed resistance,and 29 strains were resistant to multiple antibiotics.The strains were divided into 72 sequence types,among which ST23 was dominant.According to the phylogenetic tree,the strains were divided into four main branches,among which 14 ST23 strains had a very close genetic relationship with the highly virulent NTUH-K2044 reference strain.KP infection persisted in fecal samples from diarrhea cases in the district of Beijing.Women and young adults were particularly susceptible.The drug resistance of KP strains in this region was very serious,and the ST types were diverse.Moreover,the ST23 pathogenic strains were closely related to high virulence strains.

Therapeutic mRNA vaccine for tumors attracted much attention as a new type of tumor treatment,and most products are in the preclinical and clinical research stage,and there has not post-market drug.However,the non-clinical evaluation of therapeutic mRNA vaccines for tumors is more complicated,due to their target features,mechanisms,delivery patterns,and the cross-species differences of immune system.The choice of animal model is not only content of the clinical effectiveness,and it was a key factor of toxicity assessment.In this work,the challenges for non-clinical evaluation of therapeutic mRNA vaccines for tumors are discussed,and the compliant requirements are reviewed,and the general considerations are suggested.

Polypeptide drugs have attracted much attention in the field of drug research and development due to their wide range of indications,especially in pharmaceutical R&D of new drugs with endocrine related indications such as diabetes and osteoporosis.With the advancement of peptide synthesis and delivery technologies,the research and application of peptide drugs have made significant breakthroughs.However,the R&D and nonclinical safety assessment of peptide drugs still face many challenges,and there are no specific guidelines for the nonclinical safety evaluation of this class of drugs domestically or abroad.This article focuses on the field of endocrine indications.By analyzing the nonclinical studies of approved peptide drugs,and considering the current R&D status and specific regulatory requirements,this paper proposes considerations on the nonclinical safety assessment of peptide drugs,including the selection of relevant animal species,key study contents,specific considerations for peptides containing non-natural amino acids,etc.The aims are to provide references for optimizing and improving the nonclinical safety evaluation of peptide drugs.

Objective To study the effect of notoginsenoside R2(NGR2)on palmitic acid(PA)-induced lipotoxicity in H9c2 cardiomyocytes.Methods The H9c2 cells were divided into control group,model group and experimental-L,-H groups.The control group was treated with 10％bovine serum albumin(BSA);the model group was treated with 250 μmol·L-1 PA to establish the lipotoxicity model;the experimental-L,-H groups were treated with 50,100 μmol·L-1 NGR2 and 250 μmol·L-1 PA.The accumulation of cellular lipid droplets was observed by oil red O staining and Bodipy staining;the mRNA expression levels of fatty acid synthase(FASN),stearoyl coenzyme A desaturase 1(SCD1)were detected by real time quantitative polymerase chain reaction;the protein expression levels of FASN and SCD1 were detected by Western blot.Results The absorbance of lipid droplet quantification after oil red O staining in the control group,the model group,the experimental-L,-H groups were 0.12±0.03,0.19±0.02,0.14±0.05 and 0.11±0.03;the relative fluorescence intensity quantified by Bodipy staining were(100.00±15.83)％,(249.65±6.44)％,(160.88±17.34)％and(136.84±4.83)％;FASN mRNA expression levels were 1.00±0.07,1.33±0.13,1.21±0.16 and 1.05±0.09;SCD1 mRNA expression levels were 1.00±0.04,1.26±0.07,1.24±0.15 and 1.02±0.09;the expression levels of FASN protein were 1.00±0.00,1.03±0.02,1.01±0.06 and 0.92±0.08;the expression levels of SCD1 protein were 1.00±0.00,1.08±0.08,0.98±0.15 and 0.87±0.18.In the above indicators,there were statistically significant differences between model group and control group,between experimental-H group and model group(P＜0.05,P＜0.01);there were significant differences in oil red O staining and Bodipy staining quantification of experimental-L group and model group(P＜0.05,P＜0.01).Conclusion NGR2 may reduce lipid accumulation and alleviate lipotoxicity in PA-induced H9c2 cardiomyocytes by decreasing the mRNA and protein expression of FASN and SCD1.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*