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.

Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

[Objective] To investigate the infection status and characteristics of HEV among voluntary blood donors in Ningbo, and to provide a basis for improving the blood screening strategy. [Methods] A total of 12 227 blood samples from voluntary blood donors in Ningbo from June 2022 to May 2023 were tested for HEV serology, enzymology, and nucleic acid testing. Furthermore, HEV gene sequencing was performed for genotyping analysis, and donors with reactive nucleic acid testing results were followed up to confirm their infection status. [Results] The reactivity rate of HEV Ag, anti-HEV IgM and anti-HEV IgG was 0.098%, 0.899% and 29.198%, respectively. There was no difference in the reactivity of anti-HEV IgM and anti-HEV IgG between genders, donation frequencies and donation types (P>0.05). The reactivity rate increased significantly with age (P<0.05). The rate of ALT disqualification (ALT>50U/L) was significantly higher than that in non-reactive samples (P<0.05). The HEV Ag reactivity rate (0.098%) was not correlated with gender, donation frequency, donation type or age. One HEV RNA positive case was found, with a positive rate of 0.008%(1/12 227). It was confirmed to be hepatitis E virus genotype 3 by sequencing analysis. Apart from HEV Ag reactivity, all other blood safety screening items were non-reactive, suggesting this case might be in the acute infection phase. The follow-up results showed that all indicators of the donor's previous blood donation were non-reactive. [Conclusion] Pre-donation ALT detection can reduce the risk of transfusion-transmitted HEV (TT-HEV) to a certain extent, and the effective way to prevent TT-HEV is to detect HEV RNA and serology of donor blood.

Objective:To investigate the brain iron status in the sensorimotor cortex of patients with chronic low back pain (CLBP) and its relationship with changes in resting-state functional connectivity (RS-FC).Methods:This was a cross-sectional study. Thirty-two patients with CLBP (CLBP group) who were treated at Wuxi People′s Hospital Affiliated to Nanjing Medical University from July 2023 to March 2024 and 30 age-and gender-matched healthy volunteers (control group) were prospectively included. All subjects underwent pain and neuropsychological assessments and head MRI examinations, including conventional sequences, quantitative susceptibility mapping (QSM), and blood oxygen level-dependent (BOLD) functional MRI. QSM values of the sensorimotor cortex and the left middle frontal gyrus, right inferior temporal gyrus, right olfactory cortex, and right posterior cingulate gyrus were extracted using the ANTs toolkit. The bilateral postcentral gyrus and posterior portion of the bilateral precentral gyrus in the sensorimotor cortex were selected as seed points using SPM software to extract the average time series of BOLD signals and evaluate the changes in RS-FC values with other brain regions. Two-sample t-tests were used to compare the differences in QSM values and RS-FC values between the two groups. Pearson correlation analysis was used to analyze the correlation between iron deposition in key brain regions and RS-FC values and clinical scale scores. Results:The QSM values in the posterior portion of the bilateral precentral gyrus and the left postcentral gyrus in the CLBP group were significantly higher than those in the control group ( t=2.17, P=0.009; t=4.44, P<0.001), and the QSM value in the left postcentral gyrus was positively correlated with pain-related scale scores ( P<0.05). Compared with the control group, the QSM values in the left orbital part of the middle frontal gyrus ( t=2.22, P=0.031) and the right inferior temporal gyrus ( t=2.98, P=0.004) were increased, while the QSM values in the right olfactory cortex ( t=2.54, P=0.014) and the right posterior cingulate gyrus ( t=2.70, P=0.009) were decreased in the CLBP group. Compared with the control group, the RS-FC values between the left postcentral gyrus, the posterior part of the bilateral precentral gyrus, and the left superior frontal gyrus were increased in the CLBP group ( P<0.001), the RS-FC value between the right postcentral gyrus and the right precuneus was increased ( P<0.001). The RS-FC of the bilateral motor cortex and the left dorsolateral superior frontal gyrus was positively correlated with the QSM values of the bilateral motor cortex ( r=0.444, P=0.015). Conclusion:Iron deposition in the sensorimotor cortex (posterior portion of the bilateral precentral gyrus and the left postcentral gyrus) is increased in CLBP patients and is correlated with abnormal functional connectivity within and between brain regions.

AIM:This study aimed to investigate the inhibitory effects and potential mechanisms of cyasterone(CYA)on inflammation and apoptosis of chondrocytes in knee osteoarthritis(KOA).METHODS:A rat model of KOA was established through anterior cruciate ligament transection(ACLT).Rats were randomly divided into 5 groups(n=6 in each group):normal control(NC),ACLT,ACLT+CYA(10 mg/kg),ACLT+CYA+SR9009(BMAL1 inhibitor),and ACLT+CYA+LY294002(PI3K inhibitor).Pathological changes in cartilage were evaluated using hematoxylin-eosin(HE)and safranin O/fast green staining,graded according to the Osteoarthritis Research Society International(OARSI)system.Immunohistochemistry was employed to measure the expression levels of BMAL1,phosphorylated phosphati-dylinositol 3-kinase(p-PI3K),phosphorylated protein kinase B(p-AKT)and phosphorylated nuclear factor-κB(p-NF-κB)in cartilage.An in vitro KOA model was created by stimulating rat chondrocytes with interleukin-1β(IL-1β).Cell vi-ability was assessed using the CCK-8 assay,while enzyme-linked immunosorbent assay(ELISA)was used to quantify pro-inflammatory cytokines(IL-6,IL-1β and TNF-α).Apoptosis was analyzed via flow cytometry,and the protein expression levels of BMAL1,PI3K,p-PI3K,AKT,p-AKT,NF-κB and p-NF-κB were evaluated using Western blot.RESULTS:In vivo,the rats in ACLT group exhibited significant chondrocyte degradation and lacunae formation compared with NC group,confirming the successful establishment of the KOA model.The rats in ACLT+CYA,ACLT+CYA+SR9009 and ACLT+CYA+LY294002 groups showed improved cartilage integrity compared with ACLT group,with reduced OARSI scores(P<0.05),increased BMAL1 expression(P<0.05),and decreased levels of p-PI3K,p-AKT and p-NF-κB(P<0.05).In vitro,the chondrocytes in IL-1β+CYA,IL-1β+CYA+SR9009 and IL-1β+CYA+LY294002 groups exhibited lower levels of IL-6,IL-1β and TNF-α(P<0.05),decreased apoptosis rates(P<0.01),increased BMAL1 protein ex-pression(P<0.05),and reduced p-PI3K/PI3K,p-AKT/AKT and p-NF-κB/NF-κB ratios(P<0.05),compared with IL-1β group.CONCLUSION:Cyasterone alleviates chondrocyte inflammation and apoptosis in KOA by activating BMAL1,which subsequently inhibits the phosphorylation of PI3K/AKT/NF-κB signaling pathway.

Objective Exploring the effect of Bian-stone-based herbal heat therapy on herbal heat ironing in gastrointestinal reactions during the preconditioning period of hematopoietic stem cell transplantation patients.Methods Convenience sampling method was used to select 68 cases of hematopoietic stem cell transplantation patients who attended the hematology department of a tertiary-level Chinese medicine hospital in Hangzhou from October 2023 to April 2024 as the study subjects,and the SPSS 26.0 statistical software was used to generate a random number for grouping into an experimental and a control group,with 34 cases in each group.On the basis of intravenous antiemetic medication and routine,the experimental group implemented the Bian-stone-based herbal heat therapy on the basis of intravenous antiemetic medication and conventional nursing care.In the control group,intravenous antiemetic drugs and routine care were used,and the intervention duration of both groups was 14 d,of which 7 d was a course of treatment,with a total of 2 courses of treatment.The incidence of gastroin-testinal reactions,Gastrointestinal Symptom Rating Scale(GSRS)score,Pepsin Ⅰ(PG Ⅰ),Pepsin Ⅱ(PG Ⅱ),and the ratio of PG Ⅰ to PG Ⅱ(PGR)before and after the intervention were compared between the 2 groups.Results The final sample of 66 cases was collected in this study,and 1 patient was dislodged from each of the control group and the experimental group.The comparison of the incidence of gastrointestinal reactions between the 2 groups within 14 days showed that the incidences of nausea,vomiting,abdominal distension,and diarrhea were lower in the experimental group than those in the control group(P＜0.05).GSRS scores on days 1,8,and 14 of intervention were compared,and there were effects between groups in both groups(F=5.338,P=0.017).The levels of PG Ⅰ,PG Ⅱ in the experimental group on day 8 of the intervention were lower than those in the control group.The levels of PGR was higher than that in the control group(all P＜0.05).The safety of the 2 groups after treatment was evaluated,and the results showed that no serious adverse events occurred in the 2 groups.Conclusion Bian-stone-based herbal heat therapy can improve gastrointestinal reactions and reduce the incidence of gastrointestinal reactions during the preconditioning period of hematopoietic stem cell transplantation patients,which provides clinical guidance for the application of Bian-stone-based herbal heat therapy by nursing staff in the future.

Recently,diffusion models have emerged as a promising paradigm for molecular design and optimization.However,most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geom-etries,with limited research on molecular sequence diffusion models.The International Union of Pure and Applied Chemistry(IUPAC)names are more akin to chemical natural language than the simplified molecular input line entry system(SMILES)for organic compounds.In this work,we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language(SMILES)and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language.We propose DiffIUPAC,a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings.Evaluation results demonstrate that our model out-performs existing methods and successfully captures the semantic rules of both chemical languages.Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints.Additionally,to illustrate the model's applicability in drug design,we conducted case studies in functional group editing,analogue design and linker design.

Objective:To investigate the brain iron status in the sensorimotor cortex of patients with chronic low back pain (CLBP) and its relationship with changes in resting-state functional connectivity (RS-FC).Methods:This was a cross-sectional study. Thirty-two patients with CLBP (CLBP group) who were treated at Wuxi People′s Hospital Affiliated to Nanjing Medical University from July 2023 to March 2024 and 30 age-and gender-matched healthy volunteers (control group) were prospectively included. All subjects underwent pain and neuropsychological assessments and head MRI examinations, including conventional sequences, quantitative susceptibility mapping (QSM), and blood oxygen level-dependent (BOLD) functional MRI. QSM values of the sensorimotor cortex and the left middle frontal gyrus, right inferior temporal gyrus, right olfactory cortex, and right posterior cingulate gyrus were extracted using the ANTs toolkit. The bilateral postcentral gyrus and posterior portion of the bilateral precentral gyrus in the sensorimotor cortex were selected as seed points using SPM software to extract the average time series of BOLD signals and evaluate the changes in RS-FC values with other brain regions. Two-sample t-tests were used to compare the differences in QSM values and RS-FC values between the two groups. Pearson correlation analysis was used to analyze the correlation between iron deposition in key brain regions and RS-FC values and clinical scale scores. Results:The QSM values in the posterior portion of the bilateral precentral gyrus and the left postcentral gyrus in the CLBP group were significantly higher than those in the control group ( t=2.17, P=0.009; t=4.44, P<0.001), and the QSM value in the left postcentral gyrus was positively correlated with pain-related scale scores ( P<0.05). Compared with the control group, the QSM values in the left orbital part of the middle frontal gyrus ( t=2.22, P=0.031) and the right inferior temporal gyrus ( t=2.98, P=0.004) were increased, while the QSM values in the right olfactory cortex ( t=2.54, P=0.014) and the right posterior cingulate gyrus ( t=2.70, P=0.009) were decreased in the CLBP group. Compared with the control group, the RS-FC values between the left postcentral gyrus, the posterior part of the bilateral precentral gyrus, and the left superior frontal gyrus were increased in the CLBP group ( P<0.001), the RS-FC value between the right postcentral gyrus and the right precuneus was increased ( P<0.001). The RS-FC of the bilateral motor cortex and the left dorsolateral superior frontal gyrus was positively correlated with the QSM values of the bilateral motor cortex ( r=0.444, P=0.015). Conclusion:Iron deposition in the sensorimotor cortex (posterior portion of the bilateral precentral gyrus and the left postcentral gyrus) is increased in CLBP patients and is correlated with abnormal functional connectivity within and between brain regions.

Objective Exploring the effect of Bian-stone-based herbal heat therapy on herbal heat ironing in gastrointestinal reactions during the preconditioning period of hematopoietic stem cell transplantation patients.Methods Convenience sampling method was used to select 68 cases of hematopoietic stem cell transplantation patients who attended the hematology department of a tertiary-level Chinese medicine hospital in Hangzhou from October 2023 to April 2024 as the study subjects,and the SPSS 26.0 statistical software was used to generate a random number for grouping into an experimental and a control group,with 34 cases in each group.On the basis of intravenous antiemetic medication and routine,the experimental group implemented the Bian-stone-based herbal heat therapy on the basis of intravenous antiemetic medication and conventional nursing care.In the control group,intravenous antiemetic drugs and routine care were used,and the intervention duration of both groups was 14 d,of which 7 d was a course of treatment,with a total of 2 courses of treatment.The incidence of gastroin-testinal reactions,Gastrointestinal Symptom Rating Scale(GSRS)score,Pepsin Ⅰ(PG Ⅰ),Pepsin Ⅱ(PG Ⅱ),and the ratio of PG Ⅰ to PG Ⅱ(PGR)before and after the intervention were compared between the 2 groups.Results The final sample of 66 cases was collected in this study,and 1 patient was dislodged from each of the control group and the experimental group.The comparison of the incidence of gastrointestinal reactions between the 2 groups within 14 days showed that the incidences of nausea,vomiting,abdominal distension,and diarrhea were lower in the experimental group than those in the control group(P＜0.05).GSRS scores on days 1,8,and 14 of intervention were compared,and there were effects between groups in both groups(F=5.338,P=0.017).The levels of PG Ⅰ,PG Ⅱ in the experimental group on day 8 of the intervention were lower than those in the control group.The levels of PGR was higher than that in the control group(all P＜0.05).The safety of the 2 groups after treatment was evaluated,and the results showed that no serious adverse events occurred in the 2 groups.Conclusion Bian-stone-based herbal heat therapy can improve gastrointestinal reactions and reduce the incidence of gastrointestinal reactions during the preconditioning period of hematopoietic stem cell transplantation patients,which provides clinical guidance for the application of Bian-stone-based herbal heat therapy by nursing staff in the future.

Objective To determine the weight of public health security risk assessment indexes in China by using analytic hierarchy process,and to provide a basis for quantitative assessment and scientific management of public health security risks.Methods The analytic hierarchy process was used to construct the hierarchical model of public health security risk assessment in China,and the pairwise comparison judgment matrix was established and the consistency test was carried out to ensure the rationality of weight distribution.Finally,the weight value and combination weight of each index were calculated.Results The index system included 3 first-level indexes,18 second-level indexes and 43 third-level indexes.The weight coefficients of each level of indexes met the consistency test,and the weight distribution and ranking of China's public health security risk assessment indexes system were finally determined.Conclusion The public health security risk assessment indexes system based on the analytic hierarchy process can scientifically and reasonably reflect the relative importance of each index,and provide important support for the quantitative assessment,early warning,prevention and control of public health security risks in China.