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.

Objective:To explore the influencing factors for skin pruritus and to construct a nomogram prediction model in peritoneal dialysis (PD) patients.Methods:It was a retrospective cross-sectional investigation study. The PD patients who were regularly followed up between July, 2023 and April, 2024 in PD center of the First Affiliated Hospital of Sun Yat-sen University were enrolled in this study. The pruritus status was evaluated by the 14-Item UP-Dial Scale. The general demographic data and clinical data were collected. The patients were divided into pruritus group and non-pruritus group according to the presence or absence of skin itching. The differences of clinical data and laboratory results were compared between the two groups. Logistic regression was used to analyze the associated factors for pruritus in PD patients. The nomogram model was constructed by R software. The receiver operating characteristic (ROC) curve analysis and the Hosmer-Lemeshow goodness-of-fit test were used to evaluate the performance of the model, and its clinical effectiveness was evaluated using the calibration curve.Results:A total of 315 PD patients were enrolled in this study, with age of (48.0±12.9) years, including 134 females (42.5%). Among them, 161 patients (51.1%) experienced skin pruritus. Of whom, 111 patients (68.9%) had mild pruritus, 34 patients (21.1%) had moderate pruritus, 16 patients (9.9%) had severe pruritus. The age ( t=-2.266, P=0.024), proportion of diabetes mellitus ( χ2=3.910, P=0.048), Charson comorbidity index ( Z=-2.458, P=0.014), blood eosinophil percentage ( Z=-2.385, P=0.017), C-reactive protein ( Z=-2.590, P=0.010), serum phosphorus ( Z=-3.233, P=0.001) and β2 microglobulin ( Z=-2.756, P=0.006) level in the pruritus group were higher than those in the non-pruritus group, and the measured glomerular filtration rate (mGFR) level ( Z=-3.708, P<0.001) of patients in the pruritus group was lower than that in the non-pruritus group. There were 262 patients in the training set and 53 patients in the validation set. The multivariate logistic regression analysis in the training set revealed that advanced age ( OR=1.032, 95% CI 1.010-1.054, P=0.004), lower mGFR ( OR=0.758, 95% CI 0.648-0.886, P<0.001), higher serum phosphorus ( OR=2.761, 95% CI 1.282-6.024, P=0.010), and elevated blood eosinophil percentage ( OR=1.098, 95% CI 1.012-1.191, P=0.025) were independent factors associated with pruritus in PD patients. The nomogram model constructed based on these indicators demonstrated good discrimination and calibration. In the training set, the area under the ROC curve ( AUC) was 0.757 (95% CI 0.699-0.816), with Hosmer-Lemeshow test χ2=4.979, P=0.760. In the validation set, the AUC was 0.779 (95% CI 0.651-0.907), and Hosmer-Lemeshow test χ2=12.938, P=0.114. Conclusions:The prevalence of skin pruritus is 51.1% in PD patient. Advanced age, lower mGFR, higher serum phosphorus and higher blood eosinophil percentage are the independent influencing factors for pruritus in PD patients. The nomogram model constructed based on these indicators shows excellent predictive performance for skin pruritus in PD patients.

Objective:To investigate the relationship between serum soluble interleukin-2 receptor(sCD25)and insulin-like growth factor-Ⅰ(IGF-Ⅰ)and the immunophenotype and therapeutic efficacy of newly diagnosed multiple myeloma(MM)patients.Methods:125 newly diagnosed MM patients(MM group)who received treatment at Tianmen First People's Hospital from January 2023 to June 2024 were selected,and another 70 healthy individuals who underwent physical examinations at our hospital during the same period were selected(control group).The serum sCD25 and IGF-Ⅰ levels in newly diagnosed MM patients of different stages were compared,and newly diagnosed MM patients were divide into remission group(76 cases)and non remission group(49 cases)based on treatment efficacy,the serum sCD25 and IGF-Ⅰ levels between the remission group and non remission group were compared.The patients were divided into high sCD25 group and low sCD25 group,high IGF-Ⅰ group and low IGF-Ⅰgroup according to the median levels of serum sCD25 and IGF-Ⅰ,the immunophenotypic differences between high sCD25 group and low sCD25 group,as well as high IGF-Ⅰ group and low IGF-Ⅰ group were analyzed.Serum sCD25 and IGF-Ⅰ for evaluating the efficacy of newly diagnosed MM patients were analyzed by receiver operating characteristic(ROC)curve.Factors affecting the therapeutic effect of newly diagnosed MM patients were analyzed by multivariate logistic regression analysis.Results:Serum sCD25 and IGF-Ⅰ levels in the control group were significantly lower than those in the MM group(P＜0.05).There was a statistically significant difference in serum sCD25 and IGF-Ⅰ levels among newly diagnosed MM patients at different stages(P＜0.05).Serum sCD25 and IGF-Ⅰ levels in stage Ⅲ newly diagnosed MM patients were significantly higher than those in stage Ⅰ and Ⅱ(P＜0.05),And stage Ⅱ was higher than that in stage Ⅰ(P＜0.05).The positive expression rate of CD56 in the high sCD25 group was higher than that in the low sCD25 group,there was no significant difference in the positive expression rates of CD117 and CD200 between the two groups(P＞0.05).The positive expression rates of CD56 and CD117 in the high IGF-Ⅰ group were higher than those in the low IGF-Ⅰ group(P＜0.05),and there was no significant difference in the positive expression rate of CD200 between the two groups(P＞0.05).Serum sCD25 and IGF-Ⅰ levels in the remission group were significantly lower than those in the non remission group(P＜0.05).ROC curve analysis showed that,the area under the curve(AUC)for evaluating the efficacy of newly diagnosed MM patients using serum sCD25 and IGF-Ⅰ detection alone and in combination were 0.748,0.775 and 0.832,respectively,and the AUC for combined detection was greater than that for each indicator detected separately.The results of multivariate Logistic regression model showed that elevated serum sCD25 level,elevated serum IGF-Ⅰ level and MM stage Ⅲ were independent risk factors affecting the efficacy of newly diagnosed MM patients(P＜0.05).Conclusion:Serum sCD25 and IGF-Ⅰ levels are closely related to the disease stage and therapeutic efficacy of newly diagnosed MM patients.Combined detection has a high evaluation value for efficacy and can be used as an important evaluation index affecting efficacy.

Objective To explore the role and mechanism of warm malate ringer's solution(MR)in resuscitation of the lethal triad caused by severe trauma.Methods A rat model of severe trauma was established in SPF-grade SD rats(half male and half female,weighing 200～220 g)using combined multiple injuries and hemorrhagic shock,and the rats were randomly divided into 8 groups(n=8):Sham group,only arterial and venous catheterization;Trauma(Tra)groups with different time points(10,30,60,90,120,180 min)and a Trauma group that were observed without any treatment for 180 min after model establishment.The changes of activated clotting time(ACT),reaction time(R),maximum amplitude(MA),and rate of blood clot formation(Angle)at different time points were detected by using thromboelastography,and tail bleeding,core body temperature and arterial blood gas parameters,were also observed and detected.The plasma von Willebrand Factor(vWF)level,mitochondrial respiratory control ratio in pulmonary venous endothelium,and expression levels of vascular endothelial cadherin(VE-Cadherin),peroxisome proliferator activating receptor gamma coactivator 1α(PGC1α),dynamin-related protein 1(Drp1),p-Drp1,and mitofusin 2(Mfn2)were detected to evaluate the vascular endothelial injury and mitochondrial dysfunction.Another group of SD rats were randomly divided into severe trauma group(no treatment for 180 min after injury),and MR solution at room temperature and at 37 ℃ groups.MR solution at room temperature or at 37 ℃ was given to the rats using a medical blood transfusion apparatus at 60 min post-trauma.Above indicators were observed and detected to investigate the resuscitation effect of the MR solution.Results Compared with the Sham group,the severely traumatic rats at 180 min after injury had significantly prolonged ACT and R values(P＜0.05),shortened MA and decreased Angle values(P＜0.05),extended tail bleeding time(P＜0.05),lower partial pressure of carbon dioxide(PCO2)and HCO3-and base excess(BE)levels(P＜0.05),and continuously increasing K+(P＜0.05)and decreasing Na+(P＜0.05)and Ca2+levels(P＜0.05).Additionally,plasma vWF level(P＜0.05)and protein levels of VE-cadherin,PGC1α and Mfn2 in pulmonary vein endothelium were significantly reduced(P＜0.05),the expression of p-Drp1 was enhanced and the mitochondrial respiration control rate was declined in the rats at 180 min after injury(P＜0.05).MR solution resuscitation shortened tail bleeding time(P＜0.05),increased core body temperature(P＜0.05),elevated plasma vWF level(P＜0.05),increased protein levels of VE-cadherin,PGC1α and Mfn2(P＜0.05),and decreased that of p-Drp1 protein expression(P＜0.05)when compared with the rats at 180 min after severe traumatic injury.The above effects were more significant in the rats infused with the solution at 37 ℃ than those at room temperature.Conclusion Warm MR solution significantly improves the lethal triad in rats after severe trauma,which may be associated with its improving mitochondrial function and attenuating vascular endothelial damage.

The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

OBJECTIVE: To investigate the clinical features, treatment and prognosis of extranodal NK/T-cell lymphoma, nasal type (ENKTL) with skin lesions as initial symptom. METHODS: The clinical data of 11 ENKTL patients with skin lesions as initial symptom were retrospectively analyzed from August 2016 to January 2023 in Wuhan First Hospital and Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. RESULTS: Among the 11 patients, there were 6 males and 5 females, with a median age of 50(32-80) years. All patients had different forms of skin lesions as initial clinical symptom, including rash, ulcerative mass, painful skin nodules, infiltrating macula, etc. Most of the skin lesions were involved in the limbs and trunk but also appeared in the lower limbs alone. Five patients had hemophagocytic lymphohistiocytosis (HLH) at initial diagnosis, and 8 patients had B symptoms. All patients were diagnosed with advanced clinical staging (Lugano staging IV), and classified as high risk (PINK-E score ≥3). Immunohistochemical examination revealed that the positive rates of CD56 and EBER were both 100%, and the median Ki-67 index was 75%(50%-80%). Plasma EBV-DNA tests were all positive (≥5×10² copies/ml). Most of the induction chemotherapy regimens were combination chemotherapy (MESA, p-Gemox, SMILE) containing pegaspargase or L-asparaginase, or combined with PD-1 monoclonal immunotherapy, or HLH regimens (HLH-04 regimen, L-DEP). The median follow-up time and overall survival (OS) time were both 4.5(0.5-27) months. During the follow-up period, all 8 patients who did not receive autologous hematopoietic stem cell transplantation (ASCT) died, most of whom died of rapid disease progression. Three patients received ASCT, one died of central nervous system recurrence after transplantation, and two survived. The OS of three patients who underwent ASCT was 21, 27, and 19 months, and PFS was 11, 20, and 13 months, respectively. The plasma EBV-DNA copy number was monitored irregularly after transplantation, and the load of EBV was consistent with the changes of the disease. CONCLUSIONS Early clinical symptoms of ENKTL patients with skin lesions as initial symptom are more atypical, and early diagnosis is particularly difficult. The disease progresses rapidly and the prognosis is poor. There is still no uniform standard for the best treatment strategy. The survival of patients can be significantly prolonged by applying ASCT as soon as possible after complete remission obtained by high-dose induction chemotherapy.
Humans ; Male ; Female ; Lymphoma, Extranodal NK-T-Cell/diagnosis* ; Middle Aged ; Adult ; Retrospective Studies ; Aged ; Prognosis ; Aged, 80 and over

OBJECTIVE: To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway. METHODS: The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway. The levels of NLRP3, Caspase-1 p20, microtubule-associated protein 1 light chain 3 II (LC3II) and P62 proteins were measured by Western blot. The release of interleukin-1β (IL-1β) was tested by enzyme linked immunosorbent assay, the mtROS level was detected by flow cytometry, and the immunofluorescence and co-localization of LC3 and mitochondria were observed under confocal laser scanning microscopy. RESULTS: Similar to the effect of Mito-TEMPO and contrary to the results of 3-MA treatment, TRQ could significantly reduce the expressions of NLRP3, Caspase-1 p20, and autophagy adaptor P62, promote the expression of autophagy marker LC3II, enhance the mitochondrial fluorescence intensity, and inhibit the release of mtROS and IL-1β (all P<0.01). Moreover, LC3 was co-localized with mitochondria, confirming the type of mitophagy. CONCLUSION TRQ could reduce the level of mtROS by promoting mitophagy in macrophages infected with influenza A virus, thus inhibiting the activation of NLRP3 inflammasome and the release of IL-1β, and attenuating the inflammatory response.
Mitophagy/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Animals ; Macrophages/virology* ; Inflammasomes/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Mitochondria/metabolism* ; Reactive Oxygen Species/metabolism* ; Influenza A virus/physiology* ; Interleukin-1beta/metabolism* ; Cell Line ; Injections

Objective:Hearing loss can seriously affect mental health status, and this study aims to investigate the influence of hearing health status on depressive symptoms among middle-aged and older individuals in the community.Methods:From June to December 2023, a stratified random sampling method was employed to select 1 238 community-dwelling middle-aged and elderly people aged 45 years and above from four cities (Hangzhou, Shanghai, Baoding, and Zhengzhou) as research subjects. A questionnaire survey was conducted to collect the subjects′ basic information, hearing health status [assessed by the Hearing Handicap Inventory for Adults-Screening Version (HHIA-S)], and depressive symptoms [assessed by the Geriatric Depression Scale-15 (GDS-15)]. T-tests, rank-sum tests and chi-square tests were used for univariate analysis, while, multiple linear regression and binary Logistic regression were applied to analyze the relationship between hearing health status and depressive symptoms.Results:A total of 1 183 community-dwelling middle-aged and elderly people aged 45 years and above were included in the final analysis (464 males and 719 females, aged from 45 to 96 years). The detection rate of hearing loss was 35.3%(418/1 183), while, the detection rate of depressive symptoms was 9.89%(117/1 183). Age, level of interaction with children, self-rated health, perceived loneliness, and hearing health significantly influenced depressive symptoms among older adults residing in the community ( P<0.05). Individuals with moderate to severe hearing loss ( β=2.04, 95% CI: 1.47, 2.62) exhibited higher GDS-15 scores compared to those without hearing impairment. Furthermore, after correcting for sex, age, marital status, monthly per capita family income, education, residence, smoking status, alcohol use, use of psychotropic medication (anxiolytic or depressant), number of illness, self-health assessment, and autonomy, middle-aged and older adults with mild to moderate hearing loss ( OR=2.89, 95% CI: 1.76, 4.88) and severe hearing loss ( OR=5.79, 95% CI: 3.05, 11.01) demonstrated an increased likelihood of experiencing depression. Conclusions:The degree of hearing loss in community-dwelling middle-aged and elderly individuals is closely associated with the risk of depressive symptoms. Therefore, it is imperative to enhance hearing health screening and to provide mental health support to individuals with hearing loss, in order to mitigate the onset and progression of depressive symptoms.

Objective To systematically evaluate the factors affecting taste alteration in patients undergoing cancer chemotherapy.Methods PubMed,Cochrane Library,Web of Science,CINAHL,Embase,CBM,CNKI,WanFang Data and VIP were searched from the establishment until August 1,2024.The retrieved literature was independently screened,evaluated and the data were extracted by 2 researchers,and statistical analysis was performed using Stata 17.0 software.Results A total of 18 studies were included,involving 4 686 patients.The incidence of taste changes is 73.46％.Totally 9 influencing factors were extracted through quantitative analysis,including oral mucositis(OR=1.98),dry mouth(OR=1.82),nausea(OR=3.05),loss of appetite(OR=2.41),use of triple antiemetic drugs(OR=2.45),gynecological cancers(OR=0.67),lung cancer(OR=0.57),paclitaxel types of chemotherapy d rugs(OR=2.86),and smoking(β=9.38).Conclusion The alteration of taste in cancer chemotherapy patients is in-fluenced by multiple factors.Nurses should regularly and dynamically assess changes in taste and implement individualized and refined nursing interventions in clinical practice to prevent or delay the development of taste alterations,thereby improving patients' quality of life and treatment adherence.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.