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.

Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.

OBJECTIVE: To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats. METHODS: A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively. RESULTS: Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01). CONCLUSION THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.
Animals ; Diabetic Cardiomyopathies/physiopathology* ; Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Myocardium/metabolism* ; Fibrosis ; Male ; Capsules ; Hypoglycemic Agents/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Rats ; Diabetes Mellitus, Experimental/drug therapy*

OBJECTIVE: To investigate the effect and mechanism of Shuangshi Tonglin Capsules (SSTL) in the treatment of prostate fibrosis (PF). METHODS: Human prostate stromal cells (WPMY-1) were used for in vitro experiments to establish PF cell models induced with estradiol (E₂). The cell proliferation, migration and clonogenic capacity were determined by cell counting kit-8, scratch assay, and crystal violet staining, respectively. Sprague-Dawley rats were used for in vivo experiments. The changes in histomorphology and organ index of rat prostate by SSTL were determined. Pathologic changes and collagen deposition changes in rat prostate were observed by haematoxylin and eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay kits were used to determine changes in rat PF markers fibroblast growth factor-23 (FGF-23), E₂ and prostate specific antigen (PSA). Mechanistically, changes in oxidative stress indicators by SSTL were determined in WPMY-1 cells and PF rats. Then the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins as well as Nrf2 and TGF-β1 mRNA were further detected by Western blot or quantitative real-time polymerase chain reaction both in vivo and in vitro. RESULTS: In the efficacy study, SSTL significantly reduced the proliferation, migration, and clonogenic ability of cells, improved the morphology of the glandular tissue, significantly reduced the prostate index, reduced glandular fibrous tissue and collagen deposition, and resulted in a significant decrease in the levels of FGF-23, E₂ and PSA (P<0.01 or P<0.05). In the mechanistic study, SSTL ameliorated oxidative stress by significantly increasing superoxide dismutase and glutathione peroxidase levels and decreasing malondialdehyde level in WPMY-1 cells and rats (P<0.01 or P<0.05). SSTL significantly elevated the expressions of Nrf2, HO-1, NAD(P)H quinone oxidoreductase 1 (NQO-1), and Smad7 proteins in both cells and rats, and significantly decreased the expressions of TGF-β1, collagen I, α-smooth muscle actin and Smad4 proteins (P<0.01 or P<0.05). SSTL also elevated the content of Nrf2 mRNA and decreased the content of TGF-β1 mRNA in cells and rats (P<0.01 or P<0.05). The Nrf2 inhibitor ML385 was added in in vitro experiments to further validate the pathway relevance. CONCLUSION SSTL was effective in improving PF in vivo and in vitro, and its mechanism of action may function through the Nrf2/TGF-β1 signaling pathway.
Male ; NF-E2-Related Factor 2/metabolism* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Humans ; Fibrosis ; Prostate/drug effects* ; Cell Proliferation/drug effects* ; Capsules ; Cell Movement/drug effects* ; Oxidative Stress/drug effects* ; Rats

Dormant tumor cells constitute a population of cancer cells that reside in a non-proliferative or low-proliferative state, typically arrested in the G0/G1 phase and exhibiting minimal mitotic activity. These cells are commonly observed across multiple cancer types, including breast, lung, and ovarian cancers, and represent a central cellular component of minimal residual disease (MRD) following surgical resection of the primary tumor. Dormant cells are closely associated with long-term clinical latency and late-stage relapse. Due to their quiescent nature, dormant cells are intrinsically resistant to conventional therapies—such as chemotherapy and radiotherapy—that preferentially target rapidly dividing cells. In addition, they display enhanced anti-apoptotic capacity and immune evasion, rendering them particularly difficult to eradicate. More critically, in response to microenvironmental changes or activation of specific signaling pathways, dormant cells can re-enter the cell cycle and initiate metastatic outgrowth or tumor recurrence. This ability to escape dormancy underscores their clinical threat and positions their effective detection and elimination as a major challenge in contemporary cancer treatment. Hypoxia, a hallmark of the solid tumor microenvironment, has been widely recognized as a potent inducer of tumor cell dormancy. However, the molecular mechanisms by which tumor cells sense and respond to hypoxic stress—initiating the transition into dormancy—remain poorly defined. In particular, the lack of a systems-level understanding of the dynamic and multifactorial regulatory landscape has impeded the identification of actionable targets and constrained the development of effective therapeutic strategies. Accumulating evidence indicates that hypoxia-induced dormancy tumor cells are accompanied by a suite of adaptive phenotypes, including cell cycle arrest, global suppression of protein synthesis, metabolic reprogramming, autophagy activation, resistance to apoptosis, immune evasion, and therapy tolerance. These changes are orchestrated by multiple converging signaling pathways—such as PI3K-AKT-mTOR, Ras-Raf-MEK-ERK, and AMPK—that together constitute a highly dynamic and interconnected regulatory network. While individual pathways have been studied in depth, most investigations remain reductionist and fail to capture the temporal progression and network-level coordination underlying dormancy transitions. Systems biology offers a powerful framework to address this complexity. By integrating high-throughput multi-omics data—such as transcriptomics and proteomics—researchers can reconstruct global regulatory networks encompassing the key signaling axes involved in dormancy regulation. These networks facilitate the identification of core regulatory modules and elucidate functional interactions among key effectors. When combined with dynamic modeling approaches—such as ordinary differential equations—these frameworks enable the simulation of temporal behaviors of critical signaling nodes, including phosphorylated AMPK (p-AMPK), phosphorylated S6 (p-S6), and the p38/ERK activity ratio, providing insights into how their dynamic changes govern transitions between proliferation and dormancy. Beyond mapping trajectories from proliferation to dormancy and from shallow to deep dormancy, such dynamic regulatory models support topological analyses to identify central hubs and molecular switches. Key factors—such as NR2F1, mTORC1, ULK1, HIF-1α, and DYRK1A—have emerged as pivotal nodes within these networks and represent promising therapeutic targets. Constructing an integrative, systems-level regulatory framework—anchored in multi-pathway coordination, omics-layer integration, and dynamic modeling—is thus essential for decoding the architecture and progression of tumor dormancy. Such a framework not only advances mechanistic understanding but also lays the foundation for precision therapies targeting dormant tumor cells during the MRD phase, addressing a critical unmet need in cancer management.

AIM To study the chemical constituents from Citri reticulatae Pericarpium Viride and their anti-triple negative breast cancer activities in vitro.METHODS The ethanolic extract of Citri reticulatae Pericarpium Viride was isolated and purified by silica gel,polyamide,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-triple negative breast cancer activities were screened by SRB assay,and their effects on the proliferation of triple negative breast cancer cell lines HCC1806,HCC1937 and MDA-MB-231 in vitro were evaluated.RESULTS Twenty compounds were isolated and identified as nobiletin(1),tangeritin(2),5,4'-dihydroxy-7,8-dimethoxy flavonoid(3),naringenin(4),artemetin(5),5-demethynobiletin(6),3,5,6,7,8,3',4'-pentamethoxy flavonoid(7),5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone(8),xanthomicrol(9),p-hydroxycinnamic acid(10),5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone(11),pectolinarigenin(12),4'-dihydroxy-5,6,7-tetramethoxyflavone(13),hispidulin(14),4',5,6,7-tetramethoxy-flavone(15),1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diol(16),umbelliferone(17),5-hydroxymethyl furfural(18),hydroquinone(19),1H-indole-3-carbaldehyde(20).Compound 8 showed a significant inhibitory effect with the IC50 value of(5.36±0.24)μmol/L on HCC1806 cells.CONCLUSION Compound 20 is isolated from genus Citrus for the first time,8,12-13,16-17 are isolated from this plant for the first time.Compound 8 show inhibitory effects on the proliferation of HCC1806,HCC1937 and MDA-MB-231 cells in vitro and have the strongest activities.Compounds 3-4,11-12,15,17 and 19 show strong inhibitory effect on HCC1806 cells.Compounds 15,19 also inhibit the proliferation of HCC1937 cells in vitro.

Objective To analyze the risk factors and prognosis of patients with advanced lung cancer complicated with immune checkpoint inhibitor-related pneumonitis(CIP).Methods A total of 220 patients with advanced lung cancer who were treated at Ganzhou Cancer Hospital from January 2022 to October 2024 were selected as the research subjects.The patients were divided into non-CIP group(n=179)and CIP group(n=41)based on whether they had concurrent CIP.Compare the clinical characteristics of two groups of patients and analyze the related influencing factors of patients with advanced lung cancer complicated with CIP.Results There were statistically significant differences in age,gender,underlying pulmonary diseases,smoking history,history of thoracic radiotherapy,treatment plans,serum albumin(Alb),platelet to lymphocyte ratio(PLR),neutrophil to lymphocyte ratio(NLR),and absolute lymphocyte count(ALC)between two groups of patients(P＜0.05).Multivariate Logistic regression analysis showed that age,underlying pulmonary diseases,treatment plan,Alb,PLR,NLR,and ALC were all influencing factors for patients with advanced lung cancer complicated with CIP(P＜0.05).The 90-day cumulative survival rate of patients in CIP group was significantly lower than that in non-CIP group(58.54％ vs.77.09％,x2=5.918,P=0.015).With the increase of CIP classification,the 90-day cumulative survival rate of patients showed a downward trend(P＜0.05).Conclusion The incidence of CIP in patients with advanced lung cancer is relatively high.Age,underlying pulmonary diseases,treatment plan,and levels of Alb,PLR,NLR,and ALC are all influencing factors.CIP can have adverse effects on the prognosis of patients.

OBJECTIVE To observe the dynamic change trends of vancomycin resistance rates of Enterococcus fae-calis and Enterococcus faecium in medical institutions of Shanghai and nationwide based on the data from China Antimicrobial Resistance Surveillance System(CARSS)between 2014 and 2023 so as to provide bases for optimi-zing the prevention and control strategies for drug-resistant organisms.METHODS The data regarding to the van-comycin resistance rates of E.faecalis and E.faecium in Shanghai and nationwide were extracted from CARSS.The annual percentage change(APC),average annual percentage change(AAPC)and its 95％confi-dence interval(CI)were calculated by Joinpoint regression model(version 5.4.0).The differences in the changing trends and its statistical significance were analyzed.RESULTS The drug resistance rate of E.faecalis showed a re-markable and continuous decline in Shanghai(AAPC=-85.301％,P＜0.001),the isolation rate of the spe-cies maintained zero after 2019.The drug resistance rate nationwide showed a moderate decreasing amplitude(AAPC=-16.237％,P＜0.001),and there was no significant difference in the changing trend after 2019(P=0.628).The drug resistance rate of E.faecium showed a continuous decline trend in Shanghai(AAPC=-27.838％,P＜0.001),while the drug resistance rate nationwide firstly declined and then rose:with the decline from 2014 to 2020(APC=-18.476％,P＜0.001),the quick rebound from 2020 to 2023(APC=43.976％,P=0.005),and there was no significant difference in the overall change(AAPC=-1.459％,P=0.638).The decreasing amplitudes of drug resistance rates of the two species of Enterococcus were greater in Shanghai than nationwide(all P＜0.001),and the rebounds of drug resistance rates did not emerge nationwide.CONCLUSIONS Shanghai has achieved remarkable effect on control of drug resistance of Enterococcus through the management of antibiotics and infection control measures.The drug resistance rate of E.faecium re-bounds nationwide in recent years,indicating that the prevention and control should be strengthened in grass-roots medical institutions.It is suggested that Shanghai experience should be promoted,and the impact of transmis-sion mechanisms of drug resistance genes and COVID-19 epidemic on the use of antibiotics should be focused on.

Objective:To characterize the etiological and genetic features of pediatric influenza outbreaks in Changzhou between 2021 and 2024，with the goal of informing evidence-based prevention strategies and guiding effective management of influenza outbreaks in school settings.Methods:During the period of 2021 to 2024，throat swabs of influenza-like cases from school outbreaks in Changzhou were collected. These samples underwent real-time reverse transcription-polymerase chain reaction（RT-PCR）testing and virus isolation. Epidemiological data were integrated to conduct pathogenetic analysis. The HA genes of isolated strains were amplified and sequenced to perform genetic characterization.Results:Between 2021 and 2024，a total of 256 influenza outbreaks were reported in schools in Changzhou. A total of 3 201 specimens were collected，of which 2 245 were tested positive for influenza viruses，resulting in a positivity rate of 70.13%. The outbreak season was primarily concentrated from December to February each year，with settings predominantly distributed in primary schools（accounting for 73.83%）. The predominant epidemic strains were influenza A viruses，including 118 outbreaks caused by H1N1 and 104 by H3N2. A total of 74 influenza virus strains were successfully isolated from positive specimens，and sequencing of the hemagglutinin（HA）gene was completed. Phylogenetic analysis revealed that certain B/Victoria lineage strains（e.g.，B/Changzhou/01/2021）clustered closely with the vaccine strain B/Austria/3594/17（bootstrap support：99%）. Among influenza H1N1 strains，multiple isolates from 2023—2024 clustered within the same major branch as A/Victoria/4897/2022（bootstrap support：100%）. In contrast，the H3N2 strains exhibited a complex evolutionary pattern，showing variable genetic distances to vaccine strains from different years（e.g.，A/Massachusetts/18/2022，A/Darwin/6/2021）；some isolates were closely related to vaccine strains，while others were more distantly related and scattered across the phylogenetic tree.Conclusions:The influenza outbreak situation in schools was severe and has significant public health implications. Continuous surveillance is essential，and preventive strategies should be promptly adjusted based on the epidemiological and genetic characteristics of circulating strains.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*