1.Exploration in Mechanism of Sini San for Inhibiting Ferroptosis and Ameliorating Isoprenaline-induced Myocardial Infarction in Mice Based on Bioinformatics and Experimental Validation
Shupeng LIU ; Zhiguang HAN ; Jiaying LI ; Jiayao XU ; Weihao GAO ; Yanping WU ; Guangguo BAN ; Yongmin LI ; Hongxia YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):67-77
ObjectiveTo explore the mechanism by which Sini San (SNS) inhibits ferroptosis, alleviates inflammation and myocardial injury, and improves myocardial infarction (MI). MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) database, its target sites were predicted using the SwissTargetPrediction Database, and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards, Online Mendelian Inheritance in Man (OMIM) database, DrugBank, Therapeutic Target Database (TTD), FerrDb database and literature review, respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction (PPI) network was constructed using the STRING database, and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in, and the biological functions were clustered by the MCODE plug-in. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group, the model group, the SNS group, and the trimetazidine (TMZ) group. The mice were subcutaneously injected with isoprenaline (ISO, 5 mg·kg-1·d-1) to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram (ECG), and the tissue morphology changes were observed by hematoxylin-eosin (HE) staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), reduced glutathione (GSH), and malondialdehyde (MDA) levels were detected by biochemical assay. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of interleukin (IL)-6 and 4-hydroxynonenal (4-HNE). Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 (p-STAT3) in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6, IL-18, solute carrier family 7 member 11 (SLC7A11), arachidonic acid 15-lipoxygenase (ALOX15), and glutathione peroxidase 4 (GPx4) in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained, and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation, and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 (P0.01), down-regulated the expression of ALOX15 mRNA (P0.01), up-regulated the level of serum GSH, and the expressions of SLC7A11 and GPx4 mRNA, reduced MDA and 4-HNE levels (P0.05, P0.01). Additionally, SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis, reduced the area of MI, alleviated inflammation and myocardial injury, lowered the levels of serum CK, CK-MB, LDH, IL-6, and the mRNA expression levels of IL-16 and IL-18 (P0.05), and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels, inhibit ferroptosis in cardiomyocytes, alleviate inflammation and myocardial injury, thereby improving MI.
2.Exploration in Mechanism of Sini San for Inhibiting Ferroptosis and Ameliorating Isoprenaline-induced Myocardial Infarction in Mice Based on Bioinformatics and Experimental Validation
Shupeng LIU ; Zhiguang HAN ; Jiaying LI ; Jiayao XU ; Weihao GAO ; Yanping WU ; Guangguo BAN ; Yongmin LI ; Hongxia YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):67-77
ObjectiveTo explore the mechanism by which Sini San (SNS) inhibits ferroptosis, alleviates inflammation and myocardial injury, and improves myocardial infarction (MI). MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) database, its target sites were predicted using the SwissTargetPrediction Database, and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards, Online Mendelian Inheritance in Man (OMIM) database, DrugBank, Therapeutic Target Database (TTD), FerrDb database and literature review, respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction (PPI) network was constructed using the STRING database, and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in, and the biological functions were clustered by the MCODE plug-in. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group, the model group, the SNS group, and the trimetazidine (TMZ) group. The mice were subcutaneously injected with isoprenaline (ISO, 5 mg·kg-1·d-1) to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram (ECG), and the tissue morphology changes were observed by hematoxylin-eosin (HE) staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), reduced glutathione (GSH), and malondialdehyde (MDA) levels were detected by biochemical assay. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of interleukin (IL)-6 and 4-hydroxynonenal (4-HNE). Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 (p-STAT3) in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6, IL-18, solute carrier family 7 member 11 (SLC7A11), arachidonic acid 15-lipoxygenase (ALOX15), and glutathione peroxidase 4 (GPx4) in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained, and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation, and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 (P0.01), down-regulated the expression of ALOX15 mRNA (P0.01), up-regulated the level of serum GSH, and the expressions of SLC7A11 and GPx4 mRNA, reduced MDA and 4-HNE levels (P0.05, P0.01). Additionally, SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis, reduced the area of MI, alleviated inflammation and myocardial injury, lowered the levels of serum CK, CK-MB, LDH, IL-6, and the mRNA expression levels of IL-16 and IL-18 (P0.05), and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels, inhibit ferroptosis in cardiomyocytes, alleviate inflammation and myocardial injury, thereby improving MI.
3.Analysis of the content of five radionuclides in wild edible fungi
Zhenglin YE ; Qiang ZHOU ; Fei TUO ; Baolu YANG ; Zeshu LI ; Weihao QIN ; Shuying KONG
Chinese Journal of Radiological Health 2025;34(2):242-248
Objective To determine the content and distribution characteristics of the artificial radionuclide 137Cs and the natural radionuclides 210Pb, 226Ra, 228Ra, and 40K in wild edible fungi, and calculate the committed effective dose due to 137Cs and 210Pb in wild edible fungi. Methods Thirty samples of wild edible fungi were collected and their caps and stems were separated. A total of 60 samples were measured for 137Cs, 210Pb, 226Ra, 228Ra, and 40K using a BE5030 wide-energy, low-background, high-purity germanium γ spectrometer. The paired analysis of the four radionuclides 226Ra, 210Pb, 137Cs, and 40K was performed using SPSS 11.5. Results Among the 60 samples, the detection rates and dry weight specific activity ranges of 137Cs, 210Pb, 226Ra, 228Ra, and 40K were 97% and 0.62-384 Bq/kg, 73% and 6.4-159 Bq/kg, 52% and 0.7-28.8 Bq/kg, 5% and 0.43-2.18 Bq/kg and 100% and (77.4-264) × 10 Bq/kg, respectively. Conclusion Based on the analysis of the 60 samples, the detection rate of radionuclides is in the order of 40K, 137Cs, 210Pb, 226Ra, and 228Ra. In terms of the specific activity, the distribution of 40K and 226Ra in wild edible fungi in the same region is basically uniform, while the content of 210Pb and 137Cs fluctuates in different samples. Although 137Cs and 210Pb can be detected in most of the wild edible fungi, the annual committed effective dose due to ingestion of wild edible fungi is negligible.
4.Novel autosomal dominant syndromic hearing loss caused by COL4A2 -related basement membrane dysfunction of cochlear capillaries and microcirculation disturbance.
Jinyuan YANG ; Ying MA ; Xue GAO ; Shiwei QIU ; Xiaoge LI ; Weihao ZHAO ; Yijin CHEN ; Guojie DONG ; Rongfeng LIN ; Gege WEI ; Huiyi NIE ; Haifeng FENG ; Xiaoning GU ; Bo GAO ; Pu DAI ; Yongyi YUAN
Chinese Medical Journal 2025;138(15):1888-1890
5.Feigan granules improve traditional Chinese medicine symptoms scale scores for influenza patients: a prospective clinical observational study.
Weihao CHEN ; Dongsheng ZHENG ; Shuangshuang DU ; Qian LI ; Guolin WU ; Dongsheng HONG ; Qingwei ZHAO
Journal of Zhejiang University. Medical sciences 2025;54(3):289-296
OBJECTIVES:
To evaluate the clinical efficacy of hospital-prepared Chinese medicine Feigan granules for influenza patients. This study has been registered at the International Traditional Medicine Clinical Trial Registry platform (ITMCTR2025000162).
METHODS:
A prospective observational study was conducted on influenza patients who visited the Fever Clinic of the First Affiliated Hospital, Zhejiang University School of Medicine between February and March 2024. Patients were divided into the observation group (Feigan granules combined with conventional Western medicine) and the control group (conventional Western medicine). Main symptoms (including fever, cough and sore throat) and secondary symptoms (including chest tightness, poor appetite, muscle soreness and dry mouth) were evaluated with traditional Chinese medicine (TCM) symptom scale on the first day of the patient's visit and the third day after treatment. The degrees of improvement in the TCM symptom scores before and after treatment were compared using paired rank-sum test, and the differences in the overall symptom efficacy index between two groups were compared using the Wilcoxon test.
RESULTS:
A total of 217 influenza patients were included. After treatment, the TCM symptom scores of both groups were significantly improved compared with those before treatment (all P<0.01). The median differences in the main symptom score before and after treatment in the observation and the control groups were 7 points (95%CI: 6.0-8.0) and 6 points (95%CI: 6.0-8.0), respectively. The median difference in the secondary symptom score was 3 points (95%CI: 2.0-4.0) in both groups. The median differences in the total score were 9 points (95%CI: 8.0-10.5) and 8 points (95%CI: 7.0-10.0) in the observation and control groups, respectively. In the subgroup with an initial cough score >2, the improvement rates of total score (97.06% vs. 92.59%) and secondary symptoms (92.31% vs. 85.11%) in observation group were significantly higher than those in the control group (P<0.05); while there was no significant difference in the improvement rate of the main symptoms (95.59% vs. 90.74%, P>0.05).
CONCLUSIONS
Feigan granules can improve the TCM syndromes of influenza patients, especially for patients with more severe cough.
Humans
;
Prospective Studies
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Influenza, Human/drug therapy*
;
Medicine, Chinese Traditional/methods*
;
Drugs, Chinese Herbal/therapeutic use*
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Female
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Male
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Middle Aged
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Adult
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Aged
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Adolescent
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Young Adult
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Treatment Outcome
6.Risk factors and their predictive efficacy for preoperative heart failure in elderly patients with intertrochanteric femur fracture
Xiwen QIAN ; Xiao MENG ; Weihao MENG ; Yuhe LI ; Chenghua HAN ; Zitao ZHANG
Chinese Journal of Trauma 2025;41(3):267-273
Objective:To investigate the risk factors associated with preoperative heart failure in elderly patients with intertrochanteric fracture and evaluate their predictive efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 163 elderly patients with intertrochanteric fracture admitted to the Affiliated Drum Tower Hospital of Nanjing University School of Medicine from July 2018 to July 2022, including 57 males and 106 females, aged 63-98 years [83.3(78.0, 87.0)years]. The patients were divided into high-risk heart failure group ( n=66) and non-high-risk group ( n=97) based on whether the serum B-type natriuretic peptide (BNP) level within 24 hours on admission was greater than 100 pg/ml. The following data in the two groups were collected, including gender, age, AO/OTA fracture classification, fracture laterality, associated underlying comorbidities (diabetes, cardiovascular diseases, cerebral infarction), past history of fracture, history of surgeries, time from injury to hospitalization less than 48 hours, first blood pressure on admission, first routine blood test on admission [leukocyte count (WBC), neutrophil count (NEUT), lymphocyte count, platelet (PLT), hemoglobin (Hb)], first blood biochemistry on admission [alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), albumin, glucose, serum calcium, creatinine, glomerular filtration rate (GFR), and first other related tests on admission [D-dimer, prothrombin time (PT), C-reactive protein (CRP)]. Independent risk factors for preoperative heart failure in elderly patients with intertrochanteric fracture were identified through univariate analysis and binary logistic regression analysis. The predictive efficacy of each indicator or two combined indicators for preoperative heart failure in elderly patients with intertrochanteric fractures was assessed by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results:Univariate analysis demonstrated that age, associated cardiovascular diseases, history of fracture, time from injury to hospitalization less than 48 hours, Hb, creatinine and GFR were significantly correlated with the preoperative heart failure ( P<0.05), while gender, AO/OTA fracture classification, fracture laterality, diabetes, cerebral infarction, history of surgeries, blood pressure, WBC, NEUT, lymphocyte count, PLT, CRP, ALT, AST, LDH, albumin, glucose, serum calcium, D-dimer, PT, and CRP were not correlated with the preoperative heart failure in elderly patients with intertrochanteric fractures ( P>0.05). Logistic regression analysis revealed that age (95% CI 1.02, 1.15, P<0.05), associated cardiovascular disease (95% CI 1.31, 5.88, P<0.01), Hb (95% CI 0.96, 1.00, P<0.05), and GFR (95% CI 0.97, 1.00, P<0.05) were independent risk factors for heart failure in elderly patients with intertrochanteric fracture. ROC curve analysis demonstrated that age, associated cardiovascular diseases, Hb, and GFR could predict preoperative heart failure in elderly patients with intertrochanteric fractures, with the combination of associated cardiovascular disease and GFR showing a relatively higher predictive ability (AUC=0.76, 95% CI 0.68, 0.84). Conclusions:Age, associated cardiovascular diseases, Hb and GFR are independent risk factors for preoperative heart failure in elderly patients with intertrochanteric fracture. Moreover, the combination of associated cardiovascular diseases and GFR possesses a relatively higher predictive value for preoperative heart failure in elderly patients with intertrochanteric fracture.
7.Practical exploration and reflection on the reform path of standardized training for general residents
Zhonghang XU ; Weihao DU ; Wenwen LIU ; Yan QIN ; Chunsheng LI ; Xuedong FANG ; Fenghua QIAN
Chinese Journal of General Practitioners 2025;24(3):364-368
General practice standardized residency training is a crucial part of postgraduate education for cultivating general practitioner. The factors influencing the quality of general practice residency training cover various aspects such as the residents themselves, teaching staff, management and decision-making levels, as well as teaching resources. Guided by the goal of "fostering virtue through education", and integrated the spirit of Norman Bethune and modern innovation theories and the educational philosophy, the China-Japan Union Hospital of Jilin University has carried out comprehensive reforms in this field. It has constructed a PDCA cycle management system based on the concept of total quality management to improve the quality of education from multiple links such as quality planning and process monitoring. In terms of faculty development, based on the dissipative structure theory, a mechanism of "selection, evaluation, incentive, and elimination" has been established. Teacher communities have been formed and a training college has been established to strengthen the teaching team. In terms of platform construction, the linkage between "teaching base-community" and "on campus-off campus" has been strengthened and resources have been integrated. The reform has achieved remarkable results, and our practice may provide a reference for general practice medical education.
8.Relationship between 137Cs and stable cesium in wild edible fungi
Zhenglin YE ; Fei TUO ; Baolu YANG ; Zeshu LI ; Jing ZHANG ; Weihao QIN ; Shuying KONG ; Qiang ZHOU
Chinese Journal of Radiological Medicine and Protection 2025;45(5):460-464
Objective:To investigate the relationship between artificial radionuclide 137Cs and stable cesium (Cs) in wild edible fungi and seek potential correlations. Methods:A total of 30 samples, including the caps (with gills) and stipes of wild edible fungi, were collected from the northeastern region of China. The measurement and analysis of 137Cs were conducted following recommended procedures in GB/T 16145-2022, and stable Cs was determined using inductively coupled plasma mass spectrometry (ICP-MS). Then, the correlation analysis of data on 137Cs and stable Cs was performed using SPSS 11.5 software, and scatter plots were prepared using the Origin 21.0 software. Results:The fungi caps exhibited a specific activity of 137Cs ranging from 0.52 to 55.9 Bq/kg (dry weight) and a stable Cs content from 0.069 mg/kg to 16.2 mg/kg (dry weight). The stipes showed a specific activity of 137Cs ranging from 0.53 Bq/kg to 101 Bq/kg (dry weight) and a stable Cs content from 0.075 to 11.5 mg/kg (dry weight). These data revealed a significant correlation between the specific activity of 137Cs and the stable cesium content in all samples including caps and stipes, with correlation coefficients r of 0.956, 0.912, and 0.931, respectively, and all significant levels P < 0.01. The ratios of the specific activity of 137Cs to stable Cs content varied from 2.09 Bq/kg to 20.1 Bq/kg (dry weight), with an average of 10.7 Bq/kg (dry weight). Conclusions:Wild edible fungi fail to distinguish between 137Cs and stable cesium when absorbing Cs elements from their growing substrates. Furthermore, there is a strong correlation between the specific activity of 137Cs and stable Cs content. In the case of exogenous 137Cs contamination, the ratio of the specific activity of 137Cs and stable Cs content will significantly change. Therefore, an increase in the ratio can be used as a reference for identifying 137Cs contamination events.
9.Comparative analysis of statistical measures to assess the capability of the γ-ray spectroscopy of radionuclides for interlaboratory comparison
Shuying KONG ; Qiang ZHOU ; Fei TUO ; Baolu YANG ; Zeshu LI ; Weihao QIN
Chinese Journal of Radiological Medicine and Protection 2025;45(6):573-578
Objective:To explore the applicability of critical statistical measures Z, Z′, Zeta ( ζ), and En value in comparative capability assessments by analyzing the data from nationwide radiological health technology institutions from 2020 to 2023, aiming to provide a reference for further improving China′s comparative assessment method for verifying the γ-ray spectroscopy capability of radionuclides. Methods:Based on the nationwide analysis and comparison of γ-ray spectroscopy of radionuclides conducted annually by the National Institute for Radiological Protection, China CDC, the deviations between laboratory result and reference values were determined using the above-mentioned four statistical measures. Finally, the qualification rates of the γ-ray spectroscopy result from relevant institutions were assessed and analyzed.Results:The result indicate that the qualification rates of the Z value exceeded 85%, which might be inaccurate in some cases since it ignored the limitation of uncertainty. In contrast, the Z′ value yielded more scientific and representative result because it considered the uncertainty of reference values, and the inter-laboratory comparison qualification rate is above 95%. In the case of low uncertainty of the γ-ray spectroscopy result, the Zeta ( ζ) or En ratio exhibited relatively high sensitivity and, accordingly, relatively low qualification rates, indicating that this ratio may not comprehensively reflect the interlaboratory comparison result. Conclusions:The Z, Z′, Zeta ( ζ), and En values demonstrate their own advantages and limitations in assessing the capability of the γ-ray spectroscopy of radionuclides. For comparison projects involving multiple laboratories and complex measurement conditions, such as the nationwide verification of the capabilities of the γ-ray spectroscopy of radionuclides, it is feasible to combine the Z′ value with the Zeta ( ζ) or En ratio, with the former and the latter used to determine the qualified and excellent capability result, respectively. This enables the comprehensive assessment of the measurement and analysis capabilities of the γ-ray spectroscopy laboratories of radiological health technology institutions in China.
10.Chitinase-like protein Ym2 regulates olfactory epithelium homeostasis and olfactory behavior in mice
Tingting WU ; Weihao LI ; Hongmeng YU ; Yiqun YU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(2):134-143
Objective:To investigate the role of Ym2 in olfactory epithelium homeostasis and olfactory behavior.Methods:Differential expression of Ym2 in the olfactory epithelium of young and aged mice was analyzed using single-cell RNA sequencing. Ym2 and related genes in the aged olfactory epithelium were identified, and their biological function was analyzed by GO enrichment analysis. The expression of Ym2 and Ym2-related genes in the young and aged olfactory epithelium was detected by immunostaining and RNAscope in situ hybridization. Buried food pullet test was used to assess the impact of Ym2 knockout on olfactory function, while immunostaining was used to evalute the effect of Ym2 knockout of on the homeostasis of olfactory epithelium. Statistical analysis was performed using GraphPad Prism 8.0.1 software.Results:Single-cell RNA sequencing revealed that Ym2 was highly expressed in multiple cell types, including horizontal basal cells and respiratory ciliated cells of the olfactory epithelium in aged mice compared to young animals. In situ hybridization and immunostaining data showed that Ym2 mRNA level were higher in the aged olfactory epithelium than that in the young tissue ( t=4.50, P<0.001). At the protein level, Ym2 expression was higher in horizontal basal cells ( t=3.03, P<0.05) and supporting cells ( t=7.76, P<0.001) of the aged epithelium compared to the young tissue. Additionally, the mRNA levels of the two Ym2-related genes, Alox15 and Cxcl5, were also higher in the aged olfactory epithelium ( t=2.72 and 2.68, respectively, both P<0.05). Behavioral testing showed that Ym2-/- mice took significantly longer to find buried food pellets compared to wild-type (WT) mice ( t=2.35, P<0.05). Histological analysis revealed a significant reduction in the number of olfactory sensory neurons and supporting cells in the olfactory epithelium of Ym2-/- mice compared to WT mice ( t=5.86 and 3.69, respectively, both P<0.01). Conclusions:Ym2 plays a critical role in smell perception. Ym2 knockout leads to reduction in the number of olfactory epithelial cell and impairs olfactory behavior of food-searching in young mice.

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