1.Advances in the application of gene copy number alteration detection technology in lymphoma
Yu PENG ; Shuang CHEN ; Tingting JIANG ; Can LIN ; Longrong RAN ; Xuelian WU ; Lian LI ; Liangmei LI ; Xinyi TANG ; Yakun ZHANG ; Huiyu XIANG ; Junxi LIU ; Dan JI ; Zailin YANG
International Journal of Laboratory Medicine 2025;46(15):1860-1866
Lymphoma is a highly heterogeneous malignancy characterized by complex molecular regulatory mechanisms that result in significant differences in aggressiveness and prognosis across its subtypes.Gene copy number alteration(CNA)analysis,an emerging technology,has become a pivotal tool in the precision re-search and management of lymphoma.By detecting DNA deletions,amplifications,and chromosomal copy number changes,CNA analysis addresses the limitations of traditional cytogenetic techniques,enhances the ac-curacy of subtype classification,and aids in evaluating tumor heterogeneity and disease progression.This re-view provides a comprehensive summary of CNA detection methods and their applications in lymphoma,with a focus on recent advancements in the field.It offers a comparative analysis of CNA detection techniques and discusses their role in precision diagnosis,subtype classification,monitoring disease progression,predicting therapeutic resistance,and assessing prognosis.Additionally,the review explores the potential applications of CNA analysis in uncovering molecular regulatory mechanisms,optimizing therapeutic strategies,and impro-ving patient survival outcomes.
2.Bioinformatics analysis and expression of the major genetic type of TcdB
Yitai Fang ; Nianzhi Ning ; Yakun Sun ; Deyu Li ; Hui Wang ; Deyan Luo
Acta Universitatis Medicinalis Anhui 2025;60(12):2273-2280
Objective:
To analyze the bioinformatics of domestic Clostridium difficile toxin B(TcdB) and prepare it to provide data support for the development of effective vaccines.
Methods:
Using bioinformatics software such as Snippy, Blast, Muscle, and the dist.alignment() and hclust() functions in R, 1 355 strains of Clostridium difficile from NCBI GenBank in China were compared and analyzed, and TcdB were grouped. The maximum likelihood tree and phylogenetic tree were beautified and displayed using iTOL. An online bioinformatics analysis website was used to predict and analyze the spatial structure and antigenic epitopes of the two largest subgroups, TcdB1 and TcdB2. The antigen protein TcdB was expressed and purified by prokaryotic system.
Results:
According to the genotype of toxin B, the 1 355 prevalent strains of Clostridium difficile in China could be roughly divided into 12 subtypes, among which TcdB1 and TcdB2 were the main subtypes, accounting for more than 93.94% of all isolated strains, and about 17.20% of the strains were nontoxigenic or lack TcdB. The antigen epitope prediction of TcdB1 and TcdB2 showed that their antigen epitope distributions were basically the same, and many of them were distributed outside the C-terminal combined repetitive oligopeptides domains.
Conclusion
A specialized typing system for C. difficile TcdB in China has been established, and its main subtypes have been predicted for antigenic epitopes. The screened TcdB has been expressed for recombinant preparation.
3.Influencing factors for atrial fibrillation in elderly patients with heart failure and construction of a nomogram model
Yakun SU ; Tingting LIN ; Qiong WANG ; Fengde LI ; Junying SONG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(8):1010-1015
Objective To elucidate the independent risk factors for AF in elderly patients with HF,develop a nomogram prediction model,and assess its predictive value for AF in elderly HF pa-tients.Methods A retrospective study was conducted on 299 patients of first HF hospitalization in Hengshui People's Hospital from June 2019 to December 2023,and based on the presence or absence of AF,they were divided into an AF group(133 cases)and a non-AF group(166 cases).The patients admitted from June 2019 to December 2022 were assigned into a modeling cohort(206 cases),while those from January 2023 to December 2023 into a validation cohort(93 cases).The general data were collected.Multivariate logistic regression analysis was performed on the modeling cohort to identify the independent predictors of AF in elderly HF patients,and a nomo-gram prediction model was constructed.ROC curve,calibration curve and clinical decision curve analyses were applied to evaluate the discrimination,calibration and clinical practicability of the prediction model.Results Multivariate logistic regression analysis revealed that the etiology of HF(CHD vs HP,OR=0.610,95%CI:0.301-1.250,P=0.178;CMD vs HP,OR=0.213,95%CI:0.052-0.883,P=0.033),LAD(OR=1.081,95%CI:1.020-1.152,P=0.015),HF classifi-cation(HFmrEF vs HFrEF,OR=5.897,95%CI:2.448-14.201,P=0.000;HFpEF vs HFrEF,OR=7.211,95%CI:2.522-20.640,P=0.001),pre-albumin(PALB)(OR=0.438,95%CI:0.217-0.901,P=0.030),UAC(OR=2.186,95%CI:1.075-4.430,P=0.025),and direct biliru-bin(DBi)(OR=4.531,95%CI:2.052-9.990,P=0.000)were independent risk factors for AF in the elderly HF patients.ROC curve analysis showed the AUC value of the prediction model based on these factors in the modeling cohort was 0.831,and the AUC value in the validation cohort was 0.840.Decision curve analysis indicated that the model possessed clinical practicability within a probability threshold range of 10%-82%for the modeling cohort and 12%-100%for the vali-dation cohort.Conclusion Our nomogram prediction model based on multivariate logistic regres-sion analysis exhibits good predictive value for the occurrence of AF in elderly HF patients,and can facilitate clinical decision-making on diagnosis and treatment.
4.Milk fat globule-epidermal growth factor 8 alleviates intestinal inflammation and ferroptosis in mice with acute pancreatitis through integrin αVβ3 receptor
Bingli LIU ; Yakun SHI ; Hua LI ; Yiming LI
Chinese Journal of Digestion 2025;45(8):548-554
Objective:To investigate the protective effects and mechanism of exogenous milk fat globule-epidermal growth factor 8(MFG-E8) on intestinal injury and ferroptosis in mice with acute pancreatitis (AP) and its mechanism.Methods:A total of 24 male C57 BL/6 mice were randomly divided into the normal control group, AP group, AP+ MFG-E8 group (MFG-E8 group), and AP+ MFG-E8+ cilengitide group (cilengitide group), with 6 mice in each group according to the random number table. The mice of normal control group were intraperitoneally injected with 0.9% sodium chloride solution. In the AP group, MFG-E8 group, and cilengitide group, the mice were intraperitoneally injected with 8% L-arginine twice at 1-hour intervals to induce the AP model. In the MFG-E8 group, mice were intraperitoneally injected with 20 g/kg of MFG-E8 at 2 hours after L-arginine injection. In the cilengitide group, mice were intraperitoneally injected with 20 mg/kg of cilengitide at 1 hour after the L-arginine injection, and 20 g/kg of MFG-E8 1 hour later. The mice were sacrificed and blood samples and intestinal tissues were collected at 72 hours after the first L-arginine injection. Hematoxylin-eosin staining was used to evaluate intestinal tissue injury. Myeloperoxidase (MPO) immunofluorescence staining was performed to detect neutrophils in intestinal tissues.Adenosinetriphosphate (ATP) levels were examined to detect changes in mitochondrial function. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were tested to check the level of intestinal oxidative stress. Dihydroethidium (DHE) fluorescent probe was used to label the oxygen free radicals in intestinal tissues. The expression of glutathione peroxidase 4 (GSH-Px4), solute carrier family 7 member 11 (also named xCT), and ferroptosos suppressor protein-1 (FSP-1) in intestinal tissues were detected by western blotting. Indepent-samples t-test, one-way ANOVA, and Student-Newman-Keuls test were performed for statistical analysis. Results:Intestinal tissue injury and inflammatory cell infiltration in mice were induced by intraperitoneal injection of L-arginine. Compared with those of AP model group, the intestinal pathology score, MPO fluorescence quantification and DHE fluorescence density of MFG-E8 group were significantly decreased (3.93±0.57 vs. 1.73±0.74, (26.33±4.49)/field vs. (11.00±3.27)/field, (39.67±5.79)/field vs. (12.33±3.68)/field), while the contents of ATP, MDA and SOD were increased ((77.09±8.52) μmol/g vs. (119.87±6.83) μmol/g, (0.10±0.01) μmol/g vs. (0.17±0.02) μmol/g, (105.67±6.93) U/mg vs. (144.49±18.55) U/mg), and the differences were statistically significant ( t=3.33, 3.93, 5.63, 8.77, 6.54, 4.38; all P<0.05). The results of Western blotting showed that GSH-Px4, xCT, and FSP-1 in the intestinal tissue of AP mice in the MFG-E8 group were all elevated compared with those of AP group, the relative expression levels were 1.22±0.19 vs. 0.55±0.09, 1.48±0.12 vs. 0.34±0.08, and 0.48±0.08 vs. 0.04±0.03, and the differences were statistically significant ( t=5.60, 14.39, 9.53; all P<0.05). Intraperitoneal injection of integrin αVβ3 receptor inhibitor cilengitide effectively antagonized the protective effects of MFG-E8 on intestinal injury in AP mice. Compared with MFG-E8 group, the histopathological score, MPO quantification and DHE fluorescence density of cilengitide group (3.53±0.50, (27.67±6.02)/field, and (31.33±3.86)/field, respectively) all increased, the expression of ATP, MDA and SOD were inhibited ((77.41±8.51) μmol/g, (0.19±0.04) mol/g, (100.46±8.15) U/mg); and GSH-Px4, xCT and FSP-1 all decreased, with the relative expression levels of 0.59±0.11, 0.16±0.06, and 0.10±0.03, respectively, and the differences were statistically significant ( t=3.02, 3.44, 5.04, 8.70, 4.01, 4.86, 5.05, 17.47, 8.34; all P<0.05). Conclusion:MFG-E8 alleviates intestinal oxidative stress and ferroptosis by integrin αVβ3 receptor, thereby reducing intestinal injury and inflammation in AP mice.
5.Research progress on mechanisms and animal models of comorbid depression and tumors
Yakun REN ; Xinpei WANG ; Xingjiu YANG ; Mengyuan LI ; Ran GAO
Acta Laboratorium Animalis Scientia Sinica 2025;33(9):1393-1402
The comorbidity of depression and cancer represents a significant global public health challenge,severely impacting patients' quality of life and clinical outcomes.This systematic review considers the epidemiological characteristics,clinical implications,and major challenges in current research regarding comorbid depression and cancer,focusing on the role of depression in promoting tumor progression and suppressing immune function via the neuroendocrine-immune regulatory network.We discuss the dynamic changes and interaction mechanisms of depression-related neurotransmitters(such as serotonin and norepinephrine)and stress hormones(such as cortisol)within the tumor microenvironment.We also reveal the molecular mechanisms by which depression regulates malignant biological behaviors such as tumor immune evasion,metastasis,and angiogenesis via activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system.This review also evaluates the application value and limitations of existing animal models for studying the mechanisms underlying the comorbidity of depression and cancer,emphasizing the importance and urgency of developing more precise comorbidity models to uncover the mechanisms and explore management strategies.This review aims to raise awareness of risk prediction,clinical interventions,and basic research on the comorbidity of depression and cancer,to provide a theoretical foundation and new research directions for developing depression-cancer comorbidity models.
6.Research progress on mechanisms and animal models of comorbid depression and tumors
Yakun REN ; Xinpei WANG ; Xingjiu YANG ; Mengyuan LI ; Ran GAO
Acta Laboratorium Animalis Scientia Sinica 2025;33(9):1393-1402
The comorbidity of depression and cancer represents a significant global public health challenge,severely impacting patients' quality of life and clinical outcomes.This systematic review considers the epidemiological characteristics,clinical implications,and major challenges in current research regarding comorbid depression and cancer,focusing on the role of depression in promoting tumor progression and suppressing immune function via the neuroendocrine-immune regulatory network.We discuss the dynamic changes and interaction mechanisms of depression-related neurotransmitters(such as serotonin and norepinephrine)and stress hormones(such as cortisol)within the tumor microenvironment.We also reveal the molecular mechanisms by which depression regulates malignant biological behaviors such as tumor immune evasion,metastasis,and angiogenesis via activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system.This review also evaluates the application value and limitations of existing animal models for studying the mechanisms underlying the comorbidity of depression and cancer,emphasizing the importance and urgency of developing more precise comorbidity models to uncover the mechanisms and explore management strategies.This review aims to raise awareness of risk prediction,clinical interventions,and basic research on the comorbidity of depression and cancer,to provide a theoretical foundation and new research directions for developing depression-cancer comorbidity models.
7.Influencing factors for atrial fibrillation in elderly patients with heart failure and construction of a nomogram model
Yakun SU ; Tingting LIN ; Qiong WANG ; Fengde LI ; Junying SONG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(8):1010-1015
Objective To elucidate the independent risk factors for AF in elderly patients with HF,develop a nomogram prediction model,and assess its predictive value for AF in elderly HF pa-tients.Methods A retrospective study was conducted on 299 patients of first HF hospitalization in Hengshui People's Hospital from June 2019 to December 2023,and based on the presence or absence of AF,they were divided into an AF group(133 cases)and a non-AF group(166 cases).The patients admitted from June 2019 to December 2022 were assigned into a modeling cohort(206 cases),while those from January 2023 to December 2023 into a validation cohort(93 cases).The general data were collected.Multivariate logistic regression analysis was performed on the modeling cohort to identify the independent predictors of AF in elderly HF patients,and a nomo-gram prediction model was constructed.ROC curve,calibration curve and clinical decision curve analyses were applied to evaluate the discrimination,calibration and clinical practicability of the prediction model.Results Multivariate logistic regression analysis revealed that the etiology of HF(CHD vs HP,OR=0.610,95%CI:0.301-1.250,P=0.178;CMD vs HP,OR=0.213,95%CI:0.052-0.883,P=0.033),LAD(OR=1.081,95%CI:1.020-1.152,P=0.015),HF classifi-cation(HFmrEF vs HFrEF,OR=5.897,95%CI:2.448-14.201,P=0.000;HFpEF vs HFrEF,OR=7.211,95%CI:2.522-20.640,P=0.001),pre-albumin(PALB)(OR=0.438,95%CI:0.217-0.901,P=0.030),UAC(OR=2.186,95%CI:1.075-4.430,P=0.025),and direct biliru-bin(DBi)(OR=4.531,95%CI:2.052-9.990,P=0.000)were independent risk factors for AF in the elderly HF patients.ROC curve analysis showed the AUC value of the prediction model based on these factors in the modeling cohort was 0.831,and the AUC value in the validation cohort was 0.840.Decision curve analysis indicated that the model possessed clinical practicability within a probability threshold range of 10%-82%for the modeling cohort and 12%-100%for the vali-dation cohort.Conclusion Our nomogram prediction model based on multivariate logistic regres-sion analysis exhibits good predictive value for the occurrence of AF in elderly HF patients,and can facilitate clinical decision-making on diagnosis and treatment.
8.Milk fat globule-epidermal growth factor 8 alleviates intestinal inflammation and ferroptosis in mice with acute pancreatitis through integrin αVβ3 receptor
Bingli LIU ; Yakun SHI ; Hua LI ; Yiming LI
Chinese Journal of Digestion 2025;45(8):548-554
Objective:To investigate the protective effects and mechanism of exogenous milk fat globule-epidermal growth factor 8(MFG-E8) on intestinal injury and ferroptosis in mice with acute pancreatitis (AP) and its mechanism.Methods:A total of 24 male C57 BL/6 mice were randomly divided into the normal control group, AP group, AP+ MFG-E8 group (MFG-E8 group), and AP+ MFG-E8+ cilengitide group (cilengitide group), with 6 mice in each group according to the random number table. The mice of normal control group were intraperitoneally injected with 0.9% sodium chloride solution. In the AP group, MFG-E8 group, and cilengitide group, the mice were intraperitoneally injected with 8% L-arginine twice at 1-hour intervals to induce the AP model. In the MFG-E8 group, mice were intraperitoneally injected with 20 g/kg of MFG-E8 at 2 hours after L-arginine injection. In the cilengitide group, mice were intraperitoneally injected with 20 mg/kg of cilengitide at 1 hour after the L-arginine injection, and 20 g/kg of MFG-E8 1 hour later. The mice were sacrificed and blood samples and intestinal tissues were collected at 72 hours after the first L-arginine injection. Hematoxylin-eosin staining was used to evaluate intestinal tissue injury. Myeloperoxidase (MPO) immunofluorescence staining was performed to detect neutrophils in intestinal tissues.Adenosinetriphosphate (ATP) levels were examined to detect changes in mitochondrial function. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were tested to check the level of intestinal oxidative stress. Dihydroethidium (DHE) fluorescent probe was used to label the oxygen free radicals in intestinal tissues. The expression of glutathione peroxidase 4 (GSH-Px4), solute carrier family 7 member 11 (also named xCT), and ferroptosos suppressor protein-1 (FSP-1) in intestinal tissues were detected by western blotting. Indepent-samples t-test, one-way ANOVA, and Student-Newman-Keuls test were performed for statistical analysis. Results:Intestinal tissue injury and inflammatory cell infiltration in mice were induced by intraperitoneal injection of L-arginine. Compared with those of AP model group, the intestinal pathology score, MPO fluorescence quantification and DHE fluorescence density of MFG-E8 group were significantly decreased (3.93±0.57 vs. 1.73±0.74, (26.33±4.49)/field vs. (11.00±3.27)/field, (39.67±5.79)/field vs. (12.33±3.68)/field), while the contents of ATP, MDA and SOD were increased ((77.09±8.52) μmol/g vs. (119.87±6.83) μmol/g, (0.10±0.01) μmol/g vs. (0.17±0.02) μmol/g, (105.67±6.93) U/mg vs. (144.49±18.55) U/mg), and the differences were statistically significant ( t=3.33, 3.93, 5.63, 8.77, 6.54, 4.38; all P<0.05). The results of Western blotting showed that GSH-Px4, xCT, and FSP-1 in the intestinal tissue of AP mice in the MFG-E8 group were all elevated compared with those of AP group, the relative expression levels were 1.22±0.19 vs. 0.55±0.09, 1.48±0.12 vs. 0.34±0.08, and 0.48±0.08 vs. 0.04±0.03, and the differences were statistically significant ( t=5.60, 14.39, 9.53; all P<0.05). Intraperitoneal injection of integrin αVβ3 receptor inhibitor cilengitide effectively antagonized the protective effects of MFG-E8 on intestinal injury in AP mice. Compared with MFG-E8 group, the histopathological score, MPO quantification and DHE fluorescence density of cilengitide group (3.53±0.50, (27.67±6.02)/field, and (31.33±3.86)/field, respectively) all increased, the expression of ATP, MDA and SOD were inhibited ((77.41±8.51) μmol/g, (0.19±0.04) mol/g, (100.46±8.15) U/mg); and GSH-Px4, xCT and FSP-1 all decreased, with the relative expression levels of 0.59±0.11, 0.16±0.06, and 0.10±0.03, respectively, and the differences were statistically significant ( t=3.02, 3.44, 5.04, 8.70, 4.01, 4.86, 5.05, 17.47, 8.34; all P<0.05). Conclusion:MFG-E8 alleviates intestinal oxidative stress and ferroptosis by integrin αVβ3 receptor, thereby reducing intestinal injury and inflammation in AP mice.
9. Progress and prospect of inhaled biological agents in asthma
Guanghui LI ; Jing HUANG ; Min ZHU ; Yakun WAN ; Zhihong CHEN ; Rui ZHAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(4):406-414
More than 300 million people worldwide suffer from asthma, and the incidence is increasing year by year. As one of the most common chronic diseases, asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity. With the in-depth study of physiological and pathological mechanisms, therapeutic small molecule and hormone drugs have been introduced to control and treat most patients, but about 5% - 10% of patients still suffer from various subtypes of difficult to control and treat asthma, that is, severe asthma. In the past decade, with the rapid development of bio-pharmaceutical research, protein and antibody have become the key drugs for the treatment of severe asthma with high efficacy, high specificity and high safety. However, biological drugs are usually administered by injection, they cannot be noninvasive and directly delivered into the lung to quickly absorb and take effect. Therefore, there is an urgent need for the introduction of inhaled biologics with quick effectiveness, convenience, economy and safety in clinical. The review summarizes the existing small molecule, hormone and biological therapy drugs, and summarizes the development of inhalable biological agents of asthma, and analyzes the future prospects of the inhalable biological drugs, which is designed to deepen the perception of the direction of the inhalable biological drugs research, and update the information of the field, in order to provide reference for the development of more inhalable biologics.
10.Effect and mechanism of Panax notoginseng saponins on wound healing after anal fistula surgery in rats
Xinmin WANG ; Yakun LIU ; Gang LI ; Juan LIU ; Huizhi XU ; Jingjie ZHANG ; Minlu LI ; Jingya NIU ; Binggui ZHANG
China Pharmacy 2024;35(6):695-700
OBJECTIVE To investigate the effect and mechanism of Panax notoginseng saponins (PNS) on wound healing after anal fistula surgery in rats by regulating the hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/ vascular endothelial growth factor receptor-2 (VEGFR2) signaling pathway. METHODS SD rats were selected to establish a postoperative rat model of anal fistula by infecting wound with Escherichia coli. The model rats were randomly grouped into model group, PNS low-dose and high-dose groups (15, 30 mg/cm2), high-dose of PNS+2-methoxyestradiol (2ME2) group (PNS 30 mg/cm2+HIF-1α inhibitor 2ME2 4 mg/kg), with 10 rats in each group. Another 10 normal rats were selected for back hair removal treatment as the control group. Each drug group was injected with the corresponding drug solution intramuscularly or (and) intraperitoneally, once a day, for 3 weeks. After the last administration, the wound healing rate (excluding the control group), microvascular density (MVD), the expression of collagen Ⅰ and fibronectin (FN) in the wound tissue were detected in each group; the levels of angiogenic factors [VEGF, E-mail:842710813@qq.com angiopoietin-Ⅰ (Ang-Ⅰ), Ang-Ⅱ] in serum, the levels of inflammatory factors [interleukin-6 (IL-6) and IL-2] in serum binggui7183@163.com and wound tissue as well as the expressions of the related proteins of HIF-1α/VEGF/VEGFR2 signaling pathway in the wound tissue of rats were also detected in each group. RESULTS The MVD, the expression of collagen Ⅰ and FN in the wound tissue, and the levels of IL-6 and IL-2 in serum and wound tissue of rats increased significantly in the model group, compared to the control group (P<0.05), while the serum levels of VEGF, Ang- Ⅰ and Ang-Ⅱ decreased significantly (P<0.05). The wound healing rate, the MVD in wound tissue, the serum levels of VEGF, Ang-Ⅰ and Ang-Ⅱ, the expressions of collagen Ⅰ and FN in the wound tissue, and protein expressions of HIF-1α, VEGF and VEGFR2 in the PNS low-dose and high-dose groups increased significantly, compared to the model group (P<0.05), while the levels of IL-6 and IL-2 in serum and wound tissue decreased significantly (P<0.05); the high-dose PNS had a stronger effect (P< 0.05). 2ME2 could weaken the effect of PNS on above indicators of rats after anal fistula surgery (P<0.05). CONCLUSIONS PNS can promote the production of angiogenic factors and inhibit the production of pro-inflammatory factors, thereby promoting wound healing in rats after anal fistula surgery. The above effects are related to the activation of HIF-1α/VEGF/VEGFR2 signaling pathway.


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