1.Establishment of reference values for clot waveform analysis parameters and their clinical application in differentiating acquired hemophilia A from lupus anticoagulant positive conditions
Bin YAN ; Mengchao CUI ; Yuanyuan WEN ; Di WU ; Luyi RU ; Huixin ZOU ; Tianxi HU ; Ruijuan WANG ; Suping ZHAI ; Weipeng DU
Chinese Journal of Laboratory Medicine 2025;48(3):371-377
Objective:To establish reference values for clot waveform analysis (CWA) and analyze their diagnostic efficacy in distinguishing acquired hemophilia A (AHA) and lupus anticoagulant (LA)-positive patients.Methods:Case-Control Study. A total of 391 healthy individuals(260 males and 131 females) with a mean age of 45.53±14.85 years were enrolled at Nanyang central Hospital between January 6, 2023 and October 10, 2024. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were measured to establish reference ranges for the CWA parameters, including maximal reaction velocity (Min1), maximal reaction acceleration (Min2), and maximal reaction deceleration (Max2). A total of 158 definitively diagnosed AHA and LA-positive patients (mean age:42.46±14.83 years), including 34 AHA patients and 124 LA-positive patients, were recruited. The Mann Whitney U test was used to analyze the differences in the CWA parameters between the two groups. The diagnostic efficacy of CWA parameters in distinguishing AHA and LA-positive patients was evaluated using the area under the receiver operating characteristic(ROC) curve AUC and the cut-off values were calculated. Results:The reference values for PT-Min1, APTT-Min1, APTT-Min2, APTT-Max2, TT-Min1, TT-Min2, TT-Max2 were 203.41-516.89, 144.63-324.03, 526.46-1 190.03, -404.96±157.22, 159.17±60.34, 272.29-686.99, and -289.47--113.76, respectively. Compared with the CWA parameters in AHA patients, APTT-Max2 was significantly lower in LA-positive patients [-422.74(-577.50, -239.22) vs. -68.87(-92.85,30.28), Z=-7.43, P<0.01], while PT-Min1, APTT-Min1, APTT-Min2, TT-Min1, TT-Min2 were significantly elevated [287.01(188.03, 382.50) vs. 107.45(90.20, 151.39), 972.88(601.20, 1 351.19) vs. 229.10(118.38, 371.67), Z=6.68, 6.69, all P<0.01]. ROC analysis demonstrated the APTT-CWA parameter exhibited high diagnostic efficacy in patients with AHA (AUC>0.900 for both).Additionally, APTT-Min1 and APTT-Max2 were found to be useful in distinguishing between AHA patients and those with LA-positive status accompanied by APTT prolongation (AUC=0.660, 0.700, respectively). Conclusions:Reference values for CWA parameters were successfully established. The APTT-CWA is useful for differentiating between AHA and LA-positive patients and APTT-Max2 demonstrated a good diagnostic value in differentiating AHA patients from those with LA-positive status accompanied by APTT prolongation.
2.Identification and pedigree study of a case with McLeod phenotype caused by XK gene c. 107G>A mutation
Yan ZHANG ; Yunxiang WU ; Fei WANG ; Aijing LI ; Hua WANG ; Minghao LI ; Demei ZHANG ; Luyi YE
Chinese Journal of Blood Transfusion 2025;38(9):1253-1258
Objective: To identify the phenotypes, antibodies and explore the molecular mechanisms of a patient who carries antibodies to RBC high-frequency antigens and his family members. Methods: The antibody identification test was performed for the proband by serological methods, and targeted NGS was subsequently used to detect mutations that occurred in blood group genes. Blood samples were collected from the proband and his family members. Sanger sequencing was used to verify the mutation of the XK gene. The expression of Kell blood group antigens was detected by serological methods and flow cytometry. K
cells were used to detect the antibody specificity of the proband. The morphology of red blood cells was detected by the scanning electron microscopy. The serum creatine kinase levels of the proband and his family members were analyzed by colorimetric methods. Results: The results of the antibody identification test suggested that the proband might have antibodies to high-frequency antigens. NGS results suggested a homozygous mutation (c. 107G>A) in exon 1 of the XK gene in the proband, resulting in a truncated XK protein. The Sanger sequencing results of the proband were consistent with the NGS results, and the mutation was not found in other family members. The expression of Kell blood group antigens of the proband was not found by serological methods and flow cytometry. The results of the antibody specificity test showed that the proband had anti-Km antibodies. Spike-like changes were identified on red blood cells, and serum creatine kinase level was elevated in the proband. Conclusion: In this study, the McLeod phenotype caused by homozygous mutation (c. 107G>A) of XK gene was identified in Chinese individuals for the first time by the phenotype and molecular mechanism studies. The results of genotyping and phenotyping suggested that the McLeod phenotype caused by the mutation was compatible with the phenotypes of McLeod and K
.
3.Mechanism of action of the nuclear factor-kappa B signaling pathway in liver diseases and its potential as a therapeutic target
Wenqian FENG ; Yang DU ; Dewen MAO ; Weiyu CHEN ; Lei FU ; Luyi YAN ; Chun YAO ; Yanmei LAN
Journal of Clinical Hepatology 2025;41(9):1949-1955
Nuclear factor-kappa B (NF-κB) is an important intracellular transcription factor widely involved in the processes such as immune response, inflammatory response, cell proliferation, and apoptosis. The abnormal activation of the NF-κB signaling pathway plays a pivotal role in various liver diseases including chronic hepatitis, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. Extensive studies have shown that inhibiting NF-κB activity may effectively reduce inflammation and fibrosis and improve metabolic disorders. Several natural compounds, such as matrine and salvianolic acid B, have shown the potential in suppressing NF-κB activity, thereby exerting anti-inflammatory, anti-fibrotic, and anti-tumor effects. This article systematically reviews the critical role of the NF-κB signaling pathway in liver diseases and its potential as a therapeutic target, in order to highlight its potential as a therapeutic target for liver diseases and provide new directions for the treatment of liver diseases.
4.Role of neutrophil extracellular traps in hepatocellular carcinoma
Xueru TIAN ; Weiyu CHEN ; Luyi YAN ; Yang HONG ; Han WANG ; Shouqin LIU ; Lei QING ; Guojuan MA ; Dewen MAO ; Chun YAO
Journal of Clinical Hepatology 2025;41(11):2410-2417
Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence and mortality rates worldwide. Recent studies have shown that neutrophil extracellular traps (NETs) play an important role in the development, progression, and immune escape of HCC. NETs are released by neutrophils and mainly consist of DNA, histones, and antimicrobial molecules, and in addition to immune defense, they are also involved in the initiation, metastasis, and thrombosis of HCC. This article elaborates on the formation and regulatory mechanisms of NETs, explores their potential mechanisms in the initiation, metastasis, immune escape, and thrombosis of HCC, and discusses the prospect of NETs as a target for the diagnosis and treatment of HCC, in order to provide new ideas for the precise treatment of HCC in the future and promote the early diagnosis and effective treatment of HCC.
5.Explore the Rules of Acupoint Selection in the Treatment of Chemotherapy-Induced Nausea and Vomiting Based on Data Mining
Luyi HUANG ; Xinrui HUANG ; Yan XU
Journal of Zhejiang Chinese Medical University 2025;49(7):903-910
[Objective]To explore the common auricular points and the rules of auricular point selection in the treatment of chemotherapy-induced nausea and vomiting by data mining technology,so as to provide reference for clinical treatment date of chemotherapy-induced nausea and vomiting in patients with malignant tumors.[Methods]China National Knowledge Infrastructure(CNKI),Wanfang Database,China Science and Technology Journal Database(VIP),China Biomedical Literature Database(CBM),PubMed,Web of Science,the Cochrane Library database were searched by computer.The search time limit was from the establishment date of the database to August 25,2024.The frequency statistics,association rule analysis and cluster analysis of auricular points in the literature were carried out to describe the compatibility association rules between auricular points.[Results]A total of 92 articles were included,involving 29 auricular points,with a total frequency of 497 times.The most commonly used auricular points were stomach point,Shenmen point,sympathetic point,spleen point,etc.In addition,the commonly used auricular points for chemotherapy-induced nausea and vomiting in breast cancer patients include liver point,subcortical point and endocrine point;the commonly used auricular points for chemotherapy-induced nausea and vomiting in lung cancer patients include subcortical point,lung point and large intestine point;the commonly used auricular points for chemotherapy-induced nausea and vomiting in colorectal cancer and gastric cancer patients included small intestine point,large intestine point and duodenal point.Association rule analysis showed that the combination with the highest support for auricular point sticking in the treatment of chemotherapy-induced nausea and vomiting was Shenmen point-sympathetic point.Cluster analysis classified high-frequency acupoints into four categories.[Conclusion]Auricular points application is effective in treating chemotherapy induced nausea and vomiting and has been widely used in clinical practice.The acupoint compatibility rules obtained based on data mining technology have certain guiding significance for the precise intervention of chemotherapy-induced nausea and vomiting,which can provide reference for acupoint selection.
6.Association between bile acid/short-chain fatty acid metabolic disorders and hepatic encephalopathy based on the traditional Chinese medicine theory of Yin and Yang
Luyi YAN ; Weiyu CHEN ; Han WANG ; Wenqian FENG ; Yang DU ; Xueru TIAN ; Yang HONG ; Dewen MAO ; Lei FU ; Chun YAO
Journal of Clinical Hepatology 2025;41(7):1443-1449
Hepatic encephalopathy is a neuropsychiatric syndrome secondary to severe liver disease.Recent studies have shown that the development of hepatic encephalopathy is closely associated with bile acid/short-chain fatty acid metabolic disorder.As the core theory of traditional Chinese medicine,the theory of Yin and Yang provides a unique perspective for analyzing the association between bile acids/short-chain fatty acids and hepatic encephalopathy.Bile acids function like Yang,governing the free flow of Qi and assisting in metabolic processes,while short-chain fatty acids belong to Yin,maintaining internal stability and conservation,preserving the intestinal barrier,and combating inflammation and toxins.Bile acids and short-chain fatty acids constrain each other and are interdependent to regulate the dynamic equilibrium of the gut-liver-brain axis.On this basis,by regulating the metabolic imbalance of bile acids and short-chain fatty acids,it is expected to restore the dynamic balance of Yin and Yang in patients with hepatic encephalopathy under the synergistic intervention of traditional Chinese medicine and Western medicine.
7.Association between bile acid/short-chain fatty acid metabolic disorders and hepatic encephalopathy based on the traditional Chinese medicine theory of Yin and Yang
Luyi YAN ; Weiyu CHEN ; Han WANG ; Wenqian FENG ; Yang DU ; Xueru TIAN ; Yang HONG ; Dewen MAO ; Lei FU ; Chun YAO
Journal of Clinical Hepatology 2025;41(7):1443-1449
Hepatic encephalopathy is a neuropsychiatric syndrome secondary to severe liver disease.Recent studies have shown that the development of hepatic encephalopathy is closely associated with bile acid/short-chain fatty acid metabolic disorder.As the core theory of traditional Chinese medicine,the theory of Yin and Yang provides a unique perspective for analyzing the association between bile acids/short-chain fatty acids and hepatic encephalopathy.Bile acids function like Yang,governing the free flow of Qi and assisting in metabolic processes,while short-chain fatty acids belong to Yin,maintaining internal stability and conservation,preserving the intestinal barrier,and combating inflammation and toxins.Bile acids and short-chain fatty acids constrain each other and are interdependent to regulate the dynamic equilibrium of the gut-liver-brain axis.On this basis,by regulating the metabolic imbalance of bile acids and short-chain fatty acids,it is expected to restore the dynamic balance of Yin and Yang in patients with hepatic encephalopathy under the synergistic intervention of traditional Chinese medicine and Western medicine.
8.Explore the Rules of Acupoint Selection in the Treatment of Chemotherapy-Induced Nausea and Vomiting Based on Data Mining
Luyi HUANG ; Xinrui HUANG ; Yan XU
Journal of Zhejiang Chinese Medical University 2025;49(7):903-910
[Objective]To explore the common auricular points and the rules of auricular point selection in the treatment of chemotherapy-induced nausea and vomiting by data mining technology,so as to provide reference for clinical treatment date of chemotherapy-induced nausea and vomiting in patients with malignant tumors.[Methods]China National Knowledge Infrastructure(CNKI),Wanfang Database,China Science and Technology Journal Database(VIP),China Biomedical Literature Database(CBM),PubMed,Web of Science,the Cochrane Library database were searched by computer.The search time limit was from the establishment date of the database to August 25,2024.The frequency statistics,association rule analysis and cluster analysis of auricular points in the literature were carried out to describe the compatibility association rules between auricular points.[Results]A total of 92 articles were included,involving 29 auricular points,with a total frequency of 497 times.The most commonly used auricular points were stomach point,Shenmen point,sympathetic point,spleen point,etc.In addition,the commonly used auricular points for chemotherapy-induced nausea and vomiting in breast cancer patients include liver point,subcortical point and endocrine point;the commonly used auricular points for chemotherapy-induced nausea and vomiting in lung cancer patients include subcortical point,lung point and large intestine point;the commonly used auricular points for chemotherapy-induced nausea and vomiting in colorectal cancer and gastric cancer patients included small intestine point,large intestine point and duodenal point.Association rule analysis showed that the combination with the highest support for auricular point sticking in the treatment of chemotherapy-induced nausea and vomiting was Shenmen point-sympathetic point.Cluster analysis classified high-frequency acupoints into four categories.[Conclusion]Auricular points application is effective in treating chemotherapy induced nausea and vomiting and has been widely used in clinical practice.The acupoint compatibility rules obtained based on data mining technology have certain guiding significance for the precise intervention of chemotherapy-induced nausea and vomiting,which can provide reference for acupoint selection.
9.Establishment of reference values for clot waveform analysis parameters and their clinical application in differentiating acquired hemophilia A from lupus anticoagulant positive conditions
Bin YAN ; Mengchao CUI ; Yuanyuan WEN ; Di WU ; Luyi RU ; Huixin ZOU ; Tianxi HU ; Ruijuan WANG ; Suping ZHAI ; Weipeng DU
Chinese Journal of Laboratory Medicine 2025;48(3):371-377
Objective:To establish reference values for clot waveform analysis (CWA) and analyze their diagnostic efficacy in distinguishing acquired hemophilia A (AHA) and lupus anticoagulant (LA)-positive patients.Methods:Case-Control Study. A total of 391 healthy individuals(260 males and 131 females) with a mean age of 45.53±14.85 years were enrolled at Nanyang central Hospital between January 6, 2023 and October 10, 2024. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were measured to establish reference ranges for the CWA parameters, including maximal reaction velocity (Min1), maximal reaction acceleration (Min2), and maximal reaction deceleration (Max2). A total of 158 definitively diagnosed AHA and LA-positive patients (mean age:42.46±14.83 years), including 34 AHA patients and 124 LA-positive patients, were recruited. The Mann Whitney U test was used to analyze the differences in the CWA parameters between the two groups. The diagnostic efficacy of CWA parameters in distinguishing AHA and LA-positive patients was evaluated using the area under the receiver operating characteristic(ROC) curve AUC and the cut-off values were calculated. Results:The reference values for PT-Min1, APTT-Min1, APTT-Min2, APTT-Max2, TT-Min1, TT-Min2, TT-Max2 were 203.41-516.89, 144.63-324.03, 526.46-1 190.03, -404.96±157.22, 159.17±60.34, 272.29-686.99, and -289.47--113.76, respectively. Compared with the CWA parameters in AHA patients, APTT-Max2 was significantly lower in LA-positive patients [-422.74(-577.50, -239.22) vs. -68.87(-92.85,30.28), Z=-7.43, P<0.01], while PT-Min1, APTT-Min1, APTT-Min2, TT-Min1, TT-Min2 were significantly elevated [287.01(188.03, 382.50) vs. 107.45(90.20, 151.39), 972.88(601.20, 1 351.19) vs. 229.10(118.38, 371.67), Z=6.68, 6.69, all P<0.01]. ROC analysis demonstrated the APTT-CWA parameter exhibited high diagnostic efficacy in patients with AHA (AUC>0.900 for both).Additionally, APTT-Min1 and APTT-Max2 were found to be useful in distinguishing between AHA patients and those with LA-positive status accompanied by APTT prolongation (AUC=0.660, 0.700, respectively). Conclusions:Reference values for CWA parameters were successfully established. The APTT-CWA is useful for differentiating between AHA and LA-positive patients and APTT-Max2 demonstrated a good diagnostic value in differentiating AHA patients from those with LA-positive status accompanied by APTT prolongation.
10.Study of the mechanism of acupuncture and moxibustion in protecting the intestinal mucosal barrier in DSS-induced UC rats based on the IL-9/IL-9R pathway
Yan HUANG ; Kexin SUN ; Jing XU ; Zhe MA ; Jimeng ZHAO ; Lingjie LI ; Chen ZHAO ; Ling YANG ; Feng LI ; Yanan LIU ; Yue ZHANG ; Luyi WU ; Rude HUANG
Journal of Acupuncture and Tuina Science 2024;22(2):91-103
Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.

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