1.Circulating inflammatory proteins and myocardial hypertrophy:large sample analysis of European populations from GWAS Catalog and FinnGen databases
Yu DING ; Jingwen CHEN ; Xiuyan CHEN ; Huimin SHI ; Yudie YANG ; Meiqi ZHOU ; Shuai CUI
Chinese Journal of Tissue Engineering Research 2026;30(4):1047-1057
BACKGROUND:Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect.Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases,yet the specific mechanisms linking them to myocardial hypertrophy remain unclear.OBJECTIVE:To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.METHODS:Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database,we employed bidirectional two-sample Mendelian randomization,multivariate Mendelian randomization,and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy.The accuracy of the results was verified through sensitivity tests including MR-PRESSO,Cochran's Q test,MR-Egger intercept assessment,leave-one-out analysis,and funnel plot analysis.RESULTS AND CONCLUSION:In the results of two-sample Mendelian randomization,the primary method used for evaluation was the Inverse Variance Weighting(IVW)approach.It was found that the level of T-cell surface glycoprotein CD6 isoform(IVW:P=0.046,OR=0.74,95%Cl:0.66-1.00),level of slit chemokine(IVW:P=2.1×10-2,OR=0.74,95%CI:0.556-0.95),level of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-4,OR=0.66,95%CI:0.49-0.87),level of interleukin-2(IVW:P=3.8×103,OR=0.667,95%CI:0.50-0.88),and sulfotransferase 1A1(IVW:P=1.42×102,OR=0.80,95%CI:0.67-0.96)had a unidirectional causal effect on cardiac hypertrophy.(2)Among the findings in multivariate Mendelian randomization,the levels of the CD6 isoform of T-cell surface glycoprotein(IVW:P=1.39×102,OR=0.81,95%CI:0.69-0.96)and the levels of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-2,OR=0.73,95%CI:0.55-0.98)were positive,indicating that the results remained significant after excluding the effects of other circulating inflammatory proteins that had an impact on myocardial hypertrophy.(3)In colocalization,T-cell surface glycoprotein CD6 isoform levels had H3+H4=0.96,with the most significant single nucleotide polymorphism being rs59570070,suggesting an intrinsic link between T-cell surface glycoprotein CD6 isoform levels and myocardial hypertrophy.(4)Sensitivity results showed no abnormalities,indicating no heterogeneity or pleiotropic effects influencing the results.(5)These results verified that T cell surface glycoprotein CD6 isoforms,Slit chemokine,Delta and Notch-like epidermal growth factor-related receptors,interleukin-2,and sulfotransferase 1A1 had a unidirectional causal effect on myocardial hypertrophy.T cell surface glycoprotein CD6 isoforms and Delta and Notch-like epidermal growth factor-related receptors had the deepest impact,suggesting that there may be related pathways between T cell surface glycoprotein CD6 isoforms and myocardial hypertrophy.Mendelian randomization studies require large amounts of clinical data and therefore often use European samples from international databases for analysis.Since this analytical method has significant advantages in causal inference,precision medicine,and cross-population validation,its research results still hold great significance for the medical development in China.As Mendelian randomization research deepens,it also promotes the collection and analysis of clinical data in China to some extent.In the future,we can further analyze key protein mechanisms,combine multiomics and clinical validation,develop an inflammatory marker monitoring system and novel anti-inflammatory therapies,thereby promoting the prevention and control of cardiovascular diseases and the development of personalized medicine.
2.Circulating inflammatory proteins and myocardial hypertrophy:large sample analysis of European populations from GWAS Catalog and FinnGen databases
Yu DING ; Jingwen CHEN ; Xiuyan CHEN ; Huimin SHI ; Yudie YANG ; Meiqi ZHOU ; Shuai CUI
Chinese Journal of Tissue Engineering Research 2026;30(4):1047-1057
BACKGROUND:Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect.Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases,yet the specific mechanisms linking them to myocardial hypertrophy remain unclear.OBJECTIVE:To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.METHODS:Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database,we employed bidirectional two-sample Mendelian randomization,multivariate Mendelian randomization,and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy.The accuracy of the results was verified through sensitivity tests including MR-PRESSO,Cochran's Q test,MR-Egger intercept assessment,leave-one-out analysis,and funnel plot analysis.RESULTS AND CONCLUSION:In the results of two-sample Mendelian randomization,the primary method used for evaluation was the Inverse Variance Weighting(IVW)approach.It was found that the level of T-cell surface glycoprotein CD6 isoform(IVW:P=0.046,OR=0.74,95%Cl:0.66-1.00),level of slit chemokine(IVW:P=2.1×10-2,OR=0.74,95%CI:0.556-0.95),level of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-4,OR=0.66,95%CI:0.49-0.87),level of interleukin-2(IVW:P=3.8×103,OR=0.667,95%CI:0.50-0.88),and sulfotransferase 1A1(IVW:P=1.42×102,OR=0.80,95%CI:0.67-0.96)had a unidirectional causal effect on cardiac hypertrophy.(2)Among the findings in multivariate Mendelian randomization,the levels of the CD6 isoform of T-cell surface glycoprotein(IVW:P=1.39×102,OR=0.81,95%CI:0.69-0.96)and the levels of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-2,OR=0.73,95%CI:0.55-0.98)were positive,indicating that the results remained significant after excluding the effects of other circulating inflammatory proteins that had an impact on myocardial hypertrophy.(3)In colocalization,T-cell surface glycoprotein CD6 isoform levels had H3+H4=0.96,with the most significant single nucleotide polymorphism being rs59570070,suggesting an intrinsic link between T-cell surface glycoprotein CD6 isoform levels and myocardial hypertrophy.(4)Sensitivity results showed no abnormalities,indicating no heterogeneity or pleiotropic effects influencing the results.(5)These results verified that T cell surface glycoprotein CD6 isoforms,Slit chemokine,Delta and Notch-like epidermal growth factor-related receptors,interleukin-2,and sulfotransferase 1A1 had a unidirectional causal effect on myocardial hypertrophy.T cell surface glycoprotein CD6 isoforms and Delta and Notch-like epidermal growth factor-related receptors had the deepest impact,suggesting that there may be related pathways between T cell surface glycoprotein CD6 isoforms and myocardial hypertrophy.Mendelian randomization studies require large amounts of clinical data and therefore often use European samples from international databases for analysis.Since this analytical method has significant advantages in causal inference,precision medicine,and cross-population validation,its research results still hold great significance for the medical development in China.As Mendelian randomization research deepens,it also promotes the collection and analysis of clinical data in China to some extent.In the future,we can further analyze key protein mechanisms,combine multiomics and clinical validation,develop an inflammatory marker monitoring system and novel anti-inflammatory therapies,thereby promoting the prevention and control of cardiovascular diseases and the development of personalized medicine.
3.Clinical observation of Zhengxintai granules in the treatment of microvascular angina for acute ST-segment elevation myocardial infarction patients with qi deficiency and blood stasis syndrome after PCI
Wenhui MA ; Ying ZHANG ; Lei LIU ; Xiuyan YU ; Yali CHEN ; Liming CHEN
China Pharmacy 2026;37(15):2023-2029
OBJECTIVE To investigate the clinical efficacy and safety of Zhengxintai granules as in the treatment of microvascular angina (MVA) following percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) and qi deficiency and blood stasis syndrome. METHODS Patients with STEMI and qi deficiency and blood stasis syndrome who underwent PCI and developed MVA and were admitted to the Jinan Fourth People’s Hospital (Jinan Cardiovascular Hospital) from March 2022 to March 2025 were selected, they were randomly divided into the control group and the observation group according to a random number table, with 76 cases in each group. Patients in the control group received conventional Western medicine treatment combined with a placebo, while patients in the observation group received Zhengxintai granules (5 mg per dose, three times daily, for 8 weeks) in addition to conventional Western medicine treatment. The clinical efficacy [including the total effective rate of traditional Chinese medicine (TCM) syndrome improvement and the total effective rates of Western clinical efficacy] was compared between the two groups. The following indicators were detected before and after treatment: TCM syndrome scores, angina pectoris episodes [daily attack frequency, duration per attack, Visual Analogue Scale (VAS) score], cardiac function indicators [lactate dehydrogenase (LDH), N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular ejection fraction (LVEF), cardiac output (CO), fractional shortening (FS)], coagulation function indicators [thrombin time (TT), prothrombin time (PT), fibrinogen (FIB)], fibrinolytic marker (D-dimer), vascular endothelial function indicators [vascular endothelial growth factor (VEGF), nitric oxide (NO), endothelin-1 (ET-1)] and myocardial microcirculation hemodynamic indicators [end-diastolic velocity (EDV), peak systolic velocity (PSV), resistance index (RI), pulsatility index (PI)]. The quality of life [Seattle Angina Questionnaire (SAQ) score] and the incidence of adverse reactions were also compared between the two groups. RESULTS There was no patient dropout during the entire course of the study. The total effective rates of improvement in TCM syndromes and the total effective rates of Western clinical efficacy in the observation group were significantly higher than those in the control group (93.42% vs. 82.89%, 94.74% vs. 84.21%, P<0.05). Before the treatment, the comparison of each examination indicator between the two groups showed no statistically significant differences (P>0.05). Compared with before treatment, the TCM syndrome scores, the number of daily angina pectoris attacks and the duration of each attack, the VAS scores, LDH, NT-proBNP, FIB, D-dimer, ET-1 levels, LVEDD, LVESD, RI and PI after treatment in both groups were significantly reduced, shortened or decreased (P<0.05); VEGF and NO levels, LVEF, CO, FS, TT, PT, EDV, PSV, and the standard scores of five dimensions including angina pectoris stability, as well as the total scores of SAQ, all significantly increased or prolonged (P<0.05). Furthermore, the improvements in the aforementioned indicators (except for LVEF) in the observation group were significantly greater than those in the control group (P<0.05). There was no statistically significant difference in the total incidence of adverse reactions between the two groups (P>0.05). CONCLUSIONS Zhengxintai granules, when used as an adjunct to conventional Western medicine, can significantly alleviate the related symptoms of MVA in STEMI patients with qi deficiency and blood stasis syndrome after PCI, repair damaged cardiac function, restore the balance of the coagulation-fibrinolysis system, improve vascular endothelial function and myocardial microcirculation perfusion, and significantly enhance the quality of life of patients
4.Detection of ST2,CA125,and HE4 levels in serum of ovarian cancer patients and their clinical significances
Chunying TIAN ; Ting LI ; Yuanyuan CHEN ; Wenyan LIU ; Ruiyao LI ; Xiuyan YU
Journal of Jilin University(Medicine Edition) 2025;51(3):778-784
Objective:To discuss the diagnostic value of levels of growth stimulation expressed gene 2 protein(ST2),carbohydrate antigen 125(CA125),and human epididymis protein 4(HE4)in serum of the ovarian cancer patients,and to clarify their relationships with clinicopathological parameters of the ovarian cancer patients.Methods:A total of 136 patients with ovarian benign lesions or primary ovarian malignancies in our hospital confirmed by postoperative histopathology were randomly selected,including 53 cases in ovarian benign ovarian disease group and 83 cases in ovarian cancer group.Additionally,55 healthy female volunteers during the same period were enrolled as healthy control group.The fasting venous blood from all the subjects was collected on the first day of admission,and serum was retained;cyclic enhanced fluorescence immunoassay was used to detect ST2 levels of the subjects in various groups;chemiluminescence method was used to detect serum CA125 and HE4 levels of the subjects in various groups;receiver operating characteristic(ROC)curve was used to assess the diagnostic performance of each indicator;the Cut-off value and area under the ROC curve(AUC)were calculated,with AUC representing the diagnostic performance;Kendall's method was used to analyze the correlations between serum ST2 levels and TNM stage,maximum tumor diameter,distant metastasis,lymphnode metastasis,peritoneal metastasis,carcinoembryonic antigen(CEA),CA125,carbohydrate antigen 199(CA199),HE4,P53,and Kiel-67(Ki67)in the ovarian cancer patients.Results:Compared with healthy control group,the serum CA125 level of the patients in ovarian benign ovarian disease group was significantly increased(P<0.05).Compared with healthy control group and ovarian benign group,the serum levels of ST2,CA125,and HE4 of the patients in ovarian cancer group were significantly increased(P<0.05).The AUC values were 0.719(95%CI:0.616-0.822)for ST2,0.868(95%CI:0.794-0.942)for CA125,and 0.867(95%CI:0.793-0.942)for HE4.The combined detection of ST2+CA125+HE4 yielded an AUC of 0.894(95%CI:0.832-0.955).Significant differences were observed in serum ST2,CA125,and HE4 levels among ovarian cancer patients with different TNM stages,lymph node metastasis,distant metastasis,and peritoneal metastasis(P<0.05),while there were no significant differences in the patients with different ages or maximum tumor diameters(P>0.05).The ST2 level in serm of the ovarian cancer patients was positively correlated with TNM stage,distant metastasis,lymph node metastasis,peritoneal metastasis,CA125 level,HE4 level,and Ki67 level(P<0.05),but was not correlated with maximum tumor diameter,CEA,CA199 level,or P53 level(P>0.05).Conclusion:ST2,CA125,and HE4 are highly expressed in the serum of the ovarian cancer patients.Combined detection of serum ST2,CA125,and HE4 exhibits good sensitivity and specificity for ovarian cancer screening and improves diagnostic efficacy.ST2 is associated with advanced TNM stage and metastasis in ovarian cancer and may participate in the occurrence and progression of ovarian cancer.
5.Advances in perioperative nursing for patients undergoing transcatheter aortic valve replacement
Junfeng LI ; Yu YANG ; Xiuyan CAO ; Zifang YIN
Journal of Navy Medicine 2025;46(6):641-645
The incidence of aortic valve disease gradually increases with age,and has become an upward trend in recent years.Transcatheter aortic valve replacement(TAVR)has become the first-line treatment for aortic stenosis(AS)due to minimal surgical trauma and fast postoperative recovery.But TAVR is a complex and high-risk technology,and the operation requires multidisciplinary collaboration and a comprehensive nursing team.Nursing care is crucial during the perioperative period of TAVR.This article aims to provide a comprehensive review of perioperative nursing for TAVR patients,based on the latest research progress both domestically and internationally,in order to enhance the care of TAVR patients during the perioperative period,especially for postoperative complications.
6.Epidemic characteristics of major natural focus diseases and vector-borne infectious diseases in Yantai City of Shandong Province from 2019 to 2023
Shanshan GAO ; Jingyu LIU ; Changlan YU ; Xiuyan LI ; Hongyu XU ; Guimei YU
Chinese Journal of Endemiology 2025;44(7):573-578
Objective:To investigate the epidemic characteristics and trends of major natural focus diseases and vector-borne infectious diseases in Yantai City, and provide a basis for formulating reasonable prevention and control strategies.Methods:The descriptive analysis was conducted on the epidemic data of natural focal diseases and vector-borne infectious diseases in Yantai City collected from the Infectious Disease Surveillance and Reporting Management System, a subsystem of the China Disease Control and Prevention Information System, covering the period from January 1, 2019, to December 31, 2023.Results:From 2019 to 2023, a total of 2 746 cases of 12 kinds of natural focus diseases, vector-borne infectious diseases and zoonosis were reported in Yantai City. The top four diseases reported in incidence rate were severe fever with thrombocytopenia syndrome (SFTS, 3.13/100 000), brucellosis (2.57/100 000), hemorrhagic fever with renal syndrome (HFRS, 1.09/100 000), and scrub typhus (0.73/100 000). There were statistically significant differences in the reported incidence rate of the four major natural focus diseases and vector-borne infectious diseases between different years (χ 2 = 92.55, 34.88, 132.33, 39.95, P < 0.001). The four major natural focal diseases and vector-borne infectious diseases had reported cases throughout the year. SFTS cases peaked in June, accounting for 28.80% (320/1 111). Brucellosis cases were predominantly reported from March to August, accounting for 65.54% (599/914). HFRS cases peaked in November, accounting for 38.66% (150/388), while scrub typhus cases peaked in October, accounting for 69.88% (181/259). The top three districts/cities with the highest incidence of the four major natural focus diseases and vector-borne infectious diseases were Laizhou City (585 cases), Zhaoyuan City (377 cases), and Haiyang City (358 cases). The incidence rates of SFTS in women was higher than that in men (χ 2 = 13.92, P < 0.001), and the incidences rates of brucellosis and HFRS in men were higher than those in women (χ 2 = 123.09, 73.32, P < 0.001). The cases of the four diseases were mainly farmers, accounting for 76.06% (845/1 111), 78.12% (714/914), 81.44% (316/388), and 85.71% (222/259), respectively. Conclusions:From 2019 to 2023, the reported incidence rate of the four major natural focus diseases and vector-borne infectious diseases in Yantai City presents an overall upward trend, with obvious seasonal, regional and demographic characteristics. Targeted prevention and control measures should be developed for high-risk areas and populations based on the characteristics of different diseases.
7.Epidemic characteristics of major natural focus diseases and vector-borne infectious diseases in Yantai City of Shandong Province from 2019 to 2023
Shanshan GAO ; Jingyu LIU ; Changlan YU ; Xiuyan LI ; Hongyu XU ; Guimei YU
Chinese Journal of Endemiology 2025;44(7):573-578
Objective:To investigate the epidemic characteristics and trends of major natural focus diseases and vector-borne infectious diseases in Yantai City, and provide a basis for formulating reasonable prevention and control strategies.Methods:The descriptive analysis was conducted on the epidemic data of natural focal diseases and vector-borne infectious diseases in Yantai City collected from the Infectious Disease Surveillance and Reporting Management System, a subsystem of the China Disease Control and Prevention Information System, covering the period from January 1, 2019, to December 31, 2023.Results:From 2019 to 2023, a total of 2 746 cases of 12 kinds of natural focus diseases, vector-borne infectious diseases and zoonosis were reported in Yantai City. The top four diseases reported in incidence rate were severe fever with thrombocytopenia syndrome (SFTS, 3.13/100 000), brucellosis (2.57/100 000), hemorrhagic fever with renal syndrome (HFRS, 1.09/100 000), and scrub typhus (0.73/100 000). There were statistically significant differences in the reported incidence rate of the four major natural focus diseases and vector-borne infectious diseases between different years (χ 2 = 92.55, 34.88, 132.33, 39.95, P < 0.001). The four major natural focal diseases and vector-borne infectious diseases had reported cases throughout the year. SFTS cases peaked in June, accounting for 28.80% (320/1 111). Brucellosis cases were predominantly reported from March to August, accounting for 65.54% (599/914). HFRS cases peaked in November, accounting for 38.66% (150/388), while scrub typhus cases peaked in October, accounting for 69.88% (181/259). The top three districts/cities with the highest incidence of the four major natural focus diseases and vector-borne infectious diseases were Laizhou City (585 cases), Zhaoyuan City (377 cases), and Haiyang City (358 cases). The incidence rates of SFTS in women was higher than that in men (χ 2 = 13.92, P < 0.001), and the incidences rates of brucellosis and HFRS in men were higher than those in women (χ 2 = 123.09, 73.32, P < 0.001). The cases of the four diseases were mainly farmers, accounting for 76.06% (845/1 111), 78.12% (714/914), 81.44% (316/388), and 85.71% (222/259), respectively. Conclusions:From 2019 to 2023, the reported incidence rate of the four major natural focus diseases and vector-borne infectious diseases in Yantai City presents an overall upward trend, with obvious seasonal, regional and demographic characteristics. Targeted prevention and control measures should be developed for high-risk areas and populations based on the characteristics of different diseases.
8.Clinical value of serum miR-19b and miR-744-5p levels in the diagnosis of non-small cell lung cancer
Dan LI ; Ruiyao LI ; Yinghan LI ; Xiuyan YU ; Xuefeng WU
Journal of International Oncology 2024;51(2):83-88
Objective:To investigate the serum levels of miR-19b and miR-744-5p in patients with non-small cell lung cancer (NSCLC), and to analyze the clinical value of miR-19b and miR-744-5p in the diagnosis of NSCLC.Methods:A total of 226 NSCLC patients (NSCLC group) and 100 healthy people (control group) admitted to Jilin Cancer Hospital from August 2019 to August 2022 were selected as research objects. Quantitative real-time PCR was used to measure and compare the serum levels of miR-19b and miR-744-5p between the NSCLC group and the control group, and the relationships between the two indicators and different clinical and pathological characteristics of NSCLC patients were analyzed. The receiver operating characteristic curve was used to analyze the clinical value of miR-19b, miR-744-5p and their joint detection in the diagnosis of NSCLC.Results:Compared with the control group, the serum miR-19b level (3.86±1.25 vs. 1.06±0.41) in the NSCLC group significantly increased ( t=21.87, P<0.001), while the miR-744-5p level (1.80±0.48 vs. 5.75±1.69) significantly decreased ( t=32.36, P<0.001). The serum miR-19b levels in NSCLC patients with pathological types of adenocarcinoma, maximum tumor diameter ≥3 cm, medium to low differentiation, stage Ⅲ-Ⅳ, and with lymph node metastasis were higher than those in squamous cell carcinoma ( t=5.94, P<0.001), maximum tumor diameter <3 cm ( t=2.65, P=0.009), well differentiation ( t=4.33, P<0.001), stageⅠ-Ⅱ ( t=12.32, P<0.001), patients without lymph node metastasis ( t=8.13, P<0.001), while miR-744-5p levels were lower than those in squamous cell carcinoma ( t=8.27, P<0.001), tumor maximum diameter <3 cm ( t=5.34, P<0.001), well differentiation ( t=6.95, P<0.001), stageⅠ-Ⅱ ( t=11.40, P<0.001), patients without lymph node metastasis ( t=10.36, P<0.001). The area under the curve (AUC) of serum miR-19b combined with miR-744-5p in the diagnosis of NSCLC was 0.914 (95% CI: 0.841-0.959), with sensitivity and specificity of 90.9% and 84.0%, respectively. AUC was significantly than that of the single indicator detection of miR-19b (AUC=0.824, 95% CI: 0.770-0.869) and miR-744-5p (AUC=0.783, 95% CI: 0.709-0.838) ( Z=2.28, P=0.021; Z=2.36, P=0.017) . Conclusion:Serum miR-19b level of NSCLC patients is increased, miR-744-5p levels is decreased, and joint detection of serum miR-19b and miR-744-5p has high clinical value in the diagnosis of NSCLC.
9.Promotion effect of chemokine CCL19-induced macrophage M1 polarization on chronic pancreatitis in mice and its mechanism
Lianzhi CUI ; Xiaowei ZHANG ; Yue ZHAI ; Yue PAN ; Xiuyan YU ; Hua ZHU
Journal of Jilin University(Medicine Edition) 2024;50(6):1587-1596
Objective:To discuss the promotion effect of chemokine C-C motif ligand 19(CCL19)induced macrophage M1 polarization on chronic pancreatitis of the mice,and to clarify its related mechanism.Methods:Ten male C57BL/6N mice were selected,and the pancreatic acinar cells and peritoneal macrophages were extracted from these mice to construct the macrophage-acinar cell co-culture system.The co-culture system cells were divided into control group,model group,and small interfering RNA CCL19(si-CCL19)group.The morphology of the acinar cells in various groups were observed under microscope.Forty mice were randomly selected and divided into normal group and chronic pancreatitis group,and there were 20 mice in each group.HE staining was used to observe the pathomorphology of pancreatic tissue of the mice in two groups;immunofluorescence staining was used to observe the expressions of cytokeratin 19(CK19),amylase,M1 macrophage-related markers inducible nitric oxide synthase(iNOS),and F4/80 in pancreatic tissue of the mice in two groups and morphology of follicular cells and the expressions of CK19,amylase in the co-culture system cells in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β in serum of the mice in two groups and in the co-culture system cells in various groups;immunohistochemistry was used to observe the expression of CCL19 protein in pancreatic tissue of the mice in two groups;Western blotting method was used to detect the expression levels of CCL19 protein and two nuclear factor-κB(NF-κB)signaling pathway-related proteins P65,phosphorylate P65(p-P65),kappa B inhibitor of kinase α/β(IKKα/β),phosphorylated IKKα/β(p-IKKα/β),IkBα,phosphorylated IκBα(p-IκBα)in pancreatic tissue of the mice in two groups and in the co-culture system cells in various groups.Results:The HE staining results showed that the acinar cells in pancreatic tissue of the mice in normal group were tightly arranged;compared with normal group,the acinar cells of the mice in chronic pancreatitis group showed obvious vacuolation and acinar cell ductal metaplasia,indicating successful preparation of the mouse pancreatitis model.The immunofluorescence staining results showed that compared with control group,the acinar cells in model group exhibited severe vacuolation,the CK19 expression was significantly increased,and the amylase expression was significantly decreased;compared with model group,the acinar cell ductal metaplasia in si-CCL19 group was decreased,the CK19 expression was significantly decreased,and the amylase expression was significantly increased;compared with normal group,the expression of amylase in pancreatic tissue of the mice in chronic pancreatitis group was significantly decreased,while the expressions of CK19 and M1 macrophage markers iNOS and F4/80 were significantly increased.The ELISA results showed that compared with normal group,the serum levels of TNF-α,IL-6,and IL-1β of the mice in chronic pancreatitis group were significantly increased(P<0.05);compared with control group,the levels of TNF-α,IL-6,and IL-1β in the cells in model group were significantly increased(P<0.05);compared with model group,the levels of TNF-α,IL-6,and IL-1β in the cells in si-CCL19 group were significantly decreased(P<0.05).The immunohistochemistry results showed that compared with normal group,the expression of CCL19 protein in pancreatic tissue of the mice in chronic pancreatitis group was significantly increased.The Western blotting results showed that compared with normal group,the expression levels of CCL19 protein and NF-κB signaling pathway-related proteins p-P65,p-IKKα/β,and p-IκBα in pancreatic tissue of the mice in chronic pancreatitis group were significantly increased(P<0.05);compared with control group,the expression levels of CCL19,p-IKKα/β,p-P65,and p-IκBα proteins in the cells in model group were significantly increased(P<0.05);compared with model group,the expression levels of CCL19,p-IKKα/β,p-P65,and p-IκBα proteins in the cells in si-CCL19 group were decreased(P<0.05).Conclusion:CCL19 promotes the macrophage M1 polarization through the NF-κB signaling pathway,induces the formation of inflammatory microenvironment,and promotes the occurrence and development of pancreatitis.
10.Genetic analysis and prenatal diagnosis of a Chinese pedigree affected with Complete androgen insensitivity syndrome due to a novel variant of AR gene
Fanrong MENG ; Xiaozhou LI ; Yunfang SHI ; Duan JU ; Xiuyan WANG ; Chunying WANG ; Xuebing LI ; Wenjun YU ; Yingmei WANG ; Xuexia ZHOU
Chinese Journal of Medical Genetics 2024;41(10):1206-1212
Objective:To explore the clinical and molecular basis for a Chinese pedigree affected with Complete androgen insensitivity syndrome (CAIS).Methods:A CAIS pedigree presented at Tianjin Medical University General Hospital between 2019 and 2021 was selected as the study subject. Clinical data of the proband was collected, along with peripheral blood samples from the proband and her family members. Chromosomal karyotyping, sex-determining region of the Y chromosome ( SRY) testing, and next-generation sequencing (NGS) were carried out for the proband, and candidate variant was verified by Sanger sequencing of her family members. Prenatal diagnosis was provided for the sister of the proband. This study was approved by Medical Ethics Committee of the Tianjin Medical University General Hospital (Ethics No. IRB2023-WZ-070). Results:The 18-year-old proband, who has a social gender of female, underwent laparoscopic examination, which showed no presence of uterus and ovaries. The karyotype of peripheral blood sample was 46, XY, with SRY gene detected. NGS indicated that the proband has harbored a heterozygous c. 1988C>G (p.Ser663Ter) variant of the AR gene. Sanger sequencing confirmed that her mother and sister had both harbored the same variant, whilst her father and younger sister were of the wild-type. Prenatal diagnosis revealed that her sister′s first fetus had harbored carried the same variant, which had led to termination of pregnancy. Her second fetus did not carry the variant, and a healthy boy was born. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+ PM4+ PP3_Moderate+ PP4). Conclusion:The c. 1988C>G (p.Ser663Ter) variant of the AR gene probably underlay the CAIS in the proband. The accurate diagnosis of sex development disorders will rely on the physicians′ thorough understanding of the clinical symptoms and pathogenic genes. Genetic testing and counseling can enable precise diagnosis, prenatal diagnosis, and guidance for reproduction

Result Analysis
Print
Save
E-mail