1.Screening key genes of PANoptosis in hepatic ischemia-reperfusion injury based on bioinformatics
Lirong ZHU ; Qian GUO ; Jie YANG ; Qiuwen ZHANG ; Guining HE ; Yanqing YU ; Ning WEN ; Jianhui DONG ; Haibin LI ; Xuyong SUN
Organ Transplantation 2025;16(1):106-113
Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.
2.Reliability of 4D flow cardiac MRI for measuring hemodynamic parameters of left ventricle
Lirong MA ; Jiaxuan GUO ; Wenling LI ; Li MA ; Yan ZHENG ; Huairong ZHANG ; Li ZHU
Chinese Journal of Medical Imaging Technology 2024;40(2):221-225
Objective To observe the reliability of regional 4D flow and whole heart 4D flow cardiac MRI(CMRI)for measuring hemodynamic parameters of left ventricle.Methods Heart ultrasonography and CMRI were prospectively obtained in 31 healthy subjects.Hemodynamic parameters of left ventricle were measured using heart ultrasound,3-chamber 4D flow CMRI(based on inflow and outflow channel of left ventricle)and whole heart 4D flow CMRI,respectively.Intra-class correlation coefficient(ICC)was performed to evaluate the consistencies of the measured left ventricle hemodynamic parameters among the above 3 methods.Results Good consistencies of peak systolic velocity in aortic supravalvular/subvalvular,E peak diastolic velocity of mitral valve,supravalvular/subvalvular aortic pressure and aortic valve pressure gradient(all ICC>0.75),while moderate consistency of A peak diastolic velocity of mitral valve(ICC=0.718)were found between heart ultrasound and 3-chamber 4D flow CMRI.Good consistencies of peak systolic velocity in aortic supravalvular/subvalvular,A peak diastolic velocity of mitral valve and supravalvular/subvalvular aortic pressure(all ICC>0.75),while moderate consistencies of E peak diastolic velocity of mitral valve and aortic valve pressure gradient(ICC=0.600,0.628)were found between heart ultrasound and whole heart 4D flow CMRI.Meanwhile,good consistencies of the above parameters were found between 3-chamber 4D flow CMRI and whole heart 4D flow CMRI(all ICC>0.75).Conclusion Measuring left ventricular hemodynamic parameters using local regional 4D flow and whole heart 4D flow CMRI were reliable,with good consistency with cardiac ultrasound.
3.Advances in HMGB1 gene and childhood disease
Lirong BAN ; Yanyan LIANG ; Hua ZHU
International Journal of Pediatrics 2024;51(8):563-566
High mobility group box 1 protein(HMGB1)gene is located on chromosome 13q12 and is widely expressed in various tissues and cells.The encoded non-histone chromosome binding protein regulates transcription and participates in DNA repair.It plays an important role in processes such as inflammation,cell differentiation and tumor cell migration,and has become a valuable biomarker in a variety of diseases. In recent years,more and more studies have found that this gene is closely related to various diseases in children,such as respiratory diseases,digestive diseases,autoimmune diseases,cardiovascular diseases and so on.This article reviews the research progress of HMGB1 gene in children ' s diseases.
4.Potential of new self-crosslinked hyaluronic acid gel on the recovery of endometrium after artificial abortion: a multicenter, prospective randomized controlled trial
Chunying LI ; Lirong TENG ; Qing LIN ; Liping ZHAO ; Yunxia ZHU ; Xin MI ; Zhenna WANG ; Xiaoye WANG ; Lisong ZHANG ; Dan HAN ; Lili MA ; Wenpei BAI ; Jianmei WANG ; Jun NI ; Huiping SHEN ; Qinfang CHEN ; Hongmei XU ; Chenchen REN ; Jing JIANG ; Guanyuan LIU ; Ping PENG ; Xinyan LIU
Chinese Journal of Obstetrics and Gynecology 2024;59(11):864-870
Objective:To evaluate the impact of self-crosslinked hyaluronic acid (SCH) gel on endometrium recovery after artificial abortion.Methods:A multicenter, prospective randomized controlled trial was conducted across 18 hospitals from December 2021 to February 2023, involving 382 women who underwent artificial abortion. Participants were randomly allocated to receive either treatment with SCH gel (SCH group) or no treatment (control group) in a 1∶1 ratio. The primary outcome was endometrium thickness in 14 to 18 days after the first postoperative menstruation. Secondary outcomes included changes in menstrual volume during the first postoperative menstruation, menstruation resumption within 6 postoperative weeks, time to menstruation resumption, duration of the first postoperative menstruation, and incidence of dysmenorrhea.Results:Baseline characteristics of participants were comparable between the two groups (all P>0.05), with 95.3% (182/191) in SCH group and 92.7% (177/191) in the control group completed the study. The postoperative endometrial thickness in SCH group was significantly greater than that in the control group [(9.78±3.15) vs (8.95±2.32) mm; P=0.005]. SCH group also had significantly fewer participants with reduced menstrual volume [23 cases (12.6%, 23/182) vs 31 cases (17.5%, 31/177); P=0.038]. Although SCH group experienced less dysmenorrhea during the first postoperative menstrual period, this difference was not statistically significant [28.5% (51/179) vs 37.1% (65/175); P=0.083]. Outcomes were similar between SCH group and the control group regarding the proportion of participants who resumed menstruation within 6 weeks postoperatively, time to menstruation resumption, and duration of the first postoperative menstruation ( P=0.792, 0.485, and 0.254, respectively). No serious adverse events were observed during the study period, and no adverse events were attributed to SCH gel treatment. Conclusion:The application of SCH gel after artificial abortion is safe and might aid in the recovery of the endometrium.
5.Comparison of two superparamagnetic purification magnetic beads-based screening and enrichment techniques for isolating cell-free fetal DNA from maternal plasma for non-invasive prenatal screening
Wen ZENG ; Jianjiang ZHU ; Hong QI ; Lirong CAI ; Xiaohui WEN ; Yao LUO ; Qiao ZHANG
Chinese Journal of Medical Genetics 2024;41(7):797-802
Objective:To assess the efficiency of modified enrichment method for cell-free fetal DNA (cffDNA) through purified superparamagnetic beads during non-invasive prenatal testing (NIPT).Methods:A total of 26 252 pregnant women undergoing NIPT at the Maternal and Child Health Care Hospital of Haidian District from December 2017 to September 2022 were recruited and randomly assigned into the conventional group ( n = 10 573) and the modified enrichment group ( n = 15 679), who were then subjected to the screening and enrichment of the cffDNA using a conventional and modified technique, respectively. High-risk pregnant women detected by NIPT were subjected to invasive prenatal diagnosis. All women were followed up for their pregnancy outcomes, and the detection efficacy of the two methods was compared in terms of fragment size, concentration of cffDNA, duplicate detection rate, and indices of clinical laboratory tests. Results:The fragment size of the main peak of the cell-free DNA library of the modified enrichment group was significantly lower than that of the conventional group [267 (264, 269) bp vs. 294 (292, 296) bp, P<0.01], while the concentration of cffDNA was significantly higher [21.86% (17.61%, 26.36%) vs. 9.08% (6.87%, 11.87%), P<0.01]. In addition, the duplicate detection rate (0.740% vs. 2.02%, χ2=83.90, P<0.01) and detection failure rate (0.006% vs. 0.057%, P<0.05) in the modified enrichment group were significantly lower than those of the conventional group. The combined positive predictive value (PPV) in both high-risk (64.3% vs. 76.1%) and low-risk (35.3% vs. 45.5%) pregnant women from the modified enrichment group was slightly lower than those from the conventional group, though no significant difference was detected. There was one false negative case for trisomy 21 among the high-risk pregnant women from the conventional group, and no false negative case was found in the modified enrichment group. Conclusion:The modified technique to screen and enrich the cffDNA has significantly enhanced the relative concentration of cffDNA and reduced the failure and duplication detection rate of NIPT, which has significantly reduced the incidence of false negative cases due to the low concentration of cffDNA, and greatly increased the overall detection efficacy of NIPT.
6.Application value of modified magnetic bead screening for enrichment of cell-free fetal DNA from maternal peripheral blood in non-invasive prenatal testing
Jianjiang ZHU ; Hong QI ; Lirong CAI ; Xiaohui WEN ; Wen ZENG ; Yao LUO ; Qiao ZHANG ; Ran MENG
Chinese Journal of Perinatal Medicine 2023;26(1):20-25
Objective:To evaluate the value of modified magnetic bead screening for enrichment of cell-free fetal DNA (cffDNA) in non-invasive prenatal testing (NIPT).Methods:This study retrospectively recruited 31 cases with low concentration of cffDNA (<6.00%), Z value in the gray zone (3.00-4.00) at the first detection, or false-positive (confirmed by invasive prenatal diagnosis) or false-negative (confirmed by postnatal chromosome test) results among 11 000 pregnant women who underwent routine NIPT in Beijing Haidian District Maternal and Child Health Care Hospital from October 2017 to December 2019. Plasma samples collected for the first-time routine NIPT were used to enrich cffDNA using modified magnetic beads for NIPT (modified NIPT). Wilcoxon rank sum test was used to compare the modified NIPT with the routine NIPT in detecting the cffDNA concentrations of male fetuses.Results:Among the 31 pregnant women, there were 13 cases with low cffDNA concentration in routine NIPT, 11 having false-positive results in the routine NIPT (three for trisomy 13, four for trisomy 18 and four for trisomy 21, all were confirmed by invasive prenatal diagnosis), six with gray-zone Z values in the first-time NIPT (retesting indicating low risk) and one having false negative result for trisomy 21 (confirmed by postnatal chromosome test). Cell-free DNA (cfDNA) fragments less than 150 bp were effectively enriched using the modified magnetic bead screening and the concentration of cffDNA was increased from 4.43% (2.45%-17.61%) in routine NIPT to 13.46% (7.75%-36.64%) in the modified NIPT ( Z=-14.22, P<0.01). Results of the modified NIPT indicated that 13 cases with low cffDNA concentration of routine NIPT were successfully detected as low risk, as well as the risks in the six cases with gray-zone Z value and six of the 11 false-positive cases in the routine NIPT were low, which were consistent with the retest results of the routine NIPT, while high risk was found in one false-negative case. Conclusions:The modified NIPT could reduce the false positive rate by lowering the failure rate caused by low concentration of cffDNA and is able to identify false-negative cases. Compared with the routine NIPT, it shows a higher success rate and a lower false positive rate.
7.Effect of Banxia Xiexintang-containing Intestinal Absorption Solution on Migration and Invasion of PMN-MDSCs in Gastric Cancer Microenvironment
Jingjing WEI ; Zhongbo ZHU ; Xiping LIU ; Peiqing LI ; Qiming CHEN ; Lirong DAI ; Lijuan SHI ; Haijing DUAN ; Qingmiao WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(10):48-57
ObjectiveTo observe the effect of Banxia Xiexintang containing intestinal absorption solution (BXCIAS) on migration and invasion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in gastric cancer microenvironment. MethodThe complex solution (containing 0.63 g·mL-1 crude drug) was prepared. Gastric cancer cells were subjected to non-contact co-culture with PMN-MDSCs in Transwell chamber to create gastric cancer microenvironment. Cell counting kit-8 (CCK-8) assay was used to screen the optimal intervention concentration and time of BXCIAS on PMN-MDSCs for subsequent experiment. The blank group, model group, FAK inhibitor group, and BXCIAS groups (26%, 18%, and 10%) were designed. Scratch assay and Transwell assay were employed to detect the migration and invasion ability of PMN-MDSCs, and enzyme-linked immunosorbent assay (ELISA) to measure the expression of vascular endothelial cell growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in tumor microenvironment. The expression levels of PMN-MDSCs pathway-related proteins FAK, phosphorylated (p)-FAK, protein tyrosine kinase (Src), and p-Src were detected by Western blot. ResultThe inhibition rates of PMN-MDSCs by 5%, 50%, 75%, and 100% BXCIAS at 48 h were higher than those at 24 h (P<0.05, P<0.01). The inhibition rate of PMN-MDSCs by 50% BXCIAS at 72 h was lower than that at 48 h (P<0.01), and the inhibition rates by 5% and 100% BXCIAS at 72 h were higher than those at 48 h (P<0.05, P<0.01). There was no significant difference in the inhibition rate by other concentration levels at 48 h. The half-maximal inhibitory concentration (IC50) at 48 h was 18.09%, indicating that 18% BXCIAS and 48 h were the optimal concentration and time, respectively. The migration distance of PMN-MDSCs was large (P<0.01), and the number of migrating and invading cells increased (P<0.01) in the mode group compared with those in the blank group. Compared with model group, FAK inhibitor and BXCIAS at different concentration decreased the migration distance of PMN-MDSCs (P<0.01), and the number of migrating and invading cells (P<0.01), especially the 26% BXCIAS (P<0.01). The expression of PMN-MDSCs pathway-related proteins FAK, p-FAK, Src and p-Src (P<0.01) and the expression of VEGF and MMP-9 (P<0.01) were higher in the model group than in the blank group. Compared with model group, FAK inhibitor and BXCIAS (26%, 18%, 10%) decreased the expression of FAK, p-FAK, and Src (P<0.01), and FAK inhibitor and 18% BXCIAS reduced the expression of p-Src (P<0.01), and the expression of VEGF and MMP-9 (P<0.01). ConclusionBXCIAS can inhibit the migration and invasion of PMN-MDSCs by down-regulating the expression of FAK, p-FAK, Src, and p-Src proteins in the FAK signaling pathway of PMN-MDSCs in gastric cancer microenvironment.
8.Effect of Banxia Xiexintang-containing Intestinal Absorption Solution on PMN-MDSCs Apoptosis in Gastric Cancer Microenvironment
Jingjing WEI ; Zhongbo ZHU ; Xiping LIU ; Peiqing LI ; Qiming CHEN ; Lirong DAI ; Lijuan SHI ; Haijing DUAN ; Qingmiao WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(10):58-64
ObjectiveTo observe the effect of Banxia Xiexintang (BXT)-containing intestinal absorption solution on the apoptosis of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in gastric cancer microenvironment. MethodBXT-containing intestinal absorption solution was prepared, and gastric cancer cells and PMN-MDSCs were non-contact co-cultured in Transwell chamber to establish gastric cancer microenvironment. Cell counting kit-8 (CCK-8) assay was used to screen the optimal intervention concentration and time of 0-100% BXT-containing intestinal absorption solution prepared by 0.63 g·mL-1 reconstitution solution. Cells were classified into blank group, model group, oxaliplatin group (10 mg·L-1), and BXT (26%, 18%, 10% BXT-containing intestinal absorption solution) group, and the apoptosis of PMN-MDSCs was detected by flow cytometry. The expression of apoptosis-related B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cysteine-aspartic acid protease-3 (Caspase-3) in PMN-MDSCs was detected by Western blot. ResultAfter treatment for 24 h and 48 h, the PMN-MDSCs-inhibiting rate was increased by 5%, 50%, 75%, and 100% BXT-containing intestinal absorption solution compared with that in the blank group (P<0.05, P<0.01). At 72 h, the PMN-MDSCs-inhibiting rate by 50% BXT-containing intestinal absorption solution was lower than that at 48 h (P<0.01), and the PMN-MDSCs-inhibiting rate by 5%, 75%, and 100% BXT-containing intestinal absorption solution showed no significant difference from that at 48 h. Moreover, the half-maximal inhibitory concentration (IC50) at 48 h was 18.40%. Thus, 18% BXT-containing intestinal absorption solution and 48 h were the optimal intervention concentration and time. The survival rate of PMN-MDSCs in model group was higher than that in the blank group (P<0.05), and the apoptosis rate was lower than that in the blank group (P<0.05). Compared with model group, BXT containing intestinal absorption solution lowered the survival rate and raised apoptosis rate of PMN-MDSCs (P<0.05), particularly the 26% BXT-containing intestinal absorption solution (P<0.05). The expression of Bax and Caspase-3 in PMN-MDSCs was lower in the model group than in the blank group (P<0.05), and the expression of Bcl-2 was higher in the model group than in the blank group (P<0.05). The expression of Caspase-3 in PMN-MDSCs increased (P<0.05) and the expression of Bcl-2 decreased (P<0.05) in oxaliplatin group and BXT group compared with those in the model group. The expression of Bax rose in oxaliplatin group and BXT group (10% BXT-containing intestinal absorption solution) (P<0.05). ConclusionBXT can induce the apoptosis of PMN-MDSCs by regulating the expression of apoptosis-related proteins Bax, Caspase-3, and Bcl-2 in gastric cancer microenvironment.
9.The Q181X Point Mutation in Nf1 Induces Cerebral Vessel Stenosis.
Chensi LIANG ; Lirong HUO ; Yan ZHU ; Zhichao YAO ; Xiaolong WU ; Jiantao LIANG
Neuroscience Bulletin 2023;39(5):813-816
10.Association of multiple anthropometric indices with in 944,760 elderly Chinese people
Lirong DONG ; Yuanyuan WANG ; Jinshui XU ; Yang ZHOU ; Guiju SUN ; Dakang JI ; Haijian GUO ; Baoli ZHU
Epidemiology and Health 2023;45(1):e2023046-
OBJECTIVES:
The aims of this study were to update the latest data on the prevalence of hypertension (HTN) in the elderly Chinese population and to assess relationships between new anthropometric indices and HTN.
METHODS:
Data were obtained from the Basic Public Health Service (BPHS) survey for Jiangsu Province, China. A total of 944,760 people aged 65 years and older were included in this study. Blood pressure was measured by trained investigators. Body weight, body mass index (BMI), waist circumference (WC), waist-to-height ratio (WtHR), conicity index (COI), body roundness index (BRI), and a body shape index (ABSI) were included in the analysis as anthropometric indices. Logistic regression analysis and restricted cubic splines were used to evaluate the association of anthropometric indices with HTN.
RESULTS:
The prevalence of HTN among elderly residents of Jiangsu Province was 64.7% (95% confidence interval, 64.6 to 64.8). After adjusting for multiple covariates, all anthropometric indices except ABSI showed significant non-linear positive dose-response associations with HTN across sex (pnonlinear<0.001). Among participants with BMI <28 kg/m2, abnormal weight, WC, WtHR, BRI, COI, and ABSI were positively associated with HTN.
CONCLUSIONS
The prevalence of HTN in the elderly in Jiangsu Province is gradually increasing. It is necessary to consider the combination of ABSI and COI with BMI for screening elderly individuals for HTN in follow-up prospective studies.

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