1.HDAC6 inhibitor ACY-738 induces apoptosis and autophagy in diffuse large B-cell lymphoma cells through P53 acetylation
Peijie JIANG ; Jinyi LIU ; Guancui YANG ; Jiarun LI ; Xiaolong TIAN ; Shijie YANG ; Jin WEI ; Xi ZHANG
Chinese Journal of Hematology 2025;46(5):437-444
Objective:To investigate the anti-tumor effect of the Histone Deacetylase 6 (HDAC6) inhibitor ACY-738 and its underlying mechanisms in Diffuse Large B-cell Lymphoma (DLBCL) .Methods:The expression of HDAC6 in various tumors and DLBCL was analyzed using bioinformatics. DLBCL cells were treated with different concentrations of ACY-738. Cell viability, DNA synthesis, and clone formation were assessed by CCK-8 assay, EdU assay, and soft agar assay, respectively. Intracellular reactive oxygen species (ROS) levels were detected by fluorescence microscopy. Morphological changes in cells were observed using transmission electron microscopy (TEM). Mitochondrial ROS levels and apoptosis were measured by flow cytometry. The expression levels of apoptosis-related and autophagy-related proteins were detected by Western blotting.Results:HDAC6 was highly expressed in DLBCL ( P<0.05). ACY-738 inhibited the proliferation, DNA synthesis, and colony formation of DLBCL cells in a dose-dependent manner ( P<0.05). Treatment with ACY-738 increased intracellular and mitochondrial ROS levels in DLBCL cells in a dose-dependent manner ( P<0.05). TEM revealed that after ACY-738 treatment, mitochondria in cells were swollen and ruptured, mitochondrial cristae were reduced or absent, autolysosomes appeared, and features characteristic of apoptosis were observed. Western blotting showed that after ACY-738 treatment, the expression of the anti-apoptotic protein BCL-2 was downregulated, while the expression of Cleaved-PARP, Cleaved caspase-3, and BAX was upregulated ( P<0.05). The expression of autophagy-related proteins Atg7, Atg3, LC3B, and P62 was downregulated, and the expression of acetylated P53 protein was upregulated ( P<0.05) . Conclusion:The HDAC6 inhibitor ACY-738 induces mitochondria-dependent apoptosis and autophagy in DLBCL cells by acetylating P53, thereby inhibiting DLBCL cell proliferation.
2.The use of cinematic rendering technology to assist laparoscopic resection of giant adrenal tumors
Jiarun TANG ; Bin XU ; Yongxia ZHOU ; Jing QING ; Ke HU ; Jiangchuan CHEN ; Qiao XU ; Yunfeng HE ; Jiamo ZHANG
Chinese Journal of Urology 2025;46(2):81-86
Objective:To explore the application value of cinematic rendering reconstruction technology in laparoscopic resection of giant adrenal tumors.Methods:As many as 21 patients with large adrenal tumors who underwent laparoscopic resection in Yongchuan Hospital Affiliated to Chongqing Medical University from January 2021 to January 2024 were retrospectively analyzed, with a median age of 54.0 (40.5, 58.0) years and a median tumor diameter of 7.3 (6.8, 8.8) cm. All patients underwent preoperative cinematic rendering 3D reconstruction imaging. All patients underwent enhanced CT scans. Their CT images were three-dimensionally reconstructed on the post-processing workstation platform. By changing image perspectives, adjusting the visualization of organs or blood vessels, and using physical volume rendering, real-shadow-rendered images were obtained. With these images, surgeons can intuitively understand important preoperative information, like the relationship between the tumor and surrounding organs and the path of tumor-feeding blood vessels, for preoperative planning. Following thorough preoperative preparation, laparoscopic transabdominal resection was performed. During surgery, 20 tumors were found to be located in the adrenal gland, and 1 in the retroperitoneum, with 13 on the left side and 8 on the right side. Preoperative cinematic rendering 3D imaging was consistent with intraoperative findings.Results:All 21 patients underwent successful surgeries, with an average operation time of (199.0±95.3) minutes, a median blood loss of 220 (150, 500) ml, and a median blood transfusion volume of 200 (150, 400) ml. No significant damage of vital organs or major blood vessels occurred, and there were no case of conversion to open surgery.Conclusions:For retroperitoneal giant adrenal tumors, utilizing cinematic rendering 3D reconstruction imaging enables a comprehensive understanding of the relationship between the tumor and surrounding organs and vessels preoperatively. This approach can reduce intraoperative bleeding and collateral injuries, improve the success rate of laparoscopic resection, and enhance overall surgical safety.
3.HDAC6 inhibitor ACY-738 induces apoptosis and autophagy in diffuse large B-cell lymphoma cells through P53 acetylation
Peijie JIANG ; Jinyi LIU ; Guancui YANG ; Jiarun LI ; Xiaolong TIAN ; Shijie YANG ; Jin WEI ; Xi ZHANG
Chinese Journal of Hematology 2025;46(5):437-444
Objective:To investigate the anti-tumor effect of the Histone Deacetylase 6 (HDAC6) inhibitor ACY-738 and its underlying mechanisms in Diffuse Large B-cell Lymphoma (DLBCL) .Methods:The expression of HDAC6 in various tumors and DLBCL was analyzed using bioinformatics. DLBCL cells were treated with different concentrations of ACY-738. Cell viability, DNA synthesis, and clone formation were assessed by CCK-8 assay, EdU assay, and soft agar assay, respectively. Intracellular reactive oxygen species (ROS) levels were detected by fluorescence microscopy. Morphological changes in cells were observed using transmission electron microscopy (TEM). Mitochondrial ROS levels and apoptosis were measured by flow cytometry. The expression levels of apoptosis-related and autophagy-related proteins were detected by Western blotting.Results:HDAC6 was highly expressed in DLBCL ( P<0.05). ACY-738 inhibited the proliferation, DNA synthesis, and colony formation of DLBCL cells in a dose-dependent manner ( P<0.05). Treatment with ACY-738 increased intracellular and mitochondrial ROS levels in DLBCL cells in a dose-dependent manner ( P<0.05). TEM revealed that after ACY-738 treatment, mitochondria in cells were swollen and ruptured, mitochondrial cristae were reduced or absent, autolysosomes appeared, and features characteristic of apoptosis were observed. Western blotting showed that after ACY-738 treatment, the expression of the anti-apoptotic protein BCL-2 was downregulated, while the expression of Cleaved-PARP, Cleaved caspase-3, and BAX was upregulated ( P<0.05). The expression of autophagy-related proteins Atg7, Atg3, LC3B, and P62 was downregulated, and the expression of acetylated P53 protein was upregulated ( P<0.05) . Conclusion:The HDAC6 inhibitor ACY-738 induces mitochondria-dependent apoptosis and autophagy in DLBCL cells by acetylating P53, thereby inhibiting DLBCL cell proliferation.
4.The use of cinematic rendering technology to assist laparoscopic resection of giant adrenal tumors
Jiarun TANG ; Bin XU ; Yongxia ZHOU ; Jing QING ; Ke HU ; Jiangchuan CHEN ; Qiao XU ; Yunfeng HE ; Jiamo ZHANG
Chinese Journal of Urology 2025;46(2):81-86
Objective:To explore the application value of cinematic rendering reconstruction technology in laparoscopic resection of giant adrenal tumors.Methods:As many as 21 patients with large adrenal tumors who underwent laparoscopic resection in Yongchuan Hospital Affiliated to Chongqing Medical University from January 2021 to January 2024 were retrospectively analyzed, with a median age of 54.0 (40.5, 58.0) years and a median tumor diameter of 7.3 (6.8, 8.8) cm. All patients underwent preoperative cinematic rendering 3D reconstruction imaging. All patients underwent enhanced CT scans. Their CT images were three-dimensionally reconstructed on the post-processing workstation platform. By changing image perspectives, adjusting the visualization of organs or blood vessels, and using physical volume rendering, real-shadow-rendered images were obtained. With these images, surgeons can intuitively understand important preoperative information, like the relationship between the tumor and surrounding organs and the path of tumor-feeding blood vessels, for preoperative planning. Following thorough preoperative preparation, laparoscopic transabdominal resection was performed. During surgery, 20 tumors were found to be located in the adrenal gland, and 1 in the retroperitoneum, with 13 on the left side and 8 on the right side. Preoperative cinematic rendering 3D imaging was consistent with intraoperative findings.Results:All 21 patients underwent successful surgeries, with an average operation time of (199.0±95.3) minutes, a median blood loss of 220 (150, 500) ml, and a median blood transfusion volume of 200 (150, 400) ml. No significant damage of vital organs or major blood vessels occurred, and there were no case of conversion to open surgery.Conclusions:For retroperitoneal giant adrenal tumors, utilizing cinematic rendering 3D reconstruction imaging enables a comprehensive understanding of the relationship between the tumor and surrounding organs and vessels preoperatively. This approach can reduce intraoperative bleeding and collateral injuries, improve the success rate of laparoscopic resection, and enhance overall surgical safety.
5.Knowledge, attitude, practice and influencing factors on influenza and influenza vaccine among pregnant women in Suzhou
Rui WANG ; Yuanyuan ZHANG ; Cheng LIU ; Pengwei CUI ; Feng XU ; Jiarun JIANG ; Liling CHEN ; Haibing YANG ; Fang LIU
Chinese Journal of Epidemiology 2024;45(12):1672-1678
Objective:To understand the current knowledge, attitude, and practice (KAP) on influenza and influenza vaccine among pregnant women in Suzhou and to analyze its influencing factors to provide technical support data for public health strategies for promoting influenza vaccination in pregnant women.Methods:A questionnaire was designed, and a stratified sampling method was used to conduct a face-to-face survey among pregnant women at different stages of pregnancy who received antenatal examinations at different levels of medical institutions in Suzhou, Jiangsu Province, in 2023. KAP status and influencing factors were analyzed by χ2 test and logistic regression analysis. Results:A total of 2 195 valid questionnaires were collected in this survey. The M( Q1, Q3) of knowledge about influenza and influenza vaccine among pregnant women in Suzhou was 7.60 (5.23, 9.80) points, and the score range was 0.20-14.71 points, the passing rate was 34.12%, the awareness rate of influenza vaccine was 57.45%, and the vaccination rate of influenza vaccine was 1.91% within one year before the survey. The willingness to receive influenza vaccine during pregnancy was only 3.57%. Multivariate analysis of influenza and influenza vaccine-related knowledge scores showed that the passing rate was positively correlated with education level and gestational age. In contrast, family income was negatively correlated with living in rural areas, working as migrant workers, and having no medical insurance. Multivariate analysis of vaccination intention showed that decreased effectiveness of influenza vaccine and increased adverse reactions decreased vaccination intention during pregnancy. Conclusions:The pregnant women in Suzhou pay more attention to influenza, and vaccination rates and intentions are generally low. Pregnant women with early and second trimester of pregnancy, low education, living in rural areas, working as migrant workers, and not purchasing medical insurance are the key groups to popularize the knowledge about influenza and influenza vaccine.
6.Ideas for Acupuncture in the Treatment of Postherpetic Neuralgia Based on Syndrome Differentiation of "Collaterals Disease"
Jiarun ZHANG ; Lu LIU ; Tianli LYU ; Bin LI
Journal of Traditional Chinese Medicine 2024;65(13):1340-1345
According to the characteristics of pain and disease process, postherpetic neuralgia (PHN) can be classified into the category of "collaterals disease" in traditional Chinese medicine. The key pathogenesis of PHN includes toxin, stasis and deficiency. The main syndromes of collaterals disease are pathogenic toxin burning collaterals, static blood blocking collaterals, and collaterals depletion. Ashi points are mainly selected for treatment of PHN. For the syndrome of pathogenic toxin burning collaterals, dense fire needling is suitable for removing toxin and relieving pain. For the syndrome of static blood blocking collaterals, collateral bloodletting is suitable to remove stasis and relieve pain. For the syndrome of collaterals depletion, the combination of encircling fire needling, hair needling and transverse insertion with filiform needles, and Jiaji acupoint (EX-B2) needling is suitable for nourishing collaterals and relieving pain. In clinical practice, the most appropriate acupuncture regimen can be selected according to the differentiated syndrome of "collaterals disease", and with adoption of the holistic pattern differentiation and treatment, the clinical efficacy can be strengthened.
7.Reliability and validity of general procrastination scale in the application of middle school students
Yongmei WU ; Yu CHEN ; Yunjia XIE ; Jili ZHANG ; Tianyi BU ; Jiawei ZHOU ; Zhengxue QIAO ; Jiarun YANG ; Xiaohui QIU ; Yanjie YANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(2):161-165
Objective:To test the reliability and validity of the general procrastination scale (GPS) in the application of middle school students.Methods:The Chinese version of GPS, the irrational procrastination scale(IPS), and the Maslach burnout inventory(MBI) were utilized to survey 10 825 middle school students in Harbin City through stratified random sampling, and 4 498 students were retested after 4 weeks. Statistical analysis was performed using SPSS 27.0 and Mplus 8.0.Results:The entries were well differentiated.Exploratory and confirmatory factor analysis indicated that GPS was composed of two factors, including active avoidance and lack of planning.The model fit was good (CFI=0.914, TLI=0.901, RMSEA=0.069, SRMR=0.072). GPS was positively correlated with the total scores of IPS and MBI ( r=0.753, 0.677, both P<0.001). The Cronbach's α coefficient of GPS was 0.864, the folded half reliability was 0.870, and the retest reliability after 4 weeks was 0.756. Conclusion:The GPS has good reliability and validity among middle school students, which provides a standard for measuring the procrastination level of middle school students and carrying out related research.
8.Bioinformatics analysis of regulatory network of long non-coding RNA LOC107987438 in depressive disorder
Tianyi BU ; Kexin QIAO ; Yan WANG ; Jili ZHANG ; Xiaohui QIU ; Zhengxue QIAO ; Jiawei ZHOU ; Jiarun YANG ; Wenjuan HE ; Yanjie YANG
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(8):714-720
Objective:To investigate the regulatory role of defferentially expressed LOC107987438 in the pathogenesis of depressive disorder and provide a theoretical basis for its clinical application in depressive disorder.Methods:Differential expression of LOC107987438 was verified by quantitative real-time polymerase chain reaction(qRT-PCR)in peripheral blood monocular cells(PBMCs)of 60 patients with depressive disorder and 60 health controls. In addition, its diagnostic value was assessed by receiver operating characteristic(ROC)curves. Based on the ceRNA mechanism of lncRNA, the miRDB database was applied to predict the target miRNAs of LOC107987438, and the miRNAs with target score ≥ 80 among them were screened out.The screened miRNAs were then used to predict their potential target mRNAs through four databases which were TargetScan 8.0, miRTarBase, mirDIP and miRPathDB. Moreover, the predicted target mRNAs were annotated for gene ontology(GO)function annotation and tokoyo encyclopedia of genes and genomes(KEGG) pathway enrichment analysis via ClusterProfiler 4.0.5 package of R 4.1.1. Finally, a protein-protein interaction network was constructed using the STRING 11.5 platform to retrieve the interacting genes.Results:The qRT-PCR results showed that normalized expression of LOC107987438 in PBMCs of patients with depressive disorder was higher than that in health controls(depressive disorder: 2.084±1.357, health controls: 1.000±0.660, P<0.001). The ROC curve results showed that the area under curves(AUC)of LOC107987438 was 0.759(95% CI: 0.675-0.842, P<0.05), indicating its high potential diagnostic value. Bioinformatics analysis showed that hsa-miR-4670-3p, hsa-miR-619-3p, hsa-miR-6721-5p and hsa-miR-297 were the miRNAs with high bindings to LOC107987438. The results of KEGG signaling pathway enrichment revealed that hypoxia-inducible factor 1(HIF-1)signaling pathway, phosphatidylinositol 3-kinase-AKT(PI3K-Akt) signaling pathway and erythroblastic oncogene B(ErbB) signaling pathway were closely associated with depressive disorder. Among the top ten key genes screened by the protein-protein interaction network, kirsten rats arcomaviral oncogene homolog(KRAS), androgen receptor(AR), cyclic-AMP response binding protein1(CREB1), insulin-like growth factor 1(IGF1), cyclin-dependent kinase inhibitor 1B(CDKN1B) and calcium/calmodulin-dependent protein kinase type Ⅱ alpha(CAMK2A)were strongly associated with depressive disorder. Conclusion:The establishment of ceRNA regulatory network of LOC107987438 provides a theoretical basis for exploring the pathophysiology of depressive disorders.
9.Association study of interaction of tryptophan hydroxylase 2 with serotonin 1A receptor gene polymorphism on major depressive disorder
Xueyan ZHAO ; Jiarun YANG ; Chunyang ZHANG ; Ning YAN ; Xusheng SONG ; Jian ZHANG ; Jingsong MA ; Lin WANG ; Xiuxian YANG ; Yanjie YANG
Chinese Journal of Behavioral Medicine and Brain Science 2018;27(2):165-168
Objective To explore the interaction between tryptophan hydroxylase 2(TPH2) gene polymorphisms (rs4570625,rs11178997) and serotonin 1A receptor (5-HT1A) gene polymorpbisms (rs878567,rs1364043,rs6265) and the association with major depressive disorder (MDD) in a Chinese Han population.Methods The DNA isolated from peripheral blood samples of 288 MDD patients 288 healthy subjects was detected by single base primer extension assay (Snapshot).The generalized multifactor dimensionality reduction (GMDR) method was used to analyze the gene-gene interaction.Results Significant differences were found in the genotype (patients (TT:27,TA:152,AA:109),controls (TT:82,TA:105,AA:101),P<0.01) and allele(patients (T:206,A:370),controls (T:269,A:307),P<0.01) frequencies of rs1 1178997 within TPH2 between MDD patients and controls.Statistically,a greater risk of developing MDD was found in individuals with an rs1 1178997 A-allele(OR=1.574,95%CI=1.243-1.993).The interaction between TPH2 (rs4570625,rs1 1178997) and 5-HT1A (rs878567,rs1364043,rs6265) was considered as the best multi-locus model,and this showed a testing accuracy of 57.67% and a CV consistency of 10/10.And this interaction had a significant effect on the risk of MDD (P=0.0107).Conclusion There may be an association between the interaction of TPH2 and 5-HT1A polymorphisms and MDD.
10.Interaction of GNβ3 gene polymorphisms and environmental factors in susceptibility to major depressive disorder
Dong QI ; Xiaohui QIU ; Yanjie YANG ; Jiarun YANG ; Jingsong MA ; Jian ZHANG ; Mingzhe ZHAO ; Lin WANG ; Zhengxue QIAO ; Xiuxian YANG
Chinese Journal of Behavioral Medicine and Brain Science 2017;26(4):289-292
Objective To explore the association between GNβ3 gene and depression,and to investigate the interaction of gene-environment(negative life events and childhood trauma) and potential possible pathogenesis of depression.Methods The sample of peripheral blood was collected from Chinese Northern patients(n=500) and controls(n=500).Snapshot technique was used to detect the genotype frequency and allele frequency of GNβ3 rs5443 polymorphism in cases and controls.The genotype and allele frequencies were analyzed by Chi-square test,the interactions of gene-environment were analyzed by Logistic regression.Results GNβ3 rs5443 genotype and allele frequencies were observed between patients and controls (x2 =20.249,P<0.01;x2 =4.803,P<0.05).There were genotype CC 102 and 158,genotype CT 280 and 217,genotype TT 118 and 125;allele C 484 and 533,allele T 516 and 467 between patients and controls,respectively.Logistic regression analysis showed that the interaction between rs5443 T+ and negative life events was associated with depression (P<0.05,OR=1.957).In addition,individual carrying rs5443T+ genotypes and negative life events could increase risk of depression.Conclusion GNβ3 rs5443 is a possible susceptibility gene of depression.The interaction between rs5443 and negative life events is associated with depression.

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