Publications by authors named "Tingmei Chen"

59 Publications

Reduced mother-to-child transmission of hepatitis B after implementation of completely charge-free active-passive immunoprophylaxis: an observational cohort study.

Expert Rev Vaccines 2021 May 19:1-7. Epub 2021 May 19.

Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.

: China has implemented universal hepatitis B vaccination since 2002 and provided charge-free hepatitis B immunoglobulin (HBIG) to infants of HBV-infected mothers since July 2011. We aimed to compare mother-to-child transmission (MTCT) in children born before and since July 2011.: In total, 5,149 children of HBV-infected mothers were tested for HBV markers. Group one contained 1,160 children born during August 2002-June 2011 and group two contained 3,989 children born during July 2011-June 2016.: In total, 92 (1.8%, 95% confidence interval [95%CI] 1.4-2.2) children were infected with HBV. None (0%, 95%CI 0.0-0.1) of 3,716 children of mothers with negative hepatitis B e antigen (HBeAg) was infected, whereas 92 (6.4%, 95%CI 5.2-7.8) of 1,433 children of HBeAg-positive mothers were infected (p < 0.0001). Among children of HBeAg-positive mothers, MTCT occurred in 10.3% (19/185) (95%CI 6.3-15.6) in group one and 5.8% (73/1,248) (95%CI 4.6-7.3) in group two (p = 0.02).: Implementing charge-free active-passive immunoprophylaxis greatly reduces MTCT of HBV in children of HBeAg-positive mothers, highlighting the importance of timely administration of both hepatitis B vaccine and HBIG to prevent MTCT. The still remaining MTCT suggests that reducing maternal virus load before delivery is an additional important measure.
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http://dx.doi.org/10.1080/14760584.2021.1927723DOI Listing
May 2021

Evaluation of cesarean delivery rates in different levels of hospitals in Jiangsu Province, China, using the 10-Group classification system.

J Matern Fetal Neonatal Med 2021 Feb 15:1-7. Epub 2021 Feb 15.

Department of Obstetrics and Gynecology, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, China.

Objective: To compare cesarean delivery (CD) rates in referral and non-referral hospitals in Maternal Safety Collaboration in Jiangsu province, China.

Methods: Sixteen participants (4 referral hospitals, 12 non-referral hospitals) from Drum Tower Hospital Collaboration for Maternal Safety reported CD rates in 2019 using ten-group classification system and maternal/neonatal morbidity and mortality.

Results: A total of 22,676 CDs were performed among 52,499 deliveries and the average CD rate was 43.2% (range 34.8-69.6%). CD rate in non-referral hospitals (44.7%) was significantly higher than it was in referral hospitals (40.4%,  < .001). Term singleton cephalic nulliparous women with spontaneous labor (Group 1) or induced labor (Group 2a) had higher CD rates if they were cared in non-referral hospitals compared with those in referral hospitals (Group 1: 11.8% vs. 4.4%,  < .001; Group 2a: 29.1% vs. 21.3%,  < .001). In non-referral hospitals, CD rate in Group 5 and the proportion of Group 5 to the overall population were also significantly higher than those in referral hospitals (98.5% vs. 92.5%,  < .001; and 21.0% vs. 14.5%,  < .001).

Conclusion: To decrease the CD rate, we need to take efforts in decreasing unnecessary operations for term singleton cephalic nulliparous women and increasing the rate of trial of labor after CD.
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http://dx.doi.org/10.1080/14767058.2021.1887124DOI Listing
February 2021

[Progranulin (PGRN) promotes invasion and migration of mouse breast cancer 4T1 cells by promoting epithelial-mesenchymal transition of cancer cells and activating ERK1/2 pathway].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Feb;37(2):125-131

Ministry-of-Education Key Laboratory of Laboratory Medical Diagnostics, Chongqing Medical University, Chongqing 400016, China. *Corresponding author, E-mail:

Objective To investigate the effect of progranulin (PGRN) on the invasion and migration of mouse breast cancer 4T1 cells and its mechanism. Methods After treated with PGRN (1 μg/mL) for 24 hours, the invasion ability of breast cancer 4T1 cells was detected by Transwell invasion assay, the migration ability was detected by scratch test, and the epithelial cadherin (E-cadherin), vimentin mRNA expression was detected by real-time fluorescent quantitative PCR. Western blot assay was used to detect the expression of E-cadherin, vimentin, extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2). After treated with 1 μg/mL PGRN and ERK1/2 signaling pathway inhibitor U0126 (10 μmol/L) simultaneously, the migration and invasion ability of 4T1 cells and the changes in the expression of E-cadherin, vimentin and p-ERK proteins were detected again. Results After treated with PGRN, the migration and invasion capabilities of breast cancer 4T1 cells were significantly enhanced; E-cadherin expression decreased; vimentin and p-ERK1/2 expression increased. After treated with ERK1/2 signaling pathway inhibitor, the ability of PGRN to promote breast cancer 4T1 cell migration, invasion and epithelial-mesenchymal transition (EMT) was significantly inhibited. Conclusion PGRN can promote the migration and invasion of breast cancer 4T1 cells by promoting EMT and activating the ERK1/2 pathway.
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February 2021

Progranulin induces immune escape in breast cancer via up-regulating PD-L1 expression on tumor-associated macrophages (TAMs) and promoting CD8 T cell exclusion.

J Exp Clin Cancer Res 2021 Jan 4;40(1). Epub 2021 Jan 4.

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

Background: Progranulin (PGRN), as a multifunctional growth factor, is overexpressed in multiple tumors, but the role of PGRN on tumor immunity is still unclear. Here, we studied the effect of PGRN on breast cancer tumor immunity and its possible molecular mechanism.

Methods: The changes of macrophage phenotypes after PGRN treatment were detected by western blot, quantitative polymerase chain reaction (PCR) and flow cytometry. Western blot was used to study the signal molecular mechanism of PGRN regulating this process. The number and localization of immune cells in Wild-type (WT) and PGRN breast cancer tissues were analyzed by immunohistochemical staining and immunofluorescence techniques. The activation and proliferation of CD8 T cells were measured by flow cytometry.

Results: After being treated with PGRN, the expressions of M2 markers and programmed death ligand 1 (PD-L1) on macrophages increased significantly. Signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitor Stattic significantly inhibited the expression of PD-L1 and M2 related markers induced by PGRN. In WT group, CD8 were co-localized with macrophages and PD-L1, but not tumor cells. The number of immune cells in PGRN breast cancer tissue increased, and their infiltration into tumor parenchyma was also enhanced. Moreover, in the co-culture system, WT peritoneal macrophages not only reduced the ratio of activated CD8 T cells but also reduced the proportion of proliferating CD8 T cells. The addition of programmed death receptor 1 (PD-1) and PD-L1 neutralizing antibodies effectively reversed this effect and restored the immune function of CD8 T cells.

Conclusion: These results demonstrate that PGRN promotes M2 polarization and PD-L1 expression by activating the STAT3 signaling pathway. Furthermore, through PD-1/PD-L1 interaction, PGRN can promote the breast tumor immune escape. Our research may provide new ideas and targets for clinical breast cancer immunotherapy.
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http://dx.doi.org/10.1186/s13046-020-01786-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780622PMC
January 2021

PGRN TAMs-derived exosomes inhibit breast cancer cell invasion and migration and its mechanism exploration.

Life Sci 2021 Jan 9;264:118687. Epub 2020 Nov 9.

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, PR China. Electronic address:

Breast cancer is one of the most malignant diseases world-wide and ranks the first among female cancers. Progranulin (PGRN) plays a carcinogenic role in breast cancer, but its mechanisms are not clear. In addition, there are few reports on the relationship between PGRN and tumor-associated macrophages (TAMs).

Aims: To investigate the effects of exosomes derived from PGRN TAMs on invasion and migration of breast cancer cells.

Main Methods: Mouse breast cancer xenograft model was constructed to explore the effect of PGRN tumor environment (TME) on breast cancer. Flow cytometry was used to compare TAMs of wild type (WT) and PGRN tumor tissue. Transwell assay, wound healing assay and western blot were used to explore the effect of WT and PGRN TAMs and their exosomes on invasion, migration and epithelial-mesenchymal transition (EMT) of breast cancer cells. MicroRNA (miRNA) assay was used to find out the differentially expressed miRNA of negative control (NC) and siPGRN-TAMs exosomes. Quantitative PCR and luciferase report assay were used to explore the target gene.

Key Findings: The lung metastasis of breast cancer of PGRN mice was inhibited. PGRN TAMs inhibited invasion, migration and EMT of breast cancer cells through their exosomes. MiR-5100 of PGRN TAMs-derived exosomes was up-regulated, which might regulate expression of CXCL12, thereby inhibiting the CXCL12/CXCR4 axis, and ultimately inhibiting the invasion, migration and EMT of breast cancer cells.

Significance: Our study elucidates a new molecular mechanism of lung metastasis of breast cancer, so it may contribute to efficient prevention and therapeutic strategies.
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http://dx.doi.org/10.1016/j.lfs.2020.118687DOI Listing
January 2021

A genome-wide association study reveals a substantial genetic basis underlying the Ebbinghaus illusion.

J Hum Genet 2021 Mar 16;66(3):261-271. Epub 2020 Sep 16.

PKU-IDG/McGovern Institute for Brain Research, and Peking-Tsinghua Center for Life Sciences, Peking University, 100871, Beijing, China.

The Ebbinghaus illusion (EI) is an optical illusion of relative size perception that reflects the contextual integration ability in the visual modality. The current study investigated the genetic basis of two subtypes of EI, EI overestimation, and EI underestimation in humans, using quantitative genomic analyses. A total of 2825 Chinese adults were tested on their magnitudes of EI overestimation and underestimation using the method of adjustment, a standard psychophysical protocol. Heritability estimation based on common single nucleotide polymorphisms (SNPs) revealed a moderate heritability (34.3%) of EI overestimation but a nonsignificant heritability of EI underestimation. A meta-analysis of two phases (phase 1: n = 1986, phase 2: n = 839) of genome-wide association study (GWAS) discovered 1969 and 58 SNPs reaching genome-wide significance for EI overestimation and EI underestimation, respectively. Among these SNPs, 55 linkage-disequilibrium-independent SNPs were associated with EI overestimation in phase 1 with genome-wide significance and their associations could be confirmed in phase 2 cohort. Gene-based analyses found seven genes to be associated with EI overestimation at the genome-wide level, two from meta-analysis, and five from classical two-stage analysis. Overall, this study provided consistent evidence for a substantial genetic basis of the Ebbinghaus illusion.
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http://dx.doi.org/10.1038/s10038-020-00827-4DOI Listing
March 2021

Increased protection of earlier use of immunoprophylaxis in preventing perinatal transmission of hepatitis B virus.

Clin Infect Dis 2020 Jul 8. Epub 2020 Jul 8.

Department of Experimental Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.

Background: Passive-active immunoprophylaxis against mother-to-child transmission (MTCT) of hepatitis B virus (HBV) recommends administer hepatitis B immunoglobulin (HBIG) and birth dose hepatitis B vaccine in infants within 12 or 24 hours after birth. With this protocol, MTCT of HBV still occurs in 5-10% infants of HBV-infected mothers with positive hepatitis B e antigen (HBeAg).

Methods: The present study aimed to investigate whether earlier administration of HBIG and hepatitis B vaccine after birth can further increase the protection efficacy.

Results: Totally, 1140 HBV-infected pregnant women were enrolled, and 982 infants (9 twins) of 973 mothers were finally followed up at 9.6 ± 1.9 months age. HBIG and birth dose vaccine were administered in newborn infants with a median 0.17 hour (0.02-1.0) after birth. The overall rate of MTCT was 0.9% (9/982), with none (0%) of 607 infants of HBeAg-negative mothers and 9 (2.4%) of 375 infants of HBeAg-positive mothers. All nine HBV-infected infants were born to mothers with HBV DNA >2.75×106 IU/ml. Maternal HBV DNA levels >1×106 IU/ml was an independent risk factor (OR = 10.627, 95% CI: 2.135-+∞) for immunoprophylaxis failure.

Conslusions: Earlier use (within one hour after birth) of HBIG and hepatitis B vaccine can provide better protection efficacy against MTCT of HBV.
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http://dx.doi.org/10.1093/cid/ciaa898DOI Listing
July 2020

Nucleus-located PDK1 regulates growth, invasion and migration of breast cancer cells.

Life Sci 2020 Jul 26;253:117722. Epub 2020 Apr 26.

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, PR China. Electronic address:

Aims: It is well known that pyruvate dehydrogenase kinase 1 (PDK1) is highly expressed in breast cancer (BC) tissues and promotes tumor growth, but the underlying mechanisms of this process are unclear. Here, we investigated the effects of nuclear PDK1 on growth, migration and invasion in human BC cells.

Main Methods: The sub-cellular localization of PDK1 in BC cells was performed with subcellular fractionation followed by Western blot and immunofluorescence. The localization of PDK1 in breast normal tissue and breast duct carcinoma was detected by Immunohistochemistry. Then the protein-protein interaction between PDK1 and Importin β was verified by co-immunoprecipitation assay. Finally, the effects of nuclear PDK1 on cell proliferation, apoptosis, migration and invasion of BC cells were assessed.

Key Findings: In addition to its well-known sub-cellular localization, PDK1 was present in the nucleus of BC cells, and EGF treatment increased nucleus distribution of PDK1. Moreover, the level of nuclear PDK1 accumulation facilitated the growth of BC cells. We also found that the entry of PDK1 into nucleus mainly relied on the nuclear localization signal (NLS), and NLS mutation inhibited the entry of PDK1 into nucleus; as a result, the migration and invasion abilities of BC cells were impaired, and the number of apoptotic cells was significantly increased.

Significance: Our findings provided a new supplement to the sub-cellular localization of PDK1 in BC cells and uncovered the function of nuclear PDK1 in facilitating BC cells growth, migration and invasion.
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http://dx.doi.org/10.1016/j.lfs.2020.117722DOI Listing
July 2020

CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells.

Cell Death Dis 2020 04 27;11(4):293. Epub 2020 Apr 27.

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Non-traumatic osteonecrosis of the femoral head (ONFH) is clinically a devastating and progressive disease without an effective treatment. Mesenchymal stem cells (MSCs) transplantation has been used to treat ONFH in early stage, but the failure rate of this therapy is high due to the reduced osteogenic differentiation and migration of the transplanted MSCs related with pathological bone tissues. However, the mechanism responsible for this decrease is still unclear. Therefore, we assume that the implanted MSCs might be influenced by signals delivered from pathological bone tissue, where the exosomes might play a critical role in this delivery. This study showed that exosomes from ONFH bone tissues (ONFH-exos) were able to induce GC-induced ONFH-like damage, in vivo and impair osteogenic differentiation and migration of MSCs, in vitro. Then, we analyzed the differentially expressed proteins (DEPs) in ONFH-exos using proteomic technology and identified 842 differentially expressed proteins (DEPs). On the basis of gene ontology (GO) enrichment analysis of DEPs, fold-changes and previous report, cell adhesion-related CD41 (integrin α2b) was selected for further investigation. Our study showed that the CD41 (integrin α2b) was distinctly decreased in ONFH-exos, compared to NOR-exos, and downregulation of CD41 could impair osteogenic differentiation and migration of the MSCs, where CD41-integrin β3-FAK-Akt-Runx2 pathway was involved. Finally, our study further suggested that CD41-affluent NOR-exos could restore the glucocorticoid-induced decline of osteogenic differentiation and migration in MSCs, and prevent GC-induced ONFH-like damage in rat models. Taken together, our study results revealed that in the progress of ONFH, exosomes from the pathological bone brought about the failure of MSCs repairing the necrotic bone for lack of some critical proteins, like integrin CD41, and prompted the progression of experimentally induced ONFH-like status in the rat. CD41 could be considered as the target of early diagnosis and therapy in ONFH.
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http://dx.doi.org/10.1038/s41419-020-2496-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184624PMC
April 2020

Early diagnosis and precision treatment of right ovarian vein and inferior vena cava thrombosis following caesarean section: A case report.

Exp Ther Med 2020 Apr 25;19(4):2923-2926. Epub 2020 Feb 25.

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.

Ovarian vein thrombosis (OVT) is a rare medical complication that is most often diagnosed in the post-partum period. OVT can lead to conditions, including sepsis, inferior vena cava (IVC), pulmonary emboli and mortality. The current study outlines a case of a patient who experienced pain in the lower abdomen and waist without fever postpartum following caesarean section (CS). Plasma FDP, D-Dimer and fibrinogen levels were markedly increased following CS and this was an indicator of the rapid progression of blood coagulation and fibrinolysis. Increased maternal lipid may be one of the risk factors for thrombosis. Based on the clinical presentation, a CT scan demonstrated thrombosis of the right ovarian vein and inferior vena cava, and a diagnosis of OVT and IVC thrombosis was subsequently made. In the current case, an anticoagulant therapy was started with a subcutaneous injection low molecular weight heparin calcium, an intravenous urokinase drip as a thrombolytic agent and implantation of inferior vena cava filters as a novel method of treatment for thrombosis. The patient was discharged from hospital 20 days following treatment in a good condition. The current study reports a case of OVT associated with IVC that was successfully managed without complication.
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http://dx.doi.org/10.3892/etm.2020.8548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086212PMC
April 2020

[Molecular mechanism of macrophages derived from PGRN gene knockout mice inhibit invasion and migration of breast cancer cells].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2019 Sep;35(9):769-775

Ministry-of-Education Key Laboratory of Laboratory Medical Diagnostics, Chongqing Medical University, Chongqing 400016, China. *Corresponding author, E-mail:

Objective To explore the functions and mechanisms of macrophages derived from PGRN gene knockout (PGRN ) C57BL/6 mice in the invasion and migration of breast cancer cells. Methods Breast cancer cells were cultured in conditioned medium of macrophages derived from WT and PGRN mice. Transwell assay and scratch assay were used to detect the invasion and migration ability of cancer cells. Western blot analysis was used to detect the expression of E-cadherin and N-cadherin in cancer cells. Cytokine array, real-time quantitative PCR and ELISA were performed to investigate the differences of cytokines secreted by macrophages derived from WT and PGRN mice. Breast cancer cells were treated by the differentially expressed cytokine interleukin-6 (IL-6), and then the above methods were used to investigate its effect on cancer cells. Western blot analysis was used to verify the roles of NF-κB and JAK/STAT3 signaling pathways. Results The macrophages derived from PGRN mice blocked NF-κB signaling pathway, reduced IL-6 secretion, and inhibited the invasion and migration of breast cancer cells. IL-6 activated JAK/STAT3 signaling pathway to promote the invasion and migration of breast cancer cells. Conclusion The macrophages derived from PGRN mice can block the NF-κB and JAK/STAT3 signaling pathways, down-regulate IL-6 expression, and inhibit the invasion and migration of breast cancer cells.
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September 2019

Gene expression profiling of the bone trabecula in patients with osteonecrosis of the femoral head by RNA sequencing.

J Biochem 2019 Dec;166(6):475-484

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, 1 Yi Xue Yuan Road, Yu Zhong District, Chongqing 400016, China.

Early diagnosis and treatment of osteonecrosis of the femoral head (ONFH) is challenging. Bone trabecula play a vital role in the severity and progression of ONFH. In the present study, the investigators used gene expression profiling of bone trabecula to investigate gene alterations in ONFH patients. Osteonecrotic bone trabecula (ONBT) such as necrosis, fibrosis, and lacuna were confirmed by histological examination in the patients. The adjacent 'normal' bone trabecula (ANBT) did not show any pathological changes. Gene sequencing data revealed that although ANBT showed no significant histological changes, alteration of mRNA profiling in ANBT was observed, similar to that in ONBT. Our results indicated that the alteration of mRNA profiling in ANBT may cause normal bone tissue to develop into necrotic bone. RNA-seq data indicated that 2,297 differentially abundant mRNAs were found in the ONBT group (1,032 upregulated and 1,265 downregulated) and 1,523 differentially abundant mRNAs in the ANBT group (744 upregulated and 799 downregulated) compared with the healthy control group. Gene ontology (GO) enrichment analysis suggested that fatty acid metabolism and degradation were the main zones enriched with differentially expressed genes (DEG). Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis indicated that peroxisome proliferator-activated receptor γ (PPAR-γ) pathway was the most significantly regulated pathway. Lipocalin-2 (LCN2), an osteoblast-enriched secreted protein, was significantly decreased in ONBT suggesting that downregulation of LCN2 might affect lipid metabolism and lead to hyperlipidemia, and thus promote pathogenesis of ONFH.
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http://dx.doi.org/10.1093/jb/mvz060DOI Listing
December 2019

Heritability of human visual contour integration-an integrated genomic study.

Eur J Hum Genet 2019 12 30;27(12):1867-1875. Epub 2019 Jul 30.

PKU-IDG/McGovern Institute for Brain Research, and Peking-Tsinghua Center for Life Sciences, Peking University, 100871, Beijing, China.

Contour integration, a key visual function to deal with occlusion and discontinuity in natural scenes, is essential to human survival. However, individuals are not equally well equipped with this ability. In particular, contour integration deficiencies are commonly detected in patients with mental disorders, especially schizophrenia. To understand the underlying sources of these individual differences, the current study investigated the genetic basis of contour integration in humans. A total of 2619 normal participants were tested on their ability to detect continuous contours embedded in a cluttered background. Quantitative genomic analysis was performed, involving heritability estimation based on single nucleotide polymorphisms (SNPs) and association testing at SNP, gene, and pathway levels. Heritability estimation showed that common SNPs contributed 49.5% (standard error of the mean = 15.6%) of overall phenotypic variation, indicating moderate heritability of contour integration. Two-stage genome-wide association analysis (GWAS) detected four SNPs reaching genome-wide significance in the discovery test (N = 1931) but not passing the replication test (N = 688). Gene-level analysis further revealed a significant genome-wide association of a microRNA-encoding gene MIR1178 in both the discovery and replication cohorts. Another gene poly(A)-binding protein nuclear 1 like, cytoplasmic (PABPN1L) showed suggestive significance in the discovery cohort (p < 1 × 10) and was replicated in the replication cohort (p = 0.009). The pathway analysis did not detect any significant pathway. Taken together, this study identified significant gene associations with contour integration and provided support for a genetic transmission of the ability to perceive continuous contours in the environment.
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http://dx.doi.org/10.1038/s41431-019-0478-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6871533PMC
December 2019

High mutation prevalence of precore and basal core promoter in pregnant women who underwent spontaneous HBeAg seroconversion within one year postpartum.

Dig Liver Dis 2020 02 15;52(2):199-204. Epub 2019 Jul 15.

Department of Laboratory Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China; Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing Medical University, Jiangsu, China. Electronic address:

Background: Seroconversion of hepatitis B e antigen (HBeAg) is a critical event in the natural course of hepatitis B virus (HBV) infection.

Aim: We herein characterize the virological factors associated with postpartum spontaneous HBeAg seroconversion.

Methods: A total of 214 pregnant women positive for both hepatitis B surface antigen (HBsAg) and HBeAg were followed up at 7-12 months postpartum.

Results: Of the subjects, 26 (12.1%) achieved spontaneous HBeAg seroconversion. Receiver operating curve analysis indicated that HBV DNA level <1.0 × 10 IU/mL, HBsAg <1.0 × 10 IU/mL and HBeAg <7.36 × 10 S/CO each independently predicted HBeAg seroconversion within 12 months postpartum. At delivery, 73.1% (19/26) women with postpartum HBeAg seroconversion had precore (PC) and/or basal core promoter (BCP) mutations, higher than that (5/36, 13.9%) in the women without postpartum seroconversion. Binary logistic regression analysis indicated that the presence of mutations in PC, BCP, and both PC and BCP at delivery was associated with an increased likelihood (OR = 13.286, 16. 238, and 22.143 respectively, all P < 0.05) to undergo postpartum spontaneous HBeAg seroconversion.

Conclusion: These results suggest that quantitative determination of virological markers and sequencing PC and BCP can predict spontaneous HBeAg seroconversion, which could be valuable in deciding antiviral therapy against HBV.
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http://dx.doi.org/10.1016/j.dld.2019.06.021DOI Listing
February 2020

Fiber optic surface plasmon resonance biosensor for detection of PDGF-BB in serum based on self-assembled aptamer and antifouling peptide monolayer.

Biosens Bioelectron 2019 Sep 25;140:111350. Epub 2019 May 25.

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, PR China. Electronic address:

Herein, a home-build fiber optic surface plasmon resonance (FO-SPR) biosensing platform has been developed for highly sensitive detection of platelet-derived growth factor (PDGF-BB) based aptamer-functionalized AuNPs for signal enhancement. In this biosensor, the PDGF-BB aptamer was used to specifically capture PDGF-BB, and the antifouling peptide demonstrated great ability for resisting non-specific adsorption. After a sandwich reaction, the aptamer, PDGF-BB and aptamer-functionalized AuNPs complexes were formed on the fiber optic (FO) probe surface to significantly amplify FO-SPR signal. This method exhibited a broad detection range from 1 to 1000 pM of PDGF-BB and a low detection limit of 0.35 pM. Moreover, this biosensor was successfully applied to the detection of PDGF-BB in 10% human serum samples without suffering from serious interference owing to the excellent antifouling property of the peptide. Thus, this developed FO-SPR biosensor could be a potential alternative device for proteins determination, even as a point-of-care diagnostic tool (POCT) in clinical application.
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http://dx.doi.org/10.1016/j.bios.2019.111350DOI Listing
September 2019

The miR-186-3p/EREG axis orchestrates tamoxifen resistance and aerobic glycolysis in breast cancer cells.

Oncogene 2019 07 9;38(28):5551-5565. Epub 2019 Apr 9.

Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, 400016, Chongqing, China.

Tamoxifen resistance is one of the major challenges for its medical uses in estrogen receptor (ER)-positive breast cancer. Aerobic glycolysis, an anomalous characteristic of glucose metabolism in cancer cells, has been shown to associate with the resistance to chemotherapeutic agents. It remains, however, largely unclear whether and how tamoxifen resistance contributes to aerobic glycolysis in breast cancer. Here, we report that tamoxifen resistance is associated with enhanced glycolysis in ER-positive breast cancer cells. We demonstrate that EREG, an agonist of EGFR, has an important role in enhancing glycolysis via activating EGFR signaling and its downstream glycolytic genes in tamoxifen-resistant breast cancer cells. We further show that EREG is a direct target of miR-186-3p and that downregulation of miR-186-3p by tamoxifen results in EREG upregulation in tamoxifen-resistant breast cancer cells. Importantly, systemic delivery of cholesterol-modified agomiR-186-3p to mice bearing tamoxifen-resistant breast tumors effectively attenuates both tumor growth and [F]-fluoro-deoxyglucose ([F]-FDG) uptake. Together, our results reveal a novel molecular mechanism of resistance to hormone therapies in which the miR-186-3p/EREG axis orchestrates tamoxifen resistance and aerobic glycolysis in ER-positive breast cancer, suggesting targeting miR-186-3p as a promising strategy for therapeutic intervention in endocrine-resistant breast tumors.
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http://dx.doi.org/10.1038/s41388-019-0817-3DOI Listing
July 2019

Global urinary metabolic profiling of the osteonecrosis of the femoral head based on UPLC-QTOF/MS.

Metabolomics 2019 02 20;15(3):26. Epub 2019 Feb 20.

Department of Orthopedics, Fuling Center Hospital of Chongqing City, Chongqing, 408000, China.

Introduction: Osteonecrosis of the femoral head (ONFH), one of the widespread orthopedic diseases with a decrease in bloodstream to the femoral head, is frequently accompanied by cellular death, trabecula fracture, and collapse of the articular surface. The exactly pathological mechanism of ONFH remains to explore and further identify.

Objectives: The aim was to identify the global urinary metabolic profiling of ONFH and to detect biomarkers of ONFH.

Methods: Urine samples were collected from 26 ONFH patients and 26 healthy people. Ultra-performance liquid chromatography-quadrupole time of flight tandem mass spectrometry (UPLC-QTOF/MS) in combination with multivariate statistical analysis was developed and performed to identify the global urinary metabolic profiling of ONFH.

Results: The urinary metabolic profiling of ONFH group was significantly separated from the control group by multivariate statistical analysis. 33 distinctly differential metabolites were detected between the ONFH patients and healthy people. Sulfate, urea, Deoxycholic acid and PE(14:0/14:1(9Z)) were screened as the potential biomarkers of ONFH. In addition, the up/down-regulation of sulfur metabolism, cysteine and methionine metabolism, glycerophospholipid metabolism, and histidine metabolism were clearly be associated with the ONFH pathogenic progress.

Conclusion: Our results suggested that metabolomics could serve as a promising approach for identifying the diagnostic biomarkers and elucidating the pathological mechanism of ONFH.
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http://dx.doi.org/10.1007/s11306-019-1491-8DOI Listing
February 2019

Successful rescue of antepartum eclampsia in a Chinese patient: Case report.

Medicine (Baltimore) 2019 Feb;98(6):e14301

Central Laboratory of Medicine, Maternity and Child Health Hospital of Zhenjiang, Zhenjiang, Jiangsu, P.R. China.

Rationale: Eclampsia is a life-threatening complication of pregnancy. Eclampsia is a leading cause of maternal and neonatal morbidity and mortality with most injury being associated with the seizures that mark the onset of the disease. It is vital that medical worker managing eclampsia have an understanding of the disease process.

Patient Concerns: A 28-year-old female, G4P1, with history of caesarean section was admitted at GA34+6, in addition to headache and severe hypertension (180/120 mm Hg) and proteinuria (+++). The evaluation of coagulation parameters showed positive D-dimer and increased fibrinogen and fibrinogen degradation product (FDP) and PT percent activity. Her biochemical analysis showed a decrease in total protein and an increase in alanine transaminase (ALT) and lactate dehydrogenase (LDH) and high serum uric acid and hyperlipidemia.

Diagnoses: She was diagnosed with severe preeclampsia (PE).

Interventions: First, the patient received magnesium sulfate therapy for convulsions control. Next, antihypertensive management of labetalol orally at a dose 100 mg and nifedipine orally at a dose 10 mg and glycerin trinitrate10 mg iv were used to maintain blood pressure in a safe range. Then, corticosteroid was given for enhancing fetal lung maturation. During preparation for cesarean section, the patient experienced suddenly seizures that lasted approximately 2 to 8 minutes. The immediate therapy is to stop the convulsions and reduce blood pressure.

Outcomes: The patient and her baby were discharged from the hospital on the 7th day after the operation with normal blood pressure and being in a satisfactory condition.

Lessons: Eclampsia is defined as the occurrence of convulsions superimposed on the preeclampsia. The awareness of eclampsia enhances early diagnosis and timely administration of magnesium sulfate and calmative drug which are critical to avoid feto-maternal complications.
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http://dx.doi.org/10.1097/MD.0000000000014301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380709PMC
February 2019

Presence of hepatitis B virus markers in umbilical cord blood: Exposure to or infection with the virus?

Dig Liver Dis 2019 06 20;51(6):864-869. Epub 2018 Nov 20.

Department of Laboratory Medicine, Nanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China; Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing Medical University, Nanjing, China. Electronic address:

Background: We aimed to clarify whether presence of hepatitis B virus (HBV) markers in cord blood indicates exposure to or infection with HBV.

Methods: We prospectively recruited HBsAg-positive pregnant women and their neonates 2012 through 2015. All neonates received postnatal immunoprophylaxis. The infants were followed up at 7-14 months of age.

Results: Totally 329 HBsAg-positive pregnant women and 333 neonates were enrolled. No cord blood was anti-HBc IgM positive. A total of 290 (87.1%) neonates were followed up at 7-14 months of age and 6 (2.1%) of them were infected with HBV. Of 146 neonates born to HBeAg-negative mothers, 38 (26.0%) and 30 (20.5%) had detectable HBsAg and HBV DNA in cord blood respectively, but none of 126 infants followed up was infected. Of 187 neonates born to HBeAg-positive mothers, 92 (49.2%) and 79 (42.2%) had detectable HBsAg and HBV DNA in cord blood respectively; 6 (3.7%) of 164 infants followed up were infected. Of seven neonates with HBV DNA > 10 IU/ml in cord blood, four had no infection and three others were infected.

Conclusion: Presence of HBsAg and/or HBV DNA, even at high levels, in cord blood just indicates exposure to, but not infection with HBV. Presence of HBV markers in cord blood cannot define intrauterine infection.
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http://dx.doi.org/10.1016/j.dld.2018.11.003DOI Listing
June 2019

Genomic Analyses of Visual Cognition: Perceptual Rivalry and Top-Down Control.

J Neurosci 2018 11 21;38(45):9668-9678. Epub 2018 Sep 21.

PKU-IDG/McGovern Institute for Brain Research,

Visual cognition in humans has traditionally been studied with cognitive behavioral methods and brain imaging, but much less with genetic methods. Perceptual rivalry, an important phenomenon in visual cognition, is the spontaneous perceptual alternation that occurs between two distinct interpretations of a physically constant visual stimulus (e.g., binocular rivalry stimuli) or a perceptually ambiguous stimulus (e.g., the Necker cube). The switching rate varies dramatically across individuals and can be voluntarily modulated by observers. Here, we adopted a genomic approach to systematically investigate the genetics underlying binocular rivalry, Necker cube rivalry and voluntary modulation of Necker cube rivalry in young Chinese adults (, 81% female, 20 ± 1 years old) at multiple levels, including common single nucleotide polymorphism (SNP)-based heritability estimation, SNP-based genome-wide association study (GWAS), gene-based analysis, and pathway analysis. We performed a pilot GWAS in 2441 individuals and replicated it in an independent cohort of 943 individuals. Common SNP-based heritability was estimated to be 25% for spontaneous perceptual rivalry. SNPs rs184765639 and rs75595941 were associated with voluntary modulation, and imaging data suggested genotypic difference of rs184765639 in the surface area of the left caudal-middle frontal cortex. Additionally, converging evidence from multilevel analyses associated genes such as with perceptual switching rate, and with voluntary modulation strength. In summary, this study discovered specific genetic contributions to perceptual rivalry and its voluntary modulation in human beings. These findings may promote our understanding of psychiatric disorders, as perceptual rivalry is a potential psychiatric biomarker. Perceptual rivalry is an important visual phenomenon in which our perception of a physically constant visual input spontaneously switches between two different states. There are individual variations in perceptual switching rate and voluntary modulation strength. Our genomic analyses reveal several loci associated with these two kinds of variation. Because perceptual rivalry is thought to be relevant to and potentially an endophenotype for psychiatric disorders, these results may help understand not only visual cognition, but also psychiatric disorders.
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http://dx.doi.org/10.1523/JNEUROSCI.1970-17.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595983PMC
November 2018

Global prevalence of hepatitis B virus infection and prevention of mother-to-child transmission.

Lancet Gastroenterol Hepatol 2018 09 8;3(9):598-599. Epub 2018 Aug 8.

Department of Obstetrics and Gynaecology, Zhenjiang Fourth People's Hospital, Jiangsu University Medical School, Zhenjiang 212001, Jiangsu, China. Electronic address:

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http://dx.doi.org/10.1016/S2468-1253(18)30198-5DOI Listing
September 2018

Comparison of hepatitis B viral loads and viral antigen levels in child-bearing age women with and without pregnancy.

BMC Pregnancy Childbirth 2018 Jul 6;18(1):292. Epub 2018 Jul 6.

Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.

Background: Pregnancy is a unique physiological condition with the cellular immune functions compromised at some extents to allow the mature of growing fetus. Whether pregnancy may influence the replication of hepatitis B virus (HBV) is less studied. The present study aimed to investigate the influence of pregnancy on the replication of HBV and expression of viral antigens by comparing the levels of HBV DNA and viral antigens in pregnant and non-pregnant women.

Methods: A total of 727 HBsAg-positive serum samples, collected from 214 pregnant women and 513 non-pregnant women of childbearing age, were included. Based on the pregnancy status, subjects were divided into four groups: nulliparous (n = 158), pregnant (n = 214), 7-12 months postpartum (n = 170), and 2-5 years postpartum (n = 185). The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were quantitatively measured with microparticle enzyme immunoassay. HBV DNA levels were detected by fluorescent real-time PCR.

Results: The median ages of four groups were 25.0, 25.3, 26.2 and 29.3 years, respectively (p < 0.01). HBeAg-positive proportions were 34.2, 33.6, 35.3 and 29.2%, respectively (p = 0.624). HBV DNA levels in HBeAg-positive women were higher than those in HBeAg-negative women (7.88 vs 2.62 log IU/ml, p < 0.001). HBV DNA levels in the four groups with positive HBeAg were 7.8, 7.7, 8.0 and 8.0 log IU/ml, respectively (p = 0.057), while HBsAg titers were 4.4, 4.5, 4.6 and 4.8 log IU/ml (p = 0.086) and HBeAg titers were 3.1, 3.0, 3.1 and 3.0 log S/CO (p = 0.198). In the four groups with negative HBeAg, HBV DNA levels were 2.3, 2.6, 2.5 and 2.8 log IU/ml, respectively (p = 0.085), while HBsAg titers were 3.1, 3.3, 3.3 and 3.0 log IU/ml (p = 0.06).

Conclusions: Serum levels of HBV DNA and viral antigens showed no significant changes in nulliparous, pregnant, and postpartum women, regardless of the HBeAg status. The results indicate that pregnancy has little influence on the replication of HBV and the expression of viral antigens.
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http://dx.doi.org/10.1186/s12884-018-1932-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035447PMC
July 2018

Maternal lipids, BMI and IL-17/IL-35 imbalance in concurrent gestational diabetes mellitus and preeclampsia.

Exp Ther Med 2018 Jul 10;16(1):427-435. Epub 2018 May 10.

Department of Obstetrics, Maternity and Child Health Hospital of Zhenjiang, Zhenjiang, Jiangsu 212001, P.R. China.

The objective of the present study was to investigate the role of blood glucose, lipid metabolism, body mass index (BMI), C-reactive protein (CRP) as well as an interleukin (IL)-17/IL-35 imbalance in the pathogenesis of concurrent gestational diabetes mellitus (GDM) and preeclampsia (PE) (DPE). The mRNA expression of forkhead box protein 3 (FoxP3), IL-35 [including Epstein-Barr virus-induced gene 3 (EBI3) and P35 subunits] and IL-17 in the peripheral blood mononuclear cells of patients with DPE (n=30), GDM (n=33), PE (n=33) and normal pregnancy (n=33) were determined by reverse transcription-quantitative polymerase chain reaction. The serum levels of IL-35, IL-17 and CRP were analyzed using ELISA. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and fasting blood glucose (FBG) were also detected. The levels of low-density lipoprotein (LDL) were calculated using the Friedewald formula. Body weight and height were determined in order to calculate the BMI. It was observed that the levels of FBG were markedly elevated in patients with GDM, PE and DPE. In addition, significantly higher serum TG, TC, LDL and very LDL were detected in patients with GDM, PE and DPE compared with those in subjects with normal pregnancies. By contrast, the concentration of HDL was lower in the patient groups. In addition, higher BMI values were identified in patients with GDM, PE and DPE. A decreased expression of FoxP3, P35 and EBI3 mRNA, and an elevated expression of IL-17 in PBMCs was detected in patients with GDM, PE and DPE. In addition, higher serum levels of IL-17 and CRP, as well as lower levels of IL-35, were observed. Furthermore, in patients with DPE, positive correlations of diastolic blood pressure with IL-17 levels, BMI and TG, as well as IL-17 levels with BMI and proteinuria were identified. In conclusion, the present study indicated that abnormal maternal lipids, hyperglycemia, high BMI, high CRP and IL-17/IL-35 imbalance may have a role in the pathophysiology of DPE. Therefore, pregnant women and clinicians should be made aware that maternal hyperlipidaemia, hyperglycemia, high BMI, high CRP levels and IL-17/IL-35 imbalance may lead to DPE.
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http://dx.doi.org/10.3892/etm.2018.6144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030913PMC
July 2018

Multi-level genomic analyses suggest new genetic variants involved in human memory.

Eur J Hum Genet 2018 11 3;26(11):1668-1678. Epub 2018 Jul 3.

PKU-IDG/McGovern Institute for Brain Research, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Beijing Innovation Center for Genomics, Peking University, 100871, Beijing, China.

Development of high-throughput genotyping platforms provides an opportunity to identify new genetic elements related to complex cognitive functions. Taking advantage of multi-level genomic analysis, here we studied the genetic basis of human short-term (STM, n = 1623) and long-term (LTM, n = 1522) memory functions. Heritability estimation based on single nucleotide polymorphism showed moderate (61%, standard error 35%) heritability of short-term memory but almost zero heritability of long-term memory. We further performed a two-step genome-wide association study, but failed to find any SNPs that could pass genome-wide significance and survive replication at the same time. However, suggestive significance for rs7011450 was found in the shared component of the two STM tasks. Further inspections on its nearby gene zinc finger and at-hook domain containing and SNPs around this gene showed suggestive association with STM. In LTM, a polymorphism within branched chain amino acid transaminase 2 showed suggestive significance in the discovery cohort and has been replicated in another independent population of 1862. Furthermore, we performed a pathway analysis based on the current genomic data and found pathways including mTOR signaling and axon guidance significantly associated with STM capacity. These findings warrant further replication in other larger populations.
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http://dx.doi.org/10.1038/s41431-018-0201-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189113PMC
November 2018

A hybridization chain reaction amplification strategy for fluorescence imaging of human telomerase activity in living cells.

Methods Appl Fluoresc 2018 Jul 13;6(4):045003. Epub 2018 Jul 13.

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, People's Republic of China.

A hybridized chain reaction (HCR)-based biosensing method has been developed for the imaging detection of intracellular telomerase activity. The telomerase-targeting responder-transmitter DNA complex (HPT) consisting of telomerase primer sequence (HP) and a HCR initiator (trigger) is transfected into cell plasma. In the presence of telomerase, HPT can be recognized and extended, producing plenty of triggers which initiate HCR amplification reaction. Finally, a long nicked dsDNA with a lot of outstretched single chains was formed by hybridizing with Q of the reporter complex, generating an enhanced fluorescence signal. The developed biosensing approach can be used for the detection of telomerase activity in cell lysate with the detection limit of 578 cells/100 μl. In addition, this strategy has been successfully applied not only for the sensitive and specific imaging of telomerase activity in living cells but also for comparing of telomerase activity among different cell lines. Therefore, the method might become a potential alternative tool for telomerase-related cancer diagnosis and therapy in medical research and early clinical diagnosis.
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http://dx.doi.org/10.1088/2050-6120/aacdedDOI Listing
July 2018

Nature vs. nurture in human sociality: multi-level genomic analyses of social conformity.

J Hum Genet 2018 May 26;63(5):605-619. Epub 2018 Feb 26.

Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing Advanced Innovation Center for Genomics, Peking University, 100871, Beijing, China.

Social conformity is fundamental to human societies and has been studied for more than six decades, but our understanding of its mechanisms remains limited. Individual differences in conformity have been attributed to social and cultural environmental influences, but not to genes. Here we demonstrate a genetic contribution to conformity after analyzing 1,140 twins and single-nucleotide polymorphism (SNP)-based studies of 2,130 young adults. A two-step genome-wide association study (GWAS) revealed replicable associations in 9 genomic loci, and a meta-analysis of three GWAS with a sample size of ~2,600 further confirmed one locus, corresponding to the NAV3 (Neuron Navigator 3) gene which encodes a protein important for axon outgrowth and guidance. Further multi-level (haplotype, gene, pathway) GWAS strongly associated genes including NAV3, PTPRD (protein tyrosine phosphatase receptor type D), ARL10 (ADP ribosylation factor-like GTPase 10), and CTNND2 (catenin delta 2), with conformity. Magnetic resonance imaging of 64 subjects shows correlation of activation or structural features of brain regions with the SNPs of these genes, supporting their functional significance. Our results suggest potential moderate genetic influence on conformity, implicate several specific genetic elements in conformity and will facilitate further research on cellular and molecular mechanisms underlying human conformity.
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http://dx.doi.org/10.1038/s10038-018-0418-yDOI Listing
May 2018

[Verteporfin inhibits proliferation, invasion and migration of MDA-MB-231 human breast cancer cells by down-regulating the expression of Yes-associated protein].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2017 Sep;33(9):1223-1227

Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, Chongqing Medical University, Chongqing 400016, China. *Corresponding author, E-mail:

Objective To investigate the effects of verteporfin on the proliferation, invasion and migration of human breast cancer MDA-MB-231 cells and the underlying mechanism. Methods MDA-MB-231 cells in the logarithmic growth phase were randomly divided into control group and verteporfin treatment group. After MDA-MB-231 cells were treated with (0, 4, 8, 12, 16) μmol/mL verteporfin, the minimal inhibitory concentration was determined by CCK-8 assay. After treatment with 4 μmol/mL verteporfin, the invasion and migration abilities of MDA-MB-231 cells were detected by Transwell invasion assay and scratch wound healing assay, respectively. The expression levels of proliferation-associated proteins c-MYC, cyclin D1, Yes-associated protein (YAP), cysteine-rich protein 61 (CYR61) and connective tissue growth factor (CTGF) in MDA-MB-231 cells treated by (0, 4, 8, 12, 16) μmol/mL verteporfin were determined by Western blotting. Results Verteporfin markedly inhibited the proliferation of MDA-MB-231 cells in a dose-dependent manner, and the minimal inhibitory concentration was 4 μmol/mL. The 4 μmol/mL verteporfin significantly inhibited the invasion and migration abilities of MDA-MB-231 cells. Verteporfin inhibited significantly the expressions of c-MYC, cyclin D1, YAP, CYR61 and CTGF. Conclusion Verteporfin significantly inhibits the proliferation, invasion and migration of MDA-MB-231 cells by down-regulating the expressions of YAP and its target genes CYR61 and CTGF.
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September 2017

Cisplatin-induced autophagy protects breast cancer cells from apoptosis by regulating yes-associated protein.

Oncol Rep 2017 Dec 16;38(6):3668-3676. Epub 2017 Oct 16.

Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China.

Breast cancer is a common cause of cancer‑related deaths in women. Treatment with cisplatin exhibits some therapeutic efficacy. However, treatment optimization is required, and the mechanisms underlying the cisplatin's proapoptotic effects remain unclear. In the present study, we demonstrated that cisplatin induced apoptosis and autophagy in breast cancer cells. Autophagy induced by cisplatin played a protective role in breast cancer cells, which impaired its proapoptotic effect. Mechanistically, for the first time, we found that cisplatin treatment activated the MAPK signaling pathway and promoted autophagy via the ERK signaling pathway. Notably, we found that nuclear translocation of yes-associated protein (YAP) was regulated by cisplatin-induced autophagy, and we identified YAP as a survival input that promoted survival in cisplatin-treated breast cancer cells. These findings revealed that administration of cisplatin along with an autophagy inhibitor is a promising therapeutic strategy for treating breast cancer.
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http://dx.doi.org/10.3892/or.2017.6035DOI Listing
December 2017

Leptin promotes the migration and invasion of breast cancer cells by upregulating ACAT2.

Cell Oncol (Dordr) 2017 Dec 2;40(6):537-547. Epub 2017 Aug 2.

Department of Otolarynology, Chongqing Medical University, Chongqing, 400016, China.

Background: Previously, it has been shown that obesity may be considered as a risk factor for breast cancer in postmenopausal women. Leptin, a hormone whose level is elevated in obesity, has been suggested to be involved in the development of breast cancer, and univariate survival analyses have shown that over-expression of ACAT2, an enzyme that is involved in the production of cholesteryl esters, may be associated with a poor prognosis. Here, we aimed to investigate the effect of leptin on the proliferation, migration and invasion of breast cancer cells, as well as to elucidate its underlying mode of action.

Methods: Gene expression changes in leptin treated breast cancer-derived MCF-7, T47D and BT474 cells were assessed using PCR array, qRT-PCR and Western blot analyses. The expression patterns of Ob-R (leptin receptor) and ACAT2 in breast cancer cells and primary breast cancer tissue samples were analyzed using immunofluorescence and immunohistochemistry, respectively. Leptin-induced proliferation of breast cancer cells was assessed using a CCK8 assay, and scratch wound and Transwell assays were used to assess breast cancer cell invasion and migration.

Results: We found that, among the genes tested, ACAT2 expression exhibited the most significant changes in the leptin treated cells. In addition, we found that inhibition of ACAT2 expression using pyripyropene A (PPPA) or siRNA-mediated gene silencing significantly decreased leptin-induced proliferation, migration and invasion of MCF-7 and T47D cells. Subsequent Western blot analyses strongly indicated that the PI3K/AKT/SREBP2 signaling pathway was involved in leptin-induced ACAT2 upregulation in both MCF-7 and T47D cells. Finally, through the analysis of primary breast cancer tissue samples we found that ACAT2 may affect cancer progression through activation of the Ob-R.

Conclusions: Our data indicate that leptin may enhance the proliferation, migration and invasion of breast cancer cells via ACAT2 up-regulation through the PI3K/AKT/SREBP2 signaling pathway. Therefore, the leptin/ACAT2 axis may represent an attractive therapeutic target for breast cancer, particularly in postmenopausal and/or obese women.
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http://dx.doi.org/10.1007/s13402-017-0342-8DOI Listing
December 2017

Pyruvate kinase M2 interacts with mammalian sterile 20-like kinase 1 and inhibits tamoxifen-induced apoptosis in human breast cancer cells.

Tumour Biol 2017 Apr;39(4):1010428317692251

1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China.

Tamoxifen has been reported to be associated with antagonism of estrogen-mediated cell growth signaling and activation of estrogen receptor-independent apoptosis events. It has been demonstrated that mammalian sterile 20-like kinase 1 is a direct target of Caspases to amplify the apoptotic signaling pathway. Here, we presented that breast cancer MCF-7 and SKBR3 cells under treatment with 4-hydroxytamoxifen displayed decreased level of pyruvate kinase M2. Western blot results also showed that 4-hydroxytamoxifen induced the activity of pro-apoptotic protein Caspase-3 in MCF-7 and SKBR3 cells, as evidenced by the cleavage of mammalian sterile 20-like kinase 1 substrate in a dose-dependent manner. Co-immunoprecipitation and immunofluorescence experiments were performed to clarify the relationship between pyruvate kinase M2 and mammalian sterile 20-like kinase 1. The results indicated that mammalian sterile 20-like kinase 1 was associated with pyruvate kinase M2 in cultured mammalian cells, and the interaction between mammalian sterile 20-like kinase 1 and pyruvate kinase M2 was decreased in response to 4-hydroxytamoxifen treatment. In addition, knockdown of pyruvate kinase M2 upregulated the level of cleaved Caspase-3 and subsequently facilitated the nuclear translocation of mammalian sterile 20-like kinase 1. Our data further supplemented the extensive functions of pyruvate kinase M2 in mediating breast cancer cell viability by substantially abating the mammalian sterile 20-like kinase 1-mediated apoptosis. In summary, our results identified that mammalian sterile 20-like kinase 1 is a novel downstream target of pyruvate kinase M2, and knockdown of pyruvate kinase M2 contributes apoptosis via promoting nuclear translocation of mammalian sterile 20-like kinase 1 by enhancing Caspase-3-dependent cleavage.
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http://dx.doi.org/10.1177/1010428317692251DOI Listing
April 2017