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学者姓名：郑鹏生
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Abstract ：
Objective To compare the prevalence of chromosomal abnormalities detected in products of conception (POCs) between recurrent pregnancy loss and sporadic pregnancy loss. Methods A systematic search was performed in the PubMed and Embase databases from inception to December 31, 2020. Relevant studies analysing the association between the number of pregnancy losses and the incidence of chromosomal abnormalities were included. Independent data extraction was conducted and study quality was assessed. Meta-analyses were carried out to calculate odds ratios by using fixed- or random-effects models according to statistical homogeneity. Results A total of 8320 POCs in 19 studies were identified for the meta-analyses. The incidence of chromosomal abnormalities in sporadic pregnancy loss was significantly higher than that in recurrent pregnancy loss. In subgroup analyses, the following studies reported a high incidence of abnormal outcomes of sporadic pregnancy loss: studies with >= 300 samples, studies published before 2014, studies conducted in European and American countries, and studies with analyses using conventional karyotype techniques. Moreover, the incidence of chromosomal abnormalities in women with two pregnancy losses was significantly higher than that in women with three or more pregnancy losses. However, there was no difference in the distribution of abnormal types between sporadic and recurrent pregnancy loss or between two and three or more pregnancy losses. Conclusions The prevalence of chromosomal abnormalities detected in POCs was lower in recurrent pregnancy loss than in sporadic pregnancy loss, and decreased with an increasing number of pregnancy losses.
Keyword ：
Foetal chromosome abnormality Pregnancy loss Products of conception
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| GB/T 7714 | Lei, Dan , Zhang, Xin-Yu , Zheng, Peng-Sheng . Recurrent pregnancy loss: fewer chromosomal abnormalities in products of conception? a meta-analysis [J]. | JOURNAL OF ASSISTED REPRODUCTION AND GENETICS , 2022 , 39 (3) : 559-572 . |
| MLA | Lei, Dan 等. "Recurrent pregnancy loss: fewer chromosomal abnormalities in products of conception? a meta-analysis" . | JOURNAL OF ASSISTED REPRODUCTION AND GENETICS 39 . 3 (2022) : 559-572 . |
| APA | Lei, Dan , Zhang, Xin-Yu , Zheng, Peng-Sheng . Recurrent pregnancy loss: fewer chromosomal abnormalities in products of conception? a meta-analysis . | JOURNAL OF ASSISTED REPRODUCTION AND GENETICS , 2022 , 39 (3) , 559-572 . |
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Abstract ：
Objective: To evaluate the current evidence of pregnancy outcomes among couples with recurrent pregnancy loss (RPL) with abnormal karyotypes vs. those with normal karyotypes and among couples with RPL and abnormal karyotypes after receiving expectant man-agement vs. preimplantation genetic diagnosis (PGD).Design: Systematic review and meta-analysis.Setting: Academic medical centers.Patient(s): Pregnancy outcomes in 6,301 couples with RPL who conceived without medical intervention in 11 studies were analyzed. However, only 2 studies addressed the outcomes of couples with RPL and abnormal karyotypes after expectant management (75 cases) vs. PGD (50 cases).Intervention(s): None.Main Outcome Measure(s): The pregnancy outcomes in couples with RPL with abnormal and normal karyotypes across included studies were evaluated.Result(s): Compared with those with a normal karyotype, a significantly lower first pregnancy live birth rate (LBR) was found in cou-ples with RPL with abnormal karyotypes (58.5% vs. 71.9%; odds ratio [OR], 0.55; 95% confidence interval [CI], 0.46-0.65; I2 =27%). A markedly decreased first pregnancy LBR was found in couples with a translocation (52.9% vs. 72.4%; OR, 0.44; 95% CI, 0.31-0.61; I2 =33%) but not in couples with an inversion. However, the differences in accumulated LBR (81.4% vs. 74.8%; OR, 0.96; 95% CI, 0.90- 1.03; I2 = 0) were nonsignificant, whereas the miscarriage rate was distinctly higher in couples with RPL and abnormal karyotypes (53.0% vs. 34.7%; OR, 2.21; 95% CI, 1.69-2.89; I2 = 0). Compared with those who chose expectant management, differences in accu-mulated LBR were nonsignificant (60% vs. 68%; OR, 0.55; 95% CI, 0.11-2.62; I2 =71%), whereas the miscarriage rate (24% vs. 65.3%; OR, 0.15; 95% CI, 0.04-0.51; I2 = 45) was markedly low in couples with RPL and abnormal karyotypes who chose PGD.Conclusion(s): Couples with RPL and abnormal karyotypes had a higher miscarriage rate than couples with normal karyotypes but achieved a noninferior accumulated LBR through multiple conception attempts. In couples with RPL and abnormal karyotypes, PGD treatment did not increase the accumulated LBR but markedly reduced miscarriage rate compared with expectant management. (Fertil Sterile 2022;118:906-14. (c) 2022 by American Society for Reproductive Medicine.)
Keyword ：
abnormal karyotype live birth rate miscarriage rate preimplantation genetic diagnosis Recurrent pregnancy loss
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| GB/T 7714 | Li, Shan , Zheng, Peng-Sheng , Ma, Hong Mei et al. Systematic review of subsequent pregnancy outcomes in couples with parental abnormal chromosomal karyotypes and recurrent pregnancy loss [J]. | FERTILITY AND STERILITY , 2022 , 118 (5) : 906-914 . |
| MLA | Li, Shan et al. "Systematic review of subsequent pregnancy outcomes in couples with parental abnormal chromosomal karyotypes and recurrent pregnancy loss" . | FERTILITY AND STERILITY 118 . 5 (2022) : 906-914 . |
| APA | Li, Shan , Zheng, Peng-Sheng , Ma, Hong Mei , Feng, Qian , Zhang, Yan Ru , Li, Qin Shu et al. Systematic review of subsequent pregnancy outcomes in couples with parental abnormal chromosomal karyotypes and recurrent pregnancy loss . | FERTILITY AND STERILITY , 2022 , 118 (5) , 906-914 . |
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Abstract ：
The never in mitosis gene A (NIMA)-related kinase 2 (NEK2) protein has been reported to be an oncoprotein that plays different oncogenic roles in multiple cancers. Here, we confirmed that NEK2 highly expressed in cervical cancer cells rather than in normal epithelial basal layer cells in cervical tissues and correlated with worse out-comes. We also demonstrated that NEK2 promoted the in vivo growth of subcutaneous xenograft tumors stemming from cervical cancer cells and the in vitro cell proliferation by decreasing Ser127-phosphorylation of the YAP protein retained in the cytoplasm while increasing the levels of active nucleus-associated YAP protein, which was followed by increases in the targeted proteins CTGF, CYR61 and GLI2. Furthermore, the Hippo signaling pathway was inactivated in manipulated NEK2-overexpressing cervical cancer cells by regulating the levels of MST1/2 dephosphorylation. Additionally, mass spectrometric sequencing and bilateral coimmunopre-cipitation were employed suggested that NEK2 acted at an early upstream step to promote dephosphorylation of MST2 and inactivate the Hippo signaling cascade by cooperating with STRIPAK complexes. We conjecture that NEK2 may be a future target for cervical cancer therapy.
Keyword ：
Cervical cancer MST2 NEK2 STRN YAP
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| GB/T 7714 | Zhang, Yan-Ru , Zheng, Peng-Sheng . NEK2 inactivates the Hippo pathway to advance the proliferation of cervical cancer cells by cooperating with STRIPAK complexes [J]. | CANCER LETTERS , 2022 , 549 . |
| MLA | Zhang, Yan-Ru et al. "NEK2 inactivates the Hippo pathway to advance the proliferation of cervical cancer cells by cooperating with STRIPAK complexes" . | CANCER LETTERS 549 (2022) . |
| APA | Zhang, Yan-Ru , Zheng, Peng-Sheng . NEK2 inactivates the Hippo pathway to advance the proliferation of cervical cancer cells by cooperating with STRIPAK complexes . | CANCER LETTERS , 2022 , 549 . |
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Abstract ：
Background Tumor resistance is a global challenge for tumor treatment. Cancer stem cells (CSCs) are the main population of tumor cells for drug resistance. We have reported that high aldehyde dehydrogenase (ALDH) activity represents a functional marker for cervical CSCs. Here, we aimed at disulfiram (DSF), an ALDH inhibitor, that has the potential to be used for cervical cancer treatment. Methods MTT assay, western blot, vector construction and transfection, cell sorting and in vivo anti-tumor assays were performed using cervical cancer cell lines SiHa and HeLa. Cell cycle distribution and cell apoptosis were carried out by flow cytometry. The cytotoxicity of DSF was detected by MTT assay and cervical cancer xenograft models. Results DSF was cytotoxic to cervical cancer cell lines in a copper (Cu)-dependent manner. Disulfiram/copper (DSF/Cu) complex induced deregulation of S-phase and inhibited the expression of stemness markers in cervical cancer cells. Furthermore, DSF/Cu could also reduce the cancer stem cell-like LGR5(+) cells which lead to cisplatin resistance in cervical cancer cells. DSF/Cu complex had the greater antitumor efficacy on cervical cancer than cisplatin in vitro and in vivo. Conclusion Our findings indicate that the cytotoxicity of DSF/Cu complex may be superior to cisplatin because of targeting LGR5-positive cervical cancer stem-like cells in cervical cancer. Thus, the DSF/Cu complex may represent a potential therapeutic strategy for cervical cancer patients.
Keyword ：
Cancer stem cell Cervical cancer Copper Disulfiram LGR5
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| GB/T 7714 | Cao, Hao-Zhe , Yang, Wen-Ting , Zheng, Peng-Sheng . Cytotoxic effect of disulfiram/copper on human cervical cancer cell lines and LGR5-positive cancer stem-like cells [J]. | BMC CANCER , 2022 , 22 (1) . |
| MLA | Cao, Hao-Zhe et al. "Cytotoxic effect of disulfiram/copper on human cervical cancer cell lines and LGR5-positive cancer stem-like cells" . | BMC CANCER 22 . 1 (2022) . |
| APA | Cao, Hao-Zhe , Yang, Wen-Ting , Zheng, Peng-Sheng . Cytotoxic effect of disulfiram/copper on human cervical cancer cell lines and LGR5-positive cancer stem-like cells . | BMC CANCER , 2022 , 22 (1) . |
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Abstract ：
Purpose: To explore the therapeutic targets and regulatory mechanisms of the antitumor drug quercetin in the treatment of cervical cancer. Methods: Cervical cancer (HeLa) cells were treated with quercetin and subjected to RNA sequencing using the BGISEQ-500 platform. By combined analysis of GEO database and RNA-seq results, the differentially expressed genes (DEGs) (namely, the genes in the GEO database that were upregulated/downregulated in cervical cancer compared with normal cervix and downregulated/upregulated after quercetin treatment) were identified. Functional enrichment and protein-protein interaction analyses were carried out for the DEGs. The candidate genes were identified using the Gentiscape2.2 and MCODE plug-ins for Cytoscape software, and the upstream miRNAs, lncRNAs, and circRNAs of the candidate genes were predicted using the online tools MirDIP, TarBase, and ENCORI. Finally, the regulatory network was constructed using Cytoscape software. Results: Quercetin significantly inhibited the proliferation of cervical cancer cells. The combined analyses of the GEO database and RNA-seq results obtained 74 DEGs, and the functional enrichment analysis of the DEGs identified 861 biological processes, 32 cellular components, 50 molecular functions, and 56 KEGG pathways. Five therapeutic candidate genes, including EGFR, JUN, AR, CD44, and MUC1, were selected, and 10 miRNAs, 1 lncRNA, and 71 circRNAs upstream of these genes were identified. Finally, a lncRNA/circRNA-miRNA-mRNA-pathway regulatory network was constructed. Conclusion: In this study, data mining was used to identify candidate genes and their regulatory network for the treatment of cervical cancer to provide a theoretical basis for targeted therapy of cervical cancer.
Keyword ：
candidate genes cervical cancer DEGs GEO quercetin regulatory network RNA-seq analysis
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| GB/T 7714 | Li, Yuanyuan , Kou, Jiushe , Wu, Tao et al. Screening of Therapeutic Candidate Genes of Quercetin for Cervical Cancer and Analysis of Their Regulatory Network [J]. | ONCOTARGETS AND THERAPY , 2021 , 14 : 857-866 . |
| MLA | Li, Yuanyuan et al. "Screening of Therapeutic Candidate Genes of Quercetin for Cervical Cancer and Analysis of Their Regulatory Network" . | ONCOTARGETS AND THERAPY 14 (2021) : 857-866 . |
| APA | Li, Yuanyuan , Kou, Jiushe , Wu, Tao , Zheng, Pengsheng , Chao, Xu . Screening of Therapeutic Candidate Genes of Quercetin for Cervical Cancer and Analysis of Their Regulatory Network . | ONCOTARGETS AND THERAPY , 2021 , 14 , 857-866 . |
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Homeobox B4 (HOXB4), which belongs to the homeobox (HOX) family, possesses transcription factor activity and has a crucial role in stem cell self-renewal and tumorigenesis. However, its biological function and exact mechanism in cervical cancer remain unknown. Here, we found that HOXB4 was markedly downregulated in cervical cancer. We demonstrated that HOXB4 obviously suppressed cervical cancer cell proliferation and tumorigenic potential in nude mice. Additionally, HOXB4-induced cell cycle arrest at the transition from the G0/G1 phase to the S phase. Conversely, loss of HOXB4 promoted cervical cancer cell growth both in vitro and in vivo. Bioinformatics analyses and mechanistic studies revealed that HOXB4 inhibited the activity of the Wnt/beta -catenin signaling pathway by direct transcriptional repression of beta -catenin. Furthermore, beta -catenin re-expression rescued HOXB4-induced cervical cancer cell defects. Taken together, these findings suggested that HOXB4 directly transcriptional repressed beta -catenin and subsequently inactivated the Wnt/beta -catenin signaling pathway, leading to significant inhibition of cervical cancer cell growth and tumor formation.
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| GB/T 7714 | Lei, Dan , Yang, Wen-Ting , Zheng, Peng-Sheng . HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/beta-catenin signaling pathway [J]. | CELL DEATH & DISEASE , 2021 , 12 (1) . |
| MLA | Lei, Dan et al. "HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/beta-catenin signaling pathway" . | CELL DEATH & DISEASE 12 . 1 (2021) . |
| APA | Lei, Dan , Yang, Wen-Ting , Zheng, Peng-Sheng . HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/beta-catenin signaling pathway . | CELL DEATH & DISEASE , 2021 , 12 (1) . |
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Abstract ：
PR domain zinc finger protein 4 (PRDM4) is a transcription factor that plays key roles in stem cell self-renewal and tumorigenesis. However, its biological role and exact mechanism in cervical cancer remain unknown. Here, both immunohistochemistry (IHC) and Western blot assays demonstrated that the expression of PRDM4 in cervical cancer tissues was much lower than that in the normal cervix. A xenograft assay showed that PRDM4 overexpression in the cervical cancer cell lines SiHa and HeLa dramatically inhibited cell proliferation and tumorigenic potential in vivo. Conversely, the silencing of PRDM4 promoted cervical cancer cell proliferation and tumorigenic potential. Mechanistically, PRDM4 induced cell cycle arrest at the transition from G0/G1 phase to S phase by upregulating p27 and p21 expression and downregulating Cyclin D1 and CDK4 expression. Furthermore, the PI3K/AKT signaling pathway was inactivated in PRDM4-overexpressing cells, which decreased the levels of p-AKT and upregulated the expression of PTEN, an inhibitor of the PI3K/AKT signaling pathway, at both the transcriptional and translational levels. Dual-luciferase reporter assays and qChIP assays confirmed that PRDM4 transactivated the expression of PTEN by binding to two specific regions in the PTEN promoter. Furthermore, PTEN silencing or a PTEN inhibitor rescued the cell defects induced by PRDM4 overexpression. Therefore, our data suggest that PRDM4 inhibits cell proliferation and tumorigenesis by downregulating the activity of the PI3K/AKT signaling pathway by directly transactivating PTEN expression in cervical cancer.
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| GB/T 7714 | Yang, Wen-Ting , Chen, Mei , Xu, Rui et al. PRDM4 inhibits cell proliferation and tumorigenesis by inactivating the PI3K/AKT signaling pathway through targeting of PTEN in cervical carcinoma [J]. | ONCOGENE , 2021 , 40 (18) : 3318-3330 . |
| MLA | Yang, Wen-Ting et al. "PRDM4 inhibits cell proliferation and tumorigenesis by inactivating the PI3K/AKT signaling pathway through targeting of PTEN in cervical carcinoma" . | ONCOGENE 40 . 18 (2021) : 3318-3330 . |
| APA | Yang, Wen-Ting , Chen, Mei , Xu, Rui , Zheng, Peng-Sheng . PRDM4 inhibits cell proliferation and tumorigenesis by inactivating the PI3K/AKT signaling pathway through targeting of PTEN in cervical carcinoma . | ONCOGENE , 2021 , 40 (18) , 3318-3330 . |
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The frequency and distribution of chromosomal abnormalities and the impact of parental chromosomal aberration on the pregnancy outcomes of couples with recurrent pregnancy loss remains controversial. 3235 RPL couples who experienced two or more miscarriages before 20 weeks were diagnosed in our tertiary referral hospital during 2008-2018 and included in the single-center retrospective cohort study covering a 10-year period. Chromosome aberration was detected in 121 (3.74%) among 3235 RPL couples which included 75 female and 46 male cases at an individual level. 101 cases were structural aberrations including balanced translocations in 46(38.0%) cases, Robertsonian translocations in 13(10.7%) cases, inversions in 42(34.7%) cases and 20(16.5%) cases were numerical aberrations. 121 carriers and 428 non-carriers were followed up for two years, 55 carriers and 229 non-carriers were subsequent pregnant after diagnosis by natural conception or intrauterine insemination. The frequency of carriers to have a health newborn was not significantly different with non-carriers (72.7% vs. 71.2%, adjusted P = 0.968). This study described the majority of carriers were balanced translocations and chromosome aberrations had a limited influence on live birth rate from the present data. The results of the study also remind us that natural conception may be also a good alternative rather than PGD (Pre-implantation Genetic Diagnosis) which is common in many other reproductive centers for such patients.
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| GB/T 7714 | Li, Shan , Chen, Mei , Zheng, Peng-Sheng . Analysis of parental abnormal chromosomal karyotype and subsequent live births in Chinese couples with recurrent pregnancy loss [J]. | SCIENTIFIC REPORTS , 2021 , 11 (1) . |
| MLA | Li, Shan et al. "Analysis of parental abnormal chromosomal karyotype and subsequent live births in Chinese couples with recurrent pregnancy loss" . | SCIENTIFIC REPORTS 11 . 1 (2021) . |
| APA | Li, Shan , Chen, Mei , Zheng, Peng-Sheng . Analysis of parental abnormal chromosomal karyotype and subsequent live births in Chinese couples with recurrent pregnancy loss . | SCIENTIFIC REPORTS , 2021 , 11 (1) . |
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Background Hexokinases 2 (HK2) is a member of the hexokinases, linking with malignant tumor growth and distant metastasis. However, evidence regarding the potential role of HK2 in regulating cell motility and tumor metastasis during the cervical cancer malignant progression remains limited. Methods In vitro migration and invasion assay, in vivo metastasis experiments were performed to detect the effective of HK2 on regulating cell motility and tumor metastasis in cervical cancer cells. RNA-Seq was performed to explore the potential molecules that participate in HK2-mediated cell motility and tumor metastasis in cervical cancer cells. The correlation between HK2 and Akt1, p-Akt1, FN1 expression in cervical cancer cells and human squamous cervical carcinoma (SCC) samples was verified in this study. Results In this study, cervical cancer cells with exogenous HK2 expression exhibited enhanced cell motility and distant metastasis. Transcriptome sequencing analysis revealed that fibronectin (FN1) was significantly increased in HK2-overexpressing HeLa cells, and the PI3K/Akt signaling pathway was identified by KEGG pathway enrichment analysis. Further studies demonstrated that this promotion of cell motility by HK2 was probably a result of it inducing FN1, MMP2 and MMP9 expression by activating Akt1 in cervical cancer cells. Additionally, HK2 expression was altered with the changing of Akt1/p-Akt1 expression, implying that HK2 expression is also modulated by Akt1/p-Akt1. Moreover, the positive correlation between HK2 and Akt1, p-Akt1, FN1 expression in human squamous cervical carcinoma (SCC) samples was verified by using Pearson correlation analysis. Conclusions This study demonstrated that HK2 could activate Akt1 in cervical cancer cells, subsequently enhancing cell motility and tumor metastasis by inducing FN1, MMP2 and MMP9 expression. There likely exists an interactive regulatory mechanism between HK2 and Akt1 during the malignant process of cervical cancer.
Keyword ：
Akt1 Cervical cancer Fibronectin (FN1) HK2 Metastasis
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| GB/T 7714 | Chen, Qian , Li, Lu , Liu, Xian et al. Hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells [J]. | CANCER CELL INTERNATIONAL , 2021 , 21 (1) . |
| MLA | Chen, Qian et al. "Hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells" . | CANCER CELL INTERNATIONAL 21 . 1 (2021) . |
| APA | Chen, Qian , Li, Lu , Liu, Xian , Feng, Qian , Zhang, Yanru , Zheng, Pengsheng et al. Hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells . | CANCER CELL INTERNATIONAL , 2021 , 21 (1) . |
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Musashi-1 (Msi1) is an RNA binding protein that functions as a regulator in multiple carcinomas. Our previous study demonstrated that Msi1 could promote the proliferation of cervical cancer cells by targeting the cell cycle proteins P21, P27 and P53. However, the mechanisms by which Msi1 affects the survival of cervical cancer cells, such as apoptosis, are still unclear. In this study, we found that the expression of Msi1 inhibited cervical cancer cell apoptosis in vitro and in vivo. Furthermore, the expression of Msi1 downregulated the expression of PTEN, while AKT signaling was activated, which resulted in a reduction in the proapoptotic protein BAK. In addition, rescue the expression of BAK in Msi1 expressing cervical cancer cells induced the increase of apoptosis cells. These findings indicate that Msi1 regulates cervical cancer cell apoptosis by inhibiting PTEN and activating AKT signaling, which leads to the downregulation of BAK.
Keyword ：
AKT signaling apoptosis cervical cancer Msi1
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| GB/T 7714 | Liu, Xian , Zhang, Yanru , Zheng, PengSheng et al. Msi1 inhibits cervical cancer cell apoptosis by downregulating BAK through AKT signaling [J]. | JOURNAL OF CANCER , 2021 , 12 (8) : 2422-2429 . |
| MLA | Liu, Xian et al. "Msi1 inhibits cervical cancer cell apoptosis by downregulating BAK through AKT signaling" . | JOURNAL OF CANCER 12 . 8 (2021) : 2422-2429 . |
| APA | Liu, Xian , Zhang, Yanru , Zheng, PengSheng , Cui, Nan . Msi1 inhibits cervical cancer cell apoptosis by downregulating BAK through AKT signaling . | JOURNAL OF CANCER , 2021 , 12 (8) , 2422-2429 . |
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