Publications by authors named "Jinhua Zhou"

73 Publications

Identification of Candidate Gene Signatures and Regulatory Networks in Endometriosis and its Related Infertility by Integrated Analysis.

Reprod Sci 2022 Jan 7. Epub 2022 Jan 7.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.

Endometriosis is a common gynecological disease associated with infertility, and it represents an economic burden worldwide. However, the molecular mechanisms underlying endometriosis development have not yet been fully elucidated. Here, we aimed to identify reliable key genes and the related regulatory network that may be involved in endometriosis. Differentially expressed genes (DEGs) were identified through integrated analysis of four expression datasets of endometriosis from Gene Expression Omnibus. Gene functional analysis and protein-protein interaction network construction were performed to reveal the potential function of DEGs. Subsequently, candidate hub genes were defined and validated in GSE105764 dataset, and the associated regulatory networks were constructed. Additionally, GSE120103 dataset was applied to identify the differential expression between the infertile and fertile groups of patients with stage IV endometriosis. Finally, real-time quantitative polymerase chain reaction analysis was performed to identify the differential expression of hub genes in the collected clinical specimens. Robust rank aggregation integrated analysis determined 158 DEGs. Epithelial cell differentiation was the most significantly enriched biological process, and leukocyte transendothelial migration was the most significantly enriched pathway. Eight hub genes including CLDN3, CLDN5, CLDN7, CLDN11, HOXC8, HOXC6, HOXB6, and HOXB7 were identified, and most of these were validated as abnormally expressed genes in both the infertile group and patients with endometriosis. Transcriptional factors and microRNAs related to these genes were identified. Altogether, our integrated analysis identified critical gene signatures, involved pathways, and regulatory networks, which could provide clinically significant insights into the molecular mechanisms underlying endometriosis and its related infertility.
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http://dx.doi.org/10.1007/s43032-021-00766-1DOI Listing
January 2022

Enhanced Anti-Atherosclerotic Efficacy of pH-Responsively Releasable Ganglioside GM3 Delivered by Reconstituted High-Density Lipoprotein.

Int J Mol Sci 2021 Dec 20;22(24). Epub 2021 Dec 20.

College of Life Sciences, Nanchang University, 999 Xuefu Ave, Honggutan District, Nanchang 330031, China.

Recently, the atheroprotective role of endogenous GM3 and an atherogenesis-inhibiting effect of exogenous GM3 suggested a possibility of exogenous GM3 being recruited as an anti-atherosclerotic drug. This study seeks to endow exogenous GM3 with atherosclerotic targetability via reconstituted high-density lipoprotein (rHDL), an atherosclerotic targeting drug nanocarrier. Unloaded rHDL, rHDL loaded with exogenous GM3 at a low concentration (GM3-rHDL), and rHDL carrying GM3 at a relatively high concentration (GM3-rHDL) were prepared and characterized. The inhibitory effect of GM3-rHDL on lipid deposition in macrophages was confirmed, and GM3-rHDL did not affect the survival of red blood cells. In vivo experiments using ApoE mice fed a high fat diet further confirmed the anti-atherosclerotic efficacy of exogenous GM3 and demonstrated that GM3 packed in HDL nanoparticles (GM3-rHDL) has an enhanced anti-atherosclerotic efficacy and a reduced effective dose of GM3. Then, the macrophage- and atherosclerotic plaque-targeting abilities of GM3-rHD, most likely via the interaction of ApoA-I on GM3-rHDL with its receptors (e.g., SR-B1) on cells, were certified via a microsphere-based method and an aortic fragment-based method, respectively. Moreover, we found that solution acidification enhanced GM3 release from GM3-rHDL nanoparticles, implying the pH-responsive GM3 release when GM3-rHDL enters the acidic atherosclerotic plaques from the neutral blood. The rHDL-mediated atherosclerotic targetability and pH-responsive GM3 release of GM3-rHDL enhanced the anti-atherosclerotic efficacy of exogenous GM3. The development of the GM3-rHDL nanoparticle may help with the application of exogenous GM3 as a clinical drug. Moreover, the data imply that the GM3-rHDL nanoparticle has the potential of being recruited as a drug nanocarrier with atherosclerotic targetability and enhanced anti-atherosclerotic efficacy.
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http://dx.doi.org/10.3390/ijms222413624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704253PMC
December 2021

Etiology of serum vitamin B12 elevation 1 month after bariatric surgery: A case-control study based on China population.

Medicine (Baltimore) 2021 Dec;100(51):e28071

College of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Chengdu, Sichuan Province, China.

Abstract: Few studies have reported an increase in vitamin B12 (VitB12) levels after bariatric surgery. This study reports the phenomenon and adverse reactions of serum VitB12 elevation 1 month after surgery and explores the possible etiologies.Retrospective analysis was performed on VitB12 data for 112 patients from January 2018 to October 2019. Then, 87 patients were included between November 2019 and August 2020. They were divided into 2 groups according to the level of VitB12 after surgery, and the demographic and clinical data were analyzed. Then, LASSO regression model analysis and multiple logistic regression analysis were performed to explore the risk factors for VitB12 elevation after surgery.Retrospective data showed that the VitB12 level was significantly increased 1 month after surgery. Comparison of data between the 2 groups found that more patients also had diabetes in the nonelevated group. The postoperative folic acid and VitB12 levels of the elevated group were significantly higher than those of the nonelevated group. More patients had concurrent constipation in the elevated group than in the nonelevated group. Two meaningful variables in LASSO regression analysis were incorporated into the multivariate logistic regression analysis, and constipation was found to be an independent risk factor for the increase in VitB12 after surgery. Of the 199 patients in this study, 111 patients had elevated VitB12 levels after surgery. Among them, 7 patients had peripheral nerve symptoms.Constipation is an independent risk factor for increased VitB12 levels after surgery. High levels of VitB12 may cause some peripheral nerve symptoms. Therefore, it is necessary to pay attention to patients with postoperative constipation, monitor their VitB12 level as soon as possible, and take measures to improve constipation to avoid some adverse reactions caused by elevated VitB12 levels.
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http://dx.doi.org/10.1097/MD.0000000000028071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8701777PMC
December 2021

Urinary heavy metals in residents from a typical city in South China: human exposure and health risks.

Environ Sci Pollut Res Int 2021 Oct 11. Epub 2021 Oct 11.

Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, People's Republic of China.

Although heavy metal pollution has developed into a major global environmental problem, most research has focused on specific elements, especially arsenic (As) and selenium (Se), and on the health risks to people in polluted areas or by occupation. This study investigated the urine of 480 participants from Guangzhou with a population of 18 million and targeted nine heavy metals: As, Se, chromium (Cr), manganese (Mn), nickel (Ni), cadmium (Cd), lead (Pb), antimony (Sb), and mercury (Hg). The heavy metals were widely detected, of which As, Se, Cd, and Pb all exceed 98%. Among the toxicants, As showed the highest concentration, followed by Se with 40.5 and 35.4 μg/L, respectively. The heavy metal levels from suburban subjects were generally higher than those in urban subjects (except for Sb), and the Cd level of males was lower than that of females. Concentrations were related to age, body mass index, alcohol consumption, and smoking. According to the health risk assessment, most subjects experienced potential non-carcinogenic risk from As, Cd, Se, and Hg, which accounted for 38.2%, 8.83%, 8.31%, and 3.38%, respectively. The carcinogenic risk of As and Cd surpassed the risk level of 10, and 90.1% and 35.4% of the subjects, respectively, exceeded 10, an unacceptable risk level. More attention to the high carcinogenic risk from heavy metals and the high detected levels of As and Cd is required.
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http://dx.doi.org/10.1007/s11356-021-16954-0DOI Listing
October 2021

Dosimetry verification of three-dimensional printed polylactic acid template-guided precision I seed implantation for lung cancer using a desktop three-dimensional printer.

J Appl Clin Med Phys 2021 Oct 6;22(10):202-209. Epub 2021 Sep 6.

Department of Geriatric Respiratory and Critical Care, Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Hefei City, China.

Introduction: The purpose of this study was to verify the effectiveness of polylactic acid (PLA) template puncture route planning by comparing preoperative and postoperative dosimetry using computerized tomography (CT)-guided implantation of I radioactive seeds.

Methods: A total of 28 patients who underwent I seed implantation between January 2018 and June 2019 were selected for the statistical study of seed dosimetry. All patients received preoperative treatment planning system (TPS) planning, of which 13 patients in the experimental 3D template group underwent intraoperative puncture and implantation using the PLA template planning route. The other 15 patients in the traditional control group underwent intraoperative puncture and implantation using CT images for guidance. By calculating the dose-volume histogram, preoperative and postoperative D90 values and postoperative V90 values were compared between the two groups.

Results: The mean D90 values in the template group before and after surgery were 136.06 ± 7.10 and 134.72 ± 7.85 Gy, respectively. There was no statistically significant difference. The preoperative and postoperative mean D90 values in the traditional group were 132.97 ± 8.04 and 126.06 ± 9.19 Gy, respectively, which were statistically significantly different. The mean postoperative V90 values in the template and traditional groups were 93.80 ± 1.34% and 88.42 ± 6.55 %, respectively, showing a statistically significant difference.

Conclusions: The preoperative TPS plan for the experimental group guided by the PLA template was almost the same as that for the final guided particle implantation. The dose parameters in the experimental group were also better than those in the traditional group, making the use of the presented PLA template more efficient for clinical applications.
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http://dx.doi.org/10.1002/acm2.13419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504606PMC
October 2021

Human health risks estimations from polycyclic aromatic hydrocarbons in serum and their hydroxylated metabolites in paired urine samples.

Environ Pollut 2021 Dec 14;290:117975. Epub 2021 Aug 14.

Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, PR China; Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Key Laboratory of City Cluster Environmental Safety and Green Development, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou, 510006, PR China. Electronic address:

Polycyclic aromatic hydrocarbons (PAHs) are compounds with two or more benzene rings whose hydroxylated metabolites (OH-PAHs) are excreted in urine. Human PAH exposure is therefore commonly estimated based on urinary OH-PAH concentrations. However, no study has compared PAH exposure estimates based on urinary OH-PAHs to measurements of PAH levels in blood samples. Estimates of PAH exposure based solely on urinary OH-PAHs may thus be subject to substantial error. To test this hypothesis, paired measurements of parent PAHs in serum and OH-PAHs in urine samples from 480 participants in Guangzhou, a typical developed city in southern China, were used to investigate differences in the estimates of human PAH exposure obtained by sampling different biological matrices. The median PAH concentration in serum was 4.05 ng mL, which was lower than that of OH-PAHs in urine (8.33 ng mL). However, serum pyrene levels were significantly higher than urinary levels of its metabolite 1-hydroxypyrene. Concentrations of parent PAHs in serum were not significantly correlated with those of their metabolites in urine with the exception of phenanthrene, which exhibited a significant negative correlation. Over 28% of the participants had carcinogenic risk values above the acceptable cancer risk level of 10. Overall, estimated human exposure and health risks based on urinary 1-hydroxypyrene levels were only 13.6% of those based on serum pyrene measurements, indicating that estimates based solely on urine sampling may substantially understate health risks due to PAH exposure.
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http://dx.doi.org/10.1016/j.envpol.2021.117975DOI Listing
December 2021

Decomposition analysis of industrial pollutant emissions in cities of Jiangsu based on the LMDI method.

Environ Sci Pollut Res Int 2022 Jan 9;29(2):2555-2565. Epub 2021 Aug 9.

School of Environment, Nanjing Normal University, Nanjing, 210023, China.

Cities are faced with various kinds of pollution issues in the process of economic development, among which industrial pollution has become the most terrifying environmental issue in recent years, so that industrial pollution control should be emphasized. Finding out the key factors influencing industrial pollutant emissions is the basis of taking corresponding measures. Previous studies only focused on one pollutant without a comparative analysis of the contribution of influencing factors to multiple pollutants. Therefore, this study aims to identify the key influencing factors of industrial pollutants in Nanjing, Suzhou, Xuzhou, and Taizhou in Jiangsu Province during the years 2008-2018 by using the logarithmic mean Divisia index (LMDI) method. The results from decomposition indicate the following. (1) Emission intensity (EI) and energy efficiency (EE) are negative factors for decreasing industrial pollutant emissions, while the economic output (EO) and population (P) are positive factors for increasing industrial pollutant emissions. (2) Emission intensity has the most significant influence to industrial wastewater in decreasing emissions; energy efficiency makes the biggest contribution to industrial solid waste in decreasing emissions, economic output and population contribute the most to industrial solid waste in increasing emissions. (3) Nanjing has the highest contribution rate of emission intensity and population, and the contribution rate of energy efficiency and economic output to Taizhou is the highest. Identifying the key driving factors of different pollutants can serve as evidence and guidance for urban environmental governance, therefore reducing emissions ulteriorly, and achieving sustainable development.
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http://dx.doi.org/10.1007/s11356-021-15741-1DOI Listing
January 2022

MTHFD2 promotes ovarian cancer growth and metastasis via activation of the STAT3 signaling pathway.

FEBS Open Bio 2021 10 18;11(10):2845-2857. Epub 2021 Sep 18.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, China.

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a bifunctional enzyme located in the mitochondria. MTHFD2 has been reported to be overexpressed in several malignant tumors and is implicated in cancer development. This study aimed to investigate the effect of MTHFD2 on ovarian cancer progression. The expression of MTHFD2 was detected by bioinformatic analysis, immunohistochemistry, RT-qPCR (real-time quantitative PCR analysis), and western blot analysis. The effects of MTHFD2 depletion on cell proliferation, migration, and invasion were determined through in vitro experiments. Cell cycle progression and apoptosis were accessed by flow cytometry. The related signaling pathway protein expression was determined by western blot analysis. We found that MTHFD2 is highly expressed in both ovarian cancer tissues and cell lines. MTHFD2 deletion suppressed cell proliferation and metastasis. Knockdown of MTHFD2 induces cell apoptosis and G2/M arrest, whereas the number of cells in S phase increased with MTHFD2 overexpression. Mechanically, our results indicate that an inhibitory effect of MTHFD2 knockdown may be mediated by the downregulation of cyclin B1/Cdc2 complex and the inhibitory effect on its activity. Additionally, MTHFD2 could regulate cell growth and aggressiveness via activation of STAT3 and the STAT3-induced epithelial-mesenchymal transition signaling pathway. These findings indicate that MTHFD2 is overexpressed in ovarian cancer and regulates cell proliferation and metastasis, presenting an attractive therapeutic target.
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http://dx.doi.org/10.1002/2211-5463.13249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487042PMC
October 2021

Overexpression of ARHI increases the sensitivity of cervical cancer cells to paclitaxel through inducing apoptosis and autophagy.

Drug Dev Res 2021 Jun 30. Epub 2021 Jun 30.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Soochow, Jiangsu, China.

Cervical cancer (CC) is a common malignant tumor of the female reproductive system. This study investigated the role of aplysia ras homolog I (ARHI) in resistance to CC in vitro and in patients' tissues. Hela cells were continuously treated with different concentrations of paclitaxel (1-10 nM) to construct paclitaxel-resistant cell model (Hela-TR). CC or CC-TR tissues were obtained from CC patients or CC patients who had developed paclitaxel resistance. The level of ARHI and multidrug resistance gene 1 (MDR1) in cells and tissues were detected by qRT-PCR and immunohistochemistry (IHC) staining. Cell viability, apoptosis and the number of colonies were assessed by MTT, flow cytometry and cell clone assay in Hela and Hela-TR cells after the ARHI plasmid or shARHI were transfected into cells. The autophagy and apoptosis signaling related proteins were analyzed by western blotting. The results revealed that the levels of ARHI mRNA and protein were down-regulated in CC tissues, and were further reduced in paclitaxel-resistant tissues and Hela cell model. High expression of ARHI inhibited the expression of MDR1 in Hela and Hela-TR cells. The cell viability and cell clone of Hela and Hela-TR cells were decreased by ARHI overexpression but increased by ARHI suppression. In addition, highly expressed ARHI promoted apoptosis and activated autophagy by increasing LC3-II/LC3-I through inactivating AKT/mTOR signaling pathway. In conclusion, overexpression of ARHI can increase the sensitivity of CC to paclitaxel through promoting apoptosis and autophagy in a AKT/mTOR inactivation dependent pathway.
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http://dx.doi.org/10.1002/ddr.21852DOI Listing
June 2021

Identification of a nomogram based on an 8-lncRNA signature as a novel diagnostic biomarker for childhood acute lymphoblastic leukemia.

Aging (Albany NY) 2021 06 9;13(11):15548-15568. Epub 2021 Jun 9.

Medical Research Center, The Third People's Hospital of Chengdu, The Second Chengdu Hospital Affiliated to Chongqing Medical University, Chengdu 610031, China.

Childhood acute lymphoblastic leukemia (cALL) still represents a major cause of disease-related death in children. This study aimed to explore the prognostic value of long non-coding RNAs (lncRNAs) in cALL. We downloaded lncRNA expression profiles from the TARGET and GEO databases. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to identify lncRNA-based signatures. We identified an eight-lncRNA signature (LINC00630, HDAC2-AS2, LINC01278, AL356599.1, AC114490.1, AL132639.3, FUT8.AS1, and TTC28.AS1), which separated the patients into two groups with significantly different overall survival rates. A nomogram based on the signature, BCR ABL1 status and white blood cell count at diagnosis was developed and showed good accuracy for predicting the 3-, 5- and 7-year survival probability of cALL patients. The C-index values of the nomogram in the training and internal validation set reached 0.8 (95% CI, 0.757 to 0.843) and 0.806 (95% CI, 0.728 to 0.884), respectively. The nomogram proposed in this study objectively and accurately predicted the prognosis of cALL. experiments suggested that LINC01278 promoted the proliferation of leukemic cells and inhibited leukemic cell apoptosis by targeting the inhibition of miR-500b-3p in cALL, and LINC01278 may be a biological target for the treatment of cALL in the future.
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http://dx.doi.org/10.18632/aging.203116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221355PMC
June 2021

Matrigel/Umbilical Cord-Derived Mesenchymal Stem Cells Promote Granulosa Cell Proliferation and Ovarian Vascularization in a Mouse Model of Premature Ovarian Failure.

Stem Cells Dev 2021 Aug 8;30(15):782-796. Epub 2021 Jul 8.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.

In women of reproductive age, severe injuries to the ovary are often accompanied by premature ovarian failure (POF), which can result in amenorrhea or infertility. Hormone replacement therapy has been used to treat POF; however, it has limited therapeutic efficiency and may cause several side effects. In this study, we aimed to fabricate a Matrigel scaffold loaded with human umbilical cord-derived mesenchymal stem cells (MSCs) and explore its potential to restore ovarian function and repair ovarian structures in vitro and in vivo. POF mouse models were established by injecting mice with cyclophosphamide for 15 consecutive days. Then, MSC/Matrigel was transplanted into the ovaries of the mice. Five weeks later, the morphology of the ovaries and follicles was observed by hematoxylin/eosin staining, and the tissue fibrosis ratio was measured using Masson's trichrome staining. The number of blood vessels was evaluated by α-smooth muscle actin and CD31 immunofluorescence, and Ki67 expression was used to determine the proliferation of granulosa cells. The expression of vascular endothelial growth factor (VEGF)-A was assessed by western blotting. The Matrigel scaffold regulated the expression of VEGF-A in vitro. Moreover, it promoted MSC survival and proliferation and prevented MSC apoptosis in vivo. After the transplantation of the MSC/Matrigel, the number of follicles was significantly increased in the mice with POF, and the tissue fibrosis ratio was reduced. Furthermore, the MSC/Matrigel significantly improved the proliferation rate of granulosa cells, increased the number of blood vessels, and upregulated the expression of VEGF-A. These findings demonstrate that MSC/Matrigel may support follicular development and help restore ovarian structures in vivo.
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http://dx.doi.org/10.1089/scd.2021.0005DOI Listing
August 2021

STK17B promotes the progression of ovarian cancer.

Ann Transl Med 2021 Mar;9(6):475

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Background: Protein kinase is increasingly receiving widespread attention because of its role in the tumor progression. Serine/threonine protein kinase (STK) is an important family involved in the development of a variety of cancers. Many studies have shown that serine/threonine kinase 17B (STK17B) is highly expressed in a variety of malignant tumors and participate in proliferation and metastasis. However, the exact function of STK17B remains uncertain in ovarian cancer. Our study aims to investigate whether STK17B plays a role in the occurrence and development of epithelial ovarian cancer.

Methods: We employed quantitative reverse transcription polymerase chain reaction to detect the relative expression of STK17B in ovarian cancer tissues. STK17B was down-regulated and up-regulated in ovarian cancer cell lines by small interfering RNA and overexpressed plasmid, respectively. The effects of STK17B on proliferation, invasion and migration of ovarian cancer cells were analyzed by CCK-8 test, Transwell test, scratch test and EDU test. The tumorigenicity of subcutaneous xenograft tumor in nude mice to study the role of STK17B in tumorigenesis . Western Blotting analysis revealed that STK17B and EMT.

Results: STK17B expression was significantly increased in ovarian cancer tissues. The STK17B silencing suppressed cell progression, while the overexpression of STK17B promoted progression or . Western bolt showed that STK17B increased the invasion and migration of ovarian cancer cell by promoting the EMT process.

Conclusions: STK17B was highly expressed in epithelial ovarian cancer tissues and increased the proliferation, invasion and migration of ovarian cancer cells by promoting EMT process.
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http://dx.doi.org/10.21037/atm-21-601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039663PMC
March 2021

Guanosine monophosphate synthase upregulation mediates cervical cancer progression by inhibiting the apoptosis of cervical cancer cells via the Stat3/P53 pathway.

Int J Oncol 2021 04 2;58(4). Epub 2021 Mar 2.

Department of Gynecology and Obstetrics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

Guanosine monophosphate synthase (GMPS) participates in chromatin and gene regulation in multiple types of organisms, and is highly expressed in a variety of human malignancies. The purpose of the present study was to explore the expression of GMPS and its role in cervical cancer (CC), and to provide ideas for improving the clinical efficacy of CC treatment. In the present study, immunohistochemistry, reverse transcription‑quantitative PCR analysis, Cell Counting Kit‑8 assay, 5‑ethynyl‑2'‑deoxyuridine assay, flow cytometry, western blotting and immunofluorescence assays were conducted to detect the expression of GMPS in normal cervical tissues, CC tissues, para‑cancerous tissues and CC cell lines. Moreover, the present study detected the effect of GMPS knockdown on CC cell proliferation, clonal formation ability, aging and apoptosis, as well as on the expression levels of apoptosis‑related proteins in tumor cells. The present results demonstrated that the expression level of GMPS in CC was significantly higher compared with that of adjacent tissues; the expression rate of GMPS in CC was 57.36%. GMPS expression was found to successively and gradually increase from that in normal cervical tissues, to that in cervical intraepithelial neoplasia and CC tissues. The abnormal expression of GMPS was positively associated with the degree of CC differentiation and the depth of early invasion. Small interfering (si)RNA knockdown of GMPS inhibited proliferation and colony formation, and promoted aging and apoptosis of CC cells. Furthermore, subcutaneous injection of GMPS‑knockdown tumor cells in nude mice resulted in a decrease in the proliferative ability of the tumor. The animal experimental results showed that the tumor growth rate of the short hairpin (sh)RNA‑GMPS group was significantly slower than that of the HeLa sh‑negative control group. It was identified that GMPS may inhibit CC cell senescence and apoptosis via the Stat3/P53 molecular pathway. Collectively, the present results suggested that GMPS may be a marker of unfavorable prognosis of CC, and it may also be a potential therapeutic target for CC.
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http://dx.doi.org/10.3892/ijo.2021.5183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891820PMC
April 2021

Biomimetic cytomembrane nanovaccines prevent breast cancer development in the long term.

Nanoscale 2021 Feb 10;13(6):3594-3601. Epub 2021 Feb 10.

Center Laboratory, Zhangjiagang Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu 215600, China.

Cytomembrane cancer nanovaccines are considered a promising approach to induce tumor-specific immunity. Most of the currently developed nanovaccines, unfortunately, fail to study the underlying mechanism for cancer prevention and therapy, as well as immune memory establishment, with their long-term anti-tumor immunity remaining unknown. Here, we present a strategy to prepare biomimetic cytomembrane nanovaccines (named [email protected]) consisting of antigenic cancer cell membrane (CCM)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with imiquimod ([email protected]) as an adjuvant to activate the immune system. We found that our [email protected] system enhanced bone-marrow-derived dendritic cell uptake and maturation, as well as increased anti-tumor response against breast cancer 4T1 cells in vitro. Moreover, an immune memory was established after three-time immunization with [email protected] in BALB/c mice. The [email protected] BALB/c mice exhibited suppressed tumor growth and a long survival period (75% of mice lived longer than 50 days after tumor formation). This long-term anti-tumor immunity was achieved by increasing CD8 T cells and decreasing regulatory T cells in the tumor while increasing effector memory T cells in the spleen. Overall, our platform demonstrates that [email protected] can be a potential candidate for preventive cancer vaccines in the clinic.
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http://dx.doi.org/10.1039/d0nr08978hDOI Listing
February 2021

Inhibition of long non-coding RNA XIST upregulates microRNA-149-3p to repress ovarian cancer cell progression.

Cell Death Dis 2021 02 1;12(2):145. Epub 2021 Feb 1.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu, China.

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play critical roles in human diseases. We aimed to clarify the role of lncRNA X-inactive specific transcript (XIST)/miR-149-3p/forkhead box P3 (FOXP3) axis in ovarian cancer (OC) cell growth. XIST, miR-149-3p and FOXP3 expression in OC tissues and cell lines was assessed, and the predictive role of XIST in prognosis of OC patients was analyzed. The OC cell lines were screened and accordingly treated with silenced/overexpressed XIST plasmid or miR-149-3p mimic/inhibitor, and then the proliferation, invasion, migration, colony formation ability, apoptosis, and cell cycle distribution of OC cells were measured. Effect of altered XIST and miR-149-3p on tumor growth in vivo was observed. Online website prediction and dual luciferase reporter gene were implemented to detect the targeting relationship of lncRNA XIST, miR-149-3p, and FOXP3. XIST and FOXP3 were upregulated, whereas miR-149-3p was downregulated in OC tissues and cells. High XIST expression indicated a poor prognosis of OC. Inhibition of XIST or elevation of miR-149-3p repressed proliferation, invasion, migration, and colony formation ability, and promoted apoptosis and cell cycle arrest of HO-8910 cells. In SKOV3 cells upon treatment of overexpressed XIST or reduction of miR-149-3p, there exhibited an opposite tendency. Based on online website prediction, dual luciferase reporter gene, and RNA pull-down assays, we found that there was a negative relationship between XIST and miR-149-3p, and miR-149-3p downregulated FOXP3 expression. This study highlights that knockdown of XIST elevates miR-149-3p expression to suppress malignant behaviors of OC cells, thereby inhibiting OC development.
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http://dx.doi.org/10.1038/s41419-020-03358-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862378PMC
February 2021

Motion and trajectory planning modeling for mobile landing mechanism systems based on improved genetic algorithm.

Math Biosci Eng 2020 11;18(1):231-252

College of Aerospace Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.

In many traditional soft-landing missions, researchers design the lander and the rover as two separate individuals, which has its limitations. At present, research on landers mainly focuses on the performance analysis of those who cannot move, and the motion of legged mobile lander has not yet been studied. In this paper, a novel Mobile Landing Mechanism (MLM) is proposed. Firstly, the monte-Carlo method is used to solve the workspace, and the motion feasibility of the mechanism is verified. Secondly, combining with the constraints of velocity, acceleration and secondary acceleration of each driving joint of the MLM, the trajectory of its joint space is planned by using cubic spline curve. And based on the weighted coefficient method, an optimal time-jerk pedestal trajectory planning model is established. Finally, by comparing the genetic algorithm (GA) with the adaptive genetic algorithm (AGA), an optimization algorithm is proposed to solve the joint trajectory optimization problem of the MLM, which can obtain better trajectory under constraints. Simulation shows that the motion performance of the mechanism is continuous and stable, which proves the rationality and effectiveness of the foot trajectory planning method.
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http://dx.doi.org/10.3934/mbe.2021012DOI Listing
November 2020

Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Cervical Cancer.

Onco Targets Ther 2020 15;13:12881-12891. Epub 2020 Dec 15.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People's Republic of China.

Background: Previous reports showed that was associated with several cancers but the function of in cervical cancer was unknown. This study aimed to investigate the clinical effect and function of in cervical cancer.

Materials And Methods: In this study, the relative expression of in cervical cancer was detected by RT-qPCR. In order to determine the cell proliferation and migration and invading ability and apoptosis more accurately, we used CCK8 assay, Edu assay, wound healing assay, migration and invasion assay, flow cytometry assay, co-immunoprecipitation, proteomics and Western blot by silencing and overexpressing , respectively. The role of on tumor progression was explored in vitro and vivo.

Results: The relative expression of in cervical cancer tissues was up-regulated (P<0.05). In cervical cancer cell lines, silencing of restrained cell progression and EMT, while over-expression of accelerated cell progression and EMT in vivo and vitro (P<0.05).

Conclusion: acts as an oncogene in cervical cancers and knockdown of inhibited cervical cancer cells growth in vitro and in vivo. There is a close relationship between the relative expression of and clinical outcome in cervical cancer patients.
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http://dx.doi.org/10.2147/OTT.S280690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751697PMC
December 2020

Effects of low-molecular-weight heparin and aspirin in recurrent pre-eclampsia: A stratified cohort study.

Int J Gynaecol Obstet 2021 Aug 31;154(2):337-342. Epub 2020 Dec 31.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Objective: To evaluate the effects of low-molecular-weight heparin (LMWH) combined with low-dose aspirin (LDA) in pregnant women with a history of pregnancy-related hypertensive disorders.

Methods: In the current retrospective stratified cohort study, 33 women with previous hypertensive disorders of pregnancy treated with LMWH and LDA were compared with 37 control women who did not undergo LMWH or LDA treatment. Rates of pre-eclampsia recurrence, placental abruption, and other adverse outcomes for the fetuses and pregnant women were compared in the two groups.

Results: The pre-eclampsia recurrence rates were 12/33 (36.4%) in the LMWH + LDA group and 28/37 (75.7%) in the control group (P < 0.01). In stratified cohort analysis, pregnant women with a history of early-onset pre-eclampsia, a body mass index of at least 24 (calculated as weight in kilograms divided by the square of height in meters), and aged less than 35 years benefited from LMWH + LDA treatment. In women with chronic hypertension or a history of placental abruption there was no protective effect. There were no significant differences in other adverse outcomes such as placental abruption and small size for gestational age in fetuses or pregnant women in the two groups.

Conclusion: Administration of LMWH + LDA only lowered the risk of pre-eclampsia recurrence in subgroups of pregnant women with a history of pregnancy-associated hypertensive disorders.
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http://dx.doi.org/10.1002/ijgo.13535DOI Listing
August 2021

Targeting miR-10a-5p/IL-6R axis for reducing IL-6-induced cartilage cell ferroptosis.

Exp Mol Pathol 2021 02 7;118:104570. Epub 2020 Nov 7.

Department of Orthopaedic, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), NO.61, Jiefang West Road, Changsha city, Hunan Province 410000, China.

Background: Intervertebral disc degeneration (IDD) causes lower back pain, and is often accompanied with robust inflammation. However, whether inflammation plays a role in IDD remains controversial, and the mechanism is ill-elucidated.

Methods: Cartilage specimens from patients with scoliosis (control) and IDD were examined for IL-6 and its receptor expression by qPCR and western blot. Primary human articular chondrocyte was employed as a model for in vitro assessment of IL-6 effects in cell viability, cellular oxidative stress and iron homeostasis by MTT, MDA, ROS and Iron Colorimetric assays. The underlying mechanism was explored by qPCR, western blot, RIP in combination with bioinformatics analysis.

Results: We found in this study that IL-6 and its receptor were aberrantly expressed in cartilage tissues of IDD patients. IL-6 down-regulated miR-10a-5p, which subsequently derepressed IL-6R expression. IL-6 exposure caused cartilage cell ferroptosis by inducing cellular oxidative stress and disturbing iron homeostasis. Overexpressing miR-10a-5p suppressed IL-6R expression, and partially abolished IL-6-induced ferroptosis.

Conclusion: Results from current study suggests that inflammatory cytokine IL-6 appeared in IVD aggravates its degeneration by inducing cartilage cell ferroptosis. This is caused partially by inhibiting miR-10a-5p and subsequently derepressing IL-6R signaling pathway. Our study provides a novel mechanism explaining inflammatory cytokine-caused cartilage cell death in degenerative IVD, and makes IL-6/miR-10a-5p/IL-6R axis a potential therapeutic target for intervention of IDD.
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http://dx.doi.org/10.1016/j.yexmp.2020.104570DOI Listing
February 2021

Improving the Buffer Energy Absorption Characteristics of Movable Lander-Numerical and Experimental Studies.

Materials (Basel) 2020 Jul 27;13(15). Epub 2020 Jul 27.

College of Astronautics, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.

To improve the soft-landing crash performance of the movable lander (ML), this study presents an investigation of a newly designed gradual energy-absorbing structure subjected to impact loads using an ML for theoretical calculation and numerical simulations. In this work, we present a novel computational approach to optimizing the energy absorption (EA) of the ML. Our framework takes as inputting the geometrical parameter (GP) as well as EA. The finite element model of the HB1, HB2, and HB3 was established and effectively verified using numerical simulation and experimental data. The relationship between the GP of the buffer material and the EA was obtained through static experiment and impact experiment, and the cushioning performance of the lander was optimized according to the ML load mass, contact speed, and EA function. According to the optimization results, we chose an outer diameter of 240 mm, an inner diameter of 50 mm, heights of HB1 = 140 mm, HB2 = 110 mm, and HB3 = 225 as the collocation, and completed the numerical simulation of three different cases. By comparing the results of theoretical calculation and numerical simulation experiments, it can be found that the overload response rates of the main body in 4 type landing, 2-2 type landing, and 1-2-1 type landing are 4.72 G, 2.61 G, and 2.33 G, respectively. It also laid the foundation for the theoretical and methodological research of the ML and manned lander in the future.
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http://dx.doi.org/10.3390/ma13153340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435996PMC
July 2020

CTL Attenuation Regulated by PS1 in Cancer-Associated Fibroblast.

Front Immunol 2020 10;11:999. Epub 2020 Jun 10.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Cancer-associated fibroblasts (CAFs) were associated with tumor progression in the tumor microenvironment (TME). However, their immunosuppressive roles in protecting cancer cells from the attack by cytotoxic T lymphocytes (CTLs) are not fully clear. In this study, we investigated whether and how CAFs regulate tumor-infiltrating lymphocytes as well as their role in tumor immunosuppression. Eighty-three cases of ovarian cancer and 10 controls were analyzed for CAFs and CD8+ tumor-infiltrating lymphocytes by gene array and immunohistochemistry. We evaluated presenilin 1 (PS1) expression in CAFs, CTL penetration, tumor burden, dendritic cell function, and migration of tumor-infiltrating lymphocytes and their function and after silencing PS1. In addition, the pathway via which PS1 affects the TME was also evaluated. PS1 was highly expressed in CAFs, and its silencing significantly promoted CD8+ CTL proliferation and penetration in multiple ovarian models ( < 0.05), resulting in tumor regression and growth inhibition. Interleukin (IL)-1β was identified as a major immune inhibitor in the TME, and it was significantly decreased after PS1 silencing ( < 0.05), which was regulated by the WNT/β-catenin pathway. It was also showed that high expression of IL-1β in CAFs inhibits CTL penetration significantly ( < 0.05). Highly expressed PS1 in CAFs plays a crucial role in regulating tumor-infiltrating lymphocyte populations in the TME via the WNT/β-catenin pathway. Targeting PS1 may retrieve functional CTLs in the TME and improve the efficacy of current immunotherapies.
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http://dx.doi.org/10.3389/fimmu.2020.00999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297945PMC
May 2021

Encapsulation of Fe nanoparticles into an N-doped carbon nanotube/nanosheet integrated hierarchical architecture as an efficient and ultrastable electrocatalyst for the oxygen reduction reaction.

Nanoscale 2020 Jul 24;12(26):13987-13995. Epub 2020 Jun 24.

Key Laboratory of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.

The exploration of cost-effective, highly efficient and robust electrocatalysts toward the oxygen reduction reaction (ORR) is of paramount significance for the advancement of future renewable energy conversion devices, and yet still remains a great challenge. Herein, we demonstrate a straightforward one-step pyrolysis strategy for the scalable synthesis of an iron-nitrogen-carbon hierarchically nanostructured catalyst, in which Fe-based nanoparticles are encapsulated in bamboo-like N-doped carbon nanotubes in situ rooted from porous N-doped carbon nanosheets ([email protected] NT/NSs). The delicate fabrication of such an 0D/1D/2D integrated hierarchical architecture with encased Fe species and open configuration renders the formed [email protected] NT/NSs with sufficient confined active sites, reduced charge transfer resistance, improved diffusion kinetics and outstanding mechanical strength. As such, compared with commercial Pt/C, the optimized [email protected] NT/NSs catalyst exhibits efficient ORR activity, superior durability and strong tolerance to methanol in KOH medium. More impressively, when assembled as a cathode catalyst in a microbial fuel cell, the [email protected] NT/NSs electrode displays significantly enhanced power density and output voltage in comparison with commercial Pt/C, holding great promise in practical energy conversion devices. What's more, the simple yet reliable synthesis strategy developed here may shed light on the future design of advanced high-efficiency hierarchical architectures for diverse electrochemical applications and beyond.
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http://dx.doi.org/10.1039/d0nr02618bDOI Listing
July 2020

Effectiveness and safety of low-dose apatinib in advanced gastric cancer: A real-world study.

Cancer Med 2020 07 22;9(14):5008-5014. Epub 2020 May 22.

Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Apatinib has been demonstrated to be effective and safe among patients with gastric cancer failing after at least two lines chemotherapy. This study aimed to evaluate its effectiveness and safety of low-dose apatinib for the treatment of gastric cancer in real-world practice. We performed a prospective, multicenter observation study in a real-world setting. Patients with advanced gastric cancer more than 18 years old were eligible and received low-dose apatinib (500 mg or 250mg per day) therapy. The median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were assessed. Between September 2017 and April 2019, a total of 747 patients were enrolled. The mPFS was 5.56 months (95% CI 4.47-6.28), and mOS was 7.5 months (95% CI 6.74-8.88). Four patients achieved complete response, 47 achieved partial response, and 374 patients achieved stable disease. The ORR was 6.83% and DCR was 56.89%. In addition, multivariate Cox regression analysis indicated that hand-foot syndrome was one independent predictor for PFS and OS. The most common adverse events (AEs) at any grade were hypertension (36.55%), proteinuria (10.26%), hand-foot syndrome (33.53%), fatigue (24.9%), anemia (57.35%), leukopenia (44.49%), thrombocytopenia (34.21%), and neutropenia (53.33%). Grade 3-4 AEs with incidences of 5% or greater were anemia (13.97%), thrombocytopenia (7.14%), and neutropenia (6.67%). No treatment-related death was observed during the treatment of apatinib. The prospective study suggested that low-dose apatinib was an effective regimen for the treatment of advanced gastric cancer with tolerable or controlled toxicity in real world. Trial registration: NCT03333967.
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http://dx.doi.org/10.1002/cam4.3105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367613PMC
July 2020

Optimal time-jerk trajectory planning for the landing and walking integration mechanism using adaptive genetic algorithm method.

Rev Sci Instrum 2020 Apr;91(4):044501

College of Astronautics, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.

Because the current research on the lander mostly has focused on the traditional lander, the Soft Landing and Walking Integration (SLWI) lunar lander has yet not been studied. To solve the problem, first, a novel type of mobile landing mechanism is proposed and its kinematics is deduced. Second, in order to ensure the motion stability of the mechanism, the cubic spline curve is used to scheme the key points of the SLWI, and based on the weighted coefficient method, an optimal time-jerk pedestal trajectory planning model is established. Finally, the adaptive genetic algorithm (AGA) is used to search the global optimal solution of time-jerk trajectory planning model. Simulation shows that the motion performance of the mechanism is continuous and stable, which proves the rationality and effectiveness of the foot trajectory planning method. At the same time, the AGA converges to the optimal solution. Thus, the blindness of the initial optimization can be greatly reduced and the amount of computation can be saved. It also laid a theoretical foundation for the follow-up research of SLWI lunar lander.
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http://dx.doi.org/10.1063/1.5133369DOI Listing
April 2020

Hypoxia-induced up-regulation of miR-27a promotes paclitaxel resistance in ovarian cancer.

Biosci Rep 2020 04;40(4)

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

Ovarian cancer (OC) is a malignant tumor with high mortality in women. Although cancer patients initially respond to paclitaxel chemotherapy following surgery, most patients will relapse after 12-24 months and gradually die from chemotherapy resistance. In OC, cancer cells become resistant to paclitaxel chemotherapy under hypoxic environment. The miR-27a has been identified as an oncogenic molecular in ovarian cancer, prostate cancer, liver cancer etc. In addition, the miR-27a is involved in hypoxia-induced chemoresistance in various cancers. However, the role of miR-27a in hypoxia-induced OC resistance remains unclear. The aim of the present study was to investigate the regulatory mechanism of miR-27a in hypoxia-induced OC resistance. The expression of HIF-1α induced Hypoxia overtly up-regulated. At the same time, hypoxia increased viability of Skov3 cells and decreased cell apoptosis when treated with paclitaxel. The expression of the miR-27a was obviously up-regulated under hypoxia and involved in hypoxia-induced paclitaxel resistance. Follow-up experiments portray that miR-27a improved paclitaxel resistance by restraining the expression of APAF1 in OC. Finally, we further elucidated the important regulatory role of the miR-27a-APAF1 axis in OC through in vivo experiments. According to our knowledge, we first reported the regulation of miR-27a in hypoxia-induced chemoresistance in OC, providing a possible target for chemoresistance treatment of OC.
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http://dx.doi.org/10.1042/BSR20192457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109003PMC
April 2020

Mir-30b-3p affects the migration and invasion function of ovarian cancer cells by targeting the CTHRC1 gene.

Biol Res 2020 Mar 10;53(1):10. Epub 2020 Mar 10.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, Jiangsu, People's Republic of China.

Background: The aim of this study was to investigate the effect role and mechanism of miR-30b-3p on ovarian cancer cells biological function.

Methods: The expression of miR-30b-3p was detected in ovarian cancer cell lines and normal ovarian epithelial cell line by qRT-PCR. Mir-30b-3p mimic was transfected into OVCAR3 cells. Cell-counting kit-8 (CCK-8) assay was conducted to explore the effect of mir-30b-3p on the OVCAR3 cells' proliferation. Cell cycle and apoptosis were detected by Flow cytometry. Cell invasion ability was detected by Transwell test. The regulation of putative target of miR-30b-3p was verified by double luciferase reporter assays and Western blot.

Result: We found that miR-30b-3p was downregulated in OVCAR3 cells. Overexpression of miR-30b-3p suppressed proliferation, promoted apoptosis, slowed cell cycle and inhibited migration and invasion of OVCAR3 cells. Bioinformatics analysis identified 3'-untranslated region (3'UTR) of Collagen triple helix repeat-containing 1 (CTHRC1) as the presumed binding site for miR-30b-3p. Detection of double luciferase reporter and Western-Blot result confirmed that CTHRC1 was the target gene of miR-30b-3p. Furthermore, E-cadherin, β-cadherin and Vimentin protein expression level were changed after transfection of miR-30b-3p.

Conclusion: miR-30b-3p function as an anti-cancer gene. Overexpression of miR-30b-3p can inhibit the biological function of ovarian cancer cells. MiR-30b-3p targets CTHRC1 gene plays an important role in epithelial-mesenchymal transformation (EMT), and supports miR-30b-3p as a potential biological indicator for ovarian cancer in the future.
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http://dx.doi.org/10.1186/s40659-020-00277-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063805PMC
March 2020

MicroRNA-708 Suppresses Cell Proliferation and Enhances Chemosensitivity of Cervical Cancer Cells to cDDP by Negatively Targeting Timeless.

Onco Targets Ther 2020 9;13:225-235. Epub 2020 Jan 9.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.

Purpose: Cervical cancer is the fourth most common cause of cancer-associated mortality in women worldwide. Previous studies have reported that microRNAs (miRNAs) are involved in multiple biological aspects of cancer progression by regulating gene expression. Here, we investigated the role of microRNA-708 (miR-708) in cervical cancer.

Methods: The expression levels of miR-708 in cervical cancer tissues and paired-normal cervical tissues were tested by quantitative polymerase chain reaction (qPCR). The interaction between miR-708 and Timeless was identified by bioinformatics method, dual-luciferase reporter assay, and Western blotting. The effects of over-expression of miR-708 on cell proliferation and cisplatin sensitivity were determined by Cell Counting Kit-8 (CCK-8) and colony formation assay. Cell cycle and apoptosis were analyzed by flow cytometry. DNA damage induced by over-expression of miR-708 was determined by comet assay. Expression levels of the genes involved in repair of DNA damage were analyzed by Western blotting.

Results: MiR-708 was down-regulated in cervical cancer tissues compared with paired-normal cervical tissues. By bioinformatics method, Western blotting, and dual-luciferase reporter assay, we found that Timeless was a direct target of miR-708. Furthermore, miR-708 suppressed cellular viability, colony formation, promoted apoptosis, and induced DNA damage levels. MiR-708 also enhanced chemosensitivity of cervical cancer cells to cDDP via impairing the ATR/CHK1 signaling pathway.

Conclusion: We conclude that miR-708 suppresses cell proliferation, facilitates cisplatin efficacy, and impairs DNA repair pathway in cervical cancer cells. These results demonstrate that miR-708 might be a candidate therapeutic target for future cervical cancer therapy.
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http://dx.doi.org/10.2147/OTT.S227015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966141PMC
January 2020

[Research Progress of Treg/Th17 in the Treatment of Chronic Obstructive Pulmonary Disease with Lung Cancer].

Zhongguo Fei Ai Za Zhi 2019 Dec;22(12):794-797

Jining No.1 People's Hospital, Jining 272000, China.

Chronic obstructive pulmonary disease (COPD) and lung cancer are global high incidence and high mortality diseases, which seriously increase the socio-economic burden. Smoke exposure, genetic susceptibility and chronic inflammation are common susceptible factors. At present, abnormal inflammatory immune response plays an important role in the occurrence and development of the two diseases. In the process of immune response, tumor microenvironment (TME) is gradually produced, which is beneficial to angiogenesis and immunosuppression, and finally leads to immune escape of tumor cells, leading to tumor formation. In this paper, the present situation of COPD complicated with lung cancer and the relationship between abnormal immune response, especially Treg/Th17, and its occurrence and development are briefly reviewed.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2019.12.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935035PMC
December 2019

Aberrantly Expressed Timeless Regulates Cell Proliferation and Cisplatin Efficacy in Cervical Cancer.

Hum Gene Ther 2020 03 24;31(5-6):385-395. Epub 2020 Jan 24.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Timeless is a regulator of molecular clockwork in Drosophila and related to cancer development in mammals. This study aimed to investigate the effect of Timeless on cell proliferation and cisplatin sensitivity in cervical cancer. Timeless expression was determined by bioinformatics analysis, immunohistochemistry, and quantitative polymerase chain reaction (qPCR). Chromatin immunoprecipitation assays and reporter gene assays were applied to determine the transcriptional factor contributing to Timeless upregulation. The effects of Timeless depletion on cell proliferation and cisplatin sensitivity were determined through and experiments. Cell apoptosis and senescence were assessed by flow cytometry and β-galactosidase staining. DNA damage and DNA repair pathways were determined by comet assay, immunofluorescent staining, and Western blot analysis. Timeless is aberrantly expressed in ∼52.5% of cervical cancer tissues. E2F1 and E2F4 contribute to the transcriptional activation of Timeless. Timeless depletion inhibits cell proliferation and increases cisplatin sensitivity and . Knockdown of Timeless induces cell apoptosis and cell senescence. Mechanically, Timeless silencing leads to DNA damage and impairs the activation of the ATR/CHK1 pathway in response to cisplatin in cervical cancer. Timeless is overexpressed in cervical cancer and regulates cell proliferation and cisplatin sensitivity, presenting an attractive target for cisplatin sensitizer in cervical cancer.
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http://dx.doi.org/10.1089/hum.2019.080DOI Listing
March 2020

Morphological characteristics of different types of distal radius die-punch fractures based on three-column theory.

J Orthop Surg Res 2019 Nov 27;14(1):390. Epub 2019 Nov 27.

Department of Orthopaedics, Wuxi Ninth People's Hospital Affiliated of Soochow University, No.999, Liangxi Road, Binhu District, Wuxi, 214061, Jiangsu, China.

Objective: The aim of this study is to investigate the morphological characteristics of distal radius die-punch fracture (DRDPF) with different types, based on the three-column theory.

Methods: The imaging data of 560 patients diagnosed with DRDPF were reviewed and divided into single-column, double-column, or three-column DRDPF according to the three-column theory, and the types, case distribution of DRDPF, and inter- and intra-agreement of classification were further analyzed.

Results: There were 65 cases of single-column DRDPF, 406 cases of double-column DRDPF, and 89 cases of three-column DRDPF. Among the single-column DRDPF, there were three cases of volar, 13 cases of dorsal, 14 cases of split, and 35 cases of collapse type fractures. Among the radius column fracture, there were 130 cases of metaphseal,155 cases of articular surface, and 210 cases of combined type. The inter-observer Kappa coefficient was 0.877-0.937, and the intra-observer kappa was 0.916-0.959, showing high agreement. At the 12th month's follow-up, according to the Gartland-Werley score system for the functionary recovery of the wrist and hand, 519 cases (92.68%) of the patients ranked excellent or good, and 41 cases (7.32%) ranked fair. All the cases were fair results, and the intermediate column of the distal radius was collapse type fractures, showing significant difference between the collapse type and other types (χ2 = 23.460, P = 0.000). The excellent and good rate in the single-, double-, and three-column DRDPFs were 93.85%, 92.16%, and 91.01%, respectively (χ2 = 0.018, P = 0.991).

Conclusion: Due to the difference of the nature and energy of the forces, the position of wrist, and the bone quality of the patients at the moment of the injury, the loading forces transmitted to the intermediate column of the distal radius could result in different types of DRDPF. The classification method in this study included all types of DRDPF, indicating the mechanism, affected sites, and the morphological characteristics of DRDPF with high consistency, which hopefully could provide insight into the treatment and prognosis of DRDPF patients.
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http://dx.doi.org/10.1186/s13018-019-1453-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882215PMC
November 2019
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