Frontiers in Endocrinology
·
2026
·
IF 5.7
Yi Yao,Min Si,Hongcheng Ding,Chengcheng Cao,Hua Yang,Qianshu Sun
Background: Polycystic ovary syndrome (PCOS) and nonalcoholic fatty liver disease (NAFLD) are prevalent endocrine-metabolic disorders with a high comorbidity rate. However, their shared molecular mechanisms remain largely unclear. This study aimed to identify and validate key co-expressed genes driving PCOS-NAFLD comorbidity.Methods: Transcriptomic datasets for PCOS (GSE34526) and NAFLD (GSE89632) were analyzed using differential expression combined with three machine learning algorithms (LASSO, Random Forest, and XGBoost). Robustness was assessed using leave-one-out (LOO) resampling and nested cross-validation. Functional enrichment and PPI network analyses identified FCGBP as a key shared gene. A DHEA + high-fat diet–induced rat model was used to simulate key features of PCOS–NAFLD, and DHT+FFA-treated KGN and HepG2 cells were used for in vitro validation, with FCGBP silencing and rescue experiments performed to assess its functional role.Results: FCGBP expression was significantly elevated in both ovarian and hepatic tissues in the rat model (P < 0.01). In KGN cells, FCGBP knockdown restored E2 secretion and upregulated CYP19A1 and HSD17B1 (P < 0.001). In HepG2 cells, FCGBP silencing reduced lipid accumulation and reversed SCD1 upregulation and ATGL downregulation (P < 0.05). These effects were partially reversed by FCGBP re-expression (rescue), further supporting the specificity of its regulatory role. These findings indicate that FCGBP is associated with both hormonal dysregulation and hepatic lipid metabolic abnormalities under hyperandrogenic conditions.Conclusion: This study identifies FCGBP as a potential molecular regulator in PCOS–NAFLD comorbidity and a candidate target for modulating both reproductive and metabolic dysfunctions.
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DOI
高影响因子
MOLECULAR HUMAN REPRODUCTION
·
2023
·Vol. 29
·期 11
·
IF 4
Fan Hairui,Zhou Dongjie,Zhang Xiaomei,Jiang Min,Kong Xiang,Xue Tongmin,Gao Lingling,Lu Dan,Tao Chenyue,Wang Liping
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease that affects women of reproductive age. It is also a significant cause of infertility. Circular RNAs have been found to have a crucial role in the development and progression of reproductive system diseases. In this study, we focused on circ_BECN1 and aimed to investigate its role and mechanism in PCOS, providing a foundation for early diagnosis and treatment of this condition. Our findings revealed an upregulation of circ_BECN1 expression in the ovarian granulosa cells (GCs) of PCOS patients. Additionally, the silencing of circ_BECN1 resulted in inhibited proliferation and enhanced apoptosis of the human ovarian granulosa-like tumor cell line (KGN), therefore implicating circ_BECN1 in the cell cycle process. Through a dual-luciferase reporting assay, we determined that circ_BECN1 acts as a sponge for miR-619-5p and that Rab5b is the target gene of miR-619-5p. Moreover, the expression of Rab5b was found to be upregulated in the ovarian tissue of PCOS patients. Knocking down circ_BECN1 resulted in decreased Rab5b expression, which was then restored by using a miR-619-5p inhibitor. Additionally, rescue experiments demonstrated that overexpressing Rab5b reversed the effects of circ_BECN1 knockdown on cell proliferation and apoptosis in KGN cells. In summary, our findings indicate that circ_BECN1 is upregulated in PCOS GCs and promotes cell growth and cell cycle progression, and reduces cell apoptosis by modulating the miR-619-5p/Rab5b axis. Therefore, circ_BECN1 may serve as a potential therapeutic target for PCOS treatment.
研究领域:
生殖内分泌学
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分子生物学
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妇科学
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DOI
PubMed
高影响因子
Drug Discoveries and Therapeutics
·
2024
·
IF 1.9
Jing Wang,Lisha Li,Jing Zhou,Xinyao Pan,Qing Qi,Hongmei Sun,Ling Wang
Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosterone-induced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions. The results showed that YHHD could reduce early miscarriage rates in PCOS patients and significantly improved glucose metabolism disorders, sex hormone levels, and the estrous cycles in PCOS mice. Quercetin could alleviate effect of high insulin levels and restore the low expression of insulin receptor substrate1/2 (IRS1/2) and glucose transporte 4 (GLUT4) in T-HESCs, demonstrating its potential to mitigate hyperinsulin-induced decidualization dysfunction via the GLUT4 signaling pathway mediated by IRS1/2. This study provides valuable molecular insights of YHHD and highlight the therapeutic potential of quercetin in treating decidualization dysfunction in PCOS.
研究领域:
妇科学
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内分泌学
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中医药学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 17
·期 5
·3501-3508
·
IF 1.448
Jing Jin,Qiao‑Yun Hu,Wen‑Wen Xu,Wen‑Jia Zhu,Bei Liu,Jing Liu,Wei Wang,Hui‑Fang Zhou
Tanshinone IIA (TSIIA) is a major component of Salvia miltiorrhiza, a Chinese herb that exhibits a therapeutic effect on polycystic ovary syndrome (PCOS). The present study replicated PCOS via the neonatal treatment of estradiol in mice. Estrous cycles, body and ovarian weight, serum levels of testosterone and estradiol were determined. Histological examination of ovaries was performed. The mRNA and protein levels of aromatase luteinizing hormone receptor and follicle‑stimulating hormone (FSHR) in ovaries and granule cells were assayed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. TSIIA was revealed to reverse all disorders induced by estradiol treatment, including prolonged estrous cycles, increased body and ovarian weight, increased atretic cyst‑like follicles and decreased corpus luteum, large antral follicles and preovulatory follicles. These improvements in PCOS as a result of TSIIA treatment are likely due to the revised testosterone/estradiol balance, as TSIIA reversed the decrease in aromatase mRNA, the enzyme that converts androgen to estrogen. As the expression of aromatase is regulated by the FSH pathway, TSIIA‑mediated elevation in FSHR expression may lead to the upregulation of aromatase. Therefore, TSIIA revises the balance of androgen and estrogen by rescuing the reduced expression of FSHR and aromatase, thus attenuating murine PCOS. The current study aimed to further the application of natural drugs in the treatment of PCOS to confront the side effects of hormone drugs and expand the use of TSIIA.
研究领域:
药理学
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内分泌学
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生殖生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2021
·
IF 6.4
Mazhar Ali Raja,Martin Maldonado,Jianying Chen,Ying Zhong,Jiang Gu
Purpose Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age and leads to metabolic disorders and infertility. The present study was conducted to investigate the therapeutic effects of curcumin (Cur) encapsulated arginine (Arg) and N-acetyl histidine (NAcHis) modified chitosan (Arg-CS-NAcHis/Cur) nanoparticles (NPs). Methods In this study, amphiphilic chitosan (CS) conjugate was developed by modification with hydrophilic arginine (Arg) and hydrophobic N-acetyl histidine (NAcHis) group (Arg-CS-NAcHis). The synthesized conjugate was well characterized by FTIR and NMR studies. Self-assembled nanoparticles based on the synthesized conjugate were developed by simple sonication method and characterized for the physicochemical properties of zeta potential, particle size and drug encapsulation. Next, in vitro drug release, cytotoxicity, and cellular uptake studies of the NPs were evaluated. Finally, the developed nanoparticles were examined for their therapeutic potential against estradiol valerate (EV) induced PCOS rats by evaluating hormone level changes and ovarian morphology. Results The results showed that zeta potential of the nanoparticles was 39.8±2.52 mV and the average size was 200 nm. The in vitro drug release profile showed sustained release pattern. Cytotoxicity and cellular uptake studies also showed preferential effectiveness than free curcumin. Both the biochemical and histopathological studies showed positive effects in reverting the symptoms of PCOS rats to normalcy. Conclusion Curcumin encapsulated arginine and N-acetyl histidine modified chitosan (Arg-CS-NAcHis/Cur) nanoparticles have been successfully developed. The present study suggested that treatment of the nanoparticles might reverse many of the PCOS symptoms. Therefore, these nanoparticles might be used as promising new candidate for delivery of curcumin to treat PCOS.
研究领域:
药学
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生物医学工程
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内分泌学
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生殖医学
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产品关联
DOI
PubMed
高影响因子
Journal of Ovarian Research
·
2024
·Vol. 17
·期 1
·1-11
·
IF 3.8
Chen Weixuan,Liao Baoying,Yun Chuyu,Zhao Min,Pang Yanli
Background Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder with multiple metabolic abnormalities. Most PCOS patients have concomitant metabolic syndromes such as insulin resistance and obesity, which often lead to the development of type II diabetes and cardiovascular disease with serious consequences. Current treatment of PCOS with symptomatic treatments such as hormone replacement, which has many side effects. Research on its origin and pathogenesis is urgently needed. Although improving the metabolic status of the body can alleviate reproductive function in some patients, there is still a subset of patients with metabolically normal PCOS that lacks therapeutic tools to address ovarian etiology.Methods The effect of IL-22 on PCOS ovarian function was verified in a non-metabolic PCOS mouse model induced by dehydroepiandrosterone (DHEA) and rosiglitazone, as well as granulosa cell -specific STAT3 knockout (Fshrcre+Stat3f/f) mice (10 groups totally and n = 5 per group). Mice were maintained under controlled temperature and lighting conditions with free access to food and water in a specific pathogen-free (SPF) facility. Secondary follicles separated from Fshrcre+Stat3f/f mice were cultured in vitro with DHEA to mimic the hyperandrogenic environment in PCOS ovaries (4 groups and n = 7 per group) and then were treated with IL-22 to investigate the specific role of IL-22 on ovarian function.Results We developed a non-metabolic mice model with rosiglitazone superimposed on DHEA. This model has normal metabolic function as evidenced by normal glucose tolerance without insulin resistance and PCOS-like ovarian function as evidenced by irregular estrous cycle, polycystic ovarian morphology (PCOM), abnormalities in sex hormone level. Supplementation with IL-22 improved these ovarian functions in non-metabolic PCOS mice. Application of DHEA in an in vitro follicular culture system to simulate PCOS follicular developmental block and ovulation impairment. Follicles from Fshrcre+Stat3f/f did not show improvement in POCS follicle development with the addition of IL-22. In DHEA-induced PCOS mice, selective ablation of STAT3 in granulosa cells significantly reversed the ameliorative effect of IL-22 on ovarian function.Conclusion IL-22 can improve non-metabolic PCOS mice ovarian function. Granulosa cells deficient in STAT3 reverses the role of IL-22 in alleviating ovary dysfunction in non-metabolic PCOS mice.
研究领域:
生殖内分泌学
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代谢学
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免疫学
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分子生物学
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
·
IF 5.7
Zhi-Qiang Liu,Chuan-Zhi Yan,Shu-Mei Zhong,Chao-Jie Chong,Ya-Qi Wu,Jun-Yang Liu,Chun-Xiang Huang,Ke-Ying Wang,He-Wei Li,Jia-Le Song
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder. This study investigated the mitigating effects of the Antrodia cinnamomea polysaccharide (ACP) on a letrozole-induced PCOS rat model. Results demonstrated that ACP reduced obesity and ameliorated dyslipidemia in PCOS rats. Moreover, ACP restored estrous cycle regularity, suppressed polycystic ovarian changes, and regulated serum levels of sex hormones, SOD, and MDA. Furthermore, ACP increased the α-diversity and modulated the abundance of phyla (Bacteroidetes, Firmicutes, and Verrucomicrobia) and genera (Lactobacillus, Helicobacter, Akkermansia, Oscillospira, Coprococcus, Roseburia, Blautia, and Allobaculum) in the gut microbiota. ACP also restored compromised intestinal barriers by upregulating the expression of ZO1, Occludin, Claudin1, and Claudin7 in the colon. ACP mitigated ovarian fibrosis by preventing activation of the NLRP3 inflammasome, decreasing the expression of fibrotic markers (TGF-β1, collagen-I, α-SMA, and CTGF), and regulating four ovarian fibrosis-associated metabolomics pathways. Generally, dietary ACP effectively ameliorated clinical symptoms and inhibited ovarian fibrosis in PCOS rats.
研究领域:
医学
·
生物学
·
营养学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Wei Jingzan,Zhao Yanyan
Polycystic Ovary Syndrome (PCOS) is a heterogeneous endocrine disease with high incidences in women of reproductive age. Although miR-185-5p (miR-185) was decreased in PCOS patients, the exact function of miR-185 on PCOS development still requires further investigation. In this study, rat injected with dehydroepiandrosterone (DHEA) was established as a PCOS model. A lentivirus carrying miR-185 was employed to examine its effect on PCOS symptoms. Then we performed the luciferase reporter assay to validate the interactions between miR-185 and vascular endothelial growth factor A (VEGFA). Finally, human ovarian microvascular endothelial cells (HOMECs) were induced by VEGF to explore the role of miR-185 in the angiogenic process. The results showed that miR-185 overexpression improved insulin level alteration and ovarian histological lesion in PCOS rats. We also found that miR-185 reduced the excessive angiogenesis as indicated by alterations of VEGFA, ANGPT1/2, PDGFB/D, α-SMA and CD31 in the ovary of PCOS rats. Luciferase reporter assay identified that VEGFA directly interacted with miR-185, and its expression level was negatively regulated by miR-185. The in vitro results further demonstrated that miR-185-induced suppression of cell proliferation, migration and tube formation was attenuated by VEGF in HOMECs. In summary, this is the first study to show that miR-185 can target VEGFA to inhibit angiogenesis, thus improving the development of PCOS. These findings develop a molecular candidate for PCOS prevention and therapy.
研究领域:
内分泌学
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分子生物学
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生殖医学
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DOI
PubMed
高影响因子
Human Cell
·
2024
·
IF 3.4
Guo Xiaoli,Cao Yijuan,He Qing,Chen Linna,Wang Qing,Zhang Jingbo,Lv Wenqiang,Zhang Bei,Zhou Xueyan
Polycystic ovary syndrome (PCOS) is a complex gynaecological endocrine disease that occurs in women of childbearing age. The pathogenesis of PCOS is still unclear and further exploration is needed. Here, proteomic analysis indicated that the expression of farnesyl diphosphate synthase (FDPS) protein in ovarian tissue of PCOS mice was significantly decreased. The purpose of this study is to investigate the relationship between potential biomarkers of PCOS and granulosa cells (GCs) function. The mechanisms by which FDPS affected the proliferation of granulosa cells were also explored both in vitro and in vivo. We found that knockdown of FDPS inhibited the proliferation of KGN (human ovarian granulosa cell line), while overexpression of FDPS had the opposite effect. FDPS activated Rac1 (Rac Family Small GTPase 1) activity and regulated MAPK/ERK signalling pathway, which affecting the proliferation of KGN cells significantly. In addition, treatment with the adeno-associated virus (AAV)-FDPS reverses the dehydroepiandrosterone (DHEA)-induced PCOS-phenotype in mice. Our data indicated that FDPS could regulate the proliferation of ovarian GCs by modulating MAPK/ERK (mitogen-activated protein kinase/extracellular regulated protein kinases) pathway via activating Rac1 activity. These findings suggest that FDPS could be of great value for the regulation of ovarian granulosa cell function and the treatment of PCOS.
研究领域:
妇科学
·
内分泌学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
TISSUE & CELL
·
2023
·
IF 2.6
Jing Cong,Mubai Li,Yu Wang,Hongli Ma,Xinming Yang,Jingshu Gao,Long Wang,Xiaoke Wu
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting women at reproductive age. The therapeutic effect of electroacupuncture (EA) on PCOS has been revealed, while the anti-PCOS mechanisms of EA have not been fully explored. In this study, PCOS were induced in rats by daily injection with dehydroepiandrosterone (DHEA) for 20 days and EA treatment was performed for 5 weeks. The mRNA expression profiles in ovarian tissues from control, PCOS, and EA-treated rats were examined by high-throughput mRNA sequencing. 5'-aminolevulinate synthase 2 (Alas2), a vital rate-limiting enzyme of the heme synthesis pathway, was selected to be further studied. PCOS led to the upregulation of Alas2 mRNA, whereas EA treatment restored this change. In vitro, primary ovarian granulosa cells (GCs) were challenged with H 2 O 2 to mimic the oxidative stress (OS) state in PCOS. H 2 O 2 induced apoptosis, OS, mitochondrial dysfunction, as well as Alas2 overexpression in GCs, while lentivirus-mediated Alas2 knockdown evidently restrained the above impairments. In summary, this study highlights the crucial role of Alas2 in cell apoptosis, OS, and mitochondrial dysfunction of PCOS GCs and provides potential therapeutic candidates for further investigation on PCOS treatment.
研究领域:
生殖医学
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内分泌学
·
分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
NEUROENDOCRINOLOGY
·
2024
·
IF 3.2
Zhang Jiaxian,Lai Wanlin,Tang Yusha,Gao Jing,Zhou Xiangyang,Chen Lei
Introduction:
In women of childbearing age with epilepsy, 40% experience the comorbidity of polycystic ovary syndrome (PCOS), which is marked by a higher prevalence of hyperandrogenism. Our recent clinical observations indicate the potential contribution of hyperandrogenism-induced PCOS to epilepsy susceptibility, and this study aimed to unravel the underlying factors that increase the susceptibility of females to epilepsy. Methods:
A letrozole-induced PCOS rat model was employed to simulate endogenous hyperandrogenism. Susceptibility was assessed through seizure kindling rates using pentetrazol and electroencephalogram recordings. Additionally, the role of androgens in epilepsy was verified through interventions using Diane-35. Results:
This study revealed that letrozole induced elevated testosterone levels and PCOS-related changes in female rats. PCOS rats, through pentetrazol-kindling, exhibited a reduced seizure threshold compared with controls. Elevated testosterone levels were observed in both the hippocampal and frontal brain tissues, accompanied by changes in circulation. Two weeks of Diane-35 intervention showed a tendency to alleviate these changes, modifying testosterone levels in both the plasma and brain tissue. Western blotting and immunohistochemistry revealed increased expression of GABA-A receptor in the hippocampus and decreased AMPA receptor expression in the frontal cortex, correlating with anti-epileptic status in PCOS rats. Conclusion:
This study delves into the impact of elevated androgen levels on seizure threshold, providing crucial insights into the underpinnings of the comorbidity between PCOS and epilepsy. These findings significantly contribute to the evolving field of epilepsy research, emphasizing the imperative consideration of hormonal influences for the development of targeted therapeutic interventions in individuals with epilepsy and PCOS
研究领域:
神经科学
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内分泌学
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癫痫研究
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生殖医学
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
·
2024
·
IF 2.9
Cong Peiwei,Shang Bing,Zhang Lina,Wu Zhaoli,Wang Yanan,Li Jia,Zhang Lin
Polycystic ovary syndrome (PCOS) is an endocrine disease, and its pathogenesis and treatment are still unclear. Hexokinase domain component 1 (HKDC1) participates in regulating mitochondrial function and glycolysis. However, its role in PCOS development remains unrevealed. Here, female C57BL/6 mice were intraperitoneally injected with dehydroepiandrosterone (DHEA; 60 mg/kg body weight) to establish an in vivo model of PCOS. In vitro, KGN cells, a human ovarian granular cell line, were used to explore the potential mechanisms. DHEA-treated mice exhibited a disrupted estrus cycle, abnormal hormone levels, and insulin resistance. Dysfunction in mitochondria and glycolysis is the main reason for PCOS-related growth inhibition of ovarian granular cells. Here, we found that the structure of mitochondria was impaired, less ATP was generated and more mitochondrial Reactive Oxygen Species were produced in HKDC1-silenced KGN cells. Moreover, HKDC1 knockdown inhibited glucose consumption and decreased the production of glucose-6-phosphate and lactic acid. Conclusively, HKDC1 protects ovarian granulocyte cells from DHEA-related damage at least partly by preserving mitochondrial function and maintaining glycolysis. Graphical abstract
研究领域:
内分泌学
·
生殖生物学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
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