Injurious Effect of Cisplatin on the Function of Hypothalamus-pituitary-adrenal/gonadal Axis in Mice and the Intervention Effect of Dehydroepiandrosterone

doi:10.12300/j.issn.1674-5817.2022.182

Abstract

Abstract:

Objective To study the pathway of cis-dichlorodiamineplatinum (DDP) inhibiting the synthesis of steroid hormones in mice, and to observe the intervention effect of dehydroepiandrosterone (DHEA). Methods Sixty adult ICR mice were randomly divided into three groups: control group, DDP modeling group, and DHEA group, with 10 male and 10 female mice in each group. The DDP modeling group mice were intraperitoneally injected with DDP solution at a dose of 2.5 mg·kg^-1·d^-1, once every 3 days, a total of 7 times. On the same day of modeling, the control group mice were injected with an equal amount of physiological saline intraperitoneally. The DEHA treatment group mice were treated with DDP and given a dose of 8.3 mg·kg^-1·d ^-1 of DHEA by gavage for 21 consecutive days. The changes of fatigue indexes of mice were observed by open field, grip and rod rotation tests. The morphology changes of adrenal gland, testicular and ovarian tissue were observed by pathological section and HE staining. The levels of serum steroid hormones were detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The mRNA and protein expression levels of the related genes of the hypothalamus, hypophysis, adrenal, testis and ovary were tested by real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting. Results Compared with control group, both male and female mice in DDP modeling group were significantly losing weight (P＜0.05), their abilities in horizontal movement and vertical movement decreased (all P＜0.05), and the stay time and grip also significantly decreased (all P＜0.05) in female mice. Indexes of fatigue were improved after DHEA supplement (all P＜0.05). In the DDP modeling group, the arrangement of spermatogenic cells at all levels in the testicular tissue was disordered and the testicular interstitial edema was observed, and a large number of primordial follicles in the ovarian tissue were activated, the number of atresia follicles increased, and the number of granulosa cells in the follicles decreased; while in the DHEA group, the damaged phenotype of testicles and ovaries was significantly improved. Compared with control group, the levels of serum testosterone and dihydrotestosterone in both male and female DDP modeling mice significantly decreased (P＜0.01), the pregnenolone was down-regulated but corticosterone was up-regulated significantly (P＜0.05) in male mice, the corticosterone was down-regulated significantly (P＜0.05) in female mice. Compared with the DDP group, after DHEA supplement, the pregnenolone in male mice and the progesterone in female mice increased significantly (P＜0.05), but the pregnenolone in female mice and the progesterone in male mice decreased significantly (P＜0.05). Compared with control group, the expression levels of Cyp21a1 and Cyp11a1 genes in the adrenal gland and Gnrh gene in the hypothalamus of male and female mice in the DDP modeling group significantly decreased (all P＜0.05); the expression levels of Hsd3b2 gene in the adrenal gland, Star, Cyp11a1, and Lhr genes in the ovaries, Crh, Pomc, and Lhb genes in the hypothalamus, pituitary, and pituitary of female mice significantly decreased (all P＜0.05); the expression levels of Star gene and StAR protein in the testicles of male mice, as well as Fshb and Lhb genes in the pituitary gland, were significantly down-regulated (all P＜0.05). After DHEA supplement, compared with the DDP modeling group, the mRNA expression levels of Cyp17a1 in the adrenal gland of male mice and Cyp17a1, Lhr and Fshr genes in testis were down-regulated significantly (P＜0.05); the expression level of Cyp11a1 gene in the adrenal gland of female mice was also decreased (P＜0.05); while the expression levels of Hsd3b2 gene in the adrenal gland, Star, Cyp11a1, Hsd3b2 and Lhr gene in the ovary, and Lhb gene in the pituitary gland were all up-regulated ( P＜0.05). Conclusion The function of hypothalamus-pituitary-adrenal/gonadal axis was inhibited by DDP intermittent injection, especially in female. Supplementation of DHEA can help regulate the homeostasis of steroid hormone levels.

Key words: Cisplatin, Dehydroepiandrosterone, Testis, Ovary, Steroid hormone, Mice

CLC Number:

R-332

Zhiqiang PAN,Zixin NONG,Haina XIE,et al. Injurious Effect of Cisplatin on the Function of Hypothalamus-pituitary-adrenal/gonadal Axis in Mice and the Intervention Effect of Dehydroepiandrosterone[J]. Laboratory Animal and Comparative Medicine, 2023, 43(3): 229-242. DOI: 10.12300/j.issn.1674-5817.2022.182.

Figures/Tables 7

Table 1 Primer sequences in real-time fluorescent quantitative PCR

基因名称 Gene name	引物序列 Primer sequence	产物大小 Length/bp
β-actin	F：5'-TGTTACCAACTGGGACGACA-3'; R：5'-GGGGTGTTGAAGGTCTCAAA-3'	165
Star	F：5'-TTGGGCATACTCAACAACCA-3'; R：5'-GAAACACCTTGCCCACATCT-3'	103
Cyp11a1	F：5'-ACTTCCGGTACTTGGGCTTT-3'; R：5'-GCTTGAGAGGCTGGAAGTTG-3'	201
Cyp11b1	F：5'-GTATCGAGAGCTGGCAGAGG-3'; R：5'-GGGTTGATGTCGTGTCAGTG-3'	140
Cyp21a1	F：5'-CTCCGGCTATGACATCCCTA-3'; R：5'-ACAGCCAAAGGATGGTGTTC-3'	151
Cyp17a1	F：5'-TGGTCATATGCATGCCAACT-3'; R：5'-CCCTTCTTCACGAGCACTTC-3'	132
Hsd3b2	F：5'-TCCAGCTCAGTTGATGTTGC-3'; R：5'-TGCCTTCTCAGCCATCTTTT-3'	129
Cyp19a1	F：5'-CTTTCAGCCTTTTGGCTTTG-3'; R：5'-ATTTCCACAAGGTGCCTGTC-3'	192
Hsd17b1	F：5'-GTTATGAGCAAGCCCTGAGC-3'; R：5'-AAGCGGTTCGTGGAGAAGTA-3'	112
Ar	F：5'-AAGCAGGTAGCTCTGGGACA-3'; R：5'-GAGCCAGCGGAAAGTTGTAG-3'	117
Fshr	F：5'-ATCACACATGCCATGCAACT-3'; R：5'-GTACGAGGAGGGCCATAACA-3'	199
Lhr	F：5'-CAATGGGACGACGCTAATCT-3'; R：5'-CTGGAGGGCAGAGTTTTCAG-3'	204
Esr1	F：5'-TTACGAAGTGGGCATGATGA-3'; R：5'-CCTGAAGCACCCATTTCATT-3'	117
Esr2	F：5'-GAAGCTGGCTGACAAGGAAC-3'; R：5'–AACGAGGTCTGGAGCAAAGA-3'	187
Gper1	F：5'-GTCAACCTTGCAGCCTTCTC-3'; R：5'-AGCACTGCTGAACCTGACCT-3'	198
Pomc	F：5'-CATTAGGCTTGGAGCAGGTC-3'; R：5'-CTTCTCGGAGGTCATGAAGC-3'	128
Fshb	F：5'-TCAGCTTTCCCCAGAAGAGA-3'; R：5'-CCGAGCTGGGTCCTTATACA-3'	249
Lhb	F：5'-CTCAGCCAGTGTGCACCTAC-3'; R：5'-GACCCCCACAGTCAGAGCTA-3'	150
GnRH	F：5'-AGCACTGGTCCTATGGGTTG-3'; R：5'-GGGCCAGTGCATCTACATCT-3'	221
Crh	F：5'-TCTCACCTTCCACCTTCTGC-3'; R：5'-AAGCGCAACATTTCATTTCC-3'	118

Figure 1 Changes of body weight and fatigue indexes in mice after DDP and DHEA treatment
Note：CON indicates control group， DDP indicates cis-dichlorodiamineplatinum （cisplatin） modeling group， DHEA indicates dehydroepian-drosterone （DHEA） treatment after cisplatin modeling group. Compared with the control group， ^?P<0.05； Compared with the cisplatin modeling group， ^#P<0.05.

Figure 2 Pathological morphology of adrenal gland （×200）， testis （×200） and ovary （×100） in mice （HE staining）
Note：CON indicates control group， DDP indicates cisplatin modeling group， DHEA indicates dehydroepiandrosterone （DHEA） treatment after cisplatin modeling group. In Fig. A-F （scale bar size is 50 μm）， ■ indicates adrenal cortex， × indicates adrenal medulla， ★ indicates zona glomerulosa， ◆indicates zona fasciculata， ▼ indicates zona reticularis. In Fig. G-I （scale bar size is 50 μm）， ○ indicates seminiferous tubule， ← indicate spermatocyte， → indicates spermatogonia， ↑ indicates primary spermatocyte， ↓ indicates secondary spermatocyte， ↘indicates sertoli cells， ↖ indicates leydig cells. In Fig. J-L （scale bar size is 100 μm）， ○ indicates follicular cavity， □ indicates corpus luteum， ▲ indicates atresia follicles， ● indicates corpus albicans of ovary， ← indicates primordial follicle， → indicates primary follicle， ↑ indicates secondary follicle， ↘ indicates follicle， ↖ indicates granulosa cells.

Figure 3 The content of serum corticosteroid and the expression levels of corticosteroid synthesis-related genes in adrenal， hypothalamic， and pituitary tissues of mice
Note：A-B， The contents of 11-deoxycorticosterone （DOC） and corticosterone （Cort） in mouse serum were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）； C-D， The expression levels of Cyp21a1and Cyp11b1 mRNA in adrenal tissue were determined by real-time fluorescent quantitative PCR （RT-qPCR）； E-G， The expression levels of CYP11B1 and CYP21A2 protein in adrenal tissue were determined by Western blotting； H-I， The expression levels of corticotropin releasing hormone （Crh） mRNA in hypothalamus and pro-opiomelanocortin-alph （Pomc） mRNA in pituitary were determined by RT-qPCR. CON indicates control group， DDP indicates cisplatin modeling group， DHEA indicates dehydroepiandrosterone （DHEA） treatment after cisplatin modeling group. Compared with control group， ^*P<0.05， ^**P<0.01； Compared with the DDP group， ^#P<0.05； Compared with male mice in the same group， ^&P<0.05.

Figure 4 The content of serum pregnenolone and the expression levels of pregnenolone-synthesis-related genes in adrenal， testis and ovary tissues of mice
Note：A， The contents of pregnenolone （Preg） in mouse serum was determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）； B-C， The expression levels of steroidogenic acute regulatory protein （Star） and Cyp11a1 mRNA in adrenal tissue were determined by real-time fluorescent quantitative PCR （RT-qPCR）； D-E， The expression levels of Star and Cyp11a1 mRNA in testis and ovary were determined by RT-qPCR； F-L， The expression levels of translocatorprotein （TSPO）， StAR and CYP11A1 proteins in adrenal， testis and ovary tissues were determined by Western blotting. CON indicates control group， DDP indicates cisplatin modeling group， DHEA indicates dehydroepiandrosterone （DHEA） treatment after cisplatin modeling group. Compared with control group， ^*P<0.05， ^**P<0.01； Compared with the DDP group， ^#P<0.05， ^##P<0.01.

Figure 5 The content of serum progesterone， 17-hydroxypregnenolone and 17-hydroxyprogesterone as well as the expression levels of their synthesis-related genes in adrenal， testis and ovary tissues of mice
Note：A-C， The contents of progesterone （Prog）， 17-hydroxypregnenolone （17-OH Preg） and 17-hydroxyprogesterone （17-OH Prog） in mouse serum were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）； D-E， The expression levels of Cyp17a1 and 3-beta-hydroxysteroid dehydrogenase type 2 （Hsd3b2） mRNA in testis and ovary were determined by real-time fluorescent quantitative PCR （RT-qPCR）； F-G， The expression levels of Cyp17a1 and Hsd3b2 mRNA in adrenal tissue were determined by RT-qPCR. CON indicates the control group， DDP indicates cisplatin modeling group， DHEA indicates dehydroepian-drosterone （DHEA） treatment after cisplatin modeling group. Compared with the control group， ^*P<0.05； Compared with the DDP group， ^#P<0.05； Compared with male mice in the same group， ^&P<0.05.

Figure 6 The content of serum androgen and the expression levels of hypothalamus-pituitary-adrenal/gonadal axis-related genes in adrenal， testis and ovary tissues of mice
Note：A-C， The contents of androstenedione （Andro）， testosterone （T） and dihydrotestosterone （DHT） in mouse serum were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）； D-F， The expression levels of gonadotropin-releasing hormone （Gnrh） mRNA in hypothalamus tissue， folicular stimulating hormone beta subunit （Fshb） and luteinizing hormone subunit beta （Lhb） mRNA in pituitary were determined by real-time fluorescent quantitative PCR （RT-qPCR）； G-I， The expression levels of folicular stimulating hormone receptor （Fshr）， luteinizing hormone receptor （Lhr）， androgen receptor （Ar）， estrogen receptor （Esr）1/2 and G-protein coupled estrogen receptor 1 （Gper1） mRNA in testis and ovary were determined by RT-qPCR； L， The expression levels of Cyp19a1 and 17-beta-hydroxysteroid dehydrogenase type 1 （Hsd7b1） mRNA in mouse ovarian tissue by RT-qPCR. CON indicates control group， DDP indicates cisplatin modeling group， DHEA indicates dehydroepiandrosterone （DHEA） treatment after cisplatin modeling group. Compared with control group， ^?P<0.05， ^??P<0.01； Compared with the DDP group， ^#P<0.05； Compared with male mice in the same group， ^&&P<0.01.

References 22

1	邓成艳, 黄荣丽, 连利娟, 等. 顺铂的毒副作用及其防治[J]. 中华妇产科杂志, 1995, 30(6): 376-379.
	DENG C Y, HUANG R L, LIAN L J, et al. Toxic and side effects of cisplatin and its prevention and treatment[J]. Chin J Obstet Gynecol, 1995, 30(6): 376-379.
2	董若曦, 朱小丹, 樊伯珍, 等. 不同剂量顺铂腹腔注射建立大鼠化疗损伤性卵巢早衰模型[J]. 实验动物与比较医学, 2020, 40(2): 104-109. DOI: 10.3969/j.issn.1674-5817.2020.02.003 .
	DONG R X, ZHU X D, FAN B Z, et al. Intraperitoneal injection in different dosages of cisplatin to establish a rat model of premature ovarian failure induced by chemotherapy[J]. Lab Anim Comp Med, 2020, 40(2): 104-109. DOI: 10.3969/j.issn.1674-5817.2020.02.003 .
3	农淄心, 邓琳, 贺健祥, 等. 顺铂短期给药诱发小鼠药源性虚证模型的评价研究[J]. 上海中医药大学学报, 2021, 35(4):35-44. DOI: 10.16306/j.1008-861x.2021.04.006 .
	NONG Z X, DENG L, HE J X, et al. Evaluation on drug-induced deficiency syndrome model by short-term administration of cisplatin in mice[J]. Acad J Shanghai Univ Tradit Chin Med, 2021, 35(4):35-44. DOI: 10.16306/j.1008-861x.2021.04.006 .
4	潘志强. "药源性证候"的新生学术问题与思考[J]. 上海中医药杂志, 2018, 52(6):5-8. DOI: 10.16305/j.1007-1334.2018.06.002 .
	PAN Z Q. New academic problems and thinking of drug-induced syndromes[J]. Shanghai J Tradit Chin Med, 2018, 52(6):5-8. DOI: 10.16305/j.1007-1334.2018.06.002 .
5	陈晓. 神经内分泌免疫网络在虚证实验动物中的变化[J]. 上海中医药大学学报, 2002, 16(2):61-65. DOI: 10.16306/j.1008-861x.2002.02.021 .
	CHEN X. Change of neuroendocrine immune network in experimental animals with deficient syndrome[J]. Acta Univ Tradit Med Sin Pharmacol Shanghai, 2002, 16(2):61-65. DOI: 10.16306/j.1008-861x.2002.02.021 .
6	沈自尹, 黄建华, 林伟, 等. 从整体论到系统生物学进行肾虚和衰老的研究[J]. 中国中西医结合杂志, 2009, 29(6):548-550. DOI: 10.3321/j.issn: 1003-5370.2005.03.017 .
	SHEN Z Y, HUANG J H, LIN W, et al. Transition of studying on Shen deficiency syndrome and aging from holistic concept to systematic biologic viewpoint[J]. Chin J Integr Tradit West Med, 2009, 29(6):548-550. DOI: 10.3321/j.issn: 1003-5370.2005.03.017 .
7	韩咏梅, 朱永廉. 减轻顺铂毒性的研究进展[J]. 国外医学(肿瘤学分册), 1999, 26(2): 86-89.
	HAN Y M, ZHU Y L. Research progress on reducing the toxicity of cisplatin[J]. Foreign Med Sci Cancer Sect, 1999, 26(2): 86-89.
8	涂钰莹, 易英, 涂玉梅, 等. 地塞米松对顺铂致斑马鱼毛细胞损伤的保护作用研究[J]. 听力学及言语疾病杂志, 2022, 30(1): 64-68. DOI: 10.3969/j10.3969/j.issn.1006-7299.2022.01.015 .
	TU Y Y, YI Y, TU Y M, et al. Protective effects of dexamethasone on cisplatin-induced hair cell injury in zebrafsih[J]. J Audiol Speech Pathol, 2022, 30(1): 64-68. DOI: 10.3969/j10.3969/j.issn.1006-7299.2022.01.015 .
9	孔庆志, 黄涛, 费雁, 等. 黄芪对大剂量顺铂所致肾毒性防护的实验研究[J]. 中国药学杂志, 1999, 34(7): 447-450. DOI: 10.3321/j.issn: 1001-2494.1999.07.006 .
	KONG Q Z, HUANG T, FEI Y, et al. Experimental study on protective effect of astragalus membranaceus on nephrotoxicity induced by high dose cisplatin[J]. Chin Pharm J, 1999, 34(7):447-450. DOI: 10.3321/j.issn: 1001-2494.1999.07.006 .
10	孙美娟, 费梅, 祝皓. 参芪水煎液防治顺铂化疗所致肾损伤临床研究[J]. 南京中医药大学学报, 2021, 37(1):21-24. DOI: 10.14148/j.issn.1672-0482.2021.0021 .
	SUN M J, FEI M, ZHU H. Clinical study on the prevention and treatment of renal injury induced by cisplatin chemotherapy with Shenqi Decoction[J]. J Nanjing Univ Tradit Chin Med, 2021, 37(1):21-24. DOI: 10.14148/j.issn.1672-0482.2021.0021 .
11	张慧琼, 李刚敏, 陈俊仁, 等. 西洋参总皂苷联合顺铂对Luc-A549肺癌小鼠瘤体生长的影响[J]. 中药药理与临床, 2021, 37(3):50-55. DOI: 10.13412/j.cnki.zyyl.2021.03.010 .
	ZHANG H Q, LI G M, CHEN J R, et al. Effect of total saponins in panacis quinquefolii Radix combined with cisplatin on tumor growth in mice bearing luc-A549 cells[J]. Pharmacol Clin Chin Mater Med, 2021, 37(3):50-55. DOI: 10.13412/j.cnki.zyyl.2021.03.010 .
12	廖英俊, 汤浩, 金亚平. 抗癌药顺铂对小鼠的耳、肾和肝毒性及其机制的研究[J]. 中国药理学通报, 2004, 20(1):82-85. DOI: 10.3321/j.issn: 1001-1978.2004.01.023 .
	LIAO Y J, TANG H, JIN Y P. Study of toxic effects on hearing, kidney and liver of mice induced by anticancer agent of cisplatin and their mechanisms[J]. Chin Pharmacol Bull, 2004, 20(1):82-85. DOI: 10.3321/j.issn: 1001-1978.2004.01.023 .
13	刘崇斌, 黄柳维, 李彩珍, 等. 阻断pannexin-1可减轻肾脏组织炎症细胞浸润和缓解顺铂诱导的急性肾损伤[J]. 南方医科大学学报, 2019, 39(5): 508-514. DOI: 10.12122/j.issn.1673-4254.2019.05.02 .
	LIU C B, HUANG L W, LI C Z, et al. Blocking pannexin-1 alleviates cisplatin-induced acute kidney injury in mice by reducing renal inflammatory cell infiltration[J]. J South Med Univ, 2019, 39(5): 508-514. DOI: 10.12122/j.issn.1673-4254.2019.05.02 .
14	舍雅莉, 闫德祺, 刘永琦, 等. 当归贝母苦参丸对顺铂化疗H22荷瘤小鼠肿瘤及肝脏、肾脏和胸腺组织病理形态的影响[J]. 中国中医药信息杂志, 2014, 21(5): 56-60. DOI: 10.3969/j.issn.1005-5304.2014.05.018 .
	SHE Y L, YAN D Q, LIU Y Q, et al. Effect of Danggui Beimu Kushen pill on pathological morphology of tumor, liver, kidney and Thymus of H22 tumor-bearing mice treated with cisplatin[J]. Chin J Inf Tradit Chin Med, 2014, 21(5): 56-60. DOI: 10.3969/j.issn.1005-5304.2014.05.018 .
15	孙铱钒, 关朕, 孙应彪, 等. 顺铂染毒大鼠睾丸定量组织学分析及睾丸酶活力的变化[J]. 毒理学杂志, 2015, 29(3):172-176. DOI: 10.16421/j.cnki.1002-3127.2015.03.003 .
	SUN Y F, GUAN Z, SUN Y B, et al. Quantitative histological analysis of testes and effect on testicular enzymes induced by cisplatin in rats[J]. J Toxicol, 2015, 29(3):172-176. DOI: 10.16421/j.cnki.1002-3127.2015.03.003 .
16	ERFANI MAJD N, TABANDEH M R, HOSSEINIFAR S H, et al. Protective effect of Aloe vera gel against cisplatin-induced testicular damage, sperm alteration and oxidative stress in rats[J]. Int J Fertil Steril, 2021, 15(3):210-218. DOI: 10.22074/IJFS.2020.134691 .
17	齐聪. 顺铂腹腔内给药对大鼠卵巢的毒性作用[J]. 上海医科大学学报, 2000, 27(4): 324-325. DOI: 10.3969/j.issn.1672-8467.2000.04.031 .
	QI C. Observation of ovarian toxicity following intraperitoneal administration of cisplatin in mice[J]. J Shanghai Med Univ, 2000, 27(4): 324-325. DOI: 10.3969/j.issn.1672-8467.2000.04.031 .
18	NILSSON M E, VANDENPUT L, TIVESTEN Å, et al. Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry[J]. Endocrinology, 2015, 156(7):2492-2502. DOI: 10.1210/en.2014-1890 .
19	SCHIFFER L, BARNARD L, BARANOWSKI E S, et al. Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review[J]. J Steroid Biochem Mol Biol, 2019, 194:105439. DOI: 10.1016/j.jsbmb.2019.105439 .
20	CUTLER G B Jr, GLENN M, BUSH M, et al. Adrenarche: a survey of rodents, domestic animals, and Primates[J]. Endocrinology, 1978, 103(6):2112-2118.
21	欧阳可育, 胡卫列, 聂奇伟. 辛二酰苯胺异羟肟酸联合顺铂对裸鼠肾上腺皮质癌的实验研究[J]. 临床泌尿外科杂志, 2014, 29(4):342-345. DOI: 10.13201/j.issn.1001-1420.2014.04.021 .
	OUYANG K Y, HU W L, NIE Q W. Effects of SAHA combined with cisplatin on adrenocortical carcinoma in nude mice model[J]. J Clin Urol, 2014, 29(4):342-345. DOI: 10.13201/j.issn.1001-1420.2014.04.021 .
22	王泽先, 郭菲菲, 公衍玲, 等. 顺铂化疗对下丘脑、血浆ghrelin和orexin表达的影响[J]. 现代生物医学进展, 2016, 16(31):6023-6027, 6041. DOI: 10.13241/j.cnki.pmb.2016.31.006 .
	WANG Z X, GUO F F, GONG Y L, et al. Effects of orexin on the cisplatin-induced Pica in rats[J]. Prog Mod Biomed, 2016, 16(31):6023-6027, 6041. DOI: 10.13241/j.cnki.pmb.2016.31.006 .

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