Journal of Shandong University (Health Sciences)

Long-term management strategy of endometriosis

LENG Jinhua, SHI Jinghua

Journal of Shandong University (Health Sciences). 2019, 57(6): 1-5. doi:10.6040/j.issn.1671-7554.0.2019.595

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Endometriosis is a common chronic disease that affects womens reproductive health and family well-being. A comprehensive long-term management scheme based on clinical symptoms, age stratification and multi-dimensional factors should be established. The timing and mode of surgery ought to be standardized, and the leading role of drug therapy should be emphasized. Due attention should be paid to the follow-up and health education so as to improve patients quality of life.

Surgical treatment of endometriosis

YAO Shuzhong, LIANG Yanchun, WEI Yajing

Journal of Shandong University (Health Sciences). 2019, 57(6): 6-15. doi:10.6040/j.issn.1671-7554.0.2019.514

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Endometriosis, one of the common benign gynecological diseases, can cause pain symptoms such as dysmenorrhea, chronic pelvic pain and dyspareunia, and is usually related to infertility. As a result, endometriosis seriously affects womens health. Surgery is an important treatment of endometriosis. This article reviews the surgical treatments of different types of endometriosis, and provides an outlook of new surgical techniques.

Clinical manifestations of endometriosis

ZHANG Xinmei, QIAN Honglang

Journal of Shandong University (Health Sciences). 2019, 57(6): 16-22. doi:10.6040/j.issn.1671-7554.0.2019.623

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Endometriosis is a chronic, inflammatory, estrogen-dependent, and benign gynecologic disease seriously affecting the physical and mental health of women. The main clinical symptoms are pelvic pain and infertility, which are manifested in a diverse and complex manner, and are closely related to the location and type of endometriotic lesions. Paying attention to the clinical manifestations can help the early diagnosis and timely treatment of endometriosis.

Fertility improvement strategies for endometriosis associated infertility

HUANG Wei, LIU Dong

Journal of Shandong University (Health Sciences). 2019, 57(6): 23-26. doi:10.6040/j.issn.1671-7554.0.2019.560

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Endometriosis is a common disease afflicting a significant proportion of women of reproductive age. It affects patients quality of life, reduces their fecundity and leads to infertility. Endometriosis associated infertility is mainly treated with laparoscopic surgery and assisted reproductive technology(ART). The optimal treatment strategy depends on the severity of the disease and the condition of patients. Controversy still remains as how and when to take therapeutic measures.

Malignant transformation of endometriosis

LIU Chongdong, LOU Tong, DONG Jing

Journal of Shandong University (Health Sciences). 2019, 57(6): 27-32. doi:10.6040/j.issn.1671-7554.0.2019.494

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Endometriosis, characterized by the presence of extra-uterine endometrium, is a common gynecologic disorder in reproductive-age women. In clinical practice, although endometriosis is recognized as a benign disease, it still has the risk of malignant change. This review mainly presents the relationship between endometriosis and ovarian tumors, and probes into the risk factors, molecular mechanism and prevention of malignant transformation.

Research advances in the pathogenesis of endometriosis

WANG Guoyun, YUAN Ming, JI Miaomiao

Journal of Shandong University (Health Sciences). 2019, 57(6): 33-39. doi:10.6040/j.issn.1671-7554.0.2019.521

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Endometriosis(EMs)is a common gynecological disease with a prevalence of 10% in women of childbearing age. The main symptoms of EMs are pain and infertility, which seriously affect patients quality of life. However, 山东大学学报 (医学版)57卷6期 -王国云,等.子宫内膜异位症发病机制研究进展 \=- there is no EMs-specific, non-invasive diagnostic method yet. Currently, EMs is treated with surgery or hormonoth-erapy, both of which have side effects and high recurrence rate. The ambiguity of EMs pathogenesis limits the diagnosis and treatment. The mainstream theory is retrograde menstruation, but the latest research shows that EMS is a complex chronic disease, which may be induced by the menstrual blood flow, while the complex interaction between genetic, immune and environmental factors plays a more important role. This paper will review the pathogenesis theories and latest research advances, especially the new research fields of EMs, and propose the problems in the EMs mechanism research.

Imaging diagnosis of endometriosis

LU Jingjing, XIA Yu

Journal of Shandong University (Health Sciences). 2019, 57(6): 40-45. doi:10.6040/j.issn.1671-7554.0.2019.522

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Endometriosis is a common and frequently-occurring disease in women of childbearing age. It is the most common cause of chronic pelvic pain. As endometriosis is widespread, imaging techniques can provide a comprehensive and objective assessment of the lesion. This article describes the application of a variety of imaging techniques in the diagnosis of endometriosis, and reviews the techniques and advances in ultrasound and magnetic resonance imaging.

Medical treatment of endometriosis: an update

PENG Chao, ZHOU Yingfang

Journal of Shandong University (Health Sciences). 2019, 57(6): 46-50. doi:10.6040/j.issn.1671-7554.0.2019.519

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Endometriosis(EMs)is a chronic and recurrent disease, and can hardly be cured by conservative surgery, so the medical treatment is very important. Many drugs have been developed for relieving pain symptoms associated with EMs, such as nonsteroids anti-inflammatory drugs(NSAIDs), conjugated oral contraceptives, progestins, gestrinone, 山东大学学报 (医学版)57卷6期 -彭超,等.子宫内膜异位症的药物治疗 \=-gonadotropin-releasing hormone-agonists or GnRH-antagonists, and traditional Chinese medicine. Experts consensus has been achieved and published in 2018 in China on long-term maintenance therapy postoperatively to relieve pain and to prevent recurrence of EMs.

Effect of Fugan Huaxian Decoction on TGF-β1/Smad signaling pathway in rats with hepatic fibrosis

XIAO Zhenghua, YANG Hui, LEI Wei, YANG Jun, YI Xu, TAN Minmin

Journal of Shandong University (Health Sciences). 2019, 57(6): 51-60. doi:10.6040/j.issn.1671-7554.0.2019.423

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Objective To explorethe effect of Fugan Huaxian Decoction on transforming growth factor β1(TGFβ1)/Smad signaling pathway in rats with hepatic fibrosis(HF)and the mechanism of anti-hepatic fibrosis. Methods A total of 120 SD rats were randomly divided into control group, model group, colchicine group, and high, medium and low dose group of decoction. Except for the control group,the other groups established HF rat models of Qi deficiency, poison weakness and blood stasis under the guidance of traditional Chinese medicine(TCM)theory based on classical subcutaneous injection of carbon tetrachloride(CCl4). After 6 weeks, when the models were successfully established, the decoction groups received gastrogavage for 3 weeks, while the control group and model group were given equal volume of pure water for 3 weeks. Next day after the last gastrogavage, the serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), albumin(ALB), hydroxyproline(Hyp),laminin(LN)and pre-collagen type Ⅲ(PⅢNP)levels were measured. The liver tissues were stained with HE and Mason stainings. The protein and mRNA expressions of TGF-beta1, Smad3 and Smad7 in liver tissues were detected with qRT-PCR and immunohistochemistry. Results Compared with the model group, decoction groups showed relieved hepatocyte injury, decreased collagen fiber proliferation, improvedhepatic fibrosis(χ2=54.722, P<0.01), and reduced proportion of liver collagen fibers(χ2=52.149, P<0.01). Compared with the control group, the model group had increased serum ALT(χ2=39.685, P<0.01), AST(F=659.984, P<0.01), Hyp(χ2=38.613, P<0.01), LN(χ2=50.057, P<0.01), PⅢNP(F=63.492, P<0.01), decreased ALB(χ2=51.908, P<0.01), increased expressions of TGF-β1(χ2=40.900, P<0.01), Smad3(χ2=38.253, P<0.01), TGF-β1 mRNA(F=92.304, P<0.01), Smad3 mRNA(F=119.563, P<0.01), and decreased Smad7(χ2=48.949, P<0.01)and Smad7 mRNA(F=42.120, P<0.01). Compared with the model group, the decoction groups inhibited the changes of the above indexes(P<0.01), especially the high dosage group(P<0.01). Conclusion The model of Qi deficiency, poison weakness and blood stasis complicated with HF was successfully established. Fugan Huaxian Decoction can protect hepatocytes, alleviate liver injury and inhibit HF, probably by regulatingthe expressions of TGF-beta1, Smad3 and Smad7.

Expressions of apelin, nucleobindin 2 and retinoic acid receptor responder protein 2 in glioblastoma based on network databases

KONG Juan, ZHANG Zhen, GUO Wei, HAN Ping

Journal of Shandong University (Health Sciences). 2019, 57(6): 61-67. doi:10.6040/j.issn.1671-7554.0.2019.426

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Objective To investigate the expressions and significances of adipokines apelin(APLN), nucleobindin 2(NUCB2)and retinoic acid receptor responder protein 2(RARRES2)in glioblastoma multiforme(GBM). Methods The mRNA expressions of APLN, NUCB2 and RARRES2 in GBM tissues and control tissues, and the correlations between them and vascular endothelial growth factor A(VEGFA), CD34 and matrix metalloproteinase 14(MMP14)were determined with GEPIA. The relationship between APLN, NUCB2 and RARRES2 expressions and GBM prognosis was analyzed with GEPIA and Survexpress. The mRNA expressions of APLN and its receptor, NUCB2, RARRES2 and its receptors in 4 glioma cell lines were analyzed with cancer cell line encyclopedia(CCLE). Results The mRNA expressions of APLN, NUCB2 and RARRES2 were significantly up-regulated in GBM patients (P<0.05); APLN was associated with VEGFA (R=0.52, P<0.05) and CD34 (R=0.39, P<0.05); NUCB2 was associated with MMP14 (R=0.43, P<0.05); The expression of RARRES2 was negatively correlated with the prognosis of GBM(GEPIA: Log rank P=0.027; Survexpress: Log rank P=0.007). NUCB2 was highly expressed in all 4 cell lines. The APLN receptor was expressed the highest in A172 cells. The RARRES2 receptor was expressed the highest in U87MG cells. Conclusion APLN, NUCB2 and RARRES2 are highly expressed in GBM tissues. APLN is closely related to GBM angiogenesis. NUCB2 may link to GBM invasion and RARRES2 is associated with poor prognosis.

Effect of ar-turmerone on poliferation, migration and invasion of cervical squamous cancer cell line SiHa

LUO Mengying, WU Bei, WANG Ye, LUO Heng, CAO Yu

Journal of Shandong University (Health Sciences). 2019, 57(6): 68-74. doi:10.6040/j.issn.1671-7554.0.2018.1443

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Objective To investigate the effect of ar-turmerone on the proliferation, migration and invasion of cervical cancer SiHa cells in vitro, and to preliminarily explore its mechanism. Methods SiHa cells were incubated with different concentrations of ar-turmerone(0, 20, 40, 80 mg/L), and cell proliferation was measured by CCK8. The apoptosis was observed by giemsa staining. The effects of ar-turmerone on migration and invasion capacity of SiHa cells were detected by cell scratch assay and transwell. The apoptosis was analyzed by flow cytometry. The expressions of MMP2, MMP9 and p53 protein in SiHa cells were detected by Western blotting. Results Ar-turmerone dose-dependently inhibited SiHa cells proliferation(F_{concentration}=162.419, P<0.001; F_time=99.442, P<0.001; F_{concentration×time}=2.111, P=0.095), migration(F_{concentration}=432.158, P<0.001; F_time=528.845, P<0.001)and invasion(F_{concentration}=434.362, P<0.001). 山东大学学报 (医学版)57卷6期 -罗梦颖,等.芳姜黄酮对SiHa细胞增殖、迁移及侵袭的影响 \=-Flow cytometry analysis showed that ar-turmerone could induce the apoptosis of SiHa cells in a dose-dependent manner(F_{concentration}=482.690, P<0.001). Western blotting results showed that ar-turmerone treatment significantly up-regulated the expression of apoptosis-related proteins p53(F_{concentration}=2.086, P=0.045)and down-regulated the expressions of invasion and metastasis related proteins MMP2 and MMP9(F_{concentration}=18.906, P=0.001; F_{concentration}=9.847, P=0.005). Conclusion Ar-turmerone has the ability to inhibit the proliferation and induce apoptosis of SiHa cells in vitro, and the mechanism is related to the regulation of apoptosis related protein p53 expression. In addition, ar-turmerone can inhibit the migration and invasion of SiHa cells, possibly through the regulation of the expressions of MMP2 and MMP9 protein.

Simultaneous determination of five components in Cibotii Rhizoma by HPLC

SHI Yue, WANG Ning, LI Feifei, WANG Shuqi

Journal of Shandong University (Health Sciences). 2019, 57(6): 75-80. doi:10.6040/j.issn.1671-7554.0.2019.351

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Objective To establish a validated HPLC method for quantitative analysis of kojic acid, 5-HMF, protocatechuic acid, maltol and protocatechuic aldehyde in Cibotii Rhizoma. Methods The samples were determined on a Shimatsu Shim-pak C18 column(4.6 mm×250 mm, 5 μm)by gradient elution with methanol as organic phase, 0.1% formic acid-ammonium formate aqueous solution as aqueous phase, at a flow rate of 1.0 mL/min. The detection wavelength was 280 nm for kojic acid, protocatechuic acid, maltol and protocatechuic aldehyde, while 260 nm for 5-HMF. The column temperature was controlled at 35 ℃. Results Kojic acid, 5-HMF, protocatechuic acid, maltol and protocatechuic aldehyde exhibited good linearity(r2=0.999 9, n=6)among the ranges of 0.53-21.17, 9.64-482.00, 2.52-100.88, 0.52-21.09, 0.52-20.87 μg/mL. The limit of quantitation(LOQ)/limit of detection(LOD)were 0.03/0.01, 0.20/0.05, 0.35/0.07, 0.05/0.02, 0.05/0.01 μg/mL, respectively. The average recoveries were 85.2%-102.8%. Conclusion C18 column was employed as stationary phase, dual wavelength detection and gradient elution HPLC method were used to determine the contents of five components in Cibotii Rhizoma. The method performs with high sensitivity and good accuracy, and can be used for quality control of Cibotii Rhizoma and its products.

Correlation between SUVmax of ¹⁸F-FDG PET/CT and programmed cell death-ligand 1 expression in lung cancer patients: a Meta-analysis

CHEN Hongyan, MA Yuanyuan, SUN Hukui

Journal of Shandong University (Health Sciences). 2019, 57(6): 81-86. doi:10.6040/j.issn.1671-7554.0.2018.1481

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Objective To study the correlation between ¹⁸F-FDG uptake and programmed cell death-ligand 1(PD-L1)expression in lung cancer patients by Meta-analysis of published articles. Methods According to the literature inclusion and exclusion criteria, PubMed(MEDLINE included), EMBASE, and Cochrane Database of Systematic Review were searched, and research articles on the relationship between ¹⁸F-FDG uptake and PD-L1 expression, which were published between January 1, 2000 and Decenber 1, 2018, were selected. The quality of included articles was evaluated according to the Jadad scale. The correlation coefficient(r)was extracted from the included articles. The combined r and the 95% confidence interval (CI) were calculated with Comprehensive Meta-Analysis software under a random-effects model. Results According to the inclusion and exclusion criteria, 4 articles, involving 1033 patients, were finally included. All the studies had a combined r value of 0.289(95%CI: 0.100~0.459, P<0.001), but with a significant 山东大学学报 (医学版)57卷6期 -陈红艳,等.肺癌患者¹⁸F-FDG PET/CT SUVmax与程序性死亡受体-配体1表达相关性的Meta分析 \=-heterogeneity(I²=86%, P=0.003). Subgroup analysis for different tumor types indicated that adenocarcinomas and squamous cell carcinomas showed a positive correction(r=0.273, P=0.003; r=0.235, P=0.001). Conclusion SUVmax positively correlates with PD-L1 expression for patients with lung cancer, and the similar trend is found in both adenocarcinomas and squamous cell carcinomas. The assessment of SUVmax value and PD-L1 immunohistochemistry score may improve the accuracy of patient selection and predicit PD-1 treatment effect.

Dapagliflozin improves lipid metabolism and visceral adipose tissues in overweight and obese patients with type 2 diabetes

JIANG Lijuan, LIU Fuqiang, JIANG Ziyun, LI Wenjuan, LIN Peng, WANG Chuan, HOU Xinguo, CHEN Li

Journal of Shandong University (Health Sciences). 2019, 57(6): 87-93. doi:10.6040/j.issn.1671-7554.0.2019.253

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Objective To evaluate the effects of sodium-glucose cotransporter protein 2(SGLT-2)inhibitor, dapagliflozin, on various body fat parameters in overweight and obese patients with type 2 diabetes, and to explore its effects on lipid metabolism and visceral adipose tissues and the potential mechanism. Methods A total of 60 hospitalized patients with type 2 diabetes who had poor blood glucose control before admission were randomly selected, including 46 males and 14 females, aged 35-65 years, average 50 years. The patients were randomly divided into control group(n=30)and dapagliflozin(Adatang)treatment group(n=30). Diabetes education was conducted in both groups. In the control group, insulin, oral antidiabetic drugs or combination medication with non-SGLT2 inhibitors were adjusted. In the dapagliflozin treatment group, 10 mg/d dapagliflozin was combined with prior insulin or oral antidiabetic drugs for 山东大学学报 (医学版)57卷6期 -姜立娟,等.达格列净改善超重及肥胖2型糖尿病患者脂代谢及内脏脂肪含量 \=-12 weeks. Parameters were recorded, including age, sex, blood glucose, glycosylated hemoglobin, blood lipid, baseline and post-treatment body composition in both groups; 24 h glycosuria quantitative and electrolytes, baseline and post-treatment blood biochemical indicators in the dapagliflozin treatment group. The incidence of adverse reactions such as urinary tract infection, genital tract infection, hypoglycemia and abnormal renal function in both groups were recorded. Results There were no statistical differences in age, sex, baseline values of glycosylated hemoglobin and body weight between the two groups(P>0.05). After 12 weeks of treatment, blood glucose was effectively controlled in both groups(P<0.01). In terms of lipid parameters, dapagliflozin significantly reduced triglyceride(P<0.05)and increased high-density lipoprotein(P<0.01), but had no significant effects on cholesterol or low-density lipoprotein(P>0.05). There was no significant change in blood lipid in the control group(P>0.05). Dapagliflozin significantly reduced the area and mass of visceral adipose tissues(P<0.01), but had no significant effects on body mass, percentage of body fat, skeletal muscle index of limbs, and bone mineral content(P>0.05). Moreover, there was a significant increase in 24 h glycosuria quantitative in the dapagliflozin treatment group(P<0.01), but no significant difference in 24 h urine electrolytes, blood electrolytes, blood routine and renal function(P>0.05). During the treatment, there was no significant difference in adverse reactions between the two groups(P>0.05). Conclusion Dapagliflozin can significantly reduce blood glucose, triglycerides, and area and mass of visceral adipose tissues in patients with type 2 diabetes, while increase high-density lipoprotein. It can reduce the risk of cardiovascular diseases, but at the same time it has no significant effects on renal function and electrolytes. It does not increase the incidence of renal impairment and hypoglycemia. Dapagliflozin is safe and effective for patients with type 2 diabetes.

Value of strain ratio of compression elastography and virtual touch tissue quantification in the diagnosis of breast lesions

SHANG Mengmeng, ZHANG Yan, CHENG Lin, SUN Xiao, SHI Dandan, MIN Xiang, LI Jie

Journal of Shandong University (Health Sciences). 2019, 57(6): 94-99. doi:10.6040/j.issn.1671-7554.0.2018.1397

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Objective To compare the diagnostic performances of strain ratio of compression elastography and virtual touch tissue quantification(VTQ)in the differentiation of benign and malignant breast lesions. Methods A total of 49 female patients with 52 breast lesions were enrolled in this study. Both compression elastography and VTQ were performed, and SR and shear wave velocity were measured. Receiver operating characteristic(ROC)curves were used to analyze the diagnostic performances and Z tests were used to compare the area under the curve. Results For the SR method, the AUC, optimal cutoff value, sensitivity, specificity, positive predictive value, negative predictive value(NPV)and accuracy was 0.919, 0.499, 93.6%, 72.0%, 78.8%, 94.7%, and 84.6%, respectively. For the VTQ method, the AUC, optimal cutoff value, sensitivity, specificity, PPV, NPV and accuracy was 0.796, 2.90 m/s, 68.0%, 山东大学学报 (医学版)57卷6期 -商蒙蒙,等.弹性应变率比值法与声触诊组织量化技术对乳腺肿块的诊断价值 \=-92.6%, 89.5%, 75.8% and 80.8%, respectively. There was no significant difference in AUC between the two methods (Z=1.580, P=0.057). When compression elastography and VTQ were used in combination, the sensitivity, specificity, PPV, NPV and accuracy was 84.0%, 88.9%, 87.5%, 85.7% and 86.5%, respectively. Conclusion Both SR and VTQ are helpful in the(semi-)quantitative evaluation of the stiffness of breast lesions. Their diagnostic performances are similar. The SR method shows higher sensitivity but lower specificity than VTQ. The combination of compression elastography and VTQ can significantly improve the diagnostic performance of ultrasound to differentiate benign and malignant breast lesions.

Job burnout subtypes and emotional problems among medical staff in a tertiary hospital

SUN Yaoyao, LIU Fei, CAO Fenglin

Journal of Shandong University (Health Sciences). 2019, 57(6): 100-105. doi:10.6040/j.issn.1671-7554.0.2018.1488

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