Table of Content

21 July 2018, Volume 39 Issue 4

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Different hormone receptors and their roles as prognostic markers in breast cancer

Zhang Ying, Ruan Xiangyan, Cai Guiju, Su Yajie, Li Na, Alfred O. Mueck

2018, 39(4):  479-485.  doi:10.3969/j.issn.1006-7795.2018.04.001

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Breast cancer is one of the leading causes of death in women,and there is an urgent need for new biomarkers and therapeutic targets.The drug treatment response and long-term prognosis of various breast cancer subtypes are different. In cases like triple negative breast cancer estrogen receptor-α(ER-α), progesterone receptor(PR), and human epidermal growth factor receptor-2 (HER-2), there is a complete lack of available biomarkers for prognosis,and therapeutic response is poor. In recent years, in vitro and in vivo experiments have shown that progesterone receptor membrane component 1 (PGRMC1) plays an important role in the occurrence and development of breast cancer. So how do different hormone receptors predict the development and prognosis of breast cancer? Will PGRMC1 be a new potential prognostic marker for breast cancer in the future? We will review the results of related researches.

Correlation between the blood membrane-bound progesterone level and clinical application in patients with breast cancer

Zhao Yue, Ruan Xiangyan, Zhang Quandong, Wang Husheng, Li Xue, Cai Guiju, Gu Muqing, Alfred O. Mueck

2018, 39(4):  486-493.  doi:10.3969/j.issn.1006-7795.2018.04.002

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Objective To detect the PGRMC1 level in blood samples from breast cancer patients and evaluate the clinical value in diagnosis of breast cancer. Methods The whole blood PGRMC1 levels were measured by enzyme linked immunosorbent assay (ELISA) and the serum CA125, CEA and CA153 levels were measured by chemiluminescent immunoassay (CLIA) technique in 90 breast cancer patients, 50 breast benign diseases and 30 healthy controls from September 2017 to January 2018. All participants signed informed consent voluntarily. Chi-square test was used for comparison between groups. Receiver operating characteristic (ROC) curve was used to evaluate diagnosis value of PGRMC1 in breast cancer. Results The level of PGRMC1 showed no difference between the benign group and the control group (P>0.05). The PGRMC1 levels showed significant difference in stage Ⅱ, Ⅲ and IV breast cancer group compared with the benign and the control groups (P<0.05 compared among groups). There was no significant change in the serum levels of CA125, CA153 and CEA in stage I and Ⅱ breast cancer patients with no statistically significant difference compared with the benign group and the control group (P>0.05). Compared with the benign group and the control group, the serum value of CA125, CA153 and CEA was significantly higher in stage Ⅲ and IV breast cancer group (P<0.05). In late stage, the area under the ROC curve (AUC) of PGRMC1, CA125, CA153 and CEA was 82.7%, 78.3%, 86.8% and 77.3% respectively. In early stage, the AUC of CA125, CA153 and CEA was below 60%, which showed nearly no significance in diagnosis for early breast cancer. While the AUC of PGRMC1 was 86.6%. The sensitivity of PGRMC1 was 94% and the specificity was 50%. Conclusion PGRMC1 was successfully detected with ELISA in blood samples from breast cancer patients and had applicable value for diagnosis in both early and late phase of breast cancer. There is a possibility that PGRMC1 may become a blood biomarker of early diagnosis and progression of breast cancer.

Etiology of premature ovarian insufficiency in Beijing and surrounding areas

Cheng Jiaojiao, Ruan Xiangyan, Li Yanglu, Du Juan, Wang Husheng, Alfred O. Mueck

2018, 39(4):  494-498.  doi:10.3969/j.issn.1006-7795.2018.04.003

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Objective Premature ovarian insufficiency (POI) not only affects women's fertility, but also significantly increases the risk of early menopause-related chronic diseases and early death. Studying the etiology/risk factors is very important for the prevention and treatment of POI. Methods From December 2016 to May 2018, 149 patients diagnosed with POI at the Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University were selected. We collected patients' informations including the age, the age of diagnosis with POI, time from hospital visit to confirming POI, menstruation, history of pelvic surgery, radiotherapy and chemotherapy history, history of mumps infection, history of thyroid dysfunction, history of immune diseases such as systemic lupus erythematosus (SLE). Body height, weight, waist circumference, hip circumference, follicle stimulating hormone (FSH), estradiol (E₂), anti-müllerian hormone (AMH), inhibin B (INHB), and karyotype analysis were measured. The 149 patients were divided into two groups according to FSH values 25-40 IU/L and FSH>40 IU/L for statistical analysis of general characteristics, endocrine parameters and etiology. Results For Age, BMI, WHI, age at diagnosis of POI, time from hospital visit to confirming POI, and INHB, there was no statistically significant difference (P>0.05). For E₂ and ANH, there was a significant difference between groups (P<0.05). The E₂ value (36.60±33.39) mg/L and AMH value (0.09±0.20) in the FSH>40 IU/L group were lower than the E₂ values (66.80±56.70) mg/L and the AMH value (0.41±0.77)ng/mL in the FSH 25-40 IU/L group. Among 149 patients with POI, 53.7% (80 cases) were idiopathic, 5.4% (8 cases) were chromosomal abnormalities, 17.4% (26 cases) were iatrogenic, and 21.5% (32 cases) had a history of infection (mumps et.), 2.0% (3 cases) were immune abnormalities;FSH 25~40 IU/L group,FSH>40 IU/L group, there was no significant difference in the etiology/risk factors between groups (P>0.05). Conclusion In addition to idiopathic factor, the more important cause of POI is iatrogenic cause, indicating that the prevention and treatment of iatrogenic POI is of utmost importance.

Effects of oral contraceptives on sexual function in PCOS patients

Du Juan, Ruan Xiangyan, Alfred O. Mueck

2018, 39(4):  499-504.  doi:10.3969/j.issn.1006-7795.2018.04.004

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Objective To investigate the effects of oral contraceptives on sexual function in polycystic ovary syndrome (PCOS) patients. Methods The online questionnaire was completed by PCOS patients in clinic. PCOS patients in the Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University were enrolled. They were divided into two groups taking oral contraceptives (OC group) not taking OC (NOC group). The primary endpoint was the Female Sexual Function Index (FSFI) score, with additional questions on contraception, sexual activity, relationship stability, pregnancy and other factors which may influence sexual function. Results Totally 210 PCOS patients were recruited in this study to participate in the survey using the online questionnaire. Of all women participating, 126 were taking oral contraceptives (OC group) and 84 were not taking OC (NOC group). Among OC users, the median FSFI total score was 26.35, and 50.79% showed high risk of female sexual dysfunction (FSD). Regarding NOC group, the median FSFI total score was 26.85, 47.62% showed high risk of FSD. There was no significant difference between two groups (P=0.635). Also, no differences of FSFI scores were seen in patients taking 35 μg ethinyl estradiol (EE)/2 mg cyproterone acetate (CPA), 30 μg EE/3 mg drospirenone(DRSP), and 30 μg EE/150 μg desogestrel. Relationship stability and sexual activity were found to be associated with sexual function in PCOS patients. Conclusion There was no significant difference between OC users and not taking OC users in PCOS patients. Different progestins in OCs and the EE dosage in OCs have no significant influence on sexual function in PCOS patients. Regarding PCOS patients, sexual activity and relationship stability may be risk factors of FSD.

Characteristics of obesity and glycolipid metabolism in polycystic ovary syndrome patients with diminished ovarian reserve

Jin Jing, Ruan Xiangyan, Hua Lin, Li Yanglu, Wang Lijuan, Wang Husheng, Zhao Yue, Alfred O. Mueck

2018, 39(4):  505-511.  doi:10.3969/j.issn.1006-7795.2018.04.005

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Objective To explore the characteristics of obesity and glycolipid metabolism in polycystic ovary syndrome (PCOS) patients with diminished ovarian reserve (DOR). Methods Totally 338 PCOS patients (including 57 PCOS with DOR patients and 281 simple PCOS patients) and 70 healthy women (control group), who came to Department of Gynecological Endocrinology in Beijing Obstetrics and Gynecology Hospital between January 2015 and January 2017, were recruited. Age and menstruation of these patients were recorded. Body height, body weight, waist circumference, hip circumference, basel follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂), testosterone (T), anti-Müllerian hormone (AMH), fasting plasma glucose (FPG), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density and lipoprotein-cholesterol (LDL-C) and baseline antral follicle count of these patients were measured. The indices between PCOS with DOR, simple PCOS and control group were compared, and the correlations between AMH and other indices in each group were analyzed. Results (1) The prevalence of central obesity (≥ 25 kg/m²) in simple PCOS, PCOS with DOR and control group was 38.1%, 40.4% and 22.9%, respectively. And the prevalence of abdominal obesity waist hip ratio (WHR) ≥ 0.85 in simple PCOS, PCOS with DOR and control group was 46.6%, 21.1% and 28.6%, respectively. The prevalence of central obesity in PCOS with DOR patients had no significant difference with simple PCOS patients and control group (P>0.05), but the prevalence of abdominal obesity was lower than simple PCOS patients (P<0.05). (2) The level of FPG, FINS and homeostasis model assessment (HOMA)-insulin resistivity (IR) in PCOS with DOR patients had no significant differences from simple PCOS patients(P>0.05), while the level of FPG and HOMA-IR was higher than control group (P<0.05). (3) The levels of TC, HDL-C and LDL-C in both simple PCOS and PCOS with DOR patients were higher than control group (P<0.05). The levels of TC, triglyceride (TG), HDL-C and LDL-C in PCOS with DOR patients had no significant difference with simple PCOS patients (P<0.05). (4) In simple PCOS patients, AMH had a negative correlation with FPG and HOMA-IR (P<0.05), while had a positive correlation with HDL-C (P<0.01). In PCOS with DOR patients, AMH had no correlation with obesity and glycolipid metabolic indices (P>0.05). In control group, AMH had a positive correlation with HDL-C (P<0.01). Conclusion The prevalence of abdominal obesity in PCOS with DOR patients is lower than simple PCOS patients. The characteristic of glycolipid metabolism in PCOS with DOR patients is similar to simple PCOS patients. But the correlation between AMH and glycolipid metabolic indices in PCOS with DOR patients is different from both simple PCOS patients and control group.

Exploration of relationship between malondialdehyde, retinol and pathogenesis of polycystic ovary syndrome

Wang Husheng, Ruan Xiangyan, Li Yanglu, Cheng Jiaojiao, Gu Muqing, Du Juan, Jin Fengyu, Alfred O. Mueck

2018, 39(4):  512-516.  doi:10.3969/j.issn.1006-7795.2018.04.006

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Objective This study aims to investigate the relationship between oxidative stress indicators malondialdehyde (MDA), retinol (RET) and the pathogenesis of polycystic ovary syndrome(PCOS). Methods From July to October 2017, 65 cases of PCOS patients in Endocrinology Department of Beijing Gynecology Hospital, Capital Medical University were selected as study group and 24 healthy women who were infertile because of fallopian tube factor or male factor or normal physical examination were selected as control group at the same time. The anthropometric indexes, endocrine indexes, metabolic and oxidative stress indexes of all participants were measured. The characteristics of oxidative stress indicators were compared between PCOS patients and control group. Results Both MDA and superoxide dismutase (SOD) were significantly higher in PCOS group than those in control group (P<0.05), but the RET in PCOS group was significantly lower than that in control group (P<0.05). There was no significant difference in oxidized glutathione (Glut oxyd), total antioxidant activity (TAA), vitamin C (VC), vitamin E (VE) in the two groups (P>0.05). There was a positive correlation between MDA and anti-Müllerian hormone (AMH) (r=0.208, P=0.05) and there was no significant correlation between MDA and testosterone(TT), fasting insulin (FINS), and homeostasis model assessment insulin resistance (HOMA-IR) (P>0.05). There was a negative correlation between RET and AMH (r=-0.232, P<0.05), and there was no significant correlation between RET and TT, FINS, and HOMA-IR (P>0.05). Conclusion The study on multiple oxidative stress markers revealed that the oxidative stress level represented by MDA was increased and the antioxidant level represented by RET was decreased in PCOS patients. Further study of the relationship between oxidative stress and PCOS might be helpful to clarify the pathogenesis of PCOS.

Establishment of MrgD knockout mice model with CRISPR/Cas9 gene targeting technology

Cao Xi, Song Lini, Zhang Yichen, Li Qi, Yang Jinkui

2018, 39(4):  517-521.  doi:10.3969/j.issn.1006-7795.2018.04.007

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Objective To establish the MrgD gene knockout mice model by using CRISPR/Cas9 gene editing technique so as to provide the tool to study the regulating role of MrgD in glucose and lipid metabolism. Methods Single guide RNA (sgRNA) plasmids against the exon 1 of MrgD were designed and constructed. Then the sgRNA and Cas9 was transcribed by T7 RNA polymerase in vitro. Cas9 mRNA and sgRNA were mixed and microinjected into fertilized eggs of C57BL/6J mice. Gene sequencing was used to detect the mutations of MrgD. Results Finally the F2 generation of homozygous MrgD deficient mice (MrgD-173/-173) were gained. Preliminary studies showed that MrgD gene homozygous mutant mice may not have disorders of glucose and lipid metabolism. ConclusionA mouse model with MrgD deficiency has been successfully established which shall lay a foundation for future investigation of MrgD.

Association between subclinical hypothyroidism and lower extremity arterial disease in male patients with diabetes mellitus

Zhang Lin, Yuan Mingxia, Yang Guangran, Liu Wei, Xie Rongrong, Du Yanfang, Yang Jinkui

2018, 39(4):  522-526.  doi:10.3969/j.issn.1006-7795.2018.04.008

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Objective To investigate the relationship between subclinical hypothyroidism (SCH) and lower extremity arterial disease(LEAD) in patients with type 2 diabetes. Methods Totally 746 patients with type 2 diabetes hospitalized in the Department of Endocrinology of Beijing Tongren Hospital, Capital Medical University were selected. The thyroid function and ankle brachial index (ABI)were examined in all patients. And then diabetic patients were divided into two groups with and without LEAD according to ABI. The basic situation, biochemical indexes and SCH prevalence rate of the two groups were compared. Univariate and multivariate Logistic regression analysis was used to analyze the risk factors of diabetic LEAD. Results 117 cases combined with SCH and the prevalence rate among women was significantly higher than that among men(P<0.05)in these 746 patients with type 2 diabetes. The level of thyroid stimulating hormone (TSH) and the prevalence of SCH in the LEAD group were higher than those in the control group. Logistic regression analysis showed that age (OR, 1.055,95% CI:1.031-1.078, P<0.001), SCH (OR, 2.162, 95% CI:1.383-3.379, P=0.001), smoking(OR, 2.129,95% CI:1.352-3.355, P=0.001), systolic blood pressure (OR, 1.014,95% CI:1.004-1.023, P=0.005), low density lipoprotein (OR, 1.189,95% CI:1.026-1.378, P=0.021)was positively correlated with LEAD, and total glomerular filtration rate (OR, 0.984,95% CI:0. 974-0.995, P=0.003)was negatively correlated with LEAD. In male patients, SCH had a more significant effect on LEAD (OR, 3.747,95% CI:1.940-7.239, P<0.001), but no correlation was found in female patients. Conclusion The results suggested a closed association between SCH and LEAD in male patients with type 2 diabetes mellitus.

Effect of angiotensin-converting enzyme 2 and angiotensin(1-7) on lipogenesis in white adipose tissue of mice

Ma Chifa, Shi Tingting, Liu Jingyi, Song Lini, Feng Jianping, Yuan Mingxia, Yang Jinkui

2018, 39(4):  527-531.  doi:10.3969/j.issn.1006-7795.2018.04.009

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Objective To identity the effect of angiotensin-converting enzyme 2(ACE2) and angiotensin (1-7) (Ang(1-7)) on lipogenesis in white adipose tissue of mice. Methods Male ACE2-knockout (ACE2KO) mice and C57BL/6(wild-type, WT) mice were chosen. The body weight, body fat percentage, total serum cholesterol, and triglycerides were measured. Hematoxylin and eosin staining was employed to observe the morphology changes of epididymal adipocyte. The protein expression of lipogenesis related genes including acetyl-CoA carboxylase a (ACCa), fatty acid synthetase(FAS) and adipocyte fatty acid binding protein (aP2) in epididymal adipose tissue was assayed by Western blotting. Male db/db mice were randomly divided into three groups. Mice were treated with normal saline (NS), A779[D-Ala7-Ang(1-7),Ang(1-7) antagonist], and Ang(1-7)+A779[Ang(1-7) antagonist] for 28 days using the micro-osmotic pump. The body weight was measured, and the protein expression of lipogenesis related genes in epididymal adipose tissue was assayed by Western blotting. Results The body fat percentage and serum triglycerides in ACE2KO mice were higher than those in WT mice. The protein expression of ACCa and FAS was increased in ACE2KO mice epididymal adipose tissue than control mice. In db/db mice, Ang(1-7) treatment downregulated the protein expression of ACCa and FAS in epididymal adipose tissue, A779 inhibited the effect. Conclusion ACE2/Ang (1-7) may inhibit lipogenesis in white adipose tissue by reduction of lipogenesis-related genes.

Ang (1-7) improves skeletal muscle lipid metabolism and insulin resistance by regulating endoplasmic reticulum stress

Lu Xingmeng, Xin Zhong

2018, 39(4):  532-536.  doi:10.3969/j.issn.1006-7795.2018.04.010

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Insulin resistance of skeletal muscle plays an important role in the pathogenesis of type 2 diabetes. Angiotensin can improve skeletal muscle lipid metabolism through endoplasmic reticulum stress and thus improve insulin resistance. In recent years, the specific molecular mechanism of endoplasmic reticulum stress has been explored. This paper mainly discusses the effect of endoplasmic reticulum stress on the lipid metabolism and insulin resistance of skeletal muscle and the possible mechanism.

Clinical analysis of acute isolated traumatic brain injury-associated coagulopathy in middle aged and older populations

Li Lizhuo, He Songbai, Zhaoge Jingwa

2018, 39(4):  537-540.  doi:10.3969/j.issn.1006-7795.2018.04.011

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Objective To explore the clinical characters of acute isolated traumatic brain injury-associated coagulopathy in middle aged and older populations. Methods A retrospective study was performed at Xuanwu Hospital of Capital Medical University and Shengjing Hospital of China Medical University from July 2014 to June 2016. Totally 144 cases of acute isolated traumatic brain injury were included and divided into two groups including middle aged and older patients group and non-age group with the ratio of 1:2. The chi-square analysis was used to investigate the prevalence, index and difference of coagulopathy in both groups. Results The prevalence of coagulopathy was higher in middle aged and older patients group than that of non-age group according to the chi-square analysis (P<0.05, χ²=4.11). Further, platelet count (PLT), but not international normalized ratio (INR), fibrinogen (Fg), prothrombin time (PT) and activated partial thromboplastin time (APTT),was significantly different between two groups and higher in middle aged and older patients group(P<0.05,χ²=4.68). Conclusion The higher prevalence of acute isolated traumatic brain injury-associated coagulopathy occurs in middle aged and older patients and PLT exists more likely in those populations. These findings will provide the guidance of the treatment of traumatic brain injury in middle aged and older patients in the clinical.

Role of pericytes in blood-brain barrier injury under chronic cerebral hypoperfusion

Cao Dandan, Sun Jing, Bai Yunfei, Wang Miao, Guo Chenjia, Cui Jing, Li Liang

2018, 39(4):  541-545.  doi:10.3969/j.issn.1006-7795.2018.04.012

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Objective To investigate the effect of chronic cerebral hypoperfusion (CCH) on the blood-brain barrier (BBB) and pericytes. Methods Bilateral common carotid artery ligation (2-VO) rat model was used. Cerebral blood flow (CBF) was measured at the 3rd, 14th and 30th day after 2-VO surgery. Pericyte and fibrinogen expression were detected by fluorescence immunohistochemistry. Primary cultured pericytes were subjected to cell proliferation experiments. Transmission electron microscopy was used to observe the ultrastructure of blood-brain barrier. Results CBF was decreased in each model group, and kept lower at 30th day after 2-VO. BBB was damaged with fibrin(ogen) extravascular leakage, thickening of the basement membrane, dense deposit in the extravascular space, astrocyte edema, and red blood cell extravascular leakage. The number of pericytes was increased on the 3rd, 14th, and 30th day after surgery. In vitro, low concentration of fibrinogen could promote the proliferation of pericytes, while high concentration (20mg/mL) of fibrinogen had toxic effects on the pericytes. Conclusion CCH disrupts the BBB accompanying with pericytes proliferation, and fibrinogen exudation may be the main cause of pericyte hyperplasia.

Clinical study of minimally invasive decompression in the treatment of malignant middle cerebral artery infarction

Hou Huanfeng, Li Rujuan, Ma Xiaohui, Yang Jinbo

2018, 39(4):  546-551.  doi:10.3969/j.issn.1006-7795.2018.04.013

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Objective To study the effect of minimally invasive decompression on the treatment of malignant middle cerebral artery infarction. Method There were 13 cases under minimally invasive decompression in the treatment of massive cerebral infarction from December 2012 to December 2016 in our department, 4 male cases, 9 female cases, and aged from 22 to 85 years old, of which 6 cases with patients older than 60 years. The telephone follow-up was conducted at 180th day after the attack, and the modified Rankin cale (mRS) was used to evaluate prognosis. mRS ≤ 2 scored favorable prognosis, mRS>2 scored unfavorable prognosis. Result 4 cases among 13 cases died from cerebral hernia and associated severe complications, and the death rate was 30.8%. 1 case died from massive hemorrhage of upper gastrointestinal tract gallstones. There were 5 cases of mRS ≤ 2, and 3 cases of mRS>2 among 8 survivor cases. There was no complication, such as intracranial infection, hemorrhage or subdural hematoma. Conclusion Minimally invasive decompression in the treatment of malignant middle cerebral artery infarction decreased significantly the death rate. This method was simple, fast, safe, and effective, without age limit and complication.

Comparison the effects of two anesthetic procedures for the establishment of a rhesus monkey model of acute cerebral infarction

Ma Yanhui, Wu Di, Tian Zhaolong, Jia Bin, Xu Na, Chen Jian, Wang Tianlong

2018, 39(4):  552-556.  doi:10.3969/j.issn.1006-7795.2018.04.014

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Objective To compare the effects of two anesthetic procedures on the establishment of a rhesus monkey model of acute cerebral infarction. Methods Sixteen male rhesus monkeys were randomized into 2 groups:propofol group (group P), propofol + dexmedetomidine group (group PD). Sumianxin injection combined with 0.1 mL/kg ketamine was given before endotracheal intubation. After intubation, the animals received mechanical ventilation. In Group P, anesthesia was maintained with propofol infusion. In Group PD, anesthesia was maintained with propofol and dexmedetomidine infusion. Sumianxin-ketamine could be given if necessary to maintain adequate anesthesia depth. The infusion of anaesthetics was stopped after the establishment of model of the M2 segment of the middle cerebral artery occlusion. Brain magnetic resonance imaging (MRI) examination was performed after the recovery of animal spontaneous breathing. Intraoperative hemodynamic changes, recovery time of spontaneous breathing, additional volume of sumianxin-ketamine mixture, the dosage of propofol, and the incidence of anesthesia related complications were recorded. Results All models survived more than 24 h after the onset of ischemia. No serious complications such as restlessness, respiratory depression, arrhythmia occurred in 16 rhesus monkeys. The hemodynamic indexes, body temperature, and arterial blood gas analysis of 16 rhesus monkeys were in normal range. The hemodynamic indexes, body temperature, and arterial blood gas analysis showed insignificant difference between the two groups at different intervals (P>0.05). All the 16 monkeys awoke in 30 min after the experiment. The spontaneous breathing recovery time of the two groups showed insignificant difference(P>0.05). Compared with the group P, the dosage of propofol and the volume of sumianxin-ketamine mixture were lower than that in the group PD (P<0.05). Conclusion Two anesthetic procedures are feasible and easy to control the anesthesia depth,which are safe to anesthetize rhesus monkey for the establishment of a model of acute cerebral infarction. Dexmedetomidine can reduce the dosage of propofol as well as mixture of ketamine and sumianxin during the establishment of the model.

Effect of lipopolysaccharide on the expression of α-synuclein in the intestinal tract

Liu Mengru, Gong Xiaoli, Wang Le, Liu Yang, Zhang Ting, Wang Xiaomin

2018, 39(4):  557-562.  doi:10.3969/j.issn.1006-7795.2018.04.015

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Objective Intraperitoneal injection of lipopolysaccharide (LPS) was used to construct Parkinson's disease (PD) mouse model. The protein level of α-synuclein (α-syn) and intestinal inflammation were detected in intestinal tissue of PD mice, to explore the expression of key pathogenic protein in the intestinal tract of early PD. Methods Male C57BL/6J mice were divided into control group and model group, mice received intraperitoneal injection of LPS or 0.9% saline. The mice model was characterized by detecting the level of inflammatory factor tumor necrosis factor-α(TNF-α) in blood and body weight. The protein level of α-synuclein(α-syn) and inflammasome NOD-like receptor protein 3 (NLRP3) in intestine were detected by Western blotting, the expression of TNF-α was measured by reverse transcription-polymerase chain reaction (RT-qPCR). Results In the acute phase, the expression of α-syn, NLRP3 and TNF-α were increased after LPS injection, the α-syn and NLRP3 returned to baseline levels at one month after LPS administration. But the expression of TNF-α was still at a high level. Conclusion LPS promoted the expression of α-syn in the intestine, which was accompanied by inflammasome activation and TNF-α expression. However, the high level of TNF-α is likely to lead to the progressive increase of α-syn in the chronic period of PD model induced by LPS.

Establishment and comparison of two hypoxic pulmonary hypertension models in mice

Gao Yang, Liu Jie, Wang Lei, Zhang Wei, Liu Yafei, Qi Xianmei, Wang Wang

2018, 39(4):  563-568.  doi:10.3969/j.issn.1006-7795.2018.04.016

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Objective To compare the similarities and differences between the model of hypoxia and hypoxia combined SU5416 modeling method, explore whether hypoxia combined with SU5416 can establish a more significant model of pulmonary hypertension in mice. Methods Totally 15 male C57BL/6 mice were randomly divided into 3 groups:normoxia, hypoxia and hypoxia+SU5416. After four weeks experiment, body weight (BW), right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), right ventricular/body weight (RV/BW), lung morphological features and medial thickness (MT%) were assessed. Results After 4 weeks, the body weight of the mice in normoxia was significantly higher than that in hypoxia and hypoxia+SU5416, whereas the RVSP, RVHI, RV/BW and MT% of the mice in hypoxia and hypoxia+SU5416 were higher than that in normoxia. The RVSP, RVHI and MT% of the hypoxia+SU5416 were higher than those in hypoxia, while the RV/BW of hypoxia+SU5416 was not significantly different from that of hypoxia. Conclusion These results suggested that hypoxia combined with SU5416 can establish a more significant pulmonary hypertension model than hypoxia alone in mice.

Expression of brain-specific angiogenesis inhibitor-1 in cervical squamous cell carcinomas correlates with human papillomavirus infection

Zhang Junjun, Wang Yan, Du Chenxiang, Jin Ximeng

2018, 39(4):  569-574.  doi:10.3969/j.issn.1006-7795.2018.04.017

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Objective To test the expression of brain-specific angiogenesis inhibitor-1 (BAI-1) in cervical lesion, and analyze the significance in the development of cervical squamous cell carcinomas and the correlation with human papillomavirus (HPV) infection. Methods By SP method and PCR reverse dot hybridization to summarize and analyze the expression of BAI-1 and infection of HPV in 30 cases of normal cervical tissue, 61 cases of cervical intraepithelial neoplasia (CIN) (CIN Ⅰ 27 cases, CIN Ⅱ-Ⅲ 34 cases) and 54 cases of cervical squamous carcinoma tissues (Ⅰ-Ⅱ 34 cases, Ⅲ-IV 20 cases), discussing the correlation in the development of cervical squamous cell carcinoma and the correlation with HPV infection. Results The positive expression rates of BAI-1 in normal cervical tissue, CIN Ⅰ, CIN Ⅱ -Ⅲ and cervical squamous cell carcinoma tissues were 96.67%, 74.07%, 44.11% and 18.52%. And the positive infection rates of HPV were 6.67%, 37.04%, 76.47% and 100%. By analyzing the data, as the cervical lesions progressed, the positive expression rate of BAI-1 was falling gradually, and the positive infection rate of HPV was rising gradually, differences between groups were statistically significant (P<0.01). The positive expression of BAI-1 was only relevant with the clinical stage (χ²=7.219, P=0.007), and has nothing to do with age, histological grade and lymph node metastasis; the positive expression of BAI-1 was negatively correlated with the positive infection rate of HPV (r_s=-0.486, P<0.01) in different cervical tissues. Conclusion BAI-1 was may participate in the early lesion process of cervical cancer of HPV infection, to provide a new direction for diagnosis, treatment and prognosis of cervical squamous carcinoma.

Relationship between mean corpuscular hemoglobin concentration and diabetes mellitus in health examination population in Beijing

Tao Lixin, Mao Qi, Guo Xiuhua, Sun Dianqin, Tian Feifei, Yan Yan

2018, 39(4):  575-580.  doi:10.3969/j.issn.1006-7795.2018.04.018

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Objective To investigate the relationship between mean corpuscular hemoglobin concentration (MCHC) and diabetes mellitus, and to provide evidence for early detection of diabetes mellitus. Methods From the health center of Beijing Xiao Tang Shan Hospital medical population, by using purposive sampling to select fixed unit groups, analysis of indicators MCHC, while controlling for age, body mass index, systolic blood pressure, diastolic blood pressure, low density lipoprotein cholesterol, high density lipoprotein, total cholesterol, triglyceride and other confounding factors. According to the three quartiles of MCHC were divided into four levels, then the crowd divided into two groups according to gender, first the quadratic inference functions (QIF) was used to analyse the relationship between MCHC and diabetes, then the Bayesian network is used to prove the correlation between MCHC and diabetes. Results After screening a total of 6 658 physical examination personnel were selected, including male 4 454, female 2 204. The general condition analysis showed that MCHC levels were different in men and women (P<0.05). According to the QIF analysis, the level of MCHC was positively correlated with the risk of diabetes in both sexes (P<0.05), and the correlation is verified again in the Bayesian network model causal path. Conclusion Mean corpuscular hemoglobin concentration is positively correlated with diabetes mellitus among men and women.

Prognostic value of absolute monocyte count in chronic lymphocytic leukemia

Ma Xiaowen, Dong Chunxia, Chen Jianfang, Wang Meifang, Zhang Ruijuan, Zhang Jianhua, Yang Linhua

2018, 39(4):  581-585.  doi:10.3969/j.issn.1006-7795.2018.04.019

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Objective To explore the possible prognostic function of absolute monocyte count (AMC) for chronic lymphocytic leukemia (CLL) through the analysis of 54 CLL patients' clinical symptoms, laboratory features and follow-up data. Methods Retrospectively analyze 54 patients admitted to Department of Hematology, the Second Hospital of Shanxi Medical University from January 2002 to December 2017 with their clinical features, laboratory examinations, treatment process and outcome. Kaplan-Meier method was used to calculate the survival rate and draw the survival curve and the risk curve. Log-rank test was used to compare the survival rates between different groups. Cox proportional hazards model was used for multivariate analysis of prognostic factors in CLL. Results The male to female ratio was 2:1 among 54 cases of patients, the median age was 64-years-old. There were 8 cases belong to Binet A, 25 cases belong to Binet B and 21 cases belong to Binet C. We used disease progression to get the receiver operating characteristics (ROC) curve of AMC, the cutoff point of AMC was 0.67×10⁹/L, the optimal curve of sensitivity was 0.710, specificity was 0.783, the area under the curve (AUC) was 0.771 (95% CI:0.644-0.899). We divided the patients into high and low AMC group according to the cutoff point. There was no significant differences between high AMC group and low AMC group in overall survival (OS)(P=0.170), but progression free survival (PFS) results suggested high AMC group may progress quicker than low AMC group (P<0.05). Cox regression analysis suggested that disease stage belong to Binet C (P=0.038) was an independent factor affecting OS, while the AMC at the diagnosis>0.67×10⁹/L (P=0.004) and the Binet C stage (P=0.049) were independent risk factors of PFS. Conclusion High AMC level at diagnosis suggested rapid disease progression and may become a new evidence for the prognosis of CLL.

Clinicopathological analysis of ulcerative gastrointestinal stromal tumor with hemorrhage

Liu Chuntao, Wu Yongdong, Wang Yongjun, Li Peng, Zhang Shutian

2018, 39(4):  586-590.  doi:10.3969/j.issn.1006-7795.2018.04.020

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Objective The objective of this study was to investigate the clinicopathological characteristics of ulcerative gastrointestinal stromal tumor with hemorrhage. Methods The clinicopathological data of patients of ulcerative gastrointestinal stromal tumor with hemorrhage in our hospital during 2015 to 2017 were retrospectively analyzed. Patients of gastrointestinal stromal tumor without ulcer or hemorrhage were collected as control. Results Totally 21 patients of ulcerative gastrointestinal stromal tumor with hemorrhage including 14 (66.7%) males and 7 (33.3%) females were evaluated for the clinicopathological characteristics. All of the patients received gastroscopic and endoultrasonographic examination prior to surgery. The tumor size ranged from 3 to 18 cm. Of these, 71.4% (15/21) was larger than 5 cm(95% CI:48-89). CD117 and DOG1 were positive in 100% (21/21), while CD34 was positive in 95.2% (20/21). Mitotic index was more than 5/50 HPF in 42.9% (9/21). Ki-67 poistives were more than 5% in 66.7% (14/21). 81% of cases belonged to the middle-high grade risk category. In the same period, 619 patients were diagnosed as gastrointestinal stromal tumor without ulcer or hemorrhage by using gastroscope and endoscopic ultrasonography. The tumor size ranged from 0.3 to 7 cm. Of these, 1.9% (12/619) was larger than 5 cm. Conclusion Most of the ulcerative gastrointestinal stromal tumors with hemorrhage were big tumors and belonged to the middle-high grade risk category.

Antibiotic resistance and serotype distribution of group B Streptococci in pregnant women in Beijing

Li Dong, Zhang Shuchen, Shi Yanli, Li Xueqing, Lu Binghuai

2018, 39(4):  591-595.  doi:10.3969/j.issn.1006-7795.2018.04.021

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Objective To investigate the molecular epidemiological characteristics of group B Streptococci (GBS) isolated from pregnant women in Beijing, and the antibiotic profiles of the microorganism.Methods A total of 96 GBS isolates were collected from vaginal/rectal swabs in pregnant women admitted to Civil Aviation General Hospital and Bejing Huafu Women & Children's Hospital from July 2016 to June 2017. PCR methods were used to analyze the serotypes and antibiotic genes. Antibiotic susceptibility tests were performed on common antibiotics against GBS. Results The most common serotypes were Ⅲ (40 strains, 41.7%), Ia (13 strains, 13.5%), and V (18 strains, 18.8%) respectively. And all strains were sensitive to penicillin, ampicillin, vancomycin and cefotaxime. However, 71% (68 strains) GBS were resistant to erythromycin, 69% (66 strains) were resistant to clindamycin. The erythromycin resistance was mainly associated with the ermB gene; 81.4% of the erythromycin resistant strains carried the gene. Conclusion The GBS strains in Beijing area have similar molecular epidemiological features to other countries around the world, but having its own characteristics.

Effect of synergism and attenuation of Guizhi Fuling decoction in patients with advanced cervical cancer treated with chemotherapy

Chang Zhonglian, Sheng Xiaobin, Shi Xinlan, Wei Wei

2018, 39(4):  596-601.  doi:10.3969/j.issn.1006-7795.2018.04.022

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Objective To investigate the effect of synergism and attenuation of Guizhi Fuling decoction in patients with advanced cervical cancer treated with chemotherapy. Methods Eighty-four patients with advanced cervical cancer were admitted from February 2015 to March 2017, who were divided into single group and combination group by random digital table method, and there were 42 cases in each group. The single group was treated with taxinol plus platinum (TP) chemotherapy, while the combination group was treated with Guizhi Fuling decoction on the basis of the single group. The clinical effect was compared, and the peripheral blood samples of patients of the two groups before and after treatment were collected, then the levels of the serum immunoglobulin (IgG, IgA, IgM) and T lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺) of the two groups were detected and compared, as well as the toxic and side reactions of patients. Results The grade distribution of the clinical effect between the two groups had a significant difference (P<0.05), and the clinical benefit rate (CBR) of the combination group was significantly higher than that of the single group (P<0.05). The levels of serum IgG, IgA, IgM, CD3⁺, CD4⁺ and CD4⁺/CD8⁺ of the single group after treatment were significantly lower than those before treatment (P<0.05), and CD8⁺ of the single group after treatment was significantly higher than that before treatment (P<0.05), but the levels of serum IgG, IgA, IgM, CD3⁺, CD4⁺, CD8⁺ and CD4⁺/CD8⁺ of the combination group before treatment and after treatment showed no significant differences (P>0.05), and the levels of serum IgG, IgA, IgM, CD3⁺, CD4⁺ and CD4⁺/CD8⁺ of the combination group after treatment were significantly higher than those of the single group (P<0.05), but CD8+ was significantly lower than that of the single group (P<0.05). The incidence rates of bone marrow suppression, rectal irritation, skin reaction and bladder irritation of the combination group were significantly lower than those of the single group (P<0.05). Conclusion Guizhi Fuling decoction in the treatment of advanced cervical cancer patients with chemotherapy can significantly improve the clinical effect, maintain the stability of the body's immune function and reduce the incidence of toxic and side reactions.

Skin cancer and precancerous skin lesions: retrospective analysis of 518 cases

Liu Zilian, Zhang Qian, Wu Wenting, Zhang Chunlei, Ma Chuan

2018, 39(4):  602-606.  doi:10.3969/j.issn.1006-7795.2018.04.023

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Objective To study the characteristics of skin cancer and precancerous lesions and elucidate possible clues for the pathogenesis and provide feasible preventive measures. Methods The statistical analysis was performed based on the clinical dataset during 2013 to 2016, taken from the Dermatology Department of Peking University Third Hospital. Results The database summarized in-total 343 Non-melanoma skin cancer(NMSC) cases, in which the number of basal cell carcinoma(BCC) was 206, squamous cell carcinoma (SCC) 73 and actinic keratosis(AK) 81. The constituent ratio of BCC, invasive SCC and SCC in situ increased during the time. In general, no significant differences were found between the genders, where the elderly (over 60 years) dominate all types of NMSC. In details, BCC has a predilection to be found on the head and neck (79.6%), especially on the nose, similarly invasive SCC mainly occurred on the head and neck (61.1%). SCC in situ, on the other hand, mainly appeared on the trunk (34.6%). In addition, there were in-total 162 precancerous patients, in which the AK takes relatively big ratio. Conclusion The statistical analysis of NMSC from the database of our hospital was performed, indicating the constituent ratio of NMSC increased, in which BCC increased rapidly during the 4 years(2013-2016), involving mostly the elderly. The result suggests the environmental risk factors (UV, exhaust, PM2.5, etc.) which may induce the malignant skin tumors and further reveals the necessity to have early prevention education and early screening of skin cancer.

Clinical analysis of 9 cases of pediatric Essential Thrombocythosis diagnosed by Gene mutation testing

Zhang Liqiang, Zheng Jie, Ma Jie, Chen Zhenping, Wu Runhui

2018, 39(4):  607-611.  doi:10.3969/j.issn.1006-7795.2018.04.024

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Objective To analyze clinical data of the essential thrombocytosis (ET) children diagnosed with gene mutation testing, and therefor to figure out the clinical features of the disease in childhood and the natural process of disease.Methods A retrospective analysis was conducted in ET patients diagnosed with gene mutation testing and treated in our hospital during Jan.2013 to Dec.2017. Results Nine patients (5 males and 4 females with a median age of 10 years) were diagnosed.Hemorrhage occurred in 1 cases(11.1%),microthrombus in 4 cases (44.4%),and asymptomatic in 4 cases (44.4%).Splenomegaly 3 cases (33.3%) at the course of 30 (7-90) days. The median platelet count at diagnosis was 1117(861-1 614)×10⁹/L, The median white blood cell (WBC) count was 11.62×10⁹/L(9.9-18.61)×10⁹/L, and the median hemoglobin (HB) count was 133(115-150)g/L. Hepatosplenomegaly occurred in 3cases (33.3%). JAK2V617F(+) was the most common mutation type (66.7%) of ET, followed by CALR(+) (22.2%) and MPL(+) (11.1%).There was no significant difference between the clinical manifestations and laboratory indicators of JAK2V617F. The patients were treated with combination of hydroxyurea, interferon, and aspirin. No serious hemorrhage and thrombosis occurred in the patients. No one was evolved any other hematologic diseases at followed-up time ranged from 4-52 months (the median 8 months). Conclusion Primary thrombocytosis disease in children is rare, which is prone to occur in the older. The clinical symptom is not obvious, but positive JAK2V617 mutations are common in specific gene mutation detection. No severe complications and disease progression and transformation occur in a certain period. Large and long-term follow-up data are needed to confirm this conclusion.