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    21 August 2021, Volume 42 Issue 4
    Menopause, Gynecological Endocrinology and Fertility Preservation
    Research progresses in the safety of cryopreserved ovarian tissue transplantation
    Cheng Jiaojiao, Ruan Xiangyan, Du Juan, Jin Fengyu, Li Yanglu, Gu Muqing
    2021, 42(4):  505-510.  doi:10.3969/j.issn.1006-7795.2021.04.001
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    Ovarian tissue cryopreservation and transplantation is an established fertility preservation technique. In some types of cancer, however there may be malignant cells in the frozen ovarian tissue, so ovarian tissue transplantation is not recommended for the patient who has recovered from the disease. In order to restore the fertility of these patients, there are two main strategies: transplantable artificial ovaries, to simulate the natural organs of the ovary and isolated follicles matured in vitro into fertilizable oocytes. This article mainly reviewed the research progresses in the safety of cryopreserved ovarian tissue transplantation and the new methods to avoid disease recurrence caused by ovarian tissue transplantation with high risk of carrying malignant cells.
    Evaluation of reliability and validity of the Comprehensive Assessment of Menopausal Symptoms Scale
    Zhang Lingyan, Ruan Xiangyan, Li Xingming, Cui Yamei, Gu Muqing, Liu Yulan, Zhen Jie
    2021, 42(4):  511-520.  doi:10.3969/j.issn.1006-7795.2021.04.002
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    Objective To investigate the reliability and validity of the Comprehensive Assessment Scale for Menopausal Symptoms in Chinese women. Methods The data were collected from 2 487 Chinese women aged 40-83 between 2018 and 2020. The critical ratio method, Cronbach's alpha coefficient method and factor analysis method were used to screen the items of menopausal symptom scale. Results The conceptual framework of the scale was define with 11 dimensions included in the Menopause Symptom Scale: negative emotional and cognitive symptoms, limb dyskinesia, sex-related symptoms, reproductive symptoms, autonomic nervous disorder symptoms, joint swelling and pain, limb paresthesia, energy loss symptoms, urinary symptoms, vasomotor symptoms, and sleep disorders. The pool consisting of 54 entries was constructed. Ten factors were extracted by exploratory factor analysis, and their cumulative variance contribution rate was 61.28%. The total Spearman-Brown correlation coefficient was 0.866, Guttman Split-half was 0.852, the correlation coefficient was 0.763, and the Cronbach's alpha coefficient range was 0.778-0.914. Conclusion The comprehensive assessment scale for menopausal symptoms developed for Chinese women has proved to be an effective and reliable tool with reasonable structure model, good internal consistency and diachronic stability of items, which can measure the related psychological symptoms of Chinese menopausal women more comprehensively and has potential application prospects. Clinicians can use this scale to measure the symptoms of menopausal patients, and then intervene accordingly and evaluate the intervention effect.
    Analysis on the characteristics of the patients and effects of ovarian tissue cryopreservation in the first ovarian tissues cryopreservation bank in China
    Jin Fengyu, Ruan Xiangyan, Du Juan, Cheng Jiaojiao, Li Yanglu, Wang Husheng, Gu Muqing, Ju Rui, Yang Yu, Wang Yuejiao, Xu Xin
    2021, 42(4):  521-525.  doi:10.3969/j.issn.1006-7795.2021.04.003
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    Objective To evaluate the characteristics of the patients and effects of ovarian tissue cryopreservation in the first ovarian tissues cryopreservation bank in China. Methods The data of 217 female patients in the ovarian tissue cryopreservation database of Beijing Obstetrics and Gynecology Hospital (the first ovarian tissue cryopreservation bank in China) were statistically analyzed, including the diseases type characteristics, area, age distribution, and chemoradiotherapy received or not. Four specimens with diameter of 2 mm were taken from 46 patients, two of which were randomly selected for follicular count directly and the other two specimens were cryopreservation/thawing. The difference of follicular viability counts between the two groups was compared. Results The main disease type of ovarian tissue cryopreservation in Beijing Obstetrics and Gynecology Hospital is cervical cancer, accounting for 49.31%. The age group was mainly between 31 and 35 years old, accounting for 36.4% of the total number,following by age group between 26-30 years old, accounting for 25.3%. There was no significant difference in follicular viability between fresh tissue group and cryopreservation/thawing group (P>0.05). Conclusion The main diease type of ovarian tissue cryopreservation patients in Beijing Obstetrics and Gynecology Hospital is cervical cancer. Our ovarian cryopreservation technique can effectively preserve patients' fertility.
    The improved protective efficacy of combined antioxidants on cryopreserved and thawed human ovarian tissue
    Li Yanglu, Ruan Xiangyan, Cheng Jiaojiao, Zhou Qi, Du Juan, Jin Fengyu, Gu Muqing
    2021, 42(4):  526-532.  doi:10.3969/j.issn.1006-7795.2021.04.004
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    Objective To investigate the protective efficacy of antioxidants N-acetyl-L-cysteine(NAC) and taurine(T) based on the currently used human ovarian tissue cryopreservation and thawing protocol in Beijing Obstetrics and Gynecology Hospital, Capital Medical University, in order to better preserve the viability of follicles and stroma cells, and improve the folliculogenesis potential. Methods The currently used cryopreservation and thawing protocol in our center was set as control group (group C), with addition of 5 mmol NAC (group N) or 0.5 mmol taurine (group T), or with addition of 5 mmol NAC and 0.5 mmol taurine (group N+T). Ovarian tissues from 16 patients were assigned into the 4 groups randomly. The biopsies were cryopreserved and thawed according to the standard operation procedure in our center. After thawing, HE staining and Calcein-AM staining were conducted to evaluate the morphological characteristics and follicle viability. After cultured in vitro for 4 days, the 17β-estradiol (E2) and anti-mullerian hormone (AMH)were measured, and the level of cellular reactive oxygen species (ROS) was also detected. Results All 4 groups obtained good preservation of follicle integrity and viability without statistical significance(P>0.05). After 4 days culture, E2 concentration in culture medium showed no significant difference in 4 groups (P>0.05), AMH concentration in group N+T were significantly higher than that in group C (P<0.05). Group N and Group N+T had lower ROS levels than group C (P<0.05). Conclusions The addition of NAC alone or taurine alone or combination of NAC and taurine could preserve the integrity and viability of the follicle. NAC and taurine could act synergistically to increase the level of E2 and AMH and improve the overall activity of ovarian tissues after thawing, decrease intracellular ROS production,lower the level of oxidative stress, and improve the potential development of follicles after ovarian tissue thawing.
    Study on the situation of female sexual dysfunction in different reproductive aging stages and postmenopausal women using hormone replacement therapy
    Ju Rui, Ruan Xiangyan, Dai Yinmei, Bai Yongtao, Yang Xingzi, Shi Yanhong, Xu Xin, Yang Yu, Cheng Jiaojiao, Sun Yanhua, Li Ruiling
    2021, 42(4):  533-539.  doi:10.3969/j.issn.1006-7795.2021.04.005
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    Objective To investigate the situation of female sexual dysfunction (FSD) at different reproductive stages and the situation of FSD at postmenopausal women using hormone replacement therapy (HRT). Methods A multicenter clinical study was conducted among 902 women in the Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University and other two medical alliance institutions from Jun. 2019 to Aug. 2020. According to the 2011 stages of the Reproductive Ageing Workshop (STRAW+10) and postmenopausal women using HRT or not, the subjects were divided into seven groups: 146 women in reproductive age (R), 199/87 women in early (ET)/late (LT) menopausal transition, 183/41 women in early (EP)/late (LP) postmenopause. Totally 207 women in early postmenopausal stage using estradiol sequentially combined with dydrogesterone (EP-HRT) and 39 women in late postmenopausal stage using estradiol combined with drospirenone administered continuously (LP-HRT). The Female Sexual Function Index (FSFI) was used to assess FSD. Results In group EP and LP, the proportion of FSD, sexual desire disorder, lubrication disorder, dissatisfaction and pain was significantly higher than those in R, ET and LT groups (P<0.05). In group LP, the proportion of arousal disorder and orgasm disorder was significantly higher than those in R and ET groups (P<0.05). The proportion of sexual desire disorder, orgasm disorder in LT group, the proportion of orgasm disorder in EP group, and the proportion of arousal disorder in LP group was significantly higher than those in R group. The proportion of lubrication disorder and pain in LP group was significantly higher than those in EP group (P<0.05). Comparing EP group versus EP-HRT group, the proportion of FSD, sexual desire disorder and dissatisfaction was significantly lower in EP-HRT group (P<0.05). Comparing LP group versus LP-HRT group, the proportion of FSD, lubrication disorder, dissatisfaction and pain was significantly lower in LP-HRT group (P<0.05). Conclusion There was a clear association between deteriorating sexual function and increasing STRAW+10 classification, suggesting the consequence of decreasing ovarian function. HRT containing ‘natural hormones' imposed a beneficial effect on FSD.
    Study on the relationship between oxidative stress and lipid metabolism in obese women with polycystic ovary syndrome
    Wang Husheng, Ruan Xiangyan, Cheng Jiaojiao, Alfred O. Mueck
    2021, 42(4):  540-546.  doi:10.3969/j.issn.1006-7795.2021.04.006
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    Objective To explore the degree of oxidative stress in obese patients with polycystic ovary syndrome(PCOS) and its relationship with lipid metabolism. Methods From August 2018 to November 2018, 130 cases of PCOS patients in the Gynecological Endocrinology Department of Beijing Gynecology Hospital, Capital Medical University were selected as study group and 40 healthy women with normal weight who were infertile because of fallopian tube factor or male factor or normal physical examination were selected as control group at the same time. According to the body mass index (BMI), PCOS was divided into three groups, with 45 cases in the PCOS group with normal weight, 42 cases in the PCOS group with overweight, and 43 cases in the PCOS group with obesity. The anthropometric indexes, endocrine indexes, metabolic and oxidative stress indexes of all participants were measured. The characteristics of oxidative stress indicators were compared between the PCOS patients and the control group. Results The malondialdehyde (MDA) of the PCOS group with obesity was significantly higher than the other three groups (P<0.05). The superoxide dismutase (SOD) and retinol (RET) of the PCOS group with obesity and the PCOS group with overweight were significantly lower than those of the PCOS group with normal weight. The total antioxidant activity (TAA) and vitamin E (VE) of the PCOS group with obesity and the PCOS group with overweight were significantly lower than those of the control group with normal weight (P<0.05). The oxidation index MDA was positively correlated with BMI, total cholesterol (TC), and triglyceride (TG) (P<0.05), while the antioxidant index SOD and RET were negatively correlated with BMI, waist circumference (WC), TC, and TG (P<0.05). Linear regression analysis indicated that MDA, RET and VE were all affected by group variable. The MDA increased with the increase of the groups according to BMI, with a regression coefficient of 0.214 (P=0.005), The RET and VE decreased with the increase of the groups according to BMI, with a regression coefficient of -0.243 (P=0.001) and -0.174 (P=0.023). The SOD and TAA decreased with the increase of TG, and the regression coefficients were -0.411 (P<0.001) and -0.269 (P<0.001), respectively. Conclusion The oxidative stress was an obvious factor in the pathogenesis of PCOS patients with obesity. The decrease of the antioxidant capacity in PCOS patients with obesity was related to the increase of TG, suggesting that obesity may aggravate the oxidative stress process of PCOS patients through lipid metabolism disorders.
    Effect of drospirenone/ethinylestradiol(Ⅱ) on serum anti-Müllerian hormone level in Chinese polycystic ovary syndrome women
    Yang Yu, Ruan Xiangyan, Ju Rui, Xu Xin, Gu Muqing, Cheng Jiaojiao
    2021, 42(4):  547-552.  doi:10.3969/j.issn.1006-7795.2021.04.007
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    Objective To evaluate the effect of drospirenone/ethinylestradiol(Ⅱ)(pills for contraception and use for the treatment of hyperandrogenenism) on serum anti-Müllerian hormone(AMH) level in Chinese polycystic ovary syndrome (PCOS) patients. Methods Totally 74 PCOS patients who were admitted to the Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,China from August 2020 to April 2021 were enrolled in this study. The serum AMH,sex hormones,liver and kidney function were measured before and after the use of drospirenone/ethinylestradiol tablets (Ⅱ). The patients were divided into three groups according to the duration of taking pills: group A(n=16) for 3 cycles,group B (n=28) for 4-6 cycles and group C(n=30) for more than 6 cycles. Results The median serum AMH level after treatment (5.80 ng/mL) was significant lower than that before treatment (9.17 ng/mL) (P<0.001). The median change of AMH level before and after the use of drospirenone/ethinylestradiol tablets(Ⅱ) was 2.53 ng/mL. The median serum AMH were 9.01 ng/mL,7.79 ng/mL and 10.19 ng/mL before treatment and 7.01 ng/mL,5.06 ng/mL and 6.70 ng/mL after treatment in group A,group B and group C,respectively. The serum AMH was decreased after treatment in all groups. Conclusion Taking drospirenone and ethinylestradiol II for 3 cycles or more could reduce the serum AMH level in PCOS patients.
    Basic Research
    Motion initiation analysis of voluntary movements in Parkinsonian mice
    Wang Mengyue, Zhao Xin, Cao Xiao, Wang Ke, Jia Jun
    2021, 42(4):  553-558.  doi:10.3969/j.issn.1006-7795.2021.04.008
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    Objective This research aimed to define a criterion for the motion initiation of voluntary movements and analyze the motion initiation dysfunction in mouse models of Parkinson's disease (PD). Methods The Parkinsonian mouse models were established by 6-hydroxydopamine (6-OHDA) administration. The behavioral states were divided into the resting and the moving states, and the motion initiation events were identified according to the movement velocity of mice. The motion initiation latency was defined as the interim from the resting state to the moving state and was used to compare the difference between parkinsonian and control mice. Results Although there was no significant difference in the average motion initiation latency between parkinsonian mice and control mice, the data showed a skewed discrete distribution. Based on the distribution characteristics, we further analyzed the latency in different time domains. In the range of latency ≤0.5 s, the number of motion initiation events was higher and the latency was shorter in parkinsonian mice, comparing with control mice (P<0.05). When latency >0.5 s, the latency of parkinsonian mice was significantly longer than that of control mice (P<0.05). Conclusion The motion initiation latency could be an effective criterion for evaluating the motion initiation of voluntary movements in mice. It provided a credible behavior paradigm for investigating the motion initiation dysfunction in PD.
    Optimization of immune cell isolation method from mouse adipose tissue and the role of subgroups in obese mice
    Wu Yongle, Shang Hongwei, Sun Guangyong, Zhang Dong, Ding Huiguo
    2021, 42(4):  559-567.  doi:10.3969/j.issn.1006-7795.2021.04.009
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    Objective To provide an efficient and low-damage method to isolate immune cells from adipose tissue to provide technical support for the study of immunological mechanisms in obesity. Methods We separated the adipose tissue around the epididymis of normal mice, and separated the immune cells by mechanical grinding or enzymatic digestion (including type Ⅱ/Ⅳ collagenase, Liberase enzyme), and screened the most efficient immune cell separation method by flow cytometry technology. Then, an obese mouse model was established through high fat diet (HFD), and the proportion and subgroup changes of macrophages and T lymphocytes in mouse adipose tissue were further analyzed. Results We compared different enzymatic digestion and mechanical grinding methods and found that CD45+ immune cells obtained through high-purity Liberase enzyme digestion had the lowest mortality rate and the highest number of live cells. The death rate of immune cells obtained by mechanical grinding was the highest, and the number of living cells was the least.Compared with mice fed a normal diet, the proportion of innate immune cells such as neutrophils and macrophages in the adipose tissue of obese mice increased, especially the proportion of M1 macrophages, while the M2 macrophages decreased. The secretion of tumor necrosis factor-α(TNF-α) by macrophages increased, and the expression of triggering receptor expressed on myeloid cells 1(TREM1) enhanced. Among the adaptive immune cells, the proportion of T lymphocytes increased, especially the ratio of Th1/Treg cells increased the most. Conclusion We have established a method to efficiently obtain viable immune cells from mouse adipose tissue, and confirmed that the proportion of macrophages and T lymphocytes in the adipose tissue of obese mice increased, and their pro-inflammatory effect were enhanced. They played an important role in inducing inflammation in adipose tissue.
    Phenotypic analysis of hepatocyte-specific Eva1a/Tmem166 gene knockout mice
    Chen Jianhong, Lin Xin, Feng Jinqiu, Ding Pengpeng, Wang Miaomiao, Lin Lin, Liu Hong, Wu Jing
    2021, 42(4):  568-574.  doi:10.3969/j.issn.1006-7795.2021.04.010
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    Objective To construct mice models with hepatocyte-specific knockout of autophagy related gene Eva1a using Cre-LoxP technique, and to preliminarily explore the effect of Eva1a gene knockout on the phenotype of mice. Methods LoxP-labeled Eva1aflox/+ mice and Alb-Cre mice were used to construct homozygous mice models with hepatocyte-specific Eva1a gene knockout (Eva1aflox/flox: Alb-Cre) through multiple generations of hybridization. Eva1aflox/flox: Alb-Cre mice and Eva1aflox/flox mice were selected for phenotypic analysis, including body mass, liver index, liver histology, liver function, glycolipid metabolism, and autophagy level. Results There was no fetal death in homozygous Eva1a knockout mice, and no significant changes in the physiological condition were found. In conventional feeding conditions, hepatocyte-specific Eva1a knockout had no significant difference in body weight, liver appearance, tissue structure, liver index, liver function, glucose and lipid metabolism, and autophagy level from wild-type mice. Conclusion Hepatocyte-specific Eva1a gene knockout had no significant effect on the phenotype of mice in the physiological condition, and our study provided an animal model to further explore the role and molecular mechanism of Eva1a in liver disease.
    Establishment of Kcnh6 gene site-specific mutant mice modeled on a pedigree with monogenic diabetes and the phenotype analysis
    Xiong Fengran, Lu Jing, Zhang Yingchao, Xie Rongrong, Zhao Ruxuan, Li Qi, Yang Jinkui
    2021, 42(4):  575-581.  doi:10.3969/j.issn.1006-7795.2021.04.011
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    Objective To establish the Kcnh6 gene P235L site-specific mutant mice model by using CRISPR/Cas9 technique and to verify whether the phenotype is consistent with the diabetes pedigree that we found previously,in order to provide a more precise experimental tool for studying the crucial role of Kcnh6 gene in the pathogenesis of diabetes. Methods sgRNA specific for the point-mutant site was designed according to the exon 5 of Kcnh6 gene. Then,we constructed the donor vector containing the homologous arm and mutant site sequence based on the sequence of the sgRNA. Finally,sgRNA,donor vector and Cas9 were mixed together and microinjected into fertilized eggs of mice.The survived oosperms were transplanted into the uteruses of pseudopregnant mice.We detected the Kcnh6 gene mutation of the progeny by PCR and gene sequencing technology. Results We established the homozygous Kcnh6 gene P235L site-specific mutant mice. Preliminary studies showed that Kcnh6 gene knock-in site-specific mutant mice have less body weight,impaired glucose tolerance and decreased insulin secretion by feeding high fat diet,compared to wild-type mice. Conclusion We successfully constructed the homozygous Kcnh6 gene P235L site-specific mutant mice model which will provide a more precise research tool to exploit the crucial role of Kcnh6 gene in the pathogenesis of diabetes.
    Constructing the social psychological counseling standard service evaluation indicators in Beijing with qualitative method
    Qi Han, Bai Binger, Liu Songhuai, Xi Yingjun, Jin Wenqing, Li Yuqing, Yan Fang
    2021, 42(4):  582-587.  doi:10.3969/j.issn.1006-7795.2021.04.012
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    Objective To construct the standard evaluation system of social psychological counseling management specification in Beijing. Methods The evaluation indicators were initially extracted by literature search, and the opinions and suggestions of experts in mental health related fields were collected through personal in-depth interviews. The Nvivo 12.0 software was used to sort, code, analyze and integrate the interview scripts, and the three-level indicator system was preliminarily formed. Then, 79 experts were invited to participate in two rounds of Delphi expert consultation by online questionnaires to evaluate the indicator system. Indicators were statistically analyzed, screened and modified according to the scores of importance, operability and sensitivity. Results Three first-level indicators, 13 second-level indicators, and 80 third-level indicators were first constructed after the literature searching and Depth personal interview. Then, 3 first-level indicators, 10 second-level indicators and 42 third-level indicators were included in the first round Delphi consultations after the pre-evaluation and discussion of experts. The enthusiasm coefficient, authority coefficient and the coordination coefficients for the first-round Delphi consultation were 96.2%, 0.80±0.03 and 0.124, respectively. The enthusiasm coefficient, authority coefficient and the coordination coefficients for the second-round Delphi consultation were 83.3%, 0.83±0.02 and 0.095, respectively. After the screening, supplement and combination of indicators, the standard index system including 3 first-level indicators, 17 second-level indicators and 45 third-level indicators were finally constructed. Conclusion This study constructed the management standard of social psychological consultation in Beijing using qualitative method, and the effects of the specification need to be further explored and improved in practice.
    Efficacy and safety of berberine on metabolic abnormalities in women with polycystic ovary syndrome by systematic review and Meta-analysis
    Liu Zhen, Yin Dongmei, Zhan Sien, Ruan Xiangyan
    2021, 42(4):  588-595.  doi:10.3969/j.issn.1006-7795.2021.04.013
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    Objectives To evaluate the efficacy and safety of berberine on polycystic ovary syndrome(PCOS)patients with metabolic abnormalities. Methods CNKI, Wanfang Data, VIP, PubMed, ELSEVIER and Cochrane Library were searched for randomized controlled trials in human beings, till June 2020. Relevant indicators were collected and the data were analyzed by using RevMan 5.0 software. Results A total of 11 studies, 2 English articles and 9 Chinese articles were included. Our study showed that berberine (BBR) improved better than metformin (MET) on waist-hip ratio(WHR)(MD=-0.03,95%CI:-0.04--0.01), fasting insulin(FIN)(MD=-1.91,95%CI:-3.56--0.25),total cholesterol(TC)((MD=-0.37,95%CI:-0.68--0.06),high density lipoprotein cholesterol(HDL-C)( MD=-0.15,95%CI:-0.31-0.00) and low density lipoprotein cholesterol (LDL-C)( MD=-0.34,95%CI:-0.56--0.13), but not on body mass index(BMI)(MD=-0.09,95%CI:-0.97-0.80),fasting plasma glucose (FPG)(MD=0.09,95%CI:-0.03-0.21),homeostasis model assessment of insulin resistance(HOMA-IR)(MD=-0.25,95%CI:-0.58-0.07),total testosterone (TT) (MD=-0.13,95%CI:-0.26-0.01), and worse on triglyceride (TG) (MD=0.11,95%CI:0.02-0.20). Compared with COC alone, BBR combined with COC improved better on WHR(MD=-0.03,95%CI:-0.04--0.03), FPG(MD=-0.34,95%CI:-0.57--0.11),FIN(MD=-3.39,95%CI:-5.16--1.62),HOMA-IR(MD=-1.12,95%CI:-1.73--0.51),TC(MD=-0.50,95%CI:-0.58--0.42),TG(MD=-0.23,95%CI:-0.36--0.11),HDL-C(MD=0.11,95%CI:0.09-0.14),LDL-C(MD=-0.43,95%CI:-0.53--0.33)和TT(MD=-0.14,95%CI:-0.25--0.03),but not on BMI(MD=-0.41,95%CI:-1.07-0.24). There was no statistically significant difference on the incidence of adverse reactions between BBR and MET (RR=0.58,95%CI:0.32-1.07),and BBR combined with COC and COC alone(RR=1.85,95%CI:0.77-4.46). Conclusion BBR could improve clinical outcomes on metabolic abnormalities in women with PCOS. However, the effectiveness and safety need to be further verified by high-quality, large-sample, multi-center RCTs.
    Effects of hypobaric hypoxia stimulation at different times on pulmonary arterial pressure and lung tissue in rats
    Deng Hui, Wang Yong, Chen Xiaolan, Qin Chong, Pan Lei
    2021, 42(4):  596-600.  doi:10.3969/j.issn.1006-7795.2021.04.014
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    Objective To observe the effects of different hypobaric and hypoxic stimulation time on the average pulmonary artery pressure, the expression levels of the vascular endothelial growth factor (VEGF), the platelet derived growth factor(PDGF) and the fibroblast growth factor(FGF) in serum of rats. Methods Thirty two male SD rats were divided into four groups: group A was fed for 21 days at normal altitude, group B was kept in hypobaric hypoxia environment for 21 days (simulated altitude of 5 000 meters in hypobaric hypoxia chamber), group C was 6 hours a day in hypobaric hypoxia environment for 21 days, group D was interrupted for 24 hours (the next day)in hypobaric hypoxia environment for 21 days, and the factors of light, diet and water were the same. The pulmonary artery pressure of each group was measured by right cardiac catheterization, the lung tissue of each group was observed by HE staining, and the expression of VEGF, PDGF and FGF in serum of each group was measured by ELISA. Results ① the average pulmonary artery pressure in group B, C and D was higher than that in group A (P<0.05), the most significant increase was (27.4±1.2) mmHg (1 mmHg=0.133 kPa) in group B, followed by (22.1±1.1) mmHg in Group D. ② In group B, C and D, lymphocyte infiltration was found around the pulmonary vessels. In group B and D, inflammatory cells and fibrous tissue caused local consolidation were found in the lung tissue, and local alveolar hyperinflation was also found, presenting as emphysema. ③ The expression of VEGF, PDGF and FGF in group B, C and D were significantly higher than that in group A (P<0.05). Conclusion Intermittent hypobaric hypoxia stimulation can increase pulmonary arterial pressure in rats, but the average pulmonary artery pressure of rats with intermittent hypobaric hypoxia for 6 hours or 24 hours did not reach 25 mmHg during 21 days; Intermittent hypobaric hypoxia leads to the increase of inflammatory cell infiltration and the destruction of alveolar wall structure, which leads to pulmonary consolidation and emphysema; The expression of VEGF, PDGF, FGF was significantly increased.
    Clinical Research
    Analysis of related risk factors of colorectal adenomatous polyps
    Xing Jie, Ren Junyao, Zhang Qian, Sun Xiujing, Yue Bing, Zhang Yijun, Li Rongxue, Zhu Shengtao, Li Peng, Zhang Shutian
    2021, 42(4):  601-608.  doi:10.3969/j.issn.1006-7795.2021.04.015
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    Objective To investigate the risk factors of colorectal adenoma incidence. Methods Data of 662 patients with polypoid lesions admitted at Beijing Friendship Hospital from March 2013 to November 2014 were retrospectively collected, including the basic information such as age, gender, body mass index(BMI), family history, past medical history etc. Totally 140 cases of the patients were pathologically diagnosed as colorectal adenoma and 522 subjects of the patients were enrolled as control group. Combined with the collected data, the risk factors had been analyzed. Results The student t test showed that the age was the risk factor of colorectal adenoma (P<0.05). The chi-square test or Fisher exact test showed that the gender, smoking, drinking and polyp-growing history were correlative factors of colorectal adenoma(P<0.05). The multivariate analysis suggested the age (P<0.001), smoking (P=0.021) and drinking (P=0.022) were independent risk factors of colorectal adenoma. Conclusion The age, cigarette smoking, alcohol intake are independent risk factors of colorectal adenoma. Therefore, we should consider the relevant risk factors of the patients and screen high-risk groups to improve the detection rate of adenoma.
    Effect of metabolic syndrome on survival outcome of chronic kidney disease
    Lai Xuan, Zhang Aihua
    2021, 42(4):  609-614.  doi:10.3969/j.issn.1006-7795.2021.04.016
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    Objective To investigate the the effect of metabolic syndrome (MS) on survival outcomes in patients with chronic kidney disease (CKD) stage 1-5. Methods The patients with CKD from January 2006 to September 2008 in the Department of Nephrology of Peking University Third Hospital were enrolled as the subjects of study. General data and laboratory results of all subjects were collected. The follow-up ended on December 31, 2016, with the all-cause death as the end point event. Kaplan-Meier method and Cox regression analysis were used to screen out independent risk factors for CKD survival outcome. Results A total of 881 survival patients with CKD stage 1-5 were enrolled and completed the follow-up, including 307 with MS and 574 without MS. Totally 82 patients died at the end point of follow-up. Survival analysis showed that age ≥65 years old, serum albumin<42 g/L, MS and cardiovascular and cerebrovascular diseases were independent risk factors for survival prognosis of CKD patients(P<0.05). Conclusions Metabolic syndrome is an independent risk factor for survival outcomes of CKD 1-5 patients, and the risk of death of CKD stage 1-5 patients with MS is increased.
    VRD versus VCD induction chemotherapy followed by autologous stem cell transplantation in newly diagnosed multiple myeloma
    Wang Huijuan, Yang Guangzhong, Jian Yuan, Geng Chuanying, Zhou Huixing, Chen Wenming
    2021, 42(4):  615-622.  doi:10.3969/j.issn.1006-7795.2021.04.017
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    Objective To evaluate the effects of bortezomib-lenalidomide-dexamethasone (VRD) and bortezomib-cyclophosphamide- dexamethasone (VCD) induction chemotherapy on the response, stem cell collection and prognosis in multiple myeloma(MM) patients undergoing autologous stem cell transplantation(ASCT). Methods We retrospective analyzed clinical data from 110 newly diagnosed multiple myeloma(NDMM) patients who received autologous stem cell transplantation after VRD or VCD induction chemotherapy with available complete follow-up data between October 2010 and October 2019 in Beijing Chaoyang Hospital. Results The depth of response and minimal residual disease(MRD)-negative rate were improved in both groups after ASCT. At the 3rd month after ASCT, the complete response(CR)/stringent complete response(sCR) rate in VCD group improved from 39.4% to 59.1% (P=0.001), and the MRD-negative rate improved from 16.7% to 41.7% (P=0.003). While the CR/sCR rate in VRD group improved from 51.2% to 67.6% (P=0.008), and the MRD-negative rate detected by next generation flow cytometry improved from 26.1% to 47.8% (P=0.059). Those who carried high-risk cytogenetics (t(4;14), t(14;16) and del(17p)) had similar response rates. As to survival analysis, the median progression-free survival(PFS) and overall survival(OS) in VCD group were 72.0 and 98.0 months, respectively, while neither had been reached in the VRD group (PFS: P=0.856; OS: P=0.382). The median number of CD34-positive cells was lower in VRD group than that in VCD group (3.52×106/kg vs 4.65×106/kg, P=0.046), while collection failure rates in the two groups did not show statistically significant difference. The number of CD34-positive cells tended to decrease after more than 4 courses of VRD induction therapies, while it remained stable between 3 to 6 courses of VCD induction therapies. Conclusion VRD induction chemotherapy could achieve deeper response than VCD, without significant effect on survival prognosis. VRD induction regimen could result in less stem cells harvested, thus the courses before stem cell collection should be no more than four.
    In vitro antibacterial activities of tigecycline in combination with 5 antimicrobial agents for Stenotrophomonas maltophilia determined by broth microdilution method and chequerboard
    Wei Jingjuan, Ma Liyan, Su Jianrong
    2021, 42(4):  623-628.  doi:10.3969/j.issn.1006-7795.2021.04.018
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    Objective To investigate the In vitro antibacterial activities of tigecycline combined with levofloxacin, sulfamethoxazole-trimethoprim(SXT), minocycline, ceftazidime, cefperazone-sulbactam for Stenotrophomonas maltophilia (SMA) isolates resistant to levofloxacin. Methods Totally 33 SMA isolates resistant to levofloxacin were cultured from patients with bacteremia and tissue infection and collected from Beijing Friendship Hospital, Capital Medical University. All SMA isolates were divided into 3 groups: levofloxacin resistant isolates(n=17); levofloxacin resistant, SXT resistant isolates(n=11);levofloxacin resistant, SXT resistant, minocycline resistant isolates(n=5). The susceptibility of 6 agents against these SMA were tested by broth microdilution method. Tigecycline combined with levofloxacin, sulfamethoxazole-trimethoprim(SXT), minocycline, ceftazidime, cefperazone-sulbactam against these isolates were performed by chequerboard dilution. The fractional inhibitory concentration (FIC) index was calculated to evaluate the efficiency of these combination. Results Susceptibilities of tigecycline to levofloxacin resistant SMA and levofloxacin resistant, SXT resistant SMA were 76.4% and 54.5%, respectively, and it's a bit lower than susceptibilities of minocycline. According to the results of chequerboard, the combination of tigecycline with levofloxacin, ceftazidime, cefperazone-sulbactam showed synergy against some SMA isolates. None of the combinations showed antagonistic activity. Conclusions Tigecycline combined with levofloxacin, ceftazidime or cefperazone-sulbactam may be a choice for treating SMA infection in clinical practice.
    Perioperative blood transfusion and risk factors in elderly patients with hip fracture
    Yue Rui, Li Xiaoyu, Yang Minghui, Zhang Ping
    2021, 42(4):  629-634.  doi:10.3969/j.issn.1006-7795.2021.04.019
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    Objective To evaluate the needs for perioperative allogeneic red blood cell transfusions (ABT) in elderly patients with hip fracture and the influence of different factors on ABT. Methods We conducted a study on elderly patients (≥65 years old) who were admitted to the geriatric trauma orthopedics ward of Beijing Jishuitan Hospital from January 2019 to December 2019 due to hip fracture. The perioperative data of the patients were collected, and univariate and multivariate stepwise Logistic regression analysis were performed to determine the risk factors for perioperative ABT. Results A total of 1 112 patients were included in this study, 50.6% of whom had a perioperative ABT. Univariate analysis showed that elderly patients with hip fracture in the perioperative ABT group were older, had more intraoperative blood loss (IBL), lower body mass index (BMI), lower hemoglobin and serum albumin at admission, longer prothrombin time (PT) and activated partial thromboplastin time (APTT), and shorter operative time. Female, intertrochanteric fractures, American Society of Anesthesiologists (ASA) classification ≥ Grade Ⅲ, general anesthesia, and patients without diabetes were more common. Multivariate stepwise Logistic regression analysis indicated that low hemoglobin at admission, intertrochanteric fracture, high IBL, advanced age, low BMI, ASA classification ≥Grade Ⅲ and general anesthesia were independent risk factors for perioperative ABT in elderly patients with hip fracture. Conclusion Perioperative ABT is very common in elderly patients with hip fracture. It is associated with low Hb at admission, intertrochanteric fracture, high IBL, advanced age, low BMI, ASA classification≥Grade Ⅲ and general anesthesia. These aspects can be considered to reduce perioperative ABT. Early and adequate blood preparation is required for the patients with immutable risk factors.
    Validity and reliability of the Chinese version ofWorld Health Organization Quality of Life-BREF among patients with end-stage renal disease
    Liu Yijun, Lin Xiangying, Zhang Yan
    2021, 42(4):  635-641.  doi:10.3969/j.issn.1006-7795.2021.04.020
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    Objective To verify the reliability and validity of the Chinese version of the World Health Organization Quality of Life-BREF(WHOQOL-BREF) among patients with end-stage renal disease. Methods A stratified proportional sampling method was used to select 55 patients with end-stage renal disease in a grade a class Ⅲ-hospital Y in Yantai City, Shandong Province. Results WHOQOL-BREF had a nice internal consistency. The content validity was conducted by the expert evaluation method and the correlation coefficient method, having a good content validity. End-stage renal disease(ESRD) patients with different subsistence allowances, dialysis age, current personal monthly income and household monthly income before illness had different scores in the area of surrounding environment (P<0.05). It meant that the scale hada passable discriminated validity. Conclusion The Chinese version of WHOQOL-BREF is suitable for evaluating the quality of life of patients with end-stage renal disease and has good reliability and validity.
    Predictive factors for the formation of a well-developed coronary collateral circulation in patients with unstable angina pectoris
    Liu Jinchun, Zheng Xiuhua, Li Ning, Zhang Ruixia, Zhang Haizhu
    2021, 42(4):  642-646.  doi:10.3969/j.issn.1006-7795.2021.04.021
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    Objective To investigate the predictive values of factors associated with the development of the coronary collateral circulation (CCC) in patients with unstable angina pectoris. Methods We evaluated 207 consecutive patients who had unstable angina pectoris and were performed coronary angiography. General information and clinical data were recorded. Patients were divided into two groups according to whether their angiographic CCC was well or poorly developed, according to Rentrop's classification. The differences of the above factors between the two groups were compared, and the predictive values of the factors with significant differences were tested by univariate and multivariate Logistic regression analysis. Results There were significant differences in the factors including diabetes history, time of disease history, TIMI grade, multiple diseased coronary vessels and coronary calcification between the two groups (P<0.05). Univariate and multivariate Logistic regression analysis were used to test their predictive values for good CCC. Significant factors at the level of P≤0.10 in the univariate logistic regression analysis were included in the multiple Logistic regression model, showing that TIMI grade of culprit vessel ≤2 and coronary calcification were independently predictive factors for good CCC. Conclusion TIMI grade of culprit vessel≤2 and coronary calcification were independently associated with the development of the CCC.
    Influencing factors of heparin anticoagulant effect in the treatment of double plasma molecular adsorption system
    Kong Ming, Li Shuang, Geng Hua, Zhou Li, Xu Manman, Liu Jing, Chen Yu
    2021, 42(4):  647-652.  doi:10.3969/j.issn.1006-7795.2021.04.022
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    Objective To observe the anticoagulant effect and safety of empirical heparin anticoagulant regimen in the treatment of double plasma molecular adsorption system (DPMAS), and analyze the factors influencing the anticoagulant effect. Methods A total of 102 patients with liver disease treated by DPMAS in our hospital from April 2018 to December 2020 were selected, 198 times in total. According to the anticoagulation effect of heparin in the course of DPMAS treatment, they were divided into good anticoagulation group, insufficient anticoagulation group and excessive anticoagulation group. The proportion of cases with good anticoagulation effect in different dosage groups were compared, and the differences of baseline clinical data among the three groups were compared. Results There were 118 cases in good anticoagulation group, 11 cases in insufficient anticoagulation group and 69 cases in excessive anticoagulation group.When prothrombin activity (PTA)>30% and platelet (PLT)≤325×109/L, the anticoagulant effect of heparin was good, and the proportion of cases was more than 70%. The body weight, hemoglobin(Hb) and PLT levels of patients with poor anticoagulation were significantly higher than those of patients with good anticoagulation (P<0.05). Compared with the good anticoagulant group, the levels of PTA, antithrombin activity(AT) and Hb in the excessive anticoagulant group were significantly lower, while the levels of PT and activated partial thromboplastin time(APTT) were significantly higher (P<0.05). Within 24 hours after 198 times of treatment, 9 patients had bleeding at the central venous catheter, 1 patient had nasal bleeding, and no other serious bleeding complications such as gastrointestinal bleeding occurred.The APTT level of heparin overdose group was (54.52±19.71)s at 24 hours after treatment, which was not significantly different from that before treatment. Conclusion When PTA>30% and PLT≤325×109/L, it is feasible to give different doses of heparin according to PTA and PLT levels within 24 hours before treatment, but the influence of body weight and hemoglobin on anticoagulant effect should be considered.
    Radiological study of different sacral S1 screw trajectories based on the anatomical parameters of the Chinese population
    Ding Hongtao, Liu Yuzeng, Hai Yong, Guan Li, Pan Aixing, Zhang Xinuo, Han Bo, Li Yue
    2021, 42(4):  653-659.  doi:10.3969/j.issn.1006-7795.2021.04.023
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    Objective To describe and compare the radiological parameters of S1 pedicle screw (PS), S1 cortical screw (CS)and sacral alar screw (SAS) utilizing the three-dimensional reconstruction of sacralcomputed tomography (CT) scan data. Methods The CT data of Chinese patients with non-orthopedic diseases who received three-dimensional CT scan of the lumbosacral segment from January 2019 to December 2019 in our hospital will be collected. A total of 42 patients were obtained, including 20 males and 22 females, with an average age of (55.14±8.35) years old. To import all CT data into MIMICS software for three-dimensional reconstruction, and measure the maximum length, transverse angle (TA), sagittal angle (SA), and average CT value of S1 SAS, CS, and PS trajectory will be done. Results The TA of the longest S1 SAS is (63.51±8.68)°, the SA is(36.62±10.97)°, the length is (41.74±3.33)mm; the TA of the longest S1 CS is about (5.62±3.69)°, the SA is about (6.60±4.88)°, the length is (31.60±4.23)mm; the TA of the longest S1 PS is (29.42±3.89)°, the SA is (15.60±6.58)°, and the length is (48.12±5.44)mm. The length of S1 PS was significantly longer than that of SAS and CS, and the average CT value of SAS was significantly higher than that of PS, but the CT value in the midpoint of SAS trajectory was significantly lower than that of CS and PS. Conclusion It is feasible for S1 sacral alar screw to be used in sacral fixation. The length of screw trajectory is longer than that of cortical screw in the same segment, and the average CT value of screw trajectory is higher than that of pedicle screw, which can be used as one of the alternatives for short segment lumbosacral fixation. However, biomechanical studies are needed to further verify the results.
    Analysis of risk factors and prevention of hypertensive cerebral hemorrhage complicated with pulmonary infection
    Zhang Shuang, Ma Xiangke, Liu Siwei
    2021, 42(4):  660-663.  doi:10.3969/j.issn.1006-7795.2021.04.024
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    Objective To explore the risk factors related to the occurrence of pulmonary infection, aiming to guide the prevention and treatment of pulmonary infection. Methods The clinical data of 368 patients with hypertensive intracerebral hemorrhage admitted to Beijing Chaoyang Hospital, Capital Medical University from March 2016 to December 2020 were retrospectively analyzed. Results Among 368 patients with hypertensive cerebral hemorrhage, 72 patients had pulmonary infection, accounting for 19.6%. Gram-negative bacilli are the most common pathogens. Chronic obstructive pulmonary disease, diabetes, Glasgow Coma Scale (GCS)>8 points, hypoproteinemia, and severe vomiting are independent risk factors for pulmonary infection in patients with cerebral hemorrhage (P<0.05). Conclusion Cerebral hemorrhage patients with severe consciousness disorder and a history of pulmonary disease are more likely to develop pulmonary infections. It is necessary to prevent and control the pulmonary infections from the aspects of keeping the airway patency, preventing vomiting, strengthening nutrition, improving the immunity, and stabilizing blood sugar.
    Risk factors of cytomegalovirus infection in patients undergoing liver transplantation
    Sun Ximu, Wang Huaguang, Zhao Xin, Lyu Shaocheng, He Qiang, Liu Lihong
    2021, 42(4):  664-671.  doi:10.3969/j.issn.1006-7795.2021.04.025
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    Objective To look for the risk factors of cytomegalovirus (CMV) infection by analyzing the characteristics of hospitalized liver transplantation patients. Methods Retrospective analysis was conducted on the clinical data of 134 patients with CMV laboratory test results who received liver transplantation in Department of Hepatobiliary and Pancreaticosplenic Surgery of Beijing Chaoyang Hospital between December 2016 to February 2019, including 113 males and 21 females, with an average age of (52±10) years. The patients were divided into the CMV infection group (n=24) and the control group (n=110) according to the presence of CMV infection within 3 months after surgery. T test, Mann-Whitney U test and Chi-square test were used for single factor analysis, and Logistic regression analysis was used for multivariate analysis to determine the risk factors of CMV infection in patients after liver transplantation. Results The results of univariate analysis showed that the history of age (P=0.005), model for end-stage liver disease (MELD) score (P=0.001), Child-Pugh score (P=0.048), total bilirubin (P=0.002), international normalized ratio (INR) (P=0.002), blood ammonia (P=0.040) and ascites(P=0.042), operation method (P=0.023), intraoperative bleeding volume (P=0.006), blood transfusion volume (P=0.004) and postoperative intensive care unit (ICU) monitoring time (P=0.016) were risk factors of CMV infection. The results of multivariate analysis suggested that MELD score (P=0.007, 95% CI: 1.027-1.187) may be an independent risk factor of CMV infection. The use of immunosuppressive agents, including calcineurin inhibitors (CNI), mycophenolate mofetils (MMF), glucocorticoids, and polyclonal antibodies were not associated with early postoperative CMV infection in patients with liver transplantation. Conclusion High MELD score may be an independent risk factor for CMV infection after liver transplantation. Immunosuppressive agents are not risk factors for early postoperative CMV infection in patients after liver transplantation.