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    21 June 2022, Volume 43 Issue 3
    Menopause Gynecological Endocrinology and Fertility Preservation
    Application progress of in vitro maturation of immature oocytes for fertility preservation
    Cheng Jiaojiao, Ruan Xiangyan, Du Juan, Gu Muqing
    2022, 43(3):  329-335.  doi:10.3969/j.issn.1006-7795.2022.03.001
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    Ovarian tissue cryopreservation and transplantation has been routinely used for fertility preservation in girls and young female patients with high risk of premature ovarian insufficiency. Autotransplantation of cryopreserved ovarian cortex after thawed can restore fertility and endocrine function. However, patients with high risk of ovarian metastasis have a higher risk of reintroducing malignant cells. The frozen ovarian cortex mainly contains primordial follicles, but immature oocytes can also be obtained from small antral follicles during ovarian tissue preparation. Some live births have been born through in vitro matured of ovarian tissue oocytes (OTO-IVM). Biphasic in vitro maturation (IVM) capacitation (CAPA)-IVM system significantly optimizes the IVM system. In the case of high risk of transplantation, IVM of oocytes from growing follicles can safely restore fertility, which will maximize the potential of all fertility preservation patients. However, the evidence of OTO-IVM is still limited and its repeatability needs to be confirmed. Children with OTO-IVM are followed up. This article mainly reviews the application progress of in vitro maturation of human immature oocytes for fertility preservation.
    SOX4 mediates TGF-β1 induced epithelial-mesenchymal transition to promote invasion and metastasis of ovarian cancer
    Liu Qun, Li Lina, Liu Jian, Miao Jinwei
    2022, 43(3):  336-342.  doi:10.3969/j.issn.1006-7795.2022.03.002
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    Objective To investigate the expression and regulation of SOX4 (SRY-related HMG-box4) in ovarian cancer and its effect on transforming growth factor-β1(TGF-β1) induction of epithelial-mesenchymal transition (EMT). Methods The mRNA expression profile of ovarian cancer sample from TCGA, GEO databases were analyzed to assess the expression of SOX4 and its correlation with EMT markers in ovarian cancer; The expression of SOX4 in ovarian cancer SKOV3 cell line was knocked down by shRNA technology. Western blotting and qRT-PCR were used to detect the effects of SOX4 knockdown on epithelial marker ZO1 and mesenchymal markers Vimentin and Slug. Transwell technique was used to detect the effect of SOX4 knockdown on the migration and invasion abilities of ovarian cancer cells. To detect the regulation of TGF-β1 on SOX4 and the effect of SOX4 knockdown on TGF-β1 induced EMT, SKOV3 cells were treated with 10 ng/mL TGF-β1 for 72 h, followed by Western blotting and qRT-PCR assays. Results SOX4 expression was significantly up-regulated in ovarian cancer, and positively correlated with expression of mesenchymal markers. Deletion of SOX4 significantly suppressed EMT and thus inhibited migration and invasion of SKOV3 cells. SOX4 was induced by TGF-β1, and SOX4 knockdown significantly inhibited the ability of TGF-β1 to induce EMT in ovarian cancer. Conclusion Upregulation of SOX4 promoted migration and invasion in ovarian cancer by activating EMT. Moreover, as a downstream target of TGF-β1, SOX4 mediated TGF-β1-induced EMT in ovarian cancer.
    Clinicopathological analysis of benign and malignant struma ovarii
    Tian Ming, Kong Qiu, Hou Xiaoxiao, Miao Jinwei
    2022, 43(3):  343-349.  doi:10.3969/j.issn.1006-7795.2022.03.003
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    Objective To investigate the clinicopathology features of benign and malignant struma ovarii (SO) and analysis the diagnosis and treatment. Methods The ages, symptoms, signs and other general data of 80 patients with benign SO and 13 patients with malignant SO confirmed by surgery and pathology were collected from March 2009 to August 2021 in Beijing Obstetrics and Gynecology Hospital, Capital Medical University and Beijing Chaoyang Integrative Medicine Emergency Medical Center. Ultrasound examination and serum tumor marker test were performed. Both benign and malignant SO patients received surgical treatment. The diagnosis was confirmed by routine postoperative pathological analysis of the gross mass and paraffin hematoxylin-eosin(HE) staining. For malignant patients, The International Federation of Gynecology and Obstetrics (FIGO) staging was performed according to surgical pathology and supplementary treatment was performed according to National Comprehensive Cancer Network (NCCN) guidelines. Results The majority of SO patients did not show obvious clinical symptoms, most of which occurred in unilateral ovary. The ultrasound findings were nonspecific and often showed regular multilocular cystic solid masses. All 13 patients with malignant SO were stage I ovarian thyroid carcinoid. Among the 15 patients who underwent immunohistochemical test, thyroid transcription factor-1(TTF-1) and thyroglobulin (TG) were positive, and Ki67 expression level was low. Only 16 patients (20%) in benign SO had elevated tumor markers, while carbohydrate antigen 199(CA199) levels of 3 patients (23.08%) in malignant SO had slightly elevated. Laparoscopy is the main approach for benign SO surgery, and 41 patients (51.25%) underwent ovarian cystectomy. Transabdominal surgery is the main approach for malignant SO surgery, only 5 cases (38.46%) were performed with ovarian tumor staging, and 4 patients received postoperative supplementary chemotherapy. Conclusion The incidence of SO is low. The clinical manifestations, ultrasound and serum tumor markers are not specific. Patients with ascites are more likely to be confused with epithelial ovarian malignancy. SO profile typically showed multilocular cystic solid, containing gelatinous objects and remote hemorrhage focus, and the texture was not bad and brittle. Surgical resection is the main diagnostic method and treatment.
    Breast cancer pathological diagnosis reveals correlation between progesterone receptor membrane component 1 and clinicopathological parameters
    Zhao Yue, Ruan Xiangyan, Cheng Jiaojiao, Gu Muqing, Xu Xin, Wang Yuejiao
    2022, 43(3):  350-356.  doi:10.3969/j.issn.1006-7795.2022.03.004
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    Objective To explore the correlation between progesterone receptor membrane component 1 (PGRMC1) and malignant proliferation of breast cancer. Methods The expression of PGRMC1 was detected immunohistochemically in 90 specimens of breast cancer (the median age was 47), 60 benign breast diseases (the median age was 45) and 60 cases of normal breast tissues from September 2017 to January 2019. All of them were women, and all tissues were diagnosed by the hollow needle biopsy or postoperative histologic examination. As a research project, all participants signed informed consent voluntarily.The pathological grade of breast cancer was determined viahematoxylin-eosin staining to determine. The association of PGRMC1 with pathological factors and the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2), nuclear-associated antigen (Ki-67) was assessed. Results Positive expression of PGRMC1 was 63.33% (57/90) in breast cancer, 28.33% (17/60) in benign breast diseases and 6.67% (4/60) in normal breast tissues. PGRMC1 expression was significantly correlated to tumor size, lymphatic metastasis and the histological grade (P<0.001, respectively), PGRMC1 positive expression rate increased with the increase of histological grade of breast cancer, but not significantly correlated with menstruation in breast cancer (P>0.05). The expression of PGRMC1 in breast cancer group was related to the expression of ER, Ki-67, PR and Her-2 (P<0.05), which was most closely related to ER (r=0.461), followed by Ki-67 (r=0.330), but weakly correlated with the expression of PR and Ki-67(r=0.132,r=0.103, respectively). The expression of PGRMC1 in benign breast disease group was related to the expression of Ki-67 and Her-2 (P<0.05), and the correlation with the expression of Ki-67 (r=0.569) was higher than that of Her-2 (r=0.228). Conclusion PGRMC1 is highly expressed in breast cancer. PGRMC1 expression is strongly associated with the biological behavior of breast cancer. It may serve as a useful prognostic indicator of the malignancy. Meanwhile, it is found that PGRMC1 is closely related to ER expression in breast cancer, suggesting that PGRMC1 may potentiate estrogen signaling.
    Influencing factors of female sexual dysfunction in Chinese women
    Ju Rui, Ruan Xiangyan, Dai Yinmei, Bai Yongtao, Yang Yu, Xu Xin, Cheng Jiaojiao, Yang Xingzi, Shi Yanhong, Sun Yanhua, Li Ruiling
    2022, 43(3):  357-363.  doi:10.3969/j.issn.1006-7795.2022.03.005
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    Objective To investigate the risk factors of female sexual dysfunction (FSD) in Chinese women and to provide clinical evidences for improving perimenopausal and postmenopausal women's quality of life. 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 April 2020 to March 2021. Socio-demographic, behavioral and clinical data were collected. The anthropometric indices of each subject were measured. FSD were evaluated using the Female Sexual Function Index (FSFI) and the subjects were divided into two groups according to the FSFI: FSD group and no FSD group. According to the 2011 stages of the Reproductive Ageing Workshop (STRAW+10) and postmenopausal women using menopause hormone therapy (MHT) or not, the subjects were divided into seven stages, Modified Kupperman Index (KMI) for climacteric syndromes, The Patient Health Questionnaire-9 (PHQ-9) for depression, the International Consultation on Incontinent Questionnaire (ICIQ) for stress urinary incontinence, the Overactive Bladder Symptom Score (OABSS) for overactive bladder. According to the obtained results, univariate and multivariate Logistic regression analyses were performed. Results Multivariate regression analysis revealed that KMI (OR=1.061,95%CI:1.039-1.083),follicle stimulating hormone (FSH) (OR=1.008,95%CI:1.002-1.014),below secondary education level (OR=1.446,95%CI:1.019-2.052), depress (OR=1.814,95%CI:1.156-2.845), early postmenopausal stage (OR=1.717,95%CI:1.106-2.667), late postmenopausal stage (OR=1.905,95%CI:1.008-3.602), neutral marital relationship (OR=2.422,95%CI:1.711-3.429) and dissatisfaction marital relationship (OR=1.945,95%CI:1.018-3.717) were the important risk factors for FSD (P<0.05). Femoston was the protective factor for FSD in early menopausal women(OR=0.229,95%CI:0.059-0.889) (P<0.05). Conclusion Many psychological, physiological and social factors induce FSD. Ovarian function failure is an important risk factor for FSD. MHT was shown to have a beneficial effect on FSD.
    Clinical effects of Dingkun pill on thin endometrium infertility
    Jin Fengyu , Ruan Xiangyan, Qin Shuang, Xu Xin, Yang Yu, Gu Muqing, Li Yanqiu, Du Juan, Cheng Jiaojiao, Yin Xiaodan
    2022, 43(3):  364-368.  doi:10.3969/j.issn.1006-7795.2022.03.006
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    Objective To optimize the treatment methods of thin endometrial infertility and provide more effective clinical options. Methods A total of 197 patients with thin endometrium infertility were randomly assigned to the control group and the experimental group. The endometrial thickness, progesterone level and clinical pregnancy rate between the two groups were compared to each other. The control group was treated with estradiol + dydrogesterone, while the experimental group was treated with Dingkun pill in addition to the treatment in the control group. Results Compared to that in the control group, the average endometrial thickness during ovulation (P<0.01),the progesterone level in luteal phase (P<0.01) ,and the cumulative clinical pregnancy rate was significantly higher (P<0.05) in the experimental group. Conclusion Dingkun pill could significantly improve the endometrial thickness, luteal function and pregnancy outcome in thin endometrial infertility.
    Relationship between mild cognitive impairment and menopausal symptoms in Chinese women
    Xu Xin, Ruan Xiangyan, Ju Rui, Yang Yu, Cheng Jiaojiao, Wang Zhikun, Alfred O. Mueck
    2022, 43(3):  369-374.  doi:10.3969/j.issn.1006-7795.2022.03.007
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    Objective To investigate the relationship between mild cognitive impairment (MCI) and various typical menopausal symptoms in Chinese women. Methods A total of 150 volunteers were included in the study,and there were 61 cases(40.7%) in MCI group and 89 cases (59.3%) in non-MCI group. Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Clinical, sociodemographic and anthropometric data were collected, and menopausal symptoms were evaluated by Modified Kupperman Index (KMI). The two groups were compared by t-test and χ2 inspection. Binary Logistic regression model was used to predict the risk factors of mild cognitive impairment. Results Univariate analysis showed that there were significant differences in age (P=0.001), education level (P=0.001), KMI score (P<0.001) and insomnia (P=0.033) between the two groups. Multivariate analysis found that, insomnia (P=0.032) and headache (P=0.021) were independent risk factors, while education (P=0.004) was independent protective risk factor for MCI in patients under 55 years. Conclusion We reported a clear association between various menopausal symptoms and MCI. This may provide novel direction for the prevention of dementia.
    Chromosomal analysis in 134 cases of fetuses with growth restriction
    Hou Lei, Wang Xiaoxin, Liu Liheng, Zhang Weiyuan, Wang Xin
    2022, 43(3):  375-379.  doi:10.3969/j.issn.1006-7795.2022.03.008
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    Objective To explore the chromosomal analysis for fetuses with fetal growth restriction (FGR). Methods This was a retrospective study on 134 pregnancies with fetal growth restriction which underwent prenatal diagnosis,including amniotic fluid, cordocentesis, or fetal tissue after abortion. The kayotype and copy number variations (CNVs) were performed by G320-banding and copy number variation sequencing, and the indication of the procedures and results were evaluated. Results Among 134 cases with indication of fetal growth restriction, 13 (9.7%, 13/134) cases were diagnosed with chromosome abnormities,including nine cases with pathogenic CNVs. There were 3 cases with chromosomal abnormalities in 41 cases with isolated FGR (3/41, 7.3%), the incidence was lower than that with syndromic FGR (10/93, 10.8%), but no significant difference between two groups (P=0.762). Conclusion The incidence of chromosomal abnormalities in fetus with FGR was higher and prenatal diagnosis is recommended for all types of the disease. It is recommended to place a priority on CNVs in prenatal diagnosis.”
    The value of three-dimensional ultrasound in diagnosis of intrauterine adhesion and establishment of a coronal imaging scoring classification system:a preliminary study
    Huang Rui, Huang Xiaowu, Lyu Xiaodan, Li Sijing, Zhao Yuting, Xia Enlan, Li Tinchiu
    2022, 43(3):  380-386.  doi:10.3969/j.issn.1006-7795.2022.03.009
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    Objective To evaluate the accuracy of three-dimensional transvaginal ultrasonography (TVS-3D) in the evaluation of intrauterine adhesions (IUA) and establish a scoring classification system for IUA. Methods A total of 112 women with suspected IUA, Who underwent TVS-3D examination and hysteroscopy were enrolled in this retrospective study from September 2019 to January 2020. Hysteroscopy was used as the gold standard, to evaluate diagnostic accuracy of TVS-3D with specificity and sensitivity, and to assess the agreement of TVS-3D and hysteroscopy in mapping extent of IUA. According to European Society of Gynecological Endoscopy ( ESGE) classification system, an independent scoring classification system based onTVS-3D coronal imaging was preliminary build up, to obtain cut-off value by area under receiver operating characteristic (ROC) curve. Results The overall sensitivity and specificity of TVS-3D were 82.6% and 65.0%, respectively, and Kappa value was 0.405 compared to hysteroscopy. The agreement of TVS-3D and hysteroscopy in mapping extent of IUA on both side walls and central upper/middle/lower segment were moderate to substantial (Kappa 0.771-0.894 and 0.500-0.610, respectively). The best cut-off value for severe adhesion with TVS-3D scoring system was 9.5 (AUC 0.929, Youden index 0.76, sensitivity 81.1%, specificity 94.9% ). Conclusion TVS-3D showed certain accuracy in the assessment of IUA, especially for the side walls and central part of the uterine cavity. The new scoring system based on three-dimensional ultrasound coronal imaging of uterine cavity has high accuracy in diagnosis of severe intrauterine adhesion and has clinical application value.
    Integrative Diagnosis and Treatment for Mental Disorder
    The effect of acupuncture at Shenmen after sleep deprivation on resting-state regional homogeneity of brain: a cortical surface-based analysis
    Feng Sitong, Jia Hongxiao, Zheng Sisi, Yao Hao, Feng Zhengtian, Liu Xinzi, Cai Yongli, Ning Yanzhe
    2022, 43(3):  387-392.  doi:10.3969/j.issn.1006-7795.2022.03.010
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    Objective To investigate the effect of acupuncture at Shenmen after 24 h sleep deprivation (SD) on the regional homogeneity (ReHo) of brain. Methods Thirty healthy participants were included in this study. After 24 h SD, the subjects underwent the bilateral acupuncture at Shenmen. The resting state magnetic resonance imaging was acquired before and after SD, and after acupuncture. The ReHo of resting-state and post-acupuncture brain regions was calculated by using DPABISurf software based on a cortical surface-based analysis. Results Compared with that before SD, ReHo were significantly higher in brain regions such as left second visual cortex, left precentral gyrus, and left transverse temporal gyrus after 24 h SD, and ReHo were significantly lower in brain regions such as bilateral posterior cingulate gyrus, bilateral angular gyrus, and bilateral dorsolateral prefrontal gyrus. Compared with that after SD, the acupuncture at Shenmen could only remarkably modify ReHo in several brain region of left cerebral hemisphere, including significantly lower ReHo in the posterior cingulate gyrus, dorsolateral prefrontal gyrus, and angular gyrus, and significantly higher ReHo in the middle temporal gyrus. Yet compared with that before SD, there was no significant difference of ReHo in brain regions after acupuncture at Shenmen. Conclusion The mechanism of acupuncture at Shenmen on improving the impairment of brain function after SD might regulate the neural activities in the corresponding brain regions to decrease individual arousal and ameliorate mood and cognitive function.
    The relationship between psychogenic erectile dysfunction of kidney deficiency type and attention network dysfunction
    Dong Linrui, Yan Bin, Feng Sitong, Ning Yanzhe, Feng Zhengtian, Jia Hongxiao
    2022, 43(3):  393-397.  doi:10.3969/j.issn.1006-7795.2022.03.011
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    Objective To investigate the relationship between psychogenic erectile dysfunction (pED) of kidney deficiency type (KD) and attention network dysfunction. Methods A total of 26 patients with pED of KD type and 24 were recruited from Xiyuan Hospital of China Academy of Chinese Medical Science from March 2021 to January 2022. And 24 healthy males were recruited as the control group according to the principle of matching between groups in terms of age, sex and years of education.Both study groups underwent attention network test (ANT). Results Compared with healthy subjects, the patients with pED of KD type showed significantly poorer efficiency on executive control network and overall mean reaction time (P<0.05). The alerting network efficiency, orienting network efficiency and mean correctness rates were not statistically significant compared to normal control subjects (P>0.05). Furthermore, efficiency on executive control network was positively associated with the scores of kidney yang deficiency(r=0.408,P=0.039).And the multi-factor Logistic regression analysis showed efficiency on executive control network was positively associated with pED of KD type (P<0.05). Conclusion Our findings suggested that patients with pED of KD type exhibited impairments of executive control network, which may be related to altered neural activities in brain regions associated with executive control functions. It provided a modern scientific basis for the treatment of psychogenic erectile dysfunction of kidney deficiency type by Chinese medicine theory of kidney.
    Relationship between Upper-heat and Lower-cold syndrome of generalized anxiety disorder based on hierarchical clustering and complex symptom network
    Feng Zhengtian, Zheng Sisi, Li Xue, Zhu Hong, Yin Dongqing, Ning Yanzhe, Jia Hongxiao
    2022, 43(3):  398-406.  doi:10.3969/j.issn.1006-7795.2022.03.012
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    Objective To comprehensively and systematically explore the symptom characteristics of generalized anxiety disorder (GAD) with Upper-heat and Lower-cold syndrome. Methods The questionnaire about traditional Chinese medicine (TCM) syndrome of GAD was developed to collect the information of TCM four diagnosis and western medicine mental symptoms of 168 patients with GAD in the outpatient clinic of Beijing Anding Hospital ,Capital Medical University. Among them, 100 cases were diagnosed as Upper-heat and Lower-cold syndrome and 68 as non Upper-heat and Lower-cold syndrome.Frequency analysis was used to display the distribution characteristics of two groups. Hierarchical Clustering analysis was used to analyze the syndrome elements of disease location and disease syndrome of Upper-heat and Lower-cold syndrome of GAD.Then through the extraction of the core symptoms of the Upper-heat and Lower-cold syndrome of GAD. The complex symptom network analysis of the core symptoms was carried out to explore the inherent logical relationship within the Upper-heat and Lower-cold syndrome. Finally, we combined the results of cluster analysis and complex network analysis, the core pathogenesis of the Upper-heat and Lower-cold syndrome of GAD was explored. Results The GAD patients with the Upper-heat and Lower-cold syndrome have a longer course of disease and a significantly higher degree of anxiety than those with non Upper-heat and Lower-cold syndrome. The common cold and heat symptoms of the Upper-heat and Lower-cold syndrome of GAD included dry tongue, white tongue coating, dry and itchy eyes, lukewarm lower limbs, facial hot flashes, bitter mouth, thirst and thirst, cold abdomen, cold waist, night sweats, head hot sweating, slippery pulse, hot hands and cold feet, cold feet and shins, and sweating on the face. The syndrome elements of disease location in the Upper-heat and Lower-cold syndrome of GAD included heart, stomach, kidney, governor-vessel, spleen, and gallbladder. The disease syndrome elements included fire-heat, cold-coagulation, Qi-stagnation, Qi-deficiency, and Yang-deficiency. Psychiatric symptoms of anxiety played the most important role in the core complex symptom network. The core pathogenesis of the syndrome of Upper-heat and Lower-cold in GAD may be the deficiency of Ministerial fire caused by excessive consumption of monarch fire. Conclusion Psychiatric symptoms of anxiety occupy a dominant position in the symptoms of Upper-heat and Lower-cold syndrome, so the core pathogenesis of GAD may be “Monarch fire loss of purity, Ministerial fire being offside”, the treatment principle is to clear heat and calm the mind supplemented by warm Yang.
    Classification model of pulse parameters of unipolar depression and bipolar depression based on machine learning
    Liu Xinzi, Li Ziyan, Zheng Sisi, Zhu Hong, Yin Dongqing, Jia Hongxiao
    2022, 43(3):  407-414.  doi:10.3969/j.issn.1006-7795.2022.03.013
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    Objective To study the characteristic difference of pulse parameters between unipolar depression and bipolar depression based on machine learning method. Methods Thirty-one patients with unipolar depression and 57 patients with bipolar depression were collected with Daosheng DS01-A TCM four diagnostic instruments, and the pulse parameters were compared with SPSS 26. The models of support vector machines (SVM) and random forest (RF) were established with R 4.0.5. We evaluated the model performance and obtained the importance ranking of model features. Results There were significant differences in pulse force, pulse rate, AD, T1/ T4, H1, H3/ H1, and (H3-H1)/ H1 between unipolar depression and bipolar depression (P<0.05). Both SVM model and RF model have good accuracy and stability. The accuracy of SVM model is 80.56%, area under curve (AUC) value is 83.04%. The accuracy of RF model is 80.56%, AUC value is 84.62%. The top 5 importance of model features are H4, H2, AD, AGE, (T4-T1)/T and H3, H4, AD, AGE, H2 respectively. Conclusion Unipolar depression and bipolar depression have obvious differences in pulse parameters, which can assist clinicians in the differentiation of unipolar and bipolar depression.
    The analysis of clinical characteristics and associating factors of untreated duration in hospitalized patients with bipolar disorder in 2010 and 2019
    Liu Shanshan, Fang Meng, Zhu Hong, Yin Dongqing, Zhao Yan, Zhao Shuang, Jia Hongxiao
    2022, 43(3):  415-420.  doi:10.3969/j.issn.1006-7795.2022.03.014
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    Objective To analyze the clinical features of hospitalized patients with bipolar disorder (BD) and the associating factors for duration of untreated BD (DUB) in 2010 and 2019. Methods A retrospective survey was conducted on BD inpatients in Beijing Anding Hospital, Capital Medical University at different years (302 cases in 2010 and 328 cases in 2019). The demographic data and clinical characteristics were collected. According to the DUB, patients were divided into short-DUB group (S-DUB) and long-DUB group (L-DUB). Then we analyzed the associating factors of L-DUB in different years. Results Compared with the patients in 2010, the education level of bipolar patients, the proportion of patients from other provinces, the proportion of patients with suicidal concept/behavior, and the number of hospitalizations in 2019 increased significantly (P<0.05). The medication compliance of patients improved significantly (P<0.05). The length of stay, the DUB, and the proportion of patients with psychotic symptoms decreased significantly (P<0.05).The Logistic regression analysis revealed that unmarried (OR=2.698), a longer duration of illness (OR=1.467), onset with depressive episode (OR=0.296), less hospitalization times (OR=0.635), and less mania times (OR=0.476) were independent factors for L-DUB in 2010. A longer duration of illness (OR=1.191), onset with depressive episode (OR=0.367), a younger age at the first manic episode (OR=0.916), and an older age at the first diagnosis of BD (OR=1.125) were independent factors for L-DUB in 2019. Conclusion The DUB was significantly shortened with the development of era. The onset with depressive episode and longer course of illness were common factors affecting DUB in different years. Paying attention to DUB and related factors and improving the identification and diagnosis of BD are the keys to shorten DUB.
    COVID -19:From Bench to Bedside
    Ability of Omicron variant of SARS-CoV-2 to utilize angiotensin-converting enzyme Ⅱ from different animals as receptors for cellular entry
    Qiu Yaruo, Li Xinglin, Chen Danying, Liu Yongmei, Song Yanjun, Li Guoli, Song Chuan, Wang Xi, Zhao Xuesen
    2022, 43(3):  421-426.  doi:10.3969/j.issn.1006-7795.2022.03.015
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    Objective To investigate the ability of Omicron variant of SARS-CoV-2 to utilize angiotensin-converting enzyme Ⅱ(ACE2) from different animals as receptors for cellular entry, and to explore the potential cross-species transmissibility of Omicron. Methods Plasmids encoding ACE2 molecules from different animals were constructed and transfected into 293T cells. The pseudoviral infection systems of D614G strain, Delta strain and Omicron strain were established to determine receptor activity of different animals’ ACE2 for cellular entry. The utilization ability of Omicron strain to ACE2 receptors were examined by luciferase assay. Results ACE2 from different animals expressed in 293T cells supported cellular entry mediated by spike protein. Compared with D614G, the ability of Omicron-pp to invade cells using mouse ACE2 molecules was significantly increased (t=16.09, P<0.05), while it decreased when using ACE2 molecules from Chinese horseshoe bat, Mexican free-tailed bat, Ferret badger, Hog badger, Feline, Rabbit, or Pangolin (t=17.80, P<0.05; t=8.43, P<0.05; t=18.10, P<0.05; t=10.46, P<0.05; t=22.00, P<0.05; t=10.08, P<0.05; t=4.83, P<0.05, respectively). Compared with Delta, the ability of Omicron-pp to entry cells was decreased when using Chinese horseshoe bat, Ferret badger, Hog badger and Feline (t=8.15, P<0.05; t=7.91, P<0.05; t=8.59, P<0.05; t=8.43, P<0.05, respectively). Conclusion The ACE2 molecules from different animals served as functional receptors for cellular entry mediated by Omicron spike protein. Our findings herein suggest that there may exist a risk of multiple cross-species transmission of Omicron among different mammal animals.
    Identification of nucleic acid contamination in false positive result within detection of SARS-CoV-2 PCR
    Wang Shuang, Pan Yang, Xu Xinmin, Li Yajie, Zhou Chun, Zhang Yue, Wang Yajie
    2022, 43(3):  427-432.  doi:10.3969/j.issn.1006-7795.2022.03.016
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    Objective To explore method to identify contamination inside laboratory within 2019-nCoV nucleic acid detection. Methods Changes in amplification reaction of DNA plasmid quality control, RNA pseudovirus quality control and samples of positive patients were observed with DNase treatment recombined with removal of reverse transcription. Results DNase treatment of DNA plasmid type positive quality control with four dilutions of 1∶5, 1∶25, 1∶125 and 1∶625 longer than 15 minutes had a good scavenging effect but had little effect on RNA type. It could be used to verify DNA type contamination. The removal of reverse transcription step had a significant impact on the target gene amplification of RNA pseudovirus quality control products but had no effect on DNA components. It could be used to identify RNA contamination. Conclusion The types of contaminated components could be identified and verified with combination of DNase treatment with removal of reverse transcription in the amplification reaction.
    The influencing factors of abnormal liver function in patients with COVID-19 and its dynamic changes in different drug treatments
    Liu Yao, Feng Ying, Ren Jie, Wang Xianbo
    2022, 43(3):  433-439.  doi:10.3969/j.issn.1006-7795.2022.03.017
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    Objective To analyze the influencing factors of abnormal liver function in patients with COVID-19 and the dynamic changes of liver function during hospitalization with different drug treatments. Methods A total of 615 COVID-19 patients were enrolled in this study. According to the baseline liver function, they were divided into two groups: abnormal liver function (225 cases) and normal liver function (390 cases).Liver function was dynamically monitored and Logistic regression analysis was used to screen for independent risk factors affecting abnormal liver function. The effects of lopinavir/ritonavir, faveravir, chloroquine phosphate, antibiotics and Yindan Jiedu Granules (YDJDG) on liver function were evaluated. Results The risk factors for abnormal liver function included age, days from onset to admission, C-reactive protein and D-dimer. The severe group showed significantly higher baseline alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and lower serum albumin (ALB) levels than the non-severe group. A total of 179 patients developed abnormal liver function during hospitalization. On day 7, the ALT and AST levels in the antiviral group were significantly lower than those in the non-antiviral group (P=0.020 and P=0.033). Conclusion Patients with abnormal liver function are at higher risk of progressing to severe COVID-19. After admission, lopinavir/ritonavir and chloroquine phosphate significantly reduced ALT and AST levels. In this study, no obvious damage to the liver was found from the use of antiviral drugs, antibiotics or YDJDG.
    Basic Research
    Chirality controls mitochondrial function of mesenchymal stem cells in three-dimensional microenvironment
    He Ying , Feng Chuanliang, Liu Jinying, Zheng Huiming, Jiang Shengjie
    2022, 43(3):  440-445.  doi:10.3969/j.issn.1006-7795.2022.03.018
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    Objective To analyze the chirality mediated mitochondrial function of stem cells and regulation of osteogenic differentiation. Methods Mesenchymal stem cells (MSCs) were cultured in vitro to monitor the mitochondrial membrane potential function of stem cells in vitro. In vivo, the expression of CXCL2 factor was observed in the early defect area after hydrogel implantation, and the difference between the related mitochondria and metabolic signaling pathways was analyzed by high throughput analysis in vitro. Results The proportion of mitotracker deep red immunoflourence staining decreased in the righ-handed group, which indicated that the mitochondrial membrane potential of stem cells was damaged in the right-handed group. In the rat cranial defects model, the expression of CXCL2 in the left-handed matrix repair area was up-regulated after early implantation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis found that mitochondrial related genes and signaling pathways were significantly differentially between different chiral groups. A global microarray gene analysis showed that the expression of mitochondrion degradation related genes up-regulated in right-handed group. The results showed that left-handed matrix could up regulate the mitochondrial NADH dehydrogenase expression, while the mitochondrial function of mesenchymal stem cells in right-handed matrix was significantly damaged. Conclusion The chirallity of biological implant materials was able to regulate the function of stem cell mitochondria.
    Transcription factor GRHL3 regulates the expression of GPR108 gene and its mechanism
    Ni Mingyue, Liu Yuanli, Tu Zhenzhen, Guo Liyu, Zang Dandan, Zhou Haisheng
    2022, 43(3):  446-455.  doi:10.3969/j.issn.1006-7795.2022.03.019
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    Objective To study the molecular mechanism of transcription factor grainyhead-like (GRHL3) involved in the regulation of GPR108 expression. Methods Bioinformatics was used to analyze the expression level and relationship of GRHL3 and G protein-coupled receptor 108(GPR108) in various cancer cells. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of GRHL3 and GPR108 genes in human epidermoid carcinoma cell line (A-431), human hepatocellular liver carcinoma cell line (Hep G2) and human neuroblastoma cell line (SH-SY5Y). The luciferase reporter gene expression vector containing GPR108 promoter and mutant GPR108 promoter was constructed by molecular cloning technology. The regulatory effect of GRHL3 on GPR108 promoter was observed by double luciferase reporter gene detection system; The relationship between GRHL3 and GPR108 promoter binding sites was analyzed by chromatin immunoprecipitation assay (ChIP). Results Bioinformatics analysis showed that the expression of GRHL3 was lower and GPR108 was higher in various cancer cells. The luciferase reporter gene expression vectors of GPR108 promoter and mutant GPR108 promoter were successfully constructed by molecular cloning technology. Luciferase results showed that GRHL3 significantly inhibited the promoter of GPR108. After deleting the binding site on the GPR108 promoter, the negative regulatory effect of GRHL3 on the GPR108 promoter was weakened; ChIP assay showed that GRHL3 could interact with GPR108 promoter binding site. Conclusion The transcription factor GRHL3 can be negatively regulated by binding to the conserved sequence 5′-AACCGGTG-3′ on the GPR108 promoter.
    Analyze to mediating effects of recommended popularity in online medical platform
    Yang Zhiyuan, Wu Yuxuan, Qiao Qingyu, Liu Xiaoli
    2022, 43(3):  456-462.  doi:10.3969/j.issn.1006-7795.2022.03.020
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    Objective To analyze the mediating effects of recommended popularity on the professional titles of doctor and the tier of hospital in online consultation. Methods The data of an online medical consultation website were collected by web crawler, and the mediating effect model was used to analyze the mediating effect on recommended popularity by using catalog regression. Results Whether or not to consider the hospital department,for the price of consultation, the recommended popularity had a partial mediating effect on the professional title of doctor and a suppression effect on the tier of hospital,the contribution of mediating effects of recommended popularity to the total effect was 34.2% and 35.6%. For the number of online consultations, the recommended popularity had a complete mediating effect on the doctor's professional title if the hospital departments were not considered. When the hospital departments were considered, the recommended popularity had a partial mediating effect on the doctor's professional title,the contribution rate was 54.1%; but the influence of the tier of hospital on the number of consultations was completely replaced by the recommended popularity. For the satisfactory evaluation, the doctor's professional title was completely replaced by the recommended popularity. Conclusion The doctors should try to improve recommended popularity in medical service, in order to reach a win-win situation between doctors and patients.
    Clinical Research
    Correlation between Helicobacter pylori virulence strains and chronic gastritis and peptic ulcer in Tibetan population in Tibet Autonomous Region
    Liu Chuntao, Su Jiayi, Dan Zengzhuoga, Yi Biranhen, Zhuo Ma, Zhang Shutian
    2022, 43(3):  463-468.  doi:10.3969/j.issn.1006-7795.2022.03.021
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    Objective To investigate the infection of different virulent strains of Helicobacter pylori (H. pylori) in the Tibetan population of the Tibet Autonomous Region and the correlation between the genotyping of different virulent strains and upper gastrointestinal diseases, such as chronic gastritis, intestinal metaplasia, and peptic ulcers. Methods The data of H. pylori infected patients who were admitted to the digestive department of Lassa people's Hospital from April 2019 to December 2020 were collected, including gender, age, occupation, serum H. pylori antibody typing test and gastroscopy and pathological examination results. Correlations between the different toxin typing and the patients' clinicopathological characteristics were analyzed. Results The majority of H. pylori infected in the Tibetan population of the Tibet Autonomous Region were hypervirulent type Ⅰ strains (CagA and/ or VacA antibody positive), accounting for 56.8%, and the proportion of type Ⅱ strains (both CagA and VacA antibody negative) was 43.2%. There were no significant differences between the CagA and VacA antibody positive population and the CagA and VacA antibody negative population in the prevalence of chronic non atrophic gastritis (49.7% vs 44.2%), atrophic gastritis and intestinal metaplasia (17.1% vs 22.9%), or peptic ulcer (33.2% vs 32.9%) (P>0.05). When stratified by age, patients older than 40 years were more prone to suffer from chronic atrophic gastritis and intestinal metaplasia (62% vs 44%, P=0.002), whereas prevalence of peptic ulcer was higher in patients younger than 40 years (40% vs 25%, P<0.001). When stratified by occupation, the prevalence of peptic ulcer was higher among non-farmers and herdsmen than among farmers and herdsmen (39% vs 30%, χ2=5.342,P=0.027); However, the prevalence of chronic nonatrophic gastritis, atrophic gastritis and intestinal metaplasia did not differ significantly among different occupational populations (P>0.05). Conclusions In this study, the majority of H. pylori infection in the Tibetan population of the Tibet Autonomous Region was the hypervirulent type I strain, but no significant differences were found in the prevalence among patients infected with different virulent strains in the upper gastrointestinal diseases, such as chronic nonatrophic gastritis, atrophic gastritis and intestinal metaplasia, and peptic ulcer. In H. pylori infected patients, the prevalence of chronic atrophic gastritis and intestinal metaplasia increased with age, while the prevalence of peptic ulcers was higher in younger age groups and in non-farmers and herdsmen.
    Impact of online oral hygiene instructions on fixed orthodontic patients with long-term non-follow-up
    Ren Yan, Li Yan, Fan Xiaochuan, Huang Rui, Wang Xi, Wang Yanwei, Huang Xiaofeng
    2022, 43(3):  469-473.  doi:10.3969/j.issn.1006-7795.2022.03.022
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    Objective To investigate the effect of online health education on periodontal health of orthodontic patients with fixed orthodontics but no return visit for a long time. Methods A total of 133 patients who received orthodontic treatment with fixed orthodontics in the Stomatology Department of Beijing Friendship Hospital during the epidemic period from January 2020 to May 2020 were selected as the research objects, including 99 patients who had not been returned for a long time and 34 patients who had been returned regularly. Ramfjord index teeth were selected to detect the periodontal health status by clinical indicators plaque index (PLI); probing depth (PD);sulcus bleeding index (SBI), and the statistical analysis was conducted. Online health education and supervision were conducted for patients who had not been returned for a long time by Wechat. Results There was no significant difference in SBI, PLI, mesial PD, distal PD and average PD between the two groups except that the PLI of left lower incisor (n=31) in follow-up group was lower than that in non-follow-up group(1.41±0.70 vs 1.79±0.90, P=0.029), and the mesial PD of right lower first premolar (n=44) in follow-up group was higher than that in non-follow-up group [(2.51±0.67)mm vs (2.25±0.48)mm, P=0.027]. Conclusion The meso-middle, far-middle and average PD of each tooth position in the long-term non-follow-up group and the regular follow-up group were all less than 3 mm, suggesting that correct online health education can avoid increasing the risk of periodontal disease in patients without follow-up visit.
    Analysis of clinical characteristics and prognosis of the very old and young old patients with mild ischemic stroke
    Gu Qiang, Yu Xiaojun, Zhang Jin
    2022, 43(3):  474-479.  doi:10.3969/j.issn.1006-7795.2022.03.023
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    Objective To explore the related factors that affect the prognosis of ischemic stroke in the elders. Methods Selected 247 elder patients with acute ischemic stroke who were hospitalized in the Department of Neurology, Dongcheng First People’s Hospital, Beijing from January 2016 to June 2019. The National Institute of Health Stroke Scale (NIHSS) score ≤3 points, according to age, divided into 113 cases in the elderly group (aged 80 years old and above)and 134 cases in the junior elder group(60-79 years old). The general data, laboratory examination results, Oxford Community Stroke Project (OCSP) classification, etiological classification, risk factors and prognosis of the two groups were compared and analyzed. Results The NIHSS score, diabetes mellitus, history of stroke, history of atrial fibrillation and post stroke pneumonia in elderly patients were significantly higher than those in the middle and low age group (P<0.05). There was no significant difference between the two groups in gender, body mass index (BMI), hypertension, hyperlipidemia, coronary heart disease, valvular heart disease, antiplatelet, anticoagulation, neurological progress, laboratory results, classification and etiology of OCSP (P>0.05). Multivariate Logistic regression analysis showed that the NIHSS score, diabetes mellitus, past stroke history, atrial fibrillation history and post stroke pneumonia were all the influencing factors of 3 months' poor prognosis in elderly patients and middle and low age patients (P<0.05). The factors influencing the prognosis of the two groups were analyzed. The rate of poor prognosis and mortality in the elderly group were higher than those in the middle and low age group (P<0.05). Conclusion NIHSS score, diabetes mellitus, history of stroke, history of atrial fibrillation, and pneumonia after stroke in elderly patients with mild ischemic stroke are higher risk factors for the prognosis of light ischemic stroke in elderly patients.
    Whether different trajectory screw combinations accelerate interbody fusion: a prospective clinical pilot study
    Zhang Tianqing, Li Yue, Guan Li, Hai Yong, Zhang Congxiao, Liu Yuzeng
    2022, 43(3):  480-489.  doi:10.3969/j.issn.1006-7795.2022.03.024
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    Objective To compared these screw locus combinations with traditional pedicle screws and traditional cortical locus screws by clinical analysis to determine the effects of different locus screw combinations on intervertebral stress and fusion rate. Methods In this study, according to different combinations of screw trajectories, we were divided into two groups: traditional cortical bone locus screw and new cortical bone locus combined screw for intraoperative and postoperative data collection. Results In postoperative follow-up, the degree of correction of the new combination was significantly higher than that of the traditional cortical locus screw, but there was no significant difference in symptom score, screw loosening and screw breakthrough during postoperative follow-up.In terms of fusion rate, the ratio of postoperative interbody fusion score of 2 was 14% higher with the new combination than with the traditional cortical locus screw.The new locus screw combination was significantly superior to the traditional cortical locus screw in the correction of lumbar lordosis. Conclusion The fusion rate of the new combination is higher than traditional trajectory of cortical bone screws, and can provide greater lumbar lordosis correction, have certain prospect of clinical use.
    Reproductive outcomes of women treated for intrauterine adhesions following uterine artery embolization
    Zhou Qiaoyun, Huang Xiaowu, Xia Enlan, Zhao Yuting, Huang Rui
    2022, 43(3):  490-494.  doi:10.3969/j.issn.1006-7795.2022.03.025
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    Objective To assess the reproductive outcomes of women treated for intrauterine adhesions (IUA) following uterine artery embolization (UAE). Methods Retrospective study of 129 women with IUA following UAE wishing to conceive, undergoing hysteroscopic adhesiolysis at a tertiary Hysteroscopic Centre of Futting Hospital. The main outcome measures included the American Fertility Society (AFS) IUA score of pre-and post-operation, improvement in menstrual flow and reproductive outcomes. Results Complete follow-up was available for 124 women. Following hysteroscopic adhesiolysis, there was a significant reduction in the AFS score [10 (8,10) vs 4 (4,6)], P<0.05), while 62/124 (50%) of patients experienced an improvement in menstrual flow. Of 124 women wishing to conceive, 29/124 (23.4%) achieved a pregnancy and 22/124 (17.7%) achieved a live birth. Of the 29 pregnant women, 6/29 (20.7%) miscarried, 9/29 (31.0%) had a preterm labour, 13/29 (44.8%) had a term live birth and 1/29 (3.4%) has an ongoing pregnancy. Among those achieving a live birth, 90.9% (20/22) suffered significant obstetric complications including abnormal placental implantation 16/22 (72.7%), significant post-partum haemorrhage 12/22 (54.5%), transfusing 5/22 (22.7%), need for further UAE 3/22 (13.6%) and caesarean hysterectomy 1/22 (4.5%). Conclusion It appears that approximately one-sixth women treated for IUA following UAE will achieve a live birth, of which the majority will suffer significant obstetric complications.