[Analysis of the relationship between MRI imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients].

Objective: To investigate the relationship between magnetic resonance imaging (MRI) imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients. Methods: The clinical characteristics of the adenomyosis questionnaire was self-designed. This was a retrospective study. From September 2015 to September 2020, totally 459 patients were diagnosed with adenomyosis and underwent pelvic MRI examination at Peking University Third Hospital. Clinical characteristics and treatment were collected, MRI was used to determine the lesion location, and to measure the maximum lesion thickness, the maximum myometrium thickness, uterine cavity length, uterine volume, the minimum distance between the lesion and serosa or endometrium, and whether combined with ovarian endometrioma. The difference of MRI imaging characteristics in patients with adenomyosis and its relationship with clinical symptoms and therapeutic efficacy were analyzed. Results: (1) Among the 459 patients, the age was (39.1±6.4) years. There were 376 patients (81.9%, 376/459) with dysmenorrhea. Whether patients had dysmenorrhea were related to uterine cavity length, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness, and whether patients had ovarian endometrioma (all P<0.001). Multivariate analysis suggested that ovarian endometrioma was the risk factor for dysmenorrhea (OR=0.438, 95%CI: 0.226-0.850, P=0.015). There were 195 patients (42.5%, 195/459) with menorrhagia. Whether patients had menorrhagia were related to age, whether patients had ovarian endometrioma, uterine cavity length, the minimum distance between lesion and endometrium or serosa, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness (all P<0.001). Multivariate analysis suggested that ratio of the maximum lesion thickness to the maximum myometrium thickness was the risk factor for menorrhagia (OR=774.791, 95%CI: 3.500-1.715×105, P=0.016). There were 145 patients (31.6%, 145/459) with infertility. Whether the patients had infertility were related to age, the minimum distance between lesion and endometrium or serosa, and whether patients had ovarian endometrioma (all P<0.01). Multivariate analysis suggested that young and large uterine volume were risk factors for infertility (OR=0.845, 95%CI: 0.809-0.882, P<0.001; OR=1.001, 95%CI: 1.000-1.002, P=0.009). (2) The success rate of in vitro fertilization-embryo transfer (IVF-ET) was 39.2% (20/51). Dysmenorrhea, high maximum visual analogue scale score and large uterine volume affected the success rate of IVF-ET (all P<0.05). The smaller the maximum lesion thickness, the smaller the distance between the lesion and serosa, the larger the distance between the lesion and endometrium, the smaller the uterine volume, and the smaller the ratio of the maximum lesion thickness to the maximum myometrium thickness, the better the therapeutic efficacy of progesterones (all P<0.05). Conclusions: Concomitant ovarian endometrioma increases the risk of dysmenorrhea in patients with adenomyosis. The ratio of the maximum lesion thickness to the maximum myometrium thickness is an independent risk factor for menorrhagia. Young and large uterine volume may increase the risk of infertility. Severe dysmenorrhea and large uterine volume affect the success rate of IVF-ET. The therapeutic efficacy of progesterones is relatively better when the lesion is small and far away from the endometrium.

[Investigation of familial tendency of endometriosis].

Objective: To investigate the familial heritability of endometriosis and to compare the clinical characteristics of patients with or without a family history of endometriosis. Methods: From January 2020 to June 2022, 850 patients with endometriosis confirmed by laparotomy or laparoscopy in Peking University Third Hospital were included in this study. Clinical data were collected, family history was followed up, and the differences of clinical indicators between patients with and without family history of endometriosis were compared. Results: A total of 850 patients were enrolled, with an average age of (33.8±7.0) years old, 315 (37.1%, 315/850) patients in stage Ⅲ and 496 (58.4%, 496/850) patients in stage Ⅳ. There were 100 patients with family history of endometriosis, accounting for 11.8% (100/850). Most of the 113 relatives involved were mothers, daughters and sisters (76.1%, 86/113), 81.5% (22/27) of the second and third degree relatives were maternal relatives. The median ages of patients with and without family history of endometriosis were 30 and 33 years old respectively at the time of diagnosis. The unmarried rate of patients with family history was higher [42.0% (42/100) vs 26.3% (197/750)]. The percentage of dysmenorrhea patients with family history was higher [89.0% (89/100) vs 55.5% (416/750)]. The medians of dysmenorrhea score in patients with and without family history were 6 and 2, and the median durations of dysmenorrhea were 10 and 1 years. There were significant differences in age, marital status, percentage of dysmenorrhea, dysmenorrhea score and duration (all P<0.001). The median levels of serum cancer antigen (CA) 125 in patients with family history and patients without family history at the time of diagnosis were 57.5 and 46.9 kU/L respectively, with a statistically significant difference (P<0.05). However, there were no significant differences between the two groups in nationality, bady mass index, menarche age, menstrual cycle, menstrual period, menstrual volume, serum CA19-9 level, cyst location and size, stage, history of adverse pregnancy and childbirth, infertility, adenomyosis and deep infiltrating endometriosis (all P>0.05). By comparing the specific conditions of dysmenorrhea patients with and without family history of endometriosis, there were no significant differences between the two groups in terms of the age of onset of dysmenorrhea, duration of dysmenorrhea, primary and secondary dysmenorrhea, and progressive aggravation of dysmenorrhea (all P>0.05). The difference in the degree of dysmenorrhea in dysmenorrhea patients with family history of endometriosis was significant (P<0.001). Conclusions: The incidence of endometriosis has a familial tendency, and most of the involved relatives are the first degree relatives. Compared with patients without family history of endometriosis, endometriosis patients with family history are diagnosed at an earlier age, with higher percentage of dysmenorrhea, had more severe dysmenorrhea and higher serum CA125 level.

[Clinical risk factors of cesarean scar pregnancies].

Objective: To explore the risk factors related to cesarean scar pregnancies (CSP). Methods: Among the patients during July 2016 to June 2021 in Peking University Third Hospital, 596 cases of CSP patients were included as study group, and 1 192 cases of intrauterine pregnancy(IUP) women with history of cesarean section(s) were chosen as control group through stratified sampling according to the civil year of previous cesarean section matched with CSP group. The correlation between the general situation of patients, the history of gravidity and parity, the history of surgeries in uterine cavity and the previous cesarean section and the occurrence of CSP was explored through multivariate logistic regression analysis. Results: The current age of 596 CSP patients was (34.6±4.4) years, and that of 1 192 IUP patients was (35.6±3.6) years (P<0.001). Multivariate logistic regression analysis showed that the following factors may increase the risk of CSP: age<35 years old (OR=2.306, 95%CI: 1.774-2.998), history of medical abortion (OR=1.629, 95%CI 1.102-2.407), pregnancy interval<2 years from the last cesarean section (OR=2.147, 95%CI: 1.237-3.726), pregnancy interval ≥8 years from the last cesarean section (OR=1.474, 95%CI: 1.110-1.957), history of surgeries in uterine cavity before the last cesarean section (OR=2.558, 95%CI: 1.809-3.615), history of surgeries in uterine cavity after the last cesarean section (OR=8.020, 95%CI: 5.966-10.781), previous cesarean delivery ≥2 times (OR=14.051, 95%CI: 9.699-20.356) and history of previous cesarean sections before labor (OR=2.683, 95%CI: 1.930-3.731)(all P<0.05). Conclusions: The occurrence of CSP is related to the age of patients, the history of medical abortion, pregnancy interval, the history of surgeries in uterine cavity and the previous cesarean section, among which previous cesarean delivery ≥2 times and history of surgeries in uterine cavity after the last cesarean section are the strongly associated risk factors.

[The influence of molecular classification in the selection of postoperative adjuvant therapy in endometrial carcinoma].

Objective: To study the value of molecular classification in postoperative adjuvant therapy for endometrial carcinoma (EC). Methods: Patients with stage Ⅰ EC who underwent surgical-pathological staging surgery and molecular classification in Peking University Third Hospital from January 2020 to April 2022 were retrospectively analyzed. The influence of different molecular types of EC on postoperative adjuvant therapy were studied. Results: The age of the 196 patients was (55.1±10.2) years old, and the body mess index (BMI) was (26.0±3.9) kg/m2. Molecular classification was performed in 196 stage ⅠEC patients, identifying the 4 subgroups: POLE mutation (POLEmut, n=19, 9.7%), mismatch repair-deficient (dMMR, n=28, 14.3%), no-specific molecular profile (NSMP, n=142, 72.4%) and p53 mutation (p53abn, n=7, 3.6%). Molecular classification was one of the influencing factors on the selection of postoperative adjuvant therapy for EC patients (P=0.003). POLEmut, dMMR and NSMP subtypes were not the variables in selecting radiotherapy or combined chemo-radiotherapy postoperatively. p53abn subtype was not the influencer for radiotherapy, however, it may contribute to the selection of combined chemo-radiotherapy postoperatively (P<0.001). Conclusion: The p53abn subtype in the molecular classification is an influencing factor in the selection of combined chemo-radiotherapy for EC patients postoperatively.

[The composition of ascites lymphocytes in high-grade serous ovarian cancer and its correlation with clinical features].

Objective: To explore the composition of ascites lymphocytes in high-grade serous ovarian carcinoma (HGSOC) and its correlation with clinical features. Methods: A total of 59 newly-diagnosed HGSOC patients, aged (58±11) years old, who were treated at the Department of Obstetrics and Gynecology of Peking University Third Hospital from July 2019 to December 2020 were included, collecting ascites and peritoneal irrigation fluid respectively. Detect the proportion of T, B, NK cell and its subpopulations by flow cytometry, and analyze its correlation with the clinical characteristics of patients. Results: Among 59 patients, 48 patients (81.4%) had ascites, and 11 patients (18.6%) had no ascites. Compared with the peritoneal irrigation fluid, the CD3+T (70.2%±15.6% vs 78.1%±6.7%, P=0.014), CD8+T (38.3%±11.2% vs 47.7%±10.1%, P=0.014) and CD16-CD56bright NK [2.0% (0.8%, 3.6%) vs 4.2% (1.5%, 7.1%), P=0.026] cells were significantly decreased in the ascites, while the CD16+CD56dim NK cells was significantly increased [6.8% (2.8%, 15.7%) vs 2.6% (1.6%, 4.3%), P=0.008]. In patients with ascites volume ≥1 000 ml, CD16-CD56bright NK cells were significantly increased than those ascites volume<1 000 ml [3.1% (1.2%, 3.9%) vs 0.8% (0.4%, 2.3%), P=0.002]. Age was significantly positively correlated with the level of CD4+T cells (r=0.332, P=0.021) and the ratio of CD4+T/CD8+T (r=0.379, P=0.008) in ascites. In ascites from patients with poor response to treatment, the proportion of CD4+T cells was increased significantly than those with better response (64.7%±4.2% vs 48.3%±11.7%, P=0.002). Conclusion: The formation of ascites in newly diagnosed high-grade serous epithelial ovarian cancer patients would affect the lymphocyte composition in the abdominal cavity microenvironment, which is related to the patient's age, cancer progression and treatment response.

[Clinical study of dienogest in the treatment of refractory endometriosis-associated pain].

Objective: To evaluate the efficacy and safety of dienogest (DNG) in the treatment of refractory endometriosis-associated pain (REAP). Methods: In this study, REAP was defined according to the following criteria: (1) the pain duration was ≥12 months and visual analogue scale (VAS)≥60 mm; (2) the previous treatments with over two medicines like oral contraceptives and levonorgestrel-releasing intrauterine system failed to achieve satisfactory relief of pain, with VAS reduction less than 50%; with gonadotropin-releasing hormone agonist or mifepristone, the pain could be controlled temporarily, but it recurred after discontinuation of medicines; (3) the pain could not be relieved by surgery or even repeated surgeries. In the present study, 48 patients with REAP were treated with DNG 2 mg/day orally and the clinical outcomes were retrospectively analyzed. The VAS scores, levels of CA125, estradiol, FSH, LH and changes in the size of endometriotic lesions before and after treatment were compared respectively. The side effects were also analyzed. Results: The average duration of DNG treatment was (20.1±12.8) months. After 3 months of medication, the VAS score was significantly reduced from (77.9±15.8) mm to (20.8±10.7) mm (P<0.01), and CA125 level was significantly reduced from (95±139) kU/L to (38±45) kU/L (P<0.05). The effects were maintained with continuation of DNG treatment. Endometriotic lesions tended to shrink, after 12 months of DNG treatment, the size of ovarian endometriomas was reduced significantly from (3.1±1.0) cm to (1.9±1.2) cm (P<0.05). The mean level of estradiol was maintained at 124.82-221.04 pmol/L and levels of FSH and LH did not change significantly during the treatment. The major side effect was irregular bleeding (75%, 36/48). Conclusions: DNG could effectively relieve REAP and is a well-tolerated therapy. It may supply an alternative option for patients with REAP.

First Evidence of Local E×B Drift in the Divertor Influencing the Structure and Stability of Confined Plasma near the Edge of Fusion Devices.

The structure of the edge plasma in a magnetic confinement system has a strong impact on the overall plasma performance. We uncover for the first time a magnetic-field-direction dependent density shelf, i.e., local flattening of the density radial profile near the magnetic separatrix, in high confinement plasmas with low edge collisionality in the DIII-D tokamak. The density shelf is correlated with a doubly peaked density profile near the divertor target plate, which tends to occur for operation with the ion B×∇B drift direction away from the X-point, as currently employed for DIII-D advanced tokamak scenarios. This double-peaked divertor plasma profile is connected via the E×B drifts, arising from a strong radial electric field induced by the radial electron temperature gradient near the divertor target. The drifts lead to the reversal of the poloidal flow above the divertor target, resulting in the formation of the density shelf. The edge density shelf can be further enhanced at higher heating power, preventing large, periodic bursts of the plasma, i.e., edge-localized modes, in the edge region, consistent with ideal magnetohydrodynamics calculations.

[Impact of the COVID-19 epidemic on anxiety among the elderly in community].

Objective: To compare the prevalence of anxiety among old people before and during the COVID-19 epidemic in China, and to provide scientific evidence for psychological intervention of the elderly during public health emergencies. Methods: In 2019, the National Psychological Care Project for the Elderly was launched, covering 818 communities across the country, and 188 407 subjects received psychological assessment. In April and May 2020, a convenient sample of 6 467 aged 65 and above subjects were followed up on the anxiety status and its influencing factors during the epidemic period by using structurized questionnaire. Data collection and management were carried out using the national elderly psychological care project data collection platform. McNemar test was used to compare the difference of the prevalence of anxiety among elderly before (October 2019 to January 23, 2020) and during the epidemic (April-May 2020). The difference of the prevalence of anxiety among elderly with different characteristics was compared by chi square test. The influencing factors of anxiety before and during the epidemic situation were analyzed by multivariate logistic regression model. Results: The prevalence of anxiety symptoms in the elderly population was 4.95% (95%CI: 4.42%-5.48%) before the outbreak of COVID-19, and 10.10% (95%CI: 9.36%-10.83%) during the epidemic which was twice as high as before the outbreak. The difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that the risk factors of anxiety symptoms before the outbreak were with one underlying disease (OR=1.57, 95%CI: 1.05-2.37), with two or more underlying diseases (OR=3.10, 95%CI: 2.13-4.51), and the protective factors were with hobbies, good relationship between children, good relationship with spouse, positive aging attitude and good psychological resilience (all P<0.05). The risk factors of developing anxiety symptoms during the epidemic were living in rural areas (OR=1.77, 95%CI: 1.42-2.20), participating in social activities regularly (OR=1.23, 95%CI: 1.02-1.48), having a good relationship with friends (OR=1.42, 95%CI: 1.11-1.82) and were quarantined or people around were quarantined for medical observation (OR=2.80, 95% CI: 1.90-4.13). Conclusion: The COVID-19 epidemic leads to a double increase in anxiety among the elderly. We should pay more attention to the psychological state of the elderly in rural area and who is being quarantined or people around being quarantined for medical observation.

[A convenience sampling questionnaire survey of the current status of diagnosis and treatment of endometriosis in China in 2018].

Objective: To further understand the current status of diagnosis and treatment of endometriosis in China, the implementation of guideline in different levels of hospitals, and the need for continuing education in endometriosis among primary doctors. Methods: The survey was conducted in the form of convenience sampling questionnaire among the Wechat public platform. The doctors were free to participate in the investigation without any reward. All questions answered were assessed as valid questionnaire. The datas were collected on the questionnaire network platform and analyzed by SPSS 19.0. Results: Totally 1 494 valid questionnaires were collected in this survey. 60.17% (899/1 494) of them were from tertiary hospital, and 32.60% (487/1 494) were from grade two hospital. Only the hospitals where 9.97% (149/1 494) participants based opened the specialist clinic for endometriosis. 70.35% (1 051/1 494) of participants said they had read the second edition of guideline for the diagnosis and treatment of endometriosis which published in 2015. The American Society for Reproductive Medicine (ASRM) staging system was adopted in the clinical practices of only 25.03% (374/1 494) participants. And 18.74% (280/1 494) participants used the endometriosis fertility index (EFI) scoring during the laparoscopic surgery for endometriosis with infertility. 45.18% (675/1 494) of participants said they had not attended any academic conference on endometriosis in the past six months. 64.46% (963/1 494) of the participants believed their diagnosis and treatment in practice should be improved and standardized. 87.15% (1 302/1 494) of the participants expressed the hope that more conferences or workshops on endometriosis would be held. Conclusions: At presents, the diagnosis and treatment of endometriosis in China has been greatly improved, but the implementation of guidelines and the new concept is still a long-term job. The specialist clinic are held only in a few hospitals. It's the expectation and voice of primary doctors to the association to organize the more academic congresses on endometriosis.

[The association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age among neonatal twins in Shaanxi Province].

Objective: To explore the association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age (SGA) among neonatal twins in Shaanxi Province. Methods: From July to December 2013, a total of 30 027 childbearing aged women, who were pregnant from January 2010 to November 2013 and had definite outcomes, were selected from 30 districts (counties) of Shaanxi Province by using the multi-stage random sampling method. The questionnaires with a face-to-face survey method were used to retrospectively collect demographic information, pregnancy history, lifestyle during pregnancy, disease history, nutritional supplements, and health care during pregnancy. Information on the gestational age and birth weight of the newborn were obtained by consulting the medical certificate of birth and were registered as twin A and twin B by birth order. Finally, 356 childbearing aged women and their twin babies with complete data were included in the analysis. A generalized estimation equation model was used to analyze the association between the frequency of prenatal care and the risk of SGA among neonatal twins. Results: The age of childbearing aged women was (27.44±4.68) years old, of which 79.49% (283 women) were rural residents and 44.38% (158 women) had seven or more times prenatal care. The gestational age and birth weight were (37.64±2.51) weeks and (2 510±497) g, respectively. The prevalence of SGA was 51.40% (183/356) for twin A and 53.37% (190/356) for twin B, respectively. The prevalence of SGA was 44.30% (70/158) for twin A with seven or more times prenatal care and 42.41% (67/158) for twin B with seven or more times prenatal care, which was lower than that for twins with less than seven times prenatal care, respectively [57.07% (113/198) and 62.12% (123/198)] (P values were 0.017 and <0.001). The results of generalized estimation equation model suggested that compared to those with less than seven times prenatal care, after adjusting for parity, birth order, place of residence, maternal age, occupation, education, family wealth index, passive smoking, pregnancy-induced hypertension syndrome, folic acid, and iron supplement during perinatal period, and gender of the newborn, the OR (95%CI) of risk of SGA among childbearing aged women with seven or more times prenatal care was 0.60 (0.40-0.91). Conclusion: Seven or more times prenatal care could reduce the risk of SGA among neonatal twins in Shanxi Province.

[Dihydromyricin alleviates doxorubicin-induced myocardial injury by inhibiting NLRP3 inflammasome in rats].

Objective: To investigate the protective effect of dihydromyricetin (DHM) on doxorubicin (DOX)-induced myocardial injury and its mechanism. Methods: Twenty-four healthy male SD rats were divided into 4 groups: control group, DOX group, DOX+DHM100 group and DOX+DHM200 group. Echocardiography was used to measure cardiac function. At the end of the 6th week, the rats were anesthetized and sacrificed, and the pathological changes of the cardiac tissues were observed by HE staining, Masson staining and WGA staining. Cardiomyocyte apoptosis was observed by TUNEL staining, and protein levels of NLRP3, caspase-1, IL-1ß, bax and bcl-2 were detected by Western blot and immunohistochemistry. Results: Compared with the control group, the left ventricular ejection fraction and left ventricular fractional shortening decreased significantly in DOX group, while left ventricular internal dimension at systole and left ventricular internal dimension at diastole increased. In DOX+DHM group, both left ventricular ejection fraction and left ventricular fractional shortening increased, while left ventricular internal dimension at systole and left ventricular internal dimension at diastole decreased (P<0.05). Furthermore, DOX group showed significant myocardial injury histologically, while DOX+DHM group significantly inhibited DOX-induced myocardial injury in rats. Meanwhile, cardiomyocyte hypertrophy was found in the DOX group, while the cardiomyocyte hypertrophy was notably inhibited in the DOX+DHM group. Compared with the control group, the apoptotic rates of cardiomyocytes and the levels of bax/bcl-2　ratio were significantly increased in DOX group, which were significantly alleviated in the DOX+DHM group (P<0.05). In addition, the levels of NLRP3, caspase-1 and IL-1ß were increased as compared with control group, while the levels of the above indicators were remarkably reversed in DOX+DHM group as compared with DOX group (P<0.05). Conclusion: DHM alleviates DOX-induced myocardial injury in rats by inhibiting NLRP3 inflammasome and reducing cardiomyocyte apoptosis.

[Analysis of baseline liver biochemical parameters in 324 cases with novel coronavirus pneumonia in Shanghai area].

Objective: To summarize the clinical characteristics and liver biochemical parameters of 324 cases admitted with novel coronavirus pneumonia in Shanghai area. Methods: Clinical data and baseline liver biochemical parameters of 324 cases with novel coronavirus pneumonia admitted to the Shanghai Public Health Clinical Center from January 20, 2020 to February 24, 2020 were retrospectively analyzed. Patients were divided into two groups based on the status of illness: mild type (mild and typical) and severe type (severe and critical).The differences in clinical data and baseline liver biochemical parameters of the two groups were described and compared. The t-test and Wilcoxon rank-sum test were used for measurement data. The enumeration data were expressed by frequency and rate, and chi-square test was used. Results: Of the 324 cases with novel coronavirus pneumonia, 26 were severe cases (8%), with median onset of 5 days, 20 cases were HBsAg positive (6.2%), and 70 cases (21.6%) with fatty liver, diagnosed with X-ray computed tomography. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bilirubin (TBil), albumin(ALB) and international normalized ratio (INR) of 324 cases at baseline were 27.86 ± 20.02 U/L, 29.33 ± 21.02 U/L, 59.93 ± 18.96 U / L, 39.00 ± 54.44 U/L, 9.46 ± 4.58 µmol / L, 40.64 ± 4.13 g / L and 1.02 ± 0.10. Of which, ALT was > than the upper limit of normal (> ULN), accounting for 15.7% (51/324). ALT and AST > ULN, accounting for 10.5% (34/324). ALP > ULN, accounting for 1.2% (4/324). ALP and GGT > ULN, accounting for 0.9% (3/324). INR > ULN was lowest, accounting for 0.6% (2/324). There were no statistically significant differences (P > 0.05) in ALT [(21.5 vs. 26) U / L, P = 0.093], ALP [(57 vs.59) U/L, P = 0.674], and GGT [(24 vs.28) U/L, P = 0.101] between the severe group and the mild group. There were statistically significant differences in AST (23 U/L vs. 34 U/L, P < 0.01), TBil (10.75 vs. 8.05 µmol / L, P < 0.01), ALB (35.79 ± 4.75 vs. 41.07 ± 3.80 g/L, P < 0.01), and INR (1.00 vs. 1.04, P < 0.01). Conclusion: The baseline liver biochemical parameters of 324 cases with novel coronavirus pneumonia in Shanghai area was comparatively lower and the liverinjury degree was mild, and the bile duct cell damage was rare.

Promising High-Confinement Regime for Steady-State Fusion.

A reproducible stationary high-confinement regime with small "edge-localized modes" (ELMs) has been achieved recently in the Experimental Advanced Superconducting Tokamak, which has a metal wall and low plasma rotation as projected for a fusion reactor. We have uncovered that this small ELM regime is enabled by a wide edge transport barrier (pedestal) with a low density gradient and a high density ratio between the pedestal foot and top. Nonlinear simulations reveal, for the first time, that the underlying mechanism for the observed small ELM crashes is the upper movement of the peeling boundary induced by an initial radially localized collapse in the pedestal, which stops the growth of instabilities and further collapse of the pedestal, thus providing a physics basis for mitigating ELMs in future steady-state fusion reactors.

Yak-milk-derived exosomes promote proliferation of intestinal epithelial cells in an hypoxic environment.

Intestinal epithelial cells (IEC) are an important part of the intestinal barrier. Barrier function was disrupted under hypoxia, but milk-derived exosomes can regulate the intestinal barrier function. However, the mechanisms underlying the association between yak milk exosomes and hypoxia in IEC remain poorly understood. In this follow-up study, we proposed an effective optimization method for purifying yak-milk-derived exosomes. The Western blot analyses indicated that the expression of the proteins of the endosomal sorting complexes required for transport (TSG101), proteins of the tetraspanin family (CD63), and heat shock protein 70 (Hsp-70) proteins from yak-milk-derived exosomes were significantly higher than those in cow-milk-derived exosomes. Flow cytometry analysis showed that yak milk had 3.7 times the number of exosomes compared with cow milk. Moreover, we explored whether yak milk exosomes could facilitate intestinal cell survival under hypoxic conditions in vitro. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide results showed that yak-milk-derived exosomes significantly increased survival of IEC-6 cells with rates of up to 29% for cells incubated in hypoxic conditions for 12 h, compared with those of cow-milk-derived exosomes posttreatment (rates of up to 22% for cells incubated in hypoxic conditions for 12 h). Confocal microscopy revealed that the IEC-6 cells uptake more yak-milk-derived exosomes than cow milk in hypoxic conditions. Furthermore, the Western blot analyses indicated that yak-milk-derived exosomes significantly promote oxygen-sensitive prolyl hydroxylase (PHD)-1 expression and decrease the expression of hypoxia-inducible factor-α and its downstream target vascular endothelial growth factor (VEGF) in the IEC-6 cells. Further, yak-milk-derived exosomes significantly inhibited p53 levels. In conclusion, our findings demonstrate that yak-milk-derived exosomes more effectively activate the hypoxia-inducible factor signaling pathway, thus promoting IEC-6 cell survival, which may result in higher hypoxia tolerance than cow-milk-derived exosomes.

[Impact of Herpud1 in the homocysteine-induced phenotypic switching of vascular smooth muscle cells].

Objective: To investigate the impact of homocysteine inducible endoplasmic reticulum(ER) protein with ubiquitin like domain 1 protein (Herpud1) in the homocysteine (Hcy) -induced phenotypic switching of vascular smooth muscle cells (VSMCs). Methods: VSMCs were derived from thoracic aortic artery of male Sprague Dawley rats and cultured VSMCs (4-7 passage) were treated with various concentrations of Hcy (0, 100, 500 and 1 000 µmol/L) and applied to immunofluorescence to observe the morphological changes of VSMCs via SM-actin staining. Western blot was used to detect the expression of VSMCs phenotypic markers, including Osteopontin, Calponin and smooth muscle myosin heavy chain (SM-MHC) and the expression of endoplasmic reticulum stress (ERS) related proteins, including C/EBP-homologous protein (CHOP), inositol-requiring kinase 1 (IRE-1) and glucose regulating protein 78 (GRP78) in the absence and presence of non-selective inhibitor of ERS, 4-phenylbutyric acid (4-PBA, 2 mg/ml). The Herpud1 mRNA and protein levels were determined in Hcy-stimulated VSMCs treated with 4-PBA or transfected with specific siRNA targeting Herpud1. Results: Compared with the control group, SM-actin staining results showed that the shape of VSMCs treated with different concentrations of Hcy for 24 hours changed from long fusiform into round form, arrangement of myofilament became irregular and the most significant alteration was found in the 500 µmol/L Hcy group. After intervention of 24 hours, various concentration of Hcy increased protein expression of Osteopontin, and reduced Calponin and SM-MHC protein expressions in VSMCs (all P<0.05). In addition, the results showed that Hcy increased the expression of CHOP, IRE-1 and GRP78 in a dose-dependent manner, which could be reversed by 4-PBA treatment (all P<0.05). However, 4-PBA inhibited Hcy induced upregulation of Osteopontin and downregulation of Calponin and SM-MHC, suggesting that ERS was involved in Hcy-induced phenotypic switching of VSMCs. Herpud1 protein was mostly expressed in the cytoplasm and was also expressed in the nucli, both in the control, Hcy and Hcy+4-PBA groups. Moreover, Hcy increased mRNA and protein levels of Herpud1 (P<0.05), whereas treatment with 4-PBA could significantly reduce Hcy-induced upregulation of Herpud1 (P<0.05). Furthermore, knockdown of Herpud1 abrogated the effects of Hcy on VSMCs phenotype markers. Conclusion: Herpud1 plays an important role in Hcy-induced phenotypic switching of VSMCs.

[Diagnostic value of albumin-bilirubin grade combined with serum ammonia in cirrhosis with hepatic encephalopathy].

Objective: To explore the value of albumin-bilirubin (ALBI) grade combined with serum ammonia in the diagnosis of cirrhosis with hepatic encephalopathy (HE). Methods: The serum level of total bilirubin(TBIL), albumin( ALB )and blood ammonia were detected in 139 patients including 73 cirrhosis patients without HE and 66 cirrhosis patients with HE from January 2015 to January 2017 in Beijing You'an Hospital, and the relationship between ALBI and blood ammonia value and Child grade and hepatic encephalopathy was analyzed. Results: The level of ALBI and blood ammonia were more and more higher with the increase of Child grade, the level of ALBI in Child A, B and C were -2.3±0.6, -1.7±0.5, -0.9±0.4, and there was a statistically significant(F=125.100, P<0.001). The blood ammonia concentration in Child A, B and C were(42.6±16.0), (56.1±31.2), (69.8±34.7) µmol/L, and there was a statistically significant(F=7.400, P<0.001). The level of ALBI was higher with the increase of model for end-stage liver disease (MELD) grade, and there was a positive correlation(r=0.547, P<0.001). The ALBI value in the HE group was higher than the cirrhosis patients without HE((-1.1±0.5)vs(-1.6±0.7)), and the difference was statistically significant (t=5.244, P<0.001). Level of blood ammonia in the HE group was(83.6±39.5)µmol/L, which was higher than the level of cirrhosis patients without HE(42.9±17.0)µmol/L, and the difference was statistically significant (t=8.130, P<0.001) . When ALBI and blood ammonia were combined, the ROC curve area was 0.911, the sensitivity was 93.9%, the specificity was 93.2%. Conclusion: There is a significant diagnosis value and high clinical application when ALBI is combined with blood ammonia to diagnose HE .

[Analysis of characteristics and influence factors of diagnostic delay of endometriosis].

Objective: To access the influence factors of diagnostic delay of endometriosis. Methods: We designed a questionnaire of diagnostic delay of endometriosis. From February 2014 to February 2016, 400 patients who had dysmenorrhea and diagnosed with endometriosis by surgery in Peking University Third Hospital were surveyed retrospectively. Time and risk factors of diagnostic delay were analyzed. Results: The diagnostic delay of 400 patients was 13.0 years (0.2-43.0 years), 78.5%(314/400) patients thought pain was a normal phenomenon and didn't see the doctor. Patients who suffered dysmenorrhea at menarche experienced longer diagnostic delay than those who had dysmenorrhea after menarche (18.0 vs 4.5 years; Z=191.800, P<0.01) . Patients who suffered aggravating dysmenorrhea experienced shorter delay time than those who suffered stable or relieving dysmenorrhea (11.0 vs 12.5 vs 18.0 years; Z=8.270, P<0.05) , with the difference statistically significant, single factor analysis shows. Severe dysmenorrhea, deep infiltration endometriosis (DIE) , family history of dysmenorrhea or endometriosis, previous surgical history of endometriosis, high stage, with infertility, adenomyoma or other symptoms, could help to shorten diagnostic delay with no significant difference (P>0.05) . By multiple logistic regression analysis, the results shown that whether have dysmenorrhea at menarche and clinical diagnosis time were the independent factors affecting delayed diagnosis (P<0.01) . Conclusions: Diagnostic delay of endometriosis is common and the mean delay time is 13.0 years mainly due to the unawareness of dysmenorrhea. Dysmenorrhea at menarche, clinical diagnosis time and dysmenorrhea intensity are the factors affecting time of diagnostic delay.

Single cell transcriptome profiling revealed differences in gene expression during oocyte maturation in Haimen white goats.

Juvenile in vitro embryo transfer is an important animal reproductive technology that can shorten the generation interval of livestock, explore the reproductive potential of dams with excellent genetic traits, accelerate genetic progress and production efficiency of the herd, and provide a wealth of genetic resources for livestock breeding. However, oocytes from kids do not develop as well as those from female goats during in vitro maturation. To identify differences during different stages of oocyte maturation, we used single cell transcriptome sequencing to compare gene expression in mature oocytes from kids and female goats. We identified 1086 differentially expressed genes in mature oocytes from kids and female goats. Of these, we observed upregulated expression in 355 genes and downregulated expression in 435 genes. The differentially expressed genes were involved in a total of 245 different pathways; of which 30 were significant (P ≤ 0.05). We used real-time quantitative polymerase chain reaction to screen and verify the expression of five genes specifically involved in oocyte maturation (MOS, RPS6KA1, CPEB1, ANAPC13, and CDK1). Further study of these genes will be of great importance for improving the reproductive performance of Haimen white goats.

Comparative pharmacokinetics of diaveridine in pigs and chickens following single intravenous and oral administration.

Comparative pharmacokinetic profiles of diaveridine following single intravenous and oral dose of 10 mg/kg body weight in healthy pigs and chickens were investigated, respectively. Concentrations of diaveridine in plasma samples were determined using a validated high-performance liquid chromatography-ultraviolet (HPLC-UV) method. The concentration-time data were subjected to noncompartmental kinetic analysis by WinNonlin program. The corresponding pharmacokinetic parameters in pigs or chickens after single intravenous administration were as follows, respectively: t1/2ß (elimination half-life) 0.74 ± 0.28 and 3.44 ± 1.07 h; Vd (apparent volume of distribution) 2.70 ± 0.99 and 3.86 ± 0.92 L/kg; ClB (body clearance) 2.59 ± 0.62 and 0.80 ± 0.14 L/h/kg; and AUC0-∞ (area under the blood concentration vs. time curve) 4.11 ± 1.13 and 12.87 ± 2.60 µg∙h/mL. The corresponding pharmacokinetic parameters in pigs or chickens after oral administration were as follows, respectively: t1/2ß 1.78 ± 0.41 and 2.91 ± 0.57 h; Cmax (maximum concentration) 0.43 ± 0.24 and 1.45 ± 0.57 µg/mL; Tmax (time to reach Cmax ) 1.04 ± 0.67 and 3.25 ± 0.71 h; and AUC0-∞ 1.33 ± 0.55 and 9.28 ± 2.69 µg∙h/mL. The oral bioavailability (F) of diaveridine in pigs or chickens was determined to be 34.6% and 72.2%, respectively. There were significant differences between the pharmacokinetics profiles in these two species.

[Role of oral contraceptives in preventing endometriosis-related pain progression].

Objective: To analyze the effect of oral contraceptives on dysmenorrhea in patients with endometriosis. Methods: We designed dysmenorrhea and chronic pelvic pain questionnaire.From February 2014 to February 2016 in the Gynecological Department of Peking University Third Hospital, patients suffered dysmenorrhea with or without endometriosis or adenomyosis were included.According to their own willingness, patients were divided into the research group and the control group.The research group periodically took oral contraceptives (Diane-35 or Yasmin), while the control group received no treatment.They were followed-up about dysmenorrhea every six months, and the total follow-up time was one and a half year. Results: The dysmenorrhea VAS scores of patients in research group after taking oral contraceptives for six or twelve months were significantly lower than that in baseline (VAS 4 vs 5 vs 7). The dysmenorrhea VAS scores increased after quitting medication, but remained still lower than baseline (VAS 6.5 vs 7). However, the dysmenorrhea VAS scores of patients in control group remained unchanged (VAS 6 vs 6). Patients who took pills for more than one year experienced the same severity of dysmenorrhea after six months' or one year's medication (VAS 2 vs 2), and they suffered slowly aggravating recurrent dysmenorrhea, while those who quitted after six months' medication suffered quickly recurrent dysmenorrhea.The relieving rate of dysmenorrhea in research group was significantly higher than that in control group (79.7% vs 8.2%), and the relieving rate in patients with severe pain was significantly higher than that with mild or moderate pain (87.0% vs 66.6 % vs 77.1%). The relieving rate in patients without lesions was significantly higher than patients with adenomyosis (92.6% vs 59.1%). Conclusions: Endometriosis is a progressing disease. Longterm medication of oral contraceptives can relieve the dysmenorrhea pain.The extent of pain relief was not connected with the length of medication.Dysmenorrhea recurred after quitting medication, and the longer of medication, the slower pain recurred.Patients without lesions experienced higher pain relieving rate than those with adenomyosis.