ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

Objective: To investigate the differential expression of Yes-associated protein(YAP) in the healthy control group and in patients with rheumatoid arthritis(RA), and to explore its correlation with the progression of the disease. Methods: Three cases each of synovial membranes from the healthy control group and RA group were selected for RNA-sequence detection to identify differentially expressed genes. Data and laboratory indicators from 50 healthy control cases and 150 RA patients who met the criteria were collected. ELISA was used to detect the expression of YAP in the serum of each group, and then its correlation with other laboratory indicators in RA patients was analyzed. The receiver operating characteristic curve was applied to explore the diagnostic efficacy of the related risk factors for RA. Results: Expression of 14-3-3-gama, which regulated the disease process, was significantly down-regulated in the synovial membranes of RA patients compared to normal synovial membranes; YAP expression was significantly up-regulated in rheumatoid arthritis fibroblast-like synoviocytes compared to healthy controls and was correlated with haematological sedimentation, C-reactive protein, interleukin(IL)-1, IL-4, IL-6, IL-10, rheumatoid factor, anti-cyclic citrullinated polypeptide antibody, interferon alpha, tumour necrosis factor alpha, protein electrophoresis α1 globulin, protein electrophoresis alpha2 globulin, disease activity scores, disease activity index, and patient-reported outcome had correlations(P0.05); multifactor Logistic regression analysis showed that YAP expression was an independent influencing factor for the prognosis of RA patient. Conclusion YAP is differentially expressed between the healthy control group and RA group, which shows a significant positive correlation with the disease activity of RA, potentially becoming a new target for clinical treatment of RA.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

The core components of the Hippo signaling pathway encompass upstream regulatory molecules,core kinase cascade complexes,and downstream transcriptional regulation complexes.This pathway modulates cellular behaviors by influencing the effector molecules of its core components and plays a pivotal role in immune regulation.Effector molecules,such as Yes-associated protein(YAP),transcriptional coactivator with PDZ-binding motif(TAZ),transcriptional enhanced associate domain transcriptional factor(TEAD),monopolar spindle-one binder(MOB1),large tumor suppressor(LATS),can stimulate fibroblast-like synovial cell migration and invasion in rheumatoid arthritis,regulate osteoarthritis disease progression,promote pathological new bone formation in ankylosing spondylitis,sustain submandibular gland development while delaying Sjogren's syndrome progression,mediate alpha-smooth muscle actin in systemic sclerosis,and refine the regulation of target genes associated with pulmonary fibrosis.This article provides an overview of the regulatory mechanisms involving Hippo signaling pathway-related effector molecules in the pathogenesis and progression of rheumatic immune system diseases,to serve as a reference for exploring novel therapeutic targets of rheumatic immune system diseases.

Objective:To analyze the clinical characteristics, pregnancy outcomes and factors affecting live birth of patients undergoing multifetal pregnancy reduction (MFPR), in order to provide reference for clinical strategies.Methods:A retrospective cohort study was conducted on all patients who underwent multifetal pregnancy reduction among polychorionic multifetal pregnancy patients at the Center for Reproductive Medicine, Department of Obstetrics and Gynecology of Peking University Third Hospital during a period of 12 years from January 1, 2009 to December 31, 2020. The overall and annual clinical characteristics were analyzed, pregnancy outcomes were followed up. Patients were divided into live birth group ( n=1 555) and not live birth group ( n=205), and factors affecting live birth were analyzed by multivariate logistic. Through further subgroup analysis, multiple pregnancies were divided into three subgroups: dichorionic diamniotic twin, triplet pregnancy, and four or more high sequence multiple pregnancy. Results:A total of 1 925 patients who underwent MFPR were included, and 1 760 pregnancy outcomes were followed up. In the past 12 years, there had been an increase in dizygotic twins, and the proportion of transabdominal fetal reduction had significantly increased, from 3% in 2009 to 77% in 2020. The annual live birth rate of reduction patients fluctuated between 83% and 94%. The live birth rate of patients with MFPR was related with the type of multiple pregnancies, the method of reducing pregnancies, and the number of retained embryos. The live birth rate of four or more high sequence multiple pregnancies [75.8% (72/95)] was lower than that of dichorionic diamniotic twins [90.0% (796/884), P<0.001], the dichorionic diamniotic twins [89.9% (241/268), P<0.001], the trichorionic triamniotic triplet pregnancy [86.9% (446/513), P=0.005]. The live birth rate of transabdominal fetal reduction [91.4% (655/717)] was higher than that of transvaginal fetal reduction with fetal cardiac activity area injection of KCl [84.9% (304/358), P=0.001], and vaginal embryo aspiration [87.0% (596/685), P=0.009]. There was no statistically significant difference in the live birth rate between vaginal KCl injection and vaginal aspiration ( P=0.351). The survival rate of patients with retained singletons [89.7% (1 062/1 184)] was higher than that of patients with retained twins [85.6% (493/576), P=0.012]. After adjusting for confounding factors such as age, assisted pregnancy method, type of multiple pregnancies, and number of retained embryos, transabdominal fetal reduction was an independent protective factor for live birth rate ( P=0.040, OR=1.604, 95% CI: 1.021-2.519). Conclusion:With the change of transplantation strategy, the proportion of dichorionic diamniotic twins increased, and the proportion of transabdominal fetal reduction increased, which pregnancy outcomes might be better. There was no difference in pregnancy outcomes between those who underwent vaginal aspiration and transvaginal fetal reduction with fetal cardiac activity area injection of KCl. The outcomes of four or more high sequence multiple pregnancies were poor, and it was necessary to strictly control the number of embryo transfers and optimize ovulation promotion plans in clinical practice.

Objective:To analyze the clinical characteristics, pregnancy outcomes and factors affecting live birth of patients undergoing multifetal pregnancy reduction (MFPR), in order to provide reference for clinical strategies.Methods:A retrospective cohort study was conducted on all patients who underwent multifetal pregnancy reduction among polychorionic multifetal pregnancy patients at the Center for Reproductive Medicine, Department of Obstetrics and Gynecology of Peking University Third Hospital during a period of 12 years from January 1, 2009 to December 31, 2020. The overall and annual clinical characteristics were analyzed, pregnancy outcomes were followed up. Patients were divided into live birth group ( n=1 555) and not live birth group ( n=205), and factors affecting live birth were analyzed by multivariate logistic. Through further subgroup analysis, multiple pregnancies were divided into three subgroups: dichorionic diamniotic twin, triplet pregnancy, and four or more high sequence multiple pregnancy. Results:A total of 1 925 patients who underwent MFPR were included, and 1 760 pregnancy outcomes were followed up. In the past 12 years, there had been an increase in dizygotic twins, and the proportion of transabdominal fetal reduction had significantly increased, from 3% in 2009 to 77% in 2020. The annual live birth rate of reduction patients fluctuated between 83% and 94%. The live birth rate of patients with MFPR was related with the type of multiple pregnancies, the method of reducing pregnancies, and the number of retained embryos. The live birth rate of four or more high sequence multiple pregnancies [75.8% (72/95)] was lower than that of dichorionic diamniotic twins [90.0% (796/884), P<0.001], the dichorionic diamniotic twins [89.9% (241/268), P<0.001], the trichorionic triamniotic triplet pregnancy [86.9% (446/513), P=0.005]. The live birth rate of transabdominal fetal reduction [91.4% (655/717)] was higher than that of transvaginal fetal reduction with fetal cardiac activity area injection of KCl [84.9% (304/358), P=0.001], and vaginal embryo aspiration [87.0% (596/685), P=0.009]. There was no statistically significant difference in the live birth rate between vaginal KCl injection and vaginal aspiration ( P=0.351). The survival rate of patients with retained singletons [89.7% (1 062/1 184)] was higher than that of patients with retained twins [85.6% (493/576), P=0.012]. After adjusting for confounding factors such as age, assisted pregnancy method, type of multiple pregnancies, and number of retained embryos, transabdominal fetal reduction was an independent protective factor for live birth rate ( P=0.040, OR=1.604, 95% CI: 1.021-2.519). Conclusion:With the change of transplantation strategy, the proportion of dichorionic diamniotic twins increased, and the proportion of transabdominal fetal reduction increased, which pregnancy outcomes might be better. There was no difference in pregnancy outcomes between those who underwent vaginal aspiration and transvaginal fetal reduction with fetal cardiac activity area injection of KCl. The outcomes of four or more high sequence multiple pregnancies were poor, and it was necessary to strictly control the number of embryo transfers and optimize ovulation promotion plans in clinical practice.

Objective: To conduct a systematic review and meta-analysis of studies evaluating the oncological and fertility outcomes of early-stage endometrial cancer (EC) treated with the levonorgestrel-releasing intrauterine system (LIUS)-based regimens. Methods: The Meta-analyses Of Observational Studies in Epidemiology statement for meta-analyses was followed. Searches were conducted on MEDLINE, Embase, PubMed, Preprints, and the Cochrane Central Register of Controlled Trials from January 1990 to August 4, 2022. The Joanna Briggs Institute Critical Appraisal Checklist was used for quality assessment. The primary endpoint was the complete response (CR) rate and the secondary endpoints were relapse, pregnancy, and live birth rate. Results: A total of 25 studies (821 women) were included. The CR rate of LIUS-based regimens was 63.4% (95% confidence interval [CI]=52.3%–73.2%), with 29.6% (95% CI=23.3%–36.8%) of cases experiencing recurrence during follow-up. In sensitivity analyses, patients younger than 45 years of age with a body mass index <30 kg/m2 who were treated with LIUS-based regimens achieved a high CR rate of 84.6% (95% CI=80.3%–88.1%) over a median follow-up of more than 24 months. Overall pregnancy and live birth rates were 37.9% (95% CI=24.1%–53.9%) and 39.3% (95% CI=24.0%–57.0%), respectively. No statistical differences were apparent in CR or relapse rates among the LIUS+GnRH agonist, LIUS+oral progesterone, or hysteroscopic resection followed by LIUS subgroups. Conclusion LIUS-based therapies are viable for the conservative management of early-stage endometrioid EC on CR and fertility outcome.

Objective:To investigate the effect of growth hormone (GH) pretreatment on in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in women with poor ovarian reserve. Methods:A retrospective cohort study was conducted to analyze the clinical data of women who underwent IVF/ICSI-ET with gonadotropin-releasing hormone (GnRH) antagonist protocol in Reproductive Medicine Center of Peking University Third Hospital from October 2018 to October 2019. Patients with poor ovarian reserve belong POSEIDON group 3 or POSEIDON group 4 were included as the research objects and were divided into GH group ( n=103) and control group ( n=197) by pretreated with GH or not. GH group received 2 U/d subcutaneous injection of GH for 4 weeks before ovulation induction, and the dosage was adjusted to 4 U/d until the trigger day during ovulation induction. GH was not used in control group. The clinical outcomes of the two groups were analyzed and compared. Results:There were no significant differences in general condition between GH group and control group including age, infertility duration, body mass index (BMI), anti-Müllerian hormone (AMH), basal follicle-stimulating hormone (FSH) and antral follicle count (AFC, all P>0.05). No significant differences were found in the duration of gonadotropin (Gn) used, total dosage of Gn used, estrogen levels and the endometrial thickness on human chorionic hormone (hCG) injection day between the two groups (all P>0.05). Furthermore, no statistically significant difference was found in the number of oocytes retrieved between GH group and control group ( P>0.05). The number of available embryos in GH group (2.62±2.41) was significantly higher than that in control group (1.51±1.56, P<0.001). There were 56 fresh embyo transfer cycles in GH group and 106 fresh embyo transfer cycles in control group. There were no statistically significant differences in endometrial thickness on fresh embyo transfer day and the number of embryos transferred between GH group and control group (all P>0.05). No statistically significant differences were found in clinical pregnancy rate, miscarriage rate and live delivery rate after fresh embyo transferred between the two groups (all P>0.05). Conclusion:GH pretreatment for 4 weeks before controlled ovarian sitmulation and continued use till the trigger day may improve number of the available embryos in poor ovarian reserve patients with GnRH antagonist.

Objective:To investigate the effect of growth hormone (GH) pretreatment on in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in women with poor ovarian reserve. Methods:A retrospective cohort study was conducted to analyze the clinical data of women who underwent IVF/ICSI-ET with gonadotropin-releasing hormone (GnRH) antagonist protocol in Reproductive Medicine Center of Peking University Third Hospital from October 2018 to October 2019. Patients with poor ovarian reserve belong POSEIDON group 3 or POSEIDON group 4 were included as the research objects and were divided into GH group ( n=103) and control group ( n=197) by pretreated with GH or not. GH group received 2 U/d subcutaneous injection of GH for 4 weeks before ovulation induction, and the dosage was adjusted to 4 U/d until the trigger day during ovulation induction. GH was not used in control group. The clinical outcomes of the two groups were analyzed and compared. Results:There were no significant differences in general condition between GH group and control group including age, infertility duration, body mass index (BMI), anti-Müllerian hormone (AMH), basal follicle-stimulating hormone (FSH) and antral follicle count (AFC, all P>0.05). No significant differences were found in the duration of gonadotropin (Gn) used, total dosage of Gn used, estrogen levels and the endometrial thickness on human chorionic hormone (hCG) injection day between the two groups (all P>0.05). Furthermore, no statistically significant difference was found in the number of oocytes retrieved between GH group and control group ( P>0.05). The number of available embryos in GH group (2.62±2.41) was significantly higher than that in control group (1.51±1.56, P<0.001). There were 56 fresh embyo transfer cycles in GH group and 106 fresh embyo transfer cycles in control group. There were no statistically significant differences in endometrial thickness on fresh embyo transfer day and the number of embryos transferred between GH group and control group (all P>0.05). No statistically significant differences were found in clinical pregnancy rate, miscarriage rate and live delivery rate after fresh embyo transferred between the two groups (all P>0.05). Conclusion:GH pretreatment for 4 weeks before controlled ovarian sitmulation and continued use till the trigger day may improve number of the available embryos in poor ovarian reserve patients with GnRH antagonist.