Background::Endometriosis (EM) is a complex benign gynecological disease, but it has malignant biological behavior and can invade any part of the body. Clinical manifestations include pelvic pain, dysmenorrhea, infertility, pelvic nodules, and masses. Our previous study successfully detected circulating endometrial cells (CECs) in the peripheral blood of patients with EM. The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method, to further accurately capture CECs, understand the characteristics of these cells, and explore the relationship between CECs and the clinical course characteristics of patients with EM.Methods::Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells (CVECs) was taken from EM patients ( n = 34) hospitalized in the Peking University People’s Hospital. We used the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method to exclude the interference of red blood cells, white blood cells, and CVECs, so as to accurately capture the CECs in the peripheral blood of patients with EM. Then we clarified the size and ploidy number of chromosome 8 of CECs, and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics. Results::The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH. Overall, 34 eligible EM patients were enrolled. The results showed that the detection rates of CECs were 58.8% in EM patients and 16.7% in the control group. However, after classification according to clinical characteristics, more CECs could be detected in the peripheral blood of patients with rapidly progressive EM, with a detection rate of 94.4% (17/18). In total, 63.5% (40/63) of these cells were small cells with diameters below 5 μm, and 44.4% (28/63) were aneuploid cells. No significant association was found between the number of CECs and EM stage.Conclusion::The number and characteristics of CECs are related to the clinical course characteristics of patients with EM, such as pain and changes in lesion size, and may be used as biomarkers for personalized treatment and management of EM in the future.

Objective:This study aimed to explore the implementation plan of the grid management joint scientific research clinic and to evaluate its impact on enhancing the scientific research capabilities of nursing staff.Methods:Nursing research team developed an implementation strategy for the grid management joint scientific research clinic in 2023 and then promoted it across the hospital. The scores of nursing staff were compared on the self-evaluation scale, general self-efficacy scale, and research innovation achievements before (April-December 2022) and after (January-September 2023) the implementation.Results:The research capabilities of nurses increased significantly from 103.13±2.56 to 141.32±18.09 ( P<0.001), and their self-efficacy increased significantly from 1.95±0.26 to 2.15±0.53 ( P<0.001). The number of college-level and above scientific research projects, the number of journal publications, the number of authorized patterns, the number of participation in academic exchanges at the municipal level and above in nursing societies, and the number of scientific research awards at the municipal level and above all increased compared with the previous ones with statistical significance. Conclusions:Implementing the grid management joint scientific research clinic is beneficial for improving overall nursing research capabilities, nurses' self-efficacy, and the effectiveness of scientific research training. This provides a reference for other hospitals to enhance the training of nursing staff's scientific research capabilities.

Objective:To construct the core indicators for entrustable professional activities in specialists in obstetrics and gynecology.Methods:A study group was formed by the specialists in obstetrics and gynecology and the experts in medical education. The core indicators for entrustable professional activities were constructed for the specialists in obstetrics and gynecology based on literature review and clinical practice, and then the Delphi method was used to conduct two rounds of expert letter consultation for screening and optimization from March 2021 to January 2023 to further identify the core indications.Results:The expert positive coefficient was 100% for the two rounds of consultation, with an expert authority coefficient of 0.82, and the Kendall's coefficient of concordance was 0.221 and 0.213, respectively (both P<0.01). Ten core indicators and their content descriptions were constructed for entrustable professional activities in obstetrics and gynecology specialists, and the experts had a degree of recognition of more than 80% for the importance of these ten entrustable professional activities, with a coefficient of variation of <0.25. This study determined the expected entrustable level of each indicator for specialists at the completion of the course, which ranged from grade 3 to 5; the highest level of 4.48 was observed for the diagnosis and treatment of outpatients, which was between the levels of mastery and expert; the lowest level of 3.52 was observed for laparoscopic hysterectomy, which was between the levels of competency and mastery. Conclusion:This study preliminarily constructs the core indicators for entrustable professional activities in specialists in obstetrics and gynecology, which provides a new exploration for the standardized training of specialists.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC. METHODS: Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages. RESULTS: Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively). CONCLUSIONS This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Prognosis ; Gene Expression Profiling ; Transcriptome ; Tumor Microenvironment ; Receptors, G-Protein-Coupled/therapeutic use* ; Tetraspanins/genetics* ; Protein Kinases ; Integrin beta1/therapeutic use*

Abstract: Objective　To understand the epidemiological characteristics of the migratory bird population with hypertension in Hainan and to provide a basis for the health management of the migratory bird population. Methods　One hundred and eighty migratory birds with hypertension who had lived in in the Mangrove Bay community of Chengmai, Hainan for 3 months or more were selected as the study population. Demographic data, including gender, age, ethnicity, occupation, medication use, family history of hypertension, hometown living environment, Hainan living environment (presence of water area and greenbelt around the residence, type of water area and greenbelt), smoking and alcohol consumption, and height and weight were collected by questionnaire and physical examination to investigate the epidemiological characteristics of the study subjects, and unconditional dichotomous logistic regression analysis was used to identify factors affecting the reduction of blood pressure among the hypertensive migratory bird population before and after taking medication in Hainan. Results　A total of 180 study subjects were included, including 77 (42.8%) males and 103 (57.2%) females, with 78 (43.3%) subjects aged ≤65. The hypertension levels were: 87 (48.3%) had normal high blood pressure, 56 (31.1%) had grade 1 hypertension and 37 (20.6%) had grade 2 hypertension. The higher the blood pressure classification, the lower the percentage of migratory individuals whose blood pressure dropped during their stay in Hainan. Age, hypertension classification, dietary habits, living environment, body mass index (BMI), and alcohol consumption were associated with a decrease in blood pressure during Hainan among the study participants who took hypertension medication regularly. Salty diet (OR=2.778, 95%CI:1.070-7.213, P=0.036) and alcohol consumption (OR=2.686, 95%CI:1.042-6.925, P=0.041) were unfavorable factors for lower diastolic blood pressure before taking medication; overweight (OR=3.487, 95%CI:1.306-9.310, P=0.013) was an unfavorable factor in the reduction of diastolic blood pressure after taking medication. Conclusion　The blood pressure reduction is more significant in migratory individuals in migratory individuals under 65 years old, with a light diet, no alcohol consumption and normal BMI. Environmental factors, age, dietary habits and lifestyle are the main causes of blood pressure, which can provide a reference basis for the health management of the migratory birds with hypertension in Hainan.

Anti-virulence strategy has been considered as one of the most promising approaches to combat drug-resistant bacterial infections. Pore-forming toxins (PFTs) are the largest class of bacterial toxins, inflicting their virulence effect through creating pores on the cell membrane. However, current solutions for eliminating PFTs are mostly designed based on their molecular structure, requiring customized design for different interactions. In the present study, we employed erythroliposome (denoted as RM-PL), a biomimetic platform constructed by artificial lipid membranes and natural erythrocyte membranes, to neutralize different hemolytic PFTs regardless of their molecular structure. When tested with model PFTs, including α-hemolysin, listeriolysin O, and streptolysin O, RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner. In vivo studies further confirmed that RM-PL could efficiently neutralize various toxins and save animals' lives without causing damage to organs or tissues. In addition, we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes. In summary, the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mechanism of lysosome-mediated toxin degradation.

Objective:To compare the clinical and prognostic characteristics of ovarian endometrioid carcinoma (OEC) patients with synchronous endometrial lesions and patients with pure OEC.Methods:A retrospective review of the medical records of patients received initial treatment and a postoperative pathological diagnosis of OEC at Peking University People′s Hospital between August 1998 and December 2017 were performed. According to the inclusion criteria, a total of 56 patients with OEC were included in the study, including 13 patients concurrent with simultaneous endometrial lesions (Group A) and 43 patients with pure OEC (Group B).Results:Patients with synchronous endometrial lesions accounted for 23% (13/56). Mean age of Group A at diagnosis was (44.9±8.3) years old, 2/13 of patients were postmenopausal, and no one had a history of hypertension, the first symptom of 5/13 people was irregular vaginal bleeding. Mean age of Group B patients at diagnosis was (52.7±10.2) years old, 53% (23/43) of patients were postmenopausal, and 28% (12/43) patients had the history of hypertension, the first symptom of 4 (9%, 4/43) people was irregular vaginal bleeding. The differences of age, menopause status, history of hypertension and initial symptoms between the two groups were statistically significant (all P<0.05). There were no significant differences in fertility history, dysmenorrhea history, age of menarche, history of endometriosis, preoperative and postoperative CA 125 level, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor grade, metastatic site and platinum-based chemotherapy drug resistance between the two groups (all P>0.05). The overall 5-year survival rate of OEC patients was 91.6%, and the overall 5-year progression-free survival rate was 76.6%. Among them, the 5-year survival rate of the OEC concurrent with simultaneous endometrial lesions group was 80.2%, and the pure OEC group was 93.4%; the 5-year progression-free survival rate of the OEC concurrent with simultaneous endometrial lesions group was 74.1%, and the 5-year progression-free survival rate of the pure OEC group was 77.3%. There were no significant differences between the two groups (all P>0.05). Multivariate analysis showed that the independent factors for the prognosis of OEC patients were FIGO stage ( P=0.006) and residual lesion size ( P=0.020). Conclusions:OEC patients have a high proportion of simultaneous endometrial lesions. OEC with simultaneous endometrial lesions are younger than patients with pure OEC. Synchronous endometrial lesions do not affect the prognosis of patients with OEC.

Objective: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). Methods: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (C_trough) was detected by ultra performance liquid chromatography tandem mass spectrometry. Results: Based on the genotype analysis, 65 subjects were identified as extensive metabolizers’ group (30 cases) and poor metabolizers’ group (35 cases). The C_trough of the 65 patients were detected for 169 times totally, and there was a significant difference of C_trough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of C_trough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ²=11.689, P=0.020). Conclusion Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their C_trough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.

Objective To investigate the clinical and pathological characteristics of atypical polypoid adenomyoma (APA) for improvement of the diagnosis, different diagnosis and treatment of the disease. Methods The clinical data, pathological characteristics, and the follow-up information were retrospectively analyzed in 27 cases of APA admitted in Peking Univeristy People′s Hospital from 2007 to 2016. Results The median age was 42.6 years old (range 25-60 years old). Fifteen patients were nullipara, 2 patients were postmenopausal. The most common presenting symptom was abnormal uterine bleeding (81%,22/27). Leisions were obtained by using hysteroscopy in 23 cases, hysterectomy 3 cases and dilatation and curettage 1 case. Fertility preserving treatments were performed in 10 patients who had strong desire for fertility, among which 1 case progressed into endometrial carcinoma. Among 15 patients underwent hysterectomy and (or) bilateral salpingo-oophorectomy, 9 cases of them had endometrial atypical hyperplasia. Endometrial carcinoma along with APA were found in three patients, 2 cases of them underwent hysterectomy and bilateral salpingo-oophorectomy and pelvic lymphadenectomy, the other one received medication for fertility preservation. Follow up information were available in 24 cases(89%,24/27)with a median follow up of 46 months (range 4-108 months), 1 case recurred and 1 case progressed into endometrial carcinoma. One case died of other malignancy, while the other patients were alive. Conclusions APA is a rare uterine neoplasm mixed with epithelial and mesenchymal component. It occurs mostly in childbearing-age women and its diagnosis is dependent on pathology. Although it′s clinical course is benign, there is risk of co-existance of endometrial carcinoma and endometrial atypical hyperplasia. For those who has desire of fertility, the treatment strategy is completely removed the lesion and closely followed up. For those who do not desire to preserve fertility, hysterectomy may be an option.

Objective To study the therapeutic effect of IGF?1R inhibitor TAE226 on malignant pleural effusion ( MPE) in nude mice. Methods Human lung carcinoma A549 cells were injected into the pleural cavity of nude mice to establish MPE model. The mice were randomly divided into model group and treatment group, and were orally administered with distilled water and TAE226 ( 20 mg/kg ) in the same volume, respectively. The volume of pleural effusion and tumor weight of the two groups were observed. HE staining was used to reveal the histological changes and enzyme?linked immunosorbent assay ( ELISA) was used to detect the IGF?1R protein expression. IGF?1R mRNA level in the tumor tissue was determined by RT?PCR. Microvessel density (MVD) and cell proliferation index (PI) were assessed by immunohistochemical analysis. The protein expression levels of IGF?1R, p?IGF?1R, PI3K and p?PI3K in the tumor tissue were determined by Western blotting. Results The volumes of pleural effusion were ( 241. 4 ± 89. 7 ) μl and (121.7±78.8) μl in the model and treatment groups, respectively (P<0.05). The tumor weight of treatment group was (316.7±186.3) mg, significantly lower than that of the model group (671.4±281.4) mg (P<0.05) . RT?PCR analysis showed that IGF?1R mRNA level was 0. 914 ± 0. 029 in the treatment group, significantly lower than that of the model group (1.152±0.037, P<0.01). The ELISA data revealed that IGF?1R protein expression level of the model group was significantly higher than that of the treatment group [(41.0±4.7) μg/L vs. (24.0±3.1) μg/L, P<0.01]. Immunohistochemical analysis showed that there were significant differences between MVD and PI in the model and treatment groups [ MVD, 34. 75 ± 3. 49 vs. 22.25±3.63;PI, (75.25±7.15)% vs. (45.75±5.12)%;P<0.01 for both). Western blot data showed that IGF?1R and PI3K protein expression levels were not significantly different between the model and treatment groups (1.03±0.33 vs. 0.98±0.37 and 1.05±0.28 vs. 0.98±0.19), respectively (P>0.05), but p?IGF?1R and p?PI3K protein expression levels had significant differences between the two groups (1.08±0.10 vs. 0.51± 0.08 and 1.12±0.09 vs. 0.86±0.09), respectively (P<0.01 for both). Conclusions The IGF?1R inhibitor can effectively inhibit the formation of malignant pleural effusion. Its mechanism may be related to the suppression of tumor cell proliferation, invasion and angiogenesis through inhibition of PI3K signaling. TAE226 treatment may be a potential therapeutic regimen of treating malignant pleural effusion.