BACKGROUND:The status of BRCA1/2 genes plays a crucial role in the treatment decision-making process for multiple cancer types. However, due to high costs and limited resources, a demand for BRCA1/2 genetic testing among patients is currently unmet. Notably, not all patients with BRCA1/2 mutations achieve favorable outcomes with poly (ADP-ribose) polymerase inhibitors (PARPi), indicating the necessity for risk stratification. In this study, we aimed to develop and validate a multimodal model for predicting BRCA1/2 gene status and prognosis with PARPi treatment. METHODS:We included 1695 slides from 1417 patients with ovarian, breast, prostate, and pancreatic cancers across three independent cohorts. Using a self-attention mechanism, we constructed a multi-instance attention model (MIAM) to detect BRCA1/2 gene status from hematoxylin and eosin (H&E) pathological images. We further combined tissue features from the MIAM model, cell features, and clinical factors (the MIAM-C model) to predict BRCA1/2 mutations and progression-free survival (PFS) with PARPi therapy. Model performance was evaluated using area under the curve (AUC) and Kaplan-Meier analysis. Morphological features contributing to MIAM-C were analyzed for interpretability. RESULTS:Across the four cancer types, MIAM-C outperformed the deep learning-based MIAM in identifying the BRCA1/2 genotype. Interpretability analysis revealed that high-attention regions included high-grade tumors and lymphocytic infiltration, which correlated with BRCA1/2 mutations. Notably, high lymphocyte ratios appeared characteristic of BRCA1/2 mutations. Furthermore, MIAM-C predicted PARPi therapy response (log-rank p < 0.05) and served as an independent prognostic factor for patients with BRCA1/2-mutant ovarian cancer (p < 0.05, hazard ratio:0.4, 95% confidence interval: 0.16-0.99). CONCLUSIONS:The MIAM-C model accurately detected BRCA1/2 gene status and effectively stratified prognosis for patients with BRCA1/2 mutations.

Efficient isolation and sensitive quantification of Pseudomonas aeruginosa (P. aeruginosa) are crucial for identifying intrauterine infections and preventing the occurrence of intrauterine adhesion (IUA). However, traditional approaches, such as culture-based approach, are time-consuming. Herein, we constructed a detection scaffold by using primer exchange reaction (PER) that integrated the low-speed centrifugation–based isolation and sensitive quantification of target pathogenic bacteria. The established approach possesses several advantages, including (i) the approach is capable of simultaneous isolation and sensitive quantification of target bacteria; (ii) low-speed centrifugation or even manual equipment could be used to isolate target bacteria; and (iii) a low limit of detection was obtained as 54 cfu/mL. Based on this, the approach is a promising approach in analyzing P. aeruginosa from uterine secretions with IUA.

Chemoresistance is a common problem in cancer treatment, and circular RNA (circRNA) has been found to be associated with the progression of chemoresistance in cancer. However, the role and mechanism of circRNA centrosomal protein 128 (circ-CEP128) in the chemoresistance of cervical cancer (CC) are still unclear. The expression of circ-CEP128, microRNA (miR)-432-5p, and myeloid cell leukemia-1 (MCL1) was measured by quantitative real-time PCR. The paclitaxel resistance of cells was assessed using MTT assay. Cell proliferation, apoptosis, migration, and invasion were determined using MTT assay, colony formation assay, flow cytometry, and transwell assay. The protein levels of metastasis markers and MCL1 were examined using western blot analysis. Mice xenograft models were constructed to assess the effect of circ-CEP128 silencing on CC tumor growth and paclitaxel sensitivity. The interaction between miR-432-5p and circ-CEP128 or MCL1 was confirmed by dual-luciferase reporter assay and RIP assay. Circ-CEP128 had highly expression in CC tumor tissues and cells. Silencing of circ-CEP128 could enhance the paclitaxel sensitivity of CC cells by decreasing cell growth, migration, and invasion. Also, knockdown of circ-CEP123 reduced CC tumor growth and promoted the paclitaxel sensitivity of CC tumors. MiR-432-5p was found to be sponged by circ-CEP128, and its inhibitor could reverse the promoting function of circ-CEP128 silencing on the paclitaxel sensitivity of CC cells. Additionally, MCL1 was a target of miR-432-5p, and circ-CEP128 could sponge miR-432-5p to regulate MCL1. Besides, overexpressed MCL1 also could reverse the enhancing effect of miR-432-5p on the paclitaxel sensitivity of CC cells. In conclusion, the present study showed that circ-CEP128 silencing could increase the paclitaxel sensitivity of CC by regulating the miR-432-5p/MCL1 axis.

BACKGROUND:and purpose:Intrauterine adhesion (IUA) and re-adhesion were common problems in women of childbearing age. The aim of our research was to evaluate the efficacy of hyaluronic acid gel on preventing IUA and improving the fertility.METHODS:A systematic search for randomized controlled trial (RCT) articles that tested the effectiveness of using hyaluronic acid gel during intrauterine surgery in prevention of IUA and improvement of fertility was performed in PubMed, Medline, Embase, the Cochrane Library and clinicaltrials.gov until December 2020. Data were extracted independently and analyzed using RevMan statistical software version 5.3.RESULTS:Twelve articles (11 studies) were deemed eligible for inclusion. There was a significantly reduced proportion of IUA after using hyaluronic acid gel during intrauterine operation (OR 0.39, 95% CI 0.29 to 0.52). It has significantly reduced the incidence of moderate-to-severe IUA after using hyaluronic acid gel, but no effect on the mild IUA. In addition, our analysis showed that the hyaluronic acid gel group was associated with a significant increased incidence of pregnancy (OR 1.64, 95% CI 1.08 to 2.50).CONCLUSION:Our analysis confirmed that using hyaluronic acid gel during intrauterine operation seemed to be more helpful for patients with high risk of IUA. However, larger and well-designed studies would be desired in the future to confirm its efficacy and safety in protecting fertility.

Objective To investigate the role of ski-related novel protein N (SnoN) in the pathogenesis of intrauterine adhesion (IUA) and its association with transforming growth factor-β1 (TGF-β1) and Smad4 in endometrial tissue in IUA patients. Methods Endometrial tissues of 20 severe IUA patients (sIUA group) and 20 healthy women with uterine septum (control group) were collected from our 2 departments during January 2019 and October 2020. Immunohistochemical assay, Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression of SnoN, TGF-β1 and Smad4 in the endometrial tissue of the control and sIUA groups. The correlations of their expression levels in the endometrial tissues were analyzed with Spearman rank correlation analysis to investigate the association of the levels and IUA. Results The expression levels of TGF-β1 and Smad4 were significantly higher, while that of SnoN was obviously lower in the sIUA group than the control group (all P < 0.01). In the endometrial tissues from the sIUA group, the expression of Smad4 was positively correlated with that of TGF-β1 (r=0.468 9, P < 0.05). However, the TGF-β1 expression was negatively correlated with that of SnoN (r=-0.483 5, P < 0.05). Conclusion SnoN may be involved in the pathogenesis of IUA via the TGF-β1/Smad4 signal pathway.

生长停滞特异性蛋白6(growth arrest specific protein 6,GAS6)在肿瘤发生发展中发挥重要作用,其信号转导参与细胞增殖、黏附与迁移,但它在子宫内膜异位症(endometriosis,EMs)的相关功能及分子机制尚不明确.本研究从GEO数据库检索并下载子宫内膜异位症相关转录物组数据集,并对其进行GEO在线分析,筛选差异表达基因并进行GO聚类和KEGG通路富集分析.利用10例无内异症且无明确疾病妇女的在位子宫内膜,以及11例卵巢巧克力囊肿病人异位子宫内膜,对3个以上数据集共有的差异基因的mRNA水平进行实时荧光定量PCR验证.在子宫内膜异位症临床样本中,采用免疫组化、实时荧光定量PCR验证关键调控因子GAS6及上皮间充质转化(epi-thelial mesenchymal transition,EMT)标记基因的表达水平,并利用免疫荧光对GAS6和E-钙黏着蛋白(E-cadherin)进行共标.研究发现:从4个转录物组数据集中共筛选出47个差异表达基因,其主要富集于细胞迁移等过程以及MAPK、PI3K-AKT、紧密连接等相关信号通路.3个以上数据集所共有的9个差异基因在子宫内膜异位症病人中的mRNA水平均符合生物信息学分析的结果.GAS6在子宫内膜异位症病人异位内膜中的表达水平高于对照组(P＜0.05),并且子宫内膜异位症病人的内膜组织中存在EMT现象,EMT的标志物E-钙黏着蛋白表达水平下调(P＜0.05)、波形蛋白(vimentin)表达水平上调(P＜0.01).在GAS6高表达的子宫内膜异位症患者异位子宫内膜腺上皮细胞中,E-cadherin显示低表达,提示GAS6可能在子宫内膜异位症中介导EMT过程.综上所述,本研究初步揭示GAS6在子宫内膜异位症病人中高表达,及其可能介导EMT过程参与子宫内膜异位症的发生与发展,为子宫内膜异位症的临床治疗提供潜在靶标.

A 31-year-old woman was admitted for a presumed intramural pregnancy at approximately 7 weeks’ gestation. She denied any history of surgery or dysmenorrhea.

Objective To analyze the difference of the delivery date reckoned by traditional and modified formula for calculating the expected date of confinement (EDC).Methods The data of 2055 women (37-41+6 week) were collected who gave monotocousa term spontaneous birth in the Chongqing Health Center for Women and Children from Jan.2014 to Feb.2015.Of which 1300 were primipara,and 755 were multipara;and the data of 1224 women (39-41week) were collected,of which 832 were primipara,and 392 were multipara.The expected date was calculated with traditional and modified calculating formula,and then the actual delivery date was used for comparison and statistical analysis.Results The coincidence of actual delivery date with the estimated due date reckoned by traditional formula (39-41week) was 8.4％ in primipara and 9.7％ in multipara,and the coincidence reckoned by modified formula was 11.9％ in primipara and 14.8％ in multipara.The EDC estimated by modified formula was more precise than that calculated by traditional formula (P＜0.05).Conclusion The EDC calculated with modified formula is more accurate than that calculated with traditional formula.

子痫前期（pre-eclampsia, PE）是严重威胁孕产妇和胎儿健康的产科疾病，其发病机制至今未明。研究表明，PE孕妇胎盘组织中Rho相关蛋白激酶（rho associated protein kinase，ROCK）表达水平显著上调[1]，提示ROCK蛋白可能参与子痫前期的发病过程，ROCK蛋白属丝氨酸/苏氨酸蛋白激酶家族成员，是Rho蛋白的下游靶效应分子。ROCK蛋白具有两种亚型，即ROCKⅠ和ROCKⅡ，两种亚型的序列同源性达到64％，在激酶活性区域达到89％，两种亚型在正常及PE孕妇的胎盘组织中均有表达[2]。ROCK蛋白主要调节细胞形状以及运动、分泌、增殖、分化、凋亡等细胞功能[3]。近年来研究认为，PE发病与胎盘缺氧有关，缺氧是PE发病的关键因素，但是低氧状态下ROCK蛋白的变化及其作用目前尚不清楚。本研究通过观察低氧状态下正常孕妇胎盘组织ROCK蛋白表达的变化，进一步明确低氧对胎盘组织中ROCK蛋白表达的影响。

Increased circulating syncytiotrophoblast microparticles (STBMs) are often associated with preeclampsia (PE) but the molecular mechanisms regulating STBM shedding remain elusive. Experimental evidence has shown that actin plays a key role in STBM shedding and that Rho/ROCK is important in regulating actin rearrangement. To investigate the role of RhoB/ROCK-regulated actin arrangement in STBM shedding in PE, chorionic villous explants were prepared from placenta of patients with normotensive or PE pregnancies and BeWo cells were fused to imitate syncytiotrophoblasts. The oxygen–glucose deprivation (OGD) conditions were applied to imitate the pathophysiology of PE in vitro. The results showed that RhoB and ROCK were activated in the preeclamptic placenta, accompanied by increased actin polymerization and decreased outgrowing microvilli. In villous tissue cultures or BeWo cells, OGD activated RhoB, ROCK1 and ROCK2 and promoted STBM shedding and actin stress fibers formation. In BeWo cells, RhoB overexpression activated ROCK1 and ROCK2, leading to F-actin redistribution and STBM shedding and the OGD-induced actin polymerization and STBM shedding could be reversed by RhoB or ROCK knockdown. These results reveal that RhoB and ROCK play a key role in PE by targeting STBM shedding through actin rearrangement and that RhoB/ROCK intervention may be a potential therapeutic strategy for PE.

With the development of science and medicine,human qualities,knowledge and ability made more demands for the military medical personnel's knowledge,ability and quality structure.This paper analyzes contemporary humanistic quality of military medical students and the necessity of educational and puts forward some concrete measures of promoting the humanistic quality education in the military medical students.

Objective To study the relationship between syncytiotrophoblast microvillous membrane (STBM) shedding in severe preeclampsia (sPE) and placenta Rho/ROCK molecule expression. Methods In this study, placenta tissue of 20 sPE lying-in women (sPE group) and 20 normal lying-in women (control group) were collected. The syncytiotrophoblast microvillous structure of the placenta tissue was scrutinized with transmission electron microscope (TEM). The microvillous numerical density (Nv), surface density (Sv), and volume density (Vv) of the cell surfaces were analyzed with stereology method. Western blotting and immunohistochemistry were used to detect the expression of Rho subfamily proteins (RhoA, RhoB, RhoC) and Rho kinases (ROCKI, ROCKII) in the placenta tissues. The correlation of the expression of Rho, ROCK proteins, and the shedding of STBM was examined with Spearman rank correlation analysis. Results The Nv, Sv, and Vv of the syncytiotrophoblast microvillous membranes in sPE group were significantly less than those of the control group (P < 0.05). Compared with the control group, the expression levels of RhoA, RhoB, ROCKI, and ROCKII proteins in sPE group were noticeably elevated (P < 0.05). In sPE group, the expressions of RhoB, ROCKI, and ROCKII proteins were positively correlated with the shedding of STBM (r=0.631, r=0.826, r=0.865, P < 0.05). Conclusion The signaling pathways constituted by RhoB and its downstream molecules ROCKI/ROCKII, may play an important regulatory role in the upregulation of STBM shedding in sPE.

Objective: To investigate the expression of RhoB and ROCK in severe preeclampsia and explore its clinical implication.Methods: Western blotting and immunohistochemical staining methods were used to detect the expression of Rho proteins(RhoB,RhoC)and kinase ROCK(ROCKI,ROCKII)in the placenta tissue including 20 severe preeclampsia pregnancy patients and 20 healthy pregnant women as control group.The correlation of the expression of RhoB,RhoC and ROCKI,ROCKII were analyzed Spearman rank correlation analysis.Results: RhoB,ROCKⅠand ROCK II were more abundant in the placenta tissue of the severe preeclampsia than in the normal placent(P0.05).In severe preeclampsia group,the expression of RhoB and ROCKI,ROCK II had positive relationship(r= 0.793,r=0.901,P0.05).Conclusion: Signaling pathway constituted RhoB and its downstream molecules ROCKI,ROCK II,may play essential role in severe preeclampsia.

<正>从传统医学教育转向现代医学教育是一项系统工程,成为21世纪医学教育改革的重要组成部分。科学发展观的引入,以人为本理念的推进,创新思维的拓展,对各类人才有了更高的要求。医学是生命科学重要的组成,医学人才不仅需要掌握医学专业知识,追踪前沿,具备良好的职业道德和高度的工作责任心,还需要具有良好的人文素质。目前普遍认为,加强医学生人文素质教育是培养新世纪人才的需要。把人文科学与高等医学教育相结合,以适应新形势对医学人才培养的新需要,已成为高等医学教育改革和发展的重要内容。

Objective To determine the expressions and the dynamic changes of Rho proteins(RhoA,RhoB and RhoC) and their kinase ROCK(ROCKⅠ and ROCKⅡ) in rat placenta at different stages of gestation.Methods A total of 20 pregnant female rats were randomly divided into 5 groups(n=4).Their placents were obtained when the rats were pregnant at 7,10,13,15,and 18 d respectively.Wet weight and diameter of the placenta were measured,and the number of the placenta was counted and recorded.The expression levels of RhoA,RhoB,RhoC,ROCKⅠ and ROCKⅡ were detected by immunohistochemical staining and Western blot analysis.Results With the increase of gestational period,the weight and diameter of the placenta were increased.The expression levels of RhoA and RhoC in 13,15,and 18 d of pregnant groups were significantly higher than those in 7 and 10 d of pregnant groups(P<0.01),but the expression of RhoB had no obvious difference among these groups(P>0.05).ROCKⅠ and ROCKⅡ in 18 d of pregnant group was expressed significantly higher than those in 7,10,13 and 15 d of pregnant groups(P<0.01).Conclusion The expression levels of RhoA,RhoC,ROCKⅠ and ROCKⅡ are increased in rat placental tissues with the elapse of pregnant period,but that of RhoB has no such significant change.These results indicate that Rho/ROCK signaling pathway may play an essential role in the development of placenta during normal pregnancy.