Aurora-A has attracted a great deal of interest as a potential therapeutic target for patients with CRC. However, the outcomes of inhibitors targeting Aurora-A are not as favorable as expected, and the basis behind the ineffectiveness remains unknown. Here, we found that signal transducer and activator of transcription 1 (STAT1) was highly expressed in colorectal cancer (CRC) xenograft mouse models that were resistant to alisertib, an Aurora-A inhibitor. Unexpectedly, we found that alisertib disrupted Aurora-A binding with ubiquitin-like with plant homeodomain and ring finger domain 1 (UHRF1), leading to UHRF1 mediated ubiquitination and degradation of DNA methyltransferase 1 (DNMT1), which in turn resulted in demethylation of CpG islands of STAT1 promoter and STAT1 overexpression. Simultaneous silencing Aurora-A and UHRF1 prevented STAT1 overexpression and effectively inhibited CRC growth. Hence, concomitant targeting Aurora-A and UHRF1 can be a promising therapeutic strategy for CRC.
Abstract Introduction HIV incidence among men who have sex with men ( MSM ) is high in China. Pre‐exposure prophylaxis (Pr EP ) is a promising mean to prevent HIV transmission but it is not widely available in China. We conducted a large Internet‐based online survey to assess the willingness of Chinese MSM to take Pr EP and associated factors to their uptake preferences. Methods Between 19 January and 6 February, 2017, 4581 MSM aged over 15 years were recruited via a social networking app to take an online Pr EP survey. HIV status at the time of the survey being conducted was not one of recruitment criteria. Participants were asked if they had heard of Pr EP , if they had concerns about Pr EP , and if they would be ready to uptake Pr EP should it be provided. When asked if participants were willing to take Pr EP , they were asked to select from the following responses: “definitely not,” “probably not,” “not sure,” “probably yes,” and “definitely yes.” In the final analysis, we grouped these five‐level Likert scale responses into three‐level responses as “definitely yes,” “probably yes,” and “no (definitely not/probably not/not sure).” Descriptive analysis and multinomial logistic regressions were conducted to assess the associations of Pr EP adoption readiness and uptake concerns with HIV risk behaviours and demographic characteristics. Results MSM from 33 geographical regions of China participated in the survey. The majority were younger than 25 (65.2%) and had attended college (68.6%). HIV prevalence was high (6.8%) and 43.3% reported a history of unprotected anal sex. Only 22.4% of participants had heard of Pr EP . When asked if they would uptake Pr EP , 26.0% said “definitely yes,” 49.6% were “probably yes,” and 24.4% said “no.” Pr EP adoption readiness was associated with having previously heard of Pr EP and expressing concerns about accessibility and cost. Worries about side effects, low perceived HIV risk, preference for condoms, and never having received HIV testing were negatively associated with Pr EP uptake willingness. Conclusion Young and well‐educated Chinese MSM reported a low willingness to uptake Pr EP despite being high‐risk for HIV . Effective education, especially through online mediums, will be critical to optimize this group's Pr EP uptake.
More than 99% of ovarian follicles undergo atresia in mammals, but the mechanism of follicular atresia remains to be elucidated. In this study, we explored microRNA (miRNA) regulation of follicular atresia in porcine ovary. A miRNA expression profile was constructed for healthy, early atretic, and progressively atretic follicles, and the differentially expressed miRNAs were selected and analyzed. We found that miR-26b, which was upregulated during follicular atresia, increased the number of DNA breaks and promoted granulosa cell apoptosis by targeting the ataxia telangiectasia mutated gene directly in vitro.
To study the illness cognition and related factors in patients with prostate cancer (PCa).Using the convenience-sampling method, we selected 231 PCa patients treated in a general hospital in Xuzhou from October 2019 to October 2020. We conducted a cross-sectional study of the cases based on the general data of the patients and their scores on the Illness Cognition Questionnaire (ICQ).The PCa patients showed a high negative and a low positive illness cognition. The ICQ scores of the patients were high on "helplessness" (13.70 ± 3.54) and low on "acceptance" (16.64 ± 3.37) and "perceived benefits" (13.93 ± 3.76). Age, disease duration, disease stage and number of children were the four factors included in the regression equation of the participants' illness cognition.Negative illness cognition is high in PCa patients, higher in those at a younger age, with a longer disease duration, or with more than one child than in those at an older age, with a shorter disease duration, or with only one or no child.
Abstract Background To evaluate the effect of placental location on the severity of placenta accreta spectrum (PAS). Methods We analyzed 390 patients with placenta previa combined with placenta accreta spectrum who underwent cesarean section between January 1, 2014 and December 30, 2020 in the electronic case database of the Second Hospital of Hebei Medical University. According to the position of the placenta, 390 placentas were divided into the posterior group ( n = 89), the anterior group ( n = 60) and the non-central group ( n = 241). Results The history of cesarean delivery rates in the anterior group (91.67%) and the non-central group (85.71%) were statistically different from the posterior group (63.74%)( P < 0.001). Univariate logistic regression results showed that employment, urban living, gestational age, complete placenta previa, fetal presentation shoulder, gravidity, cesarean section and vaginal delivery were all predictors for the severity of placenta accreta ( P < 0.05). The anterior group ( P = 0.001, OR = 4.13, 95%CI: 1.84–9.24) and the non-central group ( P = 0.001, OR = 2.90, 95%CI: 1.55–5.45) had a higher incidence of invasive accreta placentation than the posterior group, and were independent risk factors for invasive accreta placentation. Conclusion Compared with posterior placenta, anterior and non-central placenta are independent risk factors for invasive PAS in patients with placenta previa, during which we should be more cautious in treatment.
Intratumoral tumor-specific activated CD8+ T cells with functions in antitumor immune surveillance predict metastasis and clinical outcome in human colorectal cancer. Intratumoral CD8+ T cells also affect treatment with immune checkpoint inhibitors. Interestingly, inhibition of Aurora kinase A (Aurora-A) by its selective inhibitor alisertib obviously induced infiltration of CD8+ T cells. However, the mechanisms by which inhibition of Aurora-A promotes infiltration of intratumoral CD8+ T cells remain unclear. Our recent results demonstrated that conditional deletion of the AURKA gene or blockade of Aurora-A by alisertib slowed tumor growth in association with an increase in the infiltration of intratumoral CD8+ T cells as well as the mRNA levels of their IL10 receptor α (IL10Rα). The antitumor effects of targeting Aurora-A were attenuated in the absence of CD8+ T cells. In addition, antibody-mediated blockade of IL10Rα dramatically decreased the percentage of intratumoral CD8+ T cells. In further experiments, we found that the levels of IL10 were elevated in the serum of azoxymethane/dextran sodium sulfate-treated AURKAflox/+;VillinCre+ mice. Unexpectedly, we found that in addition to Aurora-A's mitotic role, inhibition of Aurora-A elevated IL10 transcription, which in turn increased the IL10Rα mRNA levels in CD8+ T cells. Thus, inhibition of Aurora-A could be a useful treatment strategy for recruiting tumor-specific intratumoral CD8+ T cells. IMPLICATIONS: Understanding the mechanisms by which inhibition of Aurora-A promotes CD8+ T-cell infiltration and activation, as mediated by the IL10 pathway could provide a potential strategy for tumor immunotherapy.
To explore the effect of family-centered psychological support (FCPS) on illness cognition and quality of life in patients with advanced prostate cancer (PCa).Using a randomized controlled study design, we divided 84 advanced PCa patients into an intervention group and a control group, all provided with PCa-related knowledge and answers to their questions, while the former group with FCPS in addition. Before, immediately after and at 1 and 3 months after intervention, we evaluated the effectiveness using the Illness Cognition Questionnaire (ICQ) and Functional Assessment of Cancer Therapy － Prostate (FACT-P).Totally, 78 of the patients completed the whole intervention procedure, 38 in the intervention and 40 in the control group. There were statistically significant differences between the intervention and control groups in the scores on the three factors of ICQ acceptance (17.89 ± 3.86 vs 15.20 ± 2.83, t = 3.528, P < 0.05), perceived benefits (18.68 ± 3.02 vs 17.08 ± 2.74, t = 2.465, P < 0.05) and helplessness (13.37 ± 3.00 vs 15.63 ± 3.11, t = －3.259, P < 0.05) immediately after intervention, and so were there at 1 and 3 months after intervention (P < 0.05). The patients in the intervention group showed remarkably higher quality of life scores than the controls immediately after (100.59 ± 11.66 vs 92.20 ± 9.54, t = 7.943, P < 0.05) and at 1 month (93.03 ± 13.33 vs83.55 ± 14.29, t = 3.481, P < 0.05) and 3 months after intervention (85.66 ± 17.39 vs 75.95 ± 16.66, t = 3.025, P < 0.05). The covariance analysis found that, excluding the time effect, FCPS significantly improved the positive illness cognition of the patients (P < 0.05).Family-centered psychological support contributes to the positive illness cognition of the patients with advanced PCa and helps improve their quality of life, and therefore deserves to be popularized in clinical practice.
Objective: To understand the cognition and related factors on the use of HIV non-occupational post-exposure prophylaxis (nPEP) among men who have sex with men (MSM). Methods: The snowballing method was applied to recruit research subjects who were ≥18 years old, had sex with men in the past three months, and were aware of nPEP in MSM groups in Beijing, Shenzhen, and Kunming from March 15 to April 14, 2019. Data on social demographics, behavioral characteristics, basic knowledge of nPEP, consultation, and using nPEP were collected through "i guardian Platform". The logistic regression model was used to analyze the related factors affecting the use of nPEP. Results: Among 1 809 investigated, 39.8% (720 persons) were aware of the basic knowledge of nPEP, 33.4% (605 persons) had consulted nPEP, and 15.0% (271 persons) had used nPEP. In addition, multivariate logistic regression analysis showed that factors as whether to have sex with men infected with HIV in the last three months (OR=2.58, 95%CI: 1.64-4.07), the frequency of HIV testing in the past year (OR=2.47, 95%CI: 1.28-5.11), nPEP knowledge awareness (OR=0.70, 95%CI: 0.49-0.99), whether to consult nPEP (OR=70.98, 95%CI: 40.51-136.83) were related to the use of nPEP. Conclusions: MSM still have poor cognition of nPEP. It is necessary to strengthen the publicity and education of nPEP in MSM and promote the use of nPEP after HIV exposure as soon as possible.目的： 了解MSM对HIV非职业暴露后预防（nPEP）的认知情况，以及使用nPEP的相关因素。 方法： 2019年3月15日至4月14日，采用滚雪球抽样方法，分别在北京市、深圳市和昆明市MSM社会组织招募年龄≥18岁男性、最近3个月发生过男男性行为、听说过HIV nPEP等符合条件的研究对象，通过“i卫士”收集人口学、行为学特征、nPEP基本知识及其咨询和使用情况。采用logistic回归模型对是否使用nPEP的相关因素进行分析。 结果： 共调查1 809人，nPEP基本知识知晓率为39.8%（720/1 809），33.4%（605/1 809）咨询过nPEP，15.0%（271/1 809）使用过nPEP。多因素logistic回归分析结果显示，研究对象使用nPEP的相关因素包括最近3个月与男性HIV感染者发生过性行为（OR=2.58，95%CI：1.64~4.07）、最近1年HIV检测次数≥2次（OR=2.47，95%CI：1.28~5.11）、nPEP基本知识知晓（OR=0.70，95%CI：0.49~0.99）、咨询过nPEP（OR=70.98，95%CI：40.51~136.83）。 结论： MSM对nPEP认知不足，应加强MSM的nPEP相关宣传教育，促进MSM发生HIV暴露后尽快使用nPEP。.
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