The heterogeneity and clonal evolution analysis of the advanced prostate cancer with castration resistance.

BACKGROUND: Nowadays, the incidence rate of advanced and metastatic prostate cancer at the first time of diagnosis grows higher in China yearly. At present, androgen deprivation therapy (ADT) is the primary treatment of advanced prostate cancer. However, after several years of ADT, most patients will ultimately progress to castration-resistant prostate cancer (CRPC). Previous studies mainly focus on Caucasian and very few on East Asian patients. METHODS: In this study, the pre- and post-ADT tumor samples were collected from five Chinese patients with advanced prostate cancer. The whole-exome sequencing, tumor heterogeneity, and clonal evolution pattern were analyzed. RESULTS: The results showed that the gene mutation pattern and heterogeneity changed significantly after androgen deprivation therapy. Tumor Mutational Burden (TMB) and Copy Number Alteration (CNA) were substantially reduced in the post-treatment group, but the Mutant-allele tumor heterogeneity (MATH), Socio-Demographic Index (SDI), Intratumor heterogeneity (ITH), and weighted Genome Instability Index (wGII) had no significant difference. According to the clone types and characteristics, the presence of main clones in five pre-and post-treatment samples, the clonal evolution pattern can be further classified into two sub-groups (the Homogeneous origin clonal model or the Heterogeneous origin clonal model). The Progression-free survival (PFS) of the patients with the "Homogeneous origin clonal model" was shorter than the "Heterogeneous origin clonal model". The longer PFS might relate to MUC7 and MUC5B mutations repaired. ZNF91 mutation might be responsible for resistance to ADT resistance. CONCLUSION: Our findings revealed potential genetic regulators to predict the castration resistance and provide insights into the castration resistance processes in advanced prostate cancer. The crosstalk between clonal evolution patterns and tumor microenvironment may also play a role in castration resistance. A multicenter-research including larger populations with different background are needed to confirm our conclusion in the future.

Increase in age at onset of moyamoya disease in China over 25 years.

BACKGROUND: To explore whether the age at onset (AAO) of Chinese patients with moyamoya disease (MMD) increased over time due to a reduced exposure to leptospiral infection. METHODS: We performed an independent, multicenter, retrospective study based on data from patients with MMD who initially attended four tertiary hospitals in Hubei, China, from 1996 to 2020. After stratifying the year of MMD onset into five periods (1996-2000, 2001-2005, 2006-2010, 2011-2015, and 2016-2020), we analyzed the temporal trends in AAO and compared different classes of AAO (early-onset, < 20 years; intermediate-onset, 20-49 years; late-onset, ≥ 50 years) in each period. RESULTS: We included 1858 patients in this study, with 878 women and 980 men. Their median (IQR) AAO was 47 (39-55) years. The case AAO significantly increased at the rate of 0.94 years per year (r = 0.406, p < .0001), while no trend was observed in birth years through time (p = .512). The birth cohorts who grew up in the leptospirosis epidemic years was stably susceptible to MMD. The median (IQR) AAO has increased significantly from 26 (14-37) years (1996-2000) to 51 (43-57) years (2016-2020) (p < .0001). The proportion of early-onset MMD was significantly higher in 1996-2000 (33.3%, p < .0001) and 2001-2005 (10.4%, p < .001). The AAO shows an aging trend that the proportion of late-onset MMD went from 4.5% (2001-2005) to 54.5% (2016-2020) (p < .0001). CONCLUSIONS: The AAO of MMD was increasing during a recent 25-year period in China, which may reflect a birth cohort effect that resulted from environmental changes. The disparity risk of birth cohorts with MMD changed with leptospirosis epidemics, suggesting leptospiral exposure might be a potential risk factor.

An ecological comparison study on the causal association between leptospirosis and moyamoya disease in Hubei, China, 2017-2019.

OBJECTIVE: The importance of environmental factors (especially leptospirosis) of moyamoya disease (MMD) has not been clarified. Here we investigated the epidemiological characteristics of MMD in Hubei province, China. METHODS: We conducted a population-based study to describe the epidemiologic characteristics of MMD in Hubei province between 2017 and 2019. The regional clusters of the hot spots (high incidence) and cold spots (low incidence) of MMD were identified using the spatial statistical method. To evaluate the role of leptospirosis in MMD, we performed an ecological comparison study to evaluate whether the socioeconomic and environmental variables of hot spots are more suitable for leptospirosis spread. RESULTS: The average annual sex and age adjusted incidence of MMD was 3.07 per 100,000 person-years from 2017 to 2019. The middle-aged had apparently higher incidence of MMD than the children. There existed an obvious geographic distribution difference of MMD at county level. The hot spots were identified mainly in the low mountainous and hilly terrain, while cold spots were located in the Jianghan Plains. Compared to cold spots, the hot spots had larger cattle density (32.0 vs 3.1, p = 0.002), higher percentages of rice field (85.6% vs 47.0%, p = 0.007), and lower elevation (33.6 vs 157.4, p < 0.001) CONCLUSIONS: There exists geographic distribution difference of MMD in Hubei province and was likely to be caused by leptospirosis in the early years. The MMD in China is dominant by middle-aged adults, which might be driven from leptospirosis outbreaks in the last century.

Joint embedding VQA model based on dynamic word vector.

The existing joint embedding Visual Question Answering models use different combinations of image characterization, text characterization and feature fusion method, but all the existing models use static word vectors for text characterization. However, in the real language environment, the same word may represent different meanings in different contexts, and may also be used as different grammatical components. These differences cannot be effectively expressed by static word vectors, so there may be semantic and grammatical deviations. In order to solve this problem, our article constructs a joint embedding model based on dynamic word vector-none KB-Specific network (N-KBSN) model which is different from commonly used Visual Question Answering models based on static word vectors. The N-KBSN model consists of three main parts: question text and image feature extraction module, self attention and guided attention module, feature fusion and classifier module. Among them, the key parts of N-KBSN model are: image characterization based on Faster R-CNN, text characterization based on ELMo and feature enhancement based on multi-head attention mechanism. The experimental results show that the N-KBSN constructed in our experiment is better than the other 2017-winner (glove) model and 2019-winner (glove) model. The introduction of dynamic word vector improves the accuracy of the overall results.

Endoscopic-assisted surgery versus microsurgery for pineal region tumors: a single-center retrospective study.

Pineal region tumors are extremely deep-seated and surgically challenging. The exposure and visualization obtained by microscopic surgery are relatively limiting. The application of high-definition endoscopes has recently provided neurosurgeons with a much more magnified and clearer view of the anatomy in the pineal region. The present study was performed to compare endoscopic-assisted surgery (ES) with microsurgery (MS) for pineal region tumors. We retrospectively analyzed patients admitted to our hospital for treatment of pineal region tumors from January 2016 to June 2019. All patients consented to undergo tumor resection with ES or MS. We compared the extent of resection, postoperative rate of hydrocephalus, complications, and outcomes between the two groups to estimate the safety and efficacy of ES. In total, 41 patients with pineal region tumors were divided into 2 groups: the ES group (n = 20) and MS group (n = 21). The rate of gross total resection was significantly higher in the ES than MS group (90.0% vs. 57.1%, p = 0.04). The rate of postoperative hydrocephalus was significantly lower in the ES than MS group (11.8% vs. 52.9%, p = 0.03). No significant differences were found in complications or the Karnofsky Performance Score between the two groups. ES can be used to safely and effectively achieve complete resection of pineal region tumors. In patients with obstructive hydrocephalus, ES provides a new way to directly open the aqueduct for cerebrospinal fluid recovery following tumor resection.

Intracerebral hemorrhage cadaver model for training in hematoma evacuation under endoscopy.

Neuroendoscopic surgery has been performed as an effective method for intracerebral hemorrhage (ICH). This study describes the know-how of constructing the ICH cadaver model and the training on the main neuroendoscopic procedures for ICH. During the training, operation time of twenty trainees in main stages of craniotomy and corticotomy (stage 2), and hematoma evacuation under endoscopy (stage 3) was recorded. To distinguish factors influencing trainees' surgical proficiency, operation time was calculated according to seniority, experience in neuroendoscopic surgery and training sequence. Questionnaire about validity of model was conducted eventually. Ten ICH cadaver models with bilateral hematoma were constructed. Seven trainees worked with seniority >5 years and eleven had experience in neuroendoscopic surgery. Operation time ranged from 20.6 to 33.4 min in stage 2 and 18.5 to 24.9 min in stage 3. In stage 2, less operation time was needed for trainees with seniority >5 years comparing to trainees with seniority ≦5 years (22.56 ±â€¯1.29 vs 29.25 ±â€¯3.02 min, p < 0.01). In stage 3, significant difference of operation time was found between trainees with experience in neuroendoscopic surgery and trainees without the experience (20.08 ±â€¯1.22 vs 22.02 ±â€¯1.82 min, p = 0.014), and the same between trainees in latter group and in former group (19.75 ±â€¯0.80 vs 22.54 ±â€¯1.45 min, p < 0.01). Questionnaire feedback proved high degree of satisfaction about the training model. Therefore, the ICH cadaver model can assist neurosurgeons with neuroendoscopic treatment learning sessions. Simulation and improvement in neuroendoscopic surgical techniques for ICH treatment were possible with the help of ICH cadaver model.

Effects of carbohydrate sources on biosorption properties of the novel exopolysaccharides produced by Arthrobacter ps-5.

The crude exopolysaccharides (EPSs) were obtained from Arthrobacter ps-5 fermentation using various carbohydrate sources followed by centrifugation, ethanol precipitation, and the isolated EPSs were further deproteinized and lyophilized. Carbohydrates from various sources resulted in different yield of EPSs from the fermentation and different molecular weight of EPSs. A maximum yield of 0.27 mg/g was achieved by using the culture medium supplemented with sucrose. The EPS produced by glucose-supplemented medium had the maximum content of acidic polysaccharides, subsequently presented the highest biosorption capacity for Cu(2+) and Pb(2+) at 257.9 mg/g and 331.8 mg/g, respectively. The ratio of acidic to neutral polysaccharides presented in EPSs was a key factor to explicate the biosorption mechanism, the higher the ratio, the stronger the biosorption capacity.