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Abstract Prostate cancer, one of the most prevalent malignancies among men worldwide, is intricately linked with androgen signaling, a key driver of its pathogenesis and progression. Understanding the diverse expression patterns of androgen-responsive genes holds paramount importance in unraveling the biological intricacies of this disease and prognosticating patient outcomes. In this study, utilizing consensus clustering analysis based on the expression profiles of androgen-responsive genes, prostate cancer patients from the TCGA database were stratified into two distinct subtypes, denoted as C1 and C2. Notably, the C1 subtype demonstrates a significant upregulation of certain genes, such as CGA and HSD17B12, along with a shorter progression-free survival duration, indicating a potentially unfavorable prognosis. Further analyses elucidated the immune infiltration disparities, mutation landscapes, and gene functional pathways characteristic of each subtype. Through integrated bioinformatics approaches and machine learning techniques, key genes such as BIRC5, CENPA, and MMP11 were identified as potential therapeutic targets, providing novel insights into tailored treatment strategies. Additionally, single-cell transcriptome analysis shed light on the heterogeneous expression patterns of these genes across different cell types within the tumor microenvironment. Furthermore, virtual screening identified candidate drugs targeting the BIRC5 receptor, offering promising avenues for drug development. Collectively, these findings deepen our understanding of prostate cancer biology, paving the way for personalized therapeutic interventions and advancing the quest for more effective treatments in prostate cancer management.

Abstract Data on prevalence of programmed death ligand-1 (PD-L1) expression and its correlation with tumor biomarkers in Chinese patients with muscle-invasive urothelial bladder cancer (MIUBC) are scarce. We investigated the prevalence of PD-L1 expression, PD-L1 expression in tumor cells (TC) and immune cells (IC), and its correlation with tumor biomarkers (CD8+ T cells and tumor mutation burden [TMB]) in Chinese patients with newly diagnosed MIUBC (NCT03433924). Of 248 patients enrolled, 229 with PD-L1 data available were analysed. High PD-L1 expression (≥ 25% of TC or IC with PD-L1 expression) was observed in 120 (52.4%) patients. 59 cases showed positive staining in ≥ 25% of TC, and 82 cases had positive staining in ≥ 25% of IC. High expression of CD8+ T cell and TMB (> 10 mutations/megabase) was observed in 44.5% and 54.1% patients, respectively. A positive correlation was observed between percentage of TC with membrane PD-L1 positivity and CD8+ T cells (0.34; P

Abstract. Background:. Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. Methods:. Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results:. A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk. Conclusions:. PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Summary: Photoacoustic imaging (PAI) with co-registered ultrasound (US) is a hybrid non-invasive imaging modality that enables visualization and quantification of tumor hypoxia in live animals. Here, using a breast tumor xenograft model as an example, we present a stepwise protocol describing animal preparation, positioning, instrument setup, and US-PAI image acquisition procedures. This protocol also guides through detailed data analysis, explains functional readouts obtained from PAI, and discusses the potential application of the technology to study the hypoxic tumor microenvironment.For complete details on the use and execution of this protocol, please refer to Dai et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Injuries to axons within the central nervous system (CNS) pose a substantial clinical challenge due to their limited regenerative capacity. This study investigates the therapeutic potential of Cell-free fat extract (CEFFE) in CNS injury. CEFFE was injected intravitreally after the optic nerve was crushed. Two weeks post-injury, quantification of regenerated axons and survival rates of retinal ganglion cells (RGCs) were performed. Subsequently, comprehensive gene ontology (GO) an-notation elucidated the cellular origins and functional attributes of CEFFE components. Molecular mechanisms underlying CEFFE’s therapeutic effects were explored through Western blotting (WB). Additionally, levels of inflammatory factors within CEFFE were determined using enzyme-linked immunosorbent assay (ELISA), and histological staining of microglia was conducted to assess its impact on neuroinflammation. CEFFE demonstrated a significant capacity to promote axon re-generation and enhance RGCs survival. GO annotation revealed the involvement of 146 proteins within CEFFE in axonogenesis and neurogenesis. WB analysis unveiled the multifaceted pathways through which CEFFE exerts its therapeutic effects. Elevated levels of inflammatory factors were detected through ELISA, and CEFFE exhibited a modulatory effect on microglial activation in the retinal tissue following optic nerve crush (ONC). The present study highlights the therapeutic promise of CEFFE in the management of CNS injuries, exemplified by its ability to foster axon regeneration and improve RGCs survival.

Bayesian network (BN) inference is an important statistical tool with additive symmetry. However, BN inference cannot deal with the uncertain, fuzzy, random, and conflicting information from experts’ knowledge in the process of conducting a risk assessment. To tackle this issue, a new fuzzy BN inference approach for risk assessments was proposed based on cloud model (CM), interval type-2 fuzzy set (IT2 FS), interval type-2 fuzzy logic system (IT2 FLS), modified Dempster–Shafer (D-S) evidence theory (ET), and Latin hypercube sampling (LHS) methods along the following lines. Firstly, CM was integrated into IT2 FS, and CM-based IT2 FS (CM-IT2 FS) was defined in the IT2 FLS. Secondly, modified D-S ET was utilized to determine the CM-IT2 FS-based a priori probabilities, and the CM-IT2 FS-based BN model was established. Thirdly, the CM-IT2 FS-based a priori probabilities were reduced to the CM-IT1 FS-based ones using a type reducer in the IT2 FLS, LHS was applied to propose a new fuzzy BN inference algorithm, and then, the new algorithm was used in a typical case to perform the fuzzy BN positive inference for risk prediction and the fuzzy BN reverse inference for risk sensitivity analysis. Finally, the BN inference results were analyzed using the proposed algorithm and the two common BN inference algorithms, and the effectiveness of the proposed approach was validated. It can be concluded that the proposed approach was both accurate and promising.

Background With the increase of the aging population, age-related health problems have garnered increasing attention. Compared to physiologic diseases with significant clinical symptoms, the mental health issues of the elderly are often overlooked. The underlying depressive states and high incidence of chronic diseases collectively contribute to a decline in quality of life in old age. Moreover, metabolic diseases, more prevalent in the elderly, significantly impact brain health, potentially leading to neurological damage and cognitive decline. Objective This study aims to investigate the relationship between depression, cognitive status, and nutritional and metabolic status among elderly individuals in the community. Methods We selected 3 767 elderly individuals who participated in physical examinations at the Youyi Street Community Health Service Center in Baoshan District, Shanghai. The demographic data on sex, age, BMI and waist-to-hip ratio were collected. The evaluations included the Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Mini Nutritional Assessment (MNA), and Activities of Daily Living Scale (ADL). Metabolic syndrome-related diseases and the 10-year cardiovascular disease risk were assessed using clinical metabolic indicators, and Pearson correlation analysis was used to explore the correlations among these indicators. Results This research showed that significant differences were found in age, MNA, MMSE scores, the proportion of people at high risk of cardiovascular disease and the 10-year cardiovascular disease risk grade among the different groups (P

Objective: The ancient classical Chinese formulation, Xie-Bai-San (XBS), was studied qualitatively and quantitatively, and its main components were characterized. Materials and Methods: The chemical compounds in XBS were identified using a combination of ultra-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry and molecular networking (MN) analysis. In addition, a multiple reaction monitoring (MRM) quantification method was established using ultra-high-performance liquid chromatography–triple quadrupole mass spectrometry. Mulberroside A, kukoamine B, liquiritin, and glycyrrhizic acid were quantitatively analyzed in ten batches of XBS using this method. Results: Using clusters of MN and databases, 91 compounds were rapidly identified, including stilbene glycosides, saponins, flavonoids, and alkaloids. Of these, 30, 33, and 28 compounds were from Mori Cortex, Lycii Cortex, and Glycyrrhizae Radix et Rhizoma, respectively. The MRM scanning mode was used for the simultaneous sensitive quantitative determination of multiple components in a wide range of complex samples. The four main components were quantified using this method, which has good linearity. Conclusions: This study provides a comprehensive and reliable method for the identification and quantitative analysis of XBS.

Background The academic value of the "Hu Line" has been extended to other related disciplines. Considering China's large population and obvious differences in distribution, this study draws on the research results of population geography to explore the population density and distribution criteria of the "Hu Line". Objective To investigate and analyze the current situation of health literacy and sedentary time among urban and rural high school students in the southeast and northwest halves of the "Hu Line", and to provide a basis for improving the physical and mental health of high school students in China. Methods A stratified cluster random sampling method was used to study the health literacy and sedentary time of freshmen and sophomores in 62 schools in 31 provinces (municipalities directly under the central government and autonomous regions) of China from January to March 2019 (12 400 questionnaires on health literacy and 12 400 questionnaires on sedentary time each were uniformly mailed and distributed in advance). Multiple linear regression models were used to analyze the coefficient of variance expansion, and after correcting for confounding factors, we analyzed the factors affecting the length of meditation time of high school students in the southeastern and northwestern halves of both sides of the "Hu Line". Results Finally, 9 057 health literacy questionnaires were included, of which 7 489 (82.7%) were from the southeast half of China and 1 568 (17.3%) from the northwest half of China, and 8 031 questionnaires on sedentary time were included, of which 6 614 (82.4%) were from the southeast half of China and 1 417 (17.6%) from the northwest half of China. Health literacy scores and sedentary time of high school students in the southeast half of China were higher than those in the northwest half of China (Z=-4.009, -9.198; P100 000 yuan, and family size of 1, 3, 7, 9, and ≥10 were higher than those of the northwestern half of China (P100 000 yuan, and the number of people in the family of 3, 4, 5, and 6 people were higher than those in the northwestern half of China in terms of the number of hours spent in meditation (P mother's educational attainment (0.131) > father's educational attainment (-0.056) > health literacy score (-0.050). The length of sedentary time of high school students in the northwestern half of China was positively correlated with health literacy score (β=0.017), father's education (β=0.789), and mother's education (β=0.540) (P mother's education (0.111) > health literacy score (0.056) . Conclusion Health literacy scores and meditation hours of high school students in the southeastern half of China were higher than those in the northwestern half of China. Meditation duration of high school students in the southeastern half of China was positively correlated with annual family income and mother's education, but negatively correlated with health literacy scores and father's education, while meditation duration of high school students in the northwestern half of China was positively correlated with health literacy scores parent's education. Annual family income had the highest weight on the effect of meditation duration for high school students in the southeast half of China, and father's education had the highest weight on the effect of meditation duration for high school students in the northwest half of China.

Background Current research on the physical fitness test scores of high school students is more localized within provinces and cities, with few multicenter, large-sample-size, domain-wide research results. The prevalence of blended online and offline teaching in schools of all types has inevitably prolonged the already long sedentary time of high school students. Whether this trend has some impact on the physical health of high school students is an urgent need for a region-wide study. Objective To investigate and analyze the levels of physical fitness test scores and related influencing factors of urban and rural high school first- and second-year students in seven regions of China, and to explore the empowering paths for the balanced improvement of physical fitness levels of first- and second-year high school students. Methods Stratified randomized cluster sampling method was used to conduct stratified sampling according to urban counties and townships and villages in high school schools in seven regions (East China, South China, North China, Central China, Northwest China, Southwest China, Northeast China) of 31 provinces (municipalities directly under the central government and autonomous regions) of China from January to March 2019, and then randomized clusters of 1 high school school in urban counties and 1 high school school in townships and villages in total of 62 schools were selected respectively. A total of 42 523 freshmen and sophomores in high schools were randomly selected to conduct the research, and the data on students' physical fitness test scores were collected at the same time (BMI reflects the level of physical development; lung capacity reflects the level of physical function; sit-and-reach reflects the level of flexibility; pull-up, 50 m run, standing long jump reflects the level of explosive strength of upper and lower limbs; 1 min sit-up reflects the level of core strength of the torso; 800 m run, 1 000 m run reflects the level of cardiorespiratory endurance), and non-parametric tests and multiple linear regression analysis were used to explore the influencing factors of the level of physical fitness test scores. Results The age distribution of 42 523 high school students was 16.0 (16.0, 17.0) years; 20 074 (47.2%) boys and 22 449 (52.8%) girls, 21 725 (51.1%) in cities, counties and districts, and 20 798 (48.9%) in towns and villages. Comparison of the gender and urban-rural distribution of high school students in the seven regions showed statistically significant differences (PNortheast China>Central China), body mass (Northeast China>North China>Central China), BMI (Central China>Northeast China>North China), lung capacity (Northeast China>Central China>South China), 50 m run (South China>Central China>East China), standing long jump (South China>North China>Northwest China), sit-and-reach (South China>Southwest China>Central China), pull-up (South China>Southwest China>Northwest China), and 1 000 m run (South China>Central China>Southwest China). High school boys in the city, county and districts had higher lung capacity scores than those in the town and country, and lower scores than those in the town and country in the 50 m run, standing long jump, sit-and-reach, pull-up, and 1 000 m run (P0.05). The differences in the scores of high school girls in each physical fitness test in the seven regions are statistically significant (PNortheast China>Northwest China), body mass (Northeast China>North China>Northwest China), BMI (Northeast China>North China>Northwest China), lung capacity (Northeast China>South China>Central China), 50 m run (South China>Central China>East China), standing long jump (South China>North China>Central China), sit-and-reach (Northeast China>Central China>South China), 1 min sit-up (North China>Central China>East China=Southwest China), 800 m run (Northeast>Central China>South China). High school girls in the city and county districts had higher height, body mass, and BMI scores than those in the town and country, and lower scores than those in the town and country in lung capacity, 50 m run, standing long jump, sit-and-reach, 1 min sit-up, and 800 m run (P