Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China: A nationwide, multi-center, population-based cross-sectional study.

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.

A polyoxyethylene sorbitan oleate modified hollow gold nanoparticle system to escape macrophage phagocytosis designed for triple combination lung cancer therapy via LDL-R mediated endocytosis.

Presently, a combination of chemotherapy, radiotherapy, thermotherapy, and other treatments has become a hot topic of research for the treatment of cancer, especially lung cancer. In this study, novel hollow gold nanoparticles (HGNPs) were used as drug carriers, and in order to improve the targeting ability of HGNPs to a lung tumor site, polyoxyethylene sorbitol oleate (PSO) was chosen here as a target ligand since it can be specifically recognized by the low-density lipoprotein (LDL) receptor which is usually over expressed on A549 lung cancer cells. In this way, a PSO-modified doxorubicin-loaded HGNP drug delivery system (PSO-HGNPs-DOX) was constructed and its physicochemical properties, photothermal conversion ability, and drug release of PSO-HGNPs-DOX was investigated. Further, the effects of triple combination therapy, the intracellular uptake, and the ability to escape macrophage phagocytosis of PSO-HGNPs-DOX were also studied using A549 cells in vitro. In addition, an in vivo mouse model was also used to study the targeting of PSO-HGNPs-DOX to lung cancer. PSO-HGNPs-DOX demonstrated a good triple therapeutic effect for lung cancer (A549 cell viability was only 10% at 500 µM) by LDL receptor mediated endocytosis and was able to escape macrophage phagocytosis to enhance its accumulation at the target site. Therefore, PSO-HGNPs-DOX is a novel, safe, promising, and targeted drug carrier designed for triple combination lung cancer therapy which should be further studied for such applications.

cRGDfK-Grafted Small-Size Quercetin Micelles For Enhancing Therapy Efficacy Of Active Ingredient From The Chinese Medicinal Herb.

BACKGROUND: As an active ingredient of Chinese herbal medicine, quercetin (QU) can significantly induce apoptosis of tumor cells and give play to other effect such as decreasing both fibroblast population and collagen in cancer cell nest. However, the antitumor efficacy of quercetin was mostly evaluated at cellular level and rarely developed in vivo by intravenous injection, which may be ascribed to its inferior physicochemical properties including water insolubility, short plasma half-time, and insufficient enrichment in the tumor tissues. METHODS: The DSPE-PEG was used to construct quercetin-loaded micelles, and the integrin ligand cRGDfK was grafted to modify the nanocarrier for enhancing its cancer-specific homing. The MALDI-TOF-MS, DLS, TEM, and UV were orderly operated to characterize guidance molecules and micelles by morphology, size distribution, Zeta potential, and drug encapsulation efficiency. In addition, the surface plasmon resonance study and real-time confocal analysis were employed to demonstrate αvß3 integrin-overexpressing B16 cells-specific binding and uptake. After further pharmacodynamics studies in vitro and in vivo, we also evaluate systemic toxicity about cRGDfK-PM-QU. RESULTS: The cRGDfK was successfully stitched with DSPE-PEG and modified on the surface of micelles. The ligand modification enhanced the negative charges of the micelles, but it did not induce significant changes in particle size. The quercetin micelles were about 15 nm in size and negatively charged, and had spherical morphology and high drug encapsulation efficiency. In vitro, the cRGDfK-modified micelles (cRGDfK-PM) showed αvß3 integrin-overexpressing B16 cells-specific binding and uptake, and cRGDfK-PM-QU (QU loaded in cRGDfK-PM) induced more significant cell apoptosis and cytotoxic effects against B16 tumor cells than counterpart micelles (PM-QU). In vivo, the cRDGfK modification enhanced enrichment in B16 tumor tissue, improved the therapeutic efficacy of the quercetin-loaded micelles against B16 tumor, and exhibited lower systemic and pulmonary toxicity compared with counterpart micelles in the mouse mode. CONCLUSION: Quercetin as a natural product has triggered increasing interest in the antitumor field. In this study, cRGDfK-modified DSPE-PEG micelles significantly optimized quercetin therapeutic efficacy and pulmonary toxicity as well as lowered systemic toxicity.

[Effect of miRNA from Glycyrrhiza uralensis decoction on gene expression of human immune cells].

MicroRNAs(miRNA) are small non-coding RNAs that regulate the expression of protein coding genes by repressing translation of protein coding mRNA or enhancing mRNA degradation. Its functions have attracted more and more attention from the public. In recent years, the cross-border regulation of miRNA has become a new research direction, and provides a new perspective for people to comprehensively understand the functions of miRNA. Plant miRNA is usually methylated and not easy to degrade. According to our previous researches, there were abundant small RNAs in the decoction of dried liquorice, which provides a new way to study the mechanism of action of licorice. In this study, small RNAs extracted from Glycyrrhiza uralensis decoction and synthesized miRNA mimics were used to treat peripheral blood mononuclear cells(PBMC) isolated from healthy volunteers. The gene expression of toll-like receptors(TLRs), some transcription factors, signal molecules and cytokines were analyzed by RT-PCR. The results showed that glycyrrhiza miRNA could significantly regulate PBMC by inhibiting the expression of genes involved in T cell differentiation, inflammation and apoptosis. The study brought new ideas to us in comprehensively studying the mechanism of licorice and developing the traditional Chinese medicine.

[Operational Characteristics of the Simultaneous Nitrogen and Phosphorus Removal and Removal of Phthalate Esters by Three-dimensional Biofilm-electrode Coupled with Iron/Sulfur Reactor].

In order to explore the technological characteristics of the simultaneous removal of phthalate esters (PAEs) as well as nitrogen and phosphorus by the novel technology of three-dimensional biofilm-electrode coupled with iron/sulfur reactor (3DBER-S-Fe), the changes of the total nitrogen (TN),total phosphorus (TP),DBP,DEHP,NO3--N, SO42- and pH value were analyzed under the hydraulic retention time (HRT) of 8 h, 6 h and 4 h respectively. The results showed that 3DBER-S-Fe could remove nitrogen, phosphorus and PAEs effectively. Under the HRT of 8 h, 6 h and 4 h, the removal rates of TN were 80.99%, 78.85% and 64.76%; TP were 65.18%, 67.17% and 43.44%; DBP were 96.72%, 97.32% and 96.53%; DEHP were 91.89%, 81.57% and 74.30%, respectively. There were heterotrophic denitrification, hydrogen autotrophic denitrification and sulfur autotrophic denitrification processes in the 3DBER-S-Fe, the elemental sulfur could compensate for the relative shortage of denitrification electron donor caused by the increase of NO3--N load in the influent as a result of maintaining a high efficiency of the denitrification system when the HRT was shortened from 8h to 4h; the iron ions produced by the corrosion of the sponge iron filler in the system had a sustainable and efficient function of removing phosphorus by precipitation; the 3DBER-S-Fe process combined the interactions of physical adsorption, biological degradation and electrochemical processes which supported its high removal rates of DBP and DEHP under the different HRT conditions.

[Allelopathy of Hydrodictyon reticulatum on Microcystis aeruginosa and its removal capacity on nitrogen and phosphorus].

The effects of liquid culture after cultured with Hydrodictyon reticulatum on the growth of Microcystis aeruginosa were investigated by measuring the D680 value and the chlorophyll-a content of M. aeruginosa. The inhibitory effects of H. reticulatum on M. aeruginosa were studied in both isolated culture and co-culture conditions. Nitrogen and phosphorus removal capacity of H. reticulatum was also tested. Results showed that H. reticulatum could inhibit the growth of M. aeruginosa obviously. After treated by the liquid culture after cultured with H. reticulatum for 8 days, the mortality rate of M. aeruginosa reached 92%. The inhibitory effects of H. reticulatum at different concentrations on M. aeruginosa were different. The strongest inhibitory effect occurred with 3 g/L H. reticulatum in the isolated culture as the D680 value reduced from 0.1 to 0.004 in 10 days, and it occurred with 4 g/L H. reticulatum in the co-culture as the suppression ratio was 96%. Comparing the large-scale death time for cells under these two conditions, the inhibitory effects of H. reticulatum in the isolated culture were stronger than those in the co-culture. The concentrations of nitrogen and phosphorus decreased sharply under both conditions, which showed that H. reticulatum had removal capacity on nitrogen and phosphorus. The decrease speed of nitrogen and phosphorus concentrations positively correlated to the concentrations of H. reticulatum. The highest decrease of nitrogen and phosphorus were 93.4 mg/L and 4.58 mg/L in 10 days, respectively.