Chinese herbal medicines for prostate cancer therapy: From experimental research to clinical practice.

Prostate cancer remains the second most common malignancy in men worldwide, is a global health issue, and poses a huge health burden. Precision medicine provides more treatment options for prostate cancer patients, but its popularity, drug resistance, and adverse reactions still need to be focused on. Chinese herbal medicines (CHMs) have been widely accepted as an alternative therapy for cancer, with the advantages of multiple targets, multiple pathways, and low toxicity. We searched the experimental research and clinical practice of CHMs for prostate cancer treatment published in PubMed, Embase, and Web of Science in the last five years. We found five CHM formulas and six single CHM extracts as well as 12 CHM-derived compounds, which showed induction of apoptosis, autophagy, and cell cycle arrest, suppression of angiogenesis, proliferation, and migration of prostate cancer cells, reversal of drug resistance, and enhancement of anti-tumor immunity. The mechanisms of action include the PI3K/Akt/mTOR, AR, EGFR and Wnt/ß-catenin signaling pathways, which are commonly implicated in the development of prostate cancer. We also summarized the advantages of CHMs in patients with hormone-sensitive and castration-resistant prostate cancer and provided ideas for their further experimental design and application.

Association Between Neutrophil-to-Lymphocyte Ratio and Benign Prostatic Hyperplasia: Results from the TCLSIH Cohort Study.

Purpose: The prevalence of benign prostatic hyperplasia (BPH) in the general Chinese adult male population has risen sharply over the past few decades. Increasing evidence suggests that inflammation plays an important role in the pathogenesis of BPH. To better understand the role of inflammation in the pathogenesis of BPH, we can use the neutrophil-to-lymphocyte ratio (NLR) because it is a simple and effective marker of inflammation and immunity. This study aims to prospectively investigate the association between NLR levels and the prevalence of BPH in a general Chinese adult male population. Patients and Methods: This study included a total of 15,783 male participants free from BPH at baseline. NLR was measured according to the complete blood count. BPH was defined as total prostate volume (TPV) ≥30 mL, and TPV was determined by transabdominal ultrasonography. Multivariable Cox proportional hazards models were fitted to calculate hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for BPH risk with NLR levels. Results: During a median follow-up of 2.7 years, 5078 BPH cases were documented. After adjusting for age, body mass index, smoking, alcohol, education, occupation, income, physical activity, total energy intake, personal and family history of disease, and inflammation markers, the multivariable-adjusted HRs of BPH were 1.00 (reference), 1.08 (95% CIs 0.99, 1.17), 1.10 (95% CIs1.02, 1.19), and 1.12 (95% CIs1.03, 1.21), respectively, for participants with NLR in the first, second, third, and fourth quartiles (P for trend <0.01). Conclusion: Higher NLR levels were associated with a higher risk of BPH in Chinese adult male population. Our findings support the notion that NLR levels may be an important target for BPH prevention and intervention.

Association Between Mean Platelet Volume and Benign Prostatic Hyperplasia: A Population Study from the TCLSIH Cohort Study.

Purpose: This study aimed to prospectively investigate the association between mean platelet volume (MPV) levels and risk of benign prostatic hyperplasia (BPH) in a general Chinese adult male population, and assessed this association in metabolic syndrome (MetS) patients. Patients and methods: This study included a total of 14,923 male participants free from BPH at baseline. MPV was measured by the method of laser-based flow cytometric impedance according to the complete blood sample. BPH was defined as total prostate volume (TPV) ≥ 30 mL, TPV was determined by transabdominal ultrasonography. Multivariable Cox proportional hazards models were fitted to calculate hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for BPH risk with NLR levels. Results: During a median follow-up of 2.7 years, 4848 BPH cases were documented in total male participants, and 1787 BPH cases were documented in MetS participants. After adjusting for age, body mass index, smoking, alcohol and personal and family history of disease, the multivariable-adjusted HRs of BPH were 1.00 (reference), 1.03 (95% CIs 0.96, 1.11), 1.00 (95% CIs 0.92, 1.08) and 0.98 (95% CIs 0.90, 1.06), respectively, for participants with MPV in the 1st, 2nd, 3rd and 4th quartiles (P for trend = 0.47). In MetS patients, the multivariable-adjusted HRs of BPH were 1.00 (reference), 1.03 (95% CIs 0.90, 1.16), 0.99 (95% CIs 0.87, 1.14) and 1.01 (95% CIs 0.89, 1.15) (P for trend= 0.98), respectively. Conclusion: A non-significant association was observed between MPV levels and risk of BPH, and no association in this association in MetS patients. Our findings support the notion that MPV levels may not be a target for BPH prevention and intervention.

Association of Thyroid-Stimulating Hormone With All-Cause Mortality: A 2-Sample Mendelian Randomization Study.

CONTEXT: Thyroid-stimulating hormone (TSH), as the most sensitive and specific marker of thyroid status, is associated with multiple health outcomes, including mortality. However, whether TSH levels are causally associated with the risk of mortality remains unclear. OBJECTIVE: This study aims to investigate the causal association between TSH levels and all-cause mortality using Mendelian randomization (MR) analyses. METHODS: MR analyses using single-nucleotide polymorphisms (SNPs) associated with TSH levels (P < 5 × 10-8) as instruments. Mortality data were obtained from the UK Biobank, including 384 344 participants who were recruited from 22 assessment centers across the UK taken between 2006 and 2010. Cox proportional hazards regression was used to estimate the association of the TSH genetic risk score (GRS) with all-cause and cause-specific mortality. RESULTS: 15 557 individuals died during a median of 9.00 years of follow-up in the UK Biobank. A total of 70 SNPs were included in the MR analysis. The main MR analyses showed that 1 SD increase in TSH was associated with a decreased risk of all-cause mortality (OR 0.972, 95% CI 0.948-0.996), which may be largely attributed to respiratory disease mortality (OR 0.881, 95% CI 0.805-0.963). The multivariable hazard ratios (HRs) (95% CI) of all-cause mortality across 3 TSH GRS categories were 1.00 (reference), 0.976 (0.940-1.014), and 0.947 (0.911-0.985), respectively (P for trend < .01). Moreover, except digestive diseases mortality, genetically predicted TSH levels were negatively associated with mortality from CVD, cancer, noncancer diseases causes, and dementia, although not statistically significant. CONCLUSION: Higher TSH levels were causally associated with lower risk of all-cause mortality, which may be largely attributed to respiratory disease mortality.

Dioscin Regulating Bone Marrow Apoptosis in Aplastic Anemia.

Background: Aplastic anemia (AA), a disease of bone marrow failure, is caused by CD8+T mediated apoptosis of hematopoietic cells. However, traditional immunosuppressive therapy (IST) has severe liver and kidney toxicity and even cannot achieve the expected therapeutic effect in some patients. Purpose: Our study is aimed to investigate the effect and mechanism of dioscin (DNS) for treating AA. Methods: Briefly, we established and evaluated the AA mouse model, DNS and positive control drugs were used for intervention treatment. After 14 days of intervention, femoral bone marrow pathology, bone marrow mononuclear cells (BMMCs) apoptosis rate, bone marrow CD34+ cell surface Fas (CD95) expression and Fas signaling pathway key proteins were detected. Results: After the establishment of the AA mouse model, the number of peripheral blood cells including granulocytes, erythrocytes, hemoglobin, platelets and reticulocytes in the AA group model was significantly decreased compared with the group control (P < 0.01). The degree of bone marrow hyperplasia in the sternum and femur is extremely low. After different drug interventions, compared with the group model, the number of peripheral blood cells in the AA mice rebounded significantly in group DNS (P < 0.01). Not only that the apoptosis rate of BM-MCs decreased (P < 0.01), meanwhile, the CD95 molecule expressed on the CD34+ bone marrow cells had a significant decline (P < 0.01), and the expression level of the key proteins of Fas signaling pathway was also significantly decreased (P < 0.01). Conclusion: DNS recovered the peripheral pancytopenia and bone marrow failure in AA mice. DNS reduced the key protein of Fas signaling pathway level to inhibit apoptosis of bone marrow cells to treat AA.

A mouse model of irradiation and spleen-thymus lymphocyte infusion induced aplastic anemia.

OBJECTIVES: The immune-induced aplastic anemia (AA) mouse model has been used for the study of AA. However, there were no uniform conditions for establishing a model and no assessment of immunological homeostasis. Our study aimed to identify the conditions of establishing a model and assess the AA model in immunology and pathology. METHODS: We induced an AA mouse model by the combination between sublethal irradiation and spleen-thymus lymphocyte infusion. The success of establishing the AA model was identified by blood routine tests and pathology of bone marrow. The frequency of Th17 and Treg cells was measured by flow cytometry. The frequency of CD34+ and CD41+ cells was detected by immunohistochemical technique.IL-6, IL-8, IL-17, TNF-α and IFN-γ were evaluated by ELISA. RESULTS: The 137Cs sublethal irradiation (5 Gy) and spleen-thymus lymphocyte infusion (5 × 106) induced the AA mouse model successfully. The AA mice had a long lifetime and manifested pancytopenia and bone marrow failure. The percentage of Th17 cells increased and the percentage of Treg cells decreased distinctly in AA mice. The area of hematopoietic tissues and count of CD34+ cells and CD41+ cells were significantly reduced in AA mice.The level of cytokines, IL-6, IL-8, IL-17, TNF-α and IFN-γ, was increased significantly in peripheral blood and bone marrow. CONCLUSION: Our data suggest that the improved AA mouse model conforms to the diagnosis standard of AA and simulates the immune internal environment of human AA. The AA mouse model has a longer lifetime and unbalances of Th17/Treg cells caused the destruction of CD34+ cells and CD41+ cells, which was immune-mediated pathogenesis to adapt to long-term research.

Research on the relationship between China's greenhouse gas emissions and industrial structure and economic growth from the perspective of energy consumption.

A comprehensive understanding of the relationships between greenhouse gas (GHG) emissions and industrial structure and economic growth holds great significance for China to realize the development of a green economy. This paper calculates GHG emissions based on China's energy consumption, divides the industrial structure in detail, and uses the extended Stochastic Impacts by Regression on Population, Affluence, and Technology model that is realized by PLS method and Tapio decoupling model to study the relationship of GHG emissions to industrial structure and economic growth. The results show that (1) China's total GHG emissions showed a year-on-year growth trend from 2000 to 2017. For CO2, CH4, and N2O, only N2O emission showed a significant downward trend, while CO2 and CH4 emissions showed a slow growth trend. (2) The proportions of added value of industry and construction are positively correlated with GHG emissions, while those of farming, forestry, animal husbandry, and fishery; wholesale and retail trade; transport; and accommodation and catering are negatively correlated with GHG emissions. (3) China's GHG emissions and overall economic growth are in a decoupling state, but in the energy field, N2O emission reduction control has the best effect. Additionally, the overall economic growth of China's industrial sector and GHG emissions have experienced the process of decoupling-link-negative decoupling-link-decoupling. Graphical abstract.

The Association between Leukocyte and Its Subtypes and Benign Breast Disease: The TCLSIH Cohort Study.

Inflammation plays a crucial role in the formation of benign breast disease. Given the limited study to explore the association between leukocyte as an indicator of immune system and benign breast disease, we used data from a large cross-sectional study to investigate association between leukocyte and its subtypes and benign breast disease among women in the general population. The data were derived from baseline data of the Tianjin chronic low-grade systemic inflammation and health (TCLSIH) cohort study during 2014 and 2016. Breast thickness and nodules status were assessed by using ultrasonography. Leukocyte and its subtype counts were carried out using the automated hematology analyzer. Multiple logistic regression analysis was used to examine the association between leukocyte and its subtypes and prevalence of benign breast disease. In the present study, the prevalence of benign breast disease was 20.9%. After adjustments for potentially confounding factors, the odds ratios (95% confidence interval) for benign breast disease across lymphocyte quintiles were as follows: 1.00 (reference), 0.99 (0.82, 1.2), 0.85 (0.69, 1.04), 0.84 (0.68, 1.02), and 0.75 (0.61, 0.92) (P for trend = 0.002). An inverse association between lymphocyte counts and benign breast disease was found, but leukocyte and other subtypes have nothing to do with benign breast disease. Further prospective studies are needed to determine the findings.