Therapeutic potential of natural products and underlying targets for the treatment of aortic aneurysm.

Aortic aneurysm is a vascular disease characterized by irreversible vasodilatation that can lead to dissection and rupture of the aortic aneurysm, a life-threatening condition. Thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) are two main types. The typical treatments for aortic aneurysms are open surgery and endovascular aortic repair, which are only indicated for more severe patients. Most patients with aneurysms have an insidious onset and slow progression, and there are no effective drugs to treat this stage. The inability of current animal models to perfectly simulate all the pathophysiological states of human aneurysms may be the key to this issue. Therefore, elucidating the molecular mechanisms of this disease, finding new therapeutic targets, and developing effective drugs to inhibit the development of aneurysms are the main issues of current research. Natural products have been applied for thousands of years to treat cardiovascular disease (CVD) in China and other Asian countries. In recent years, natural products have combined multi-omics, computational biology, and integrated pharmacology to accurately analyze drug components and targets. Therefore, the multi-component and multi-target complexity of natural products have made them a potentially ideal treatment for multifactorial diseases such as aortic aneurysms. Natural products have regained popularity worldwide. This review provides an overview of the known natural products for the treatment of TAA and AAA and searches for potential cardiovascular-targeted natural products that may treat TAA and AAA based on various cellular molecular mechanisms associated with aneurysm development.

Occupational differences in the effects of retirement on hospitalizations for mental illness among female workers: Evidence from administrative data in China.

Retirement, a major transition in the life course, may affect many aspects of retirees' well-being, including health and health care utilization. Leveraging differential statutory retirement age (SRA) by occupation for China's urban female workers, we provide some of the first evidence on the causal effect of retirement on hospitalizations attributable to mental illness and its heterogeneity. To address endogeneity in retirement decisions, we take advantage of exogeneity of the differing SRA cut-offs for blue-collar (age 50) and white-collar (age 55) female urban employees. We apply a Fuzzy Regression Discontinuity Design (RDD) around the SRA cut-offs using nationally representative hospital inpatient claims data that cover these workers. We show that blue-collar females incur more hospitalizations for mental illness after retirement, while no similar change is found for white-collar females. Conditional on blue-collar females being hospitalized, probabilities of overall and ER admissions due to mental illness increase by 2.3 and 1.2 percentage points upon retirement, respectively. The effects are primarily driven by patients within the categories of schizophrenia, schizotypal and delusional disorders; and neurotic, stress-related and somatoform disorders. Moreover, the 'Donut' RDD estimates suggest that pent-up demand at retirement unlikely dominates our findings for blue-collar females. Rather, our results lend support to their worsening mental health at retirement. These findings suggest that occupational differences in mental illness and related health care utilization at retirement should be considered when optimizing retirement policy schemes.

Small money, big change: The distributional impact of differentiated doctor's visit fee on healthcare utilization.

A prominent issue in China's healthcare sector is the overcrowding of high-tier hospitals, whereas low-tier hospitals and community health centers are severely underutilized. This study aims to examine whether doctor's visit fee and copay differentiated by the level of healthcare providers can change the distribution of outpatient visits across different levels of healthcare providers. By leveraging the exogeneity of the policy change implemented in a megacity in China in 2017, we apply a parametric discontinuity regression model to study the causal impact of differentiated pricing on patients' health-seeking behavior, using a large-scale insurance claim database. We find that the reform of differentiated doctor's visit fee schedule effectively increases the proportion of visits to primary care facilities among all outpatient visits. This effect is driven by a decline in visits to the highest-tier hospitals and an increase in visits to community healthcare centers. Furthermore, the policy effects are more pronounced among the elderly and people with chronic diseases. Our results suggest that shifting the focus of pricing policies from coinsurance to copays while continuing to improve the capacity of primary care facilities is an effective way to facilitate triaging patients into different levels of care without triggering moral hazard.

A Novel Bromophenol Compound from Leathesia nana Inhibits Breast Cancer in a Direct Tumor Killing and Immunotherapy Manner.

Considering the resistance and toxicity of traditional chemotherapeutic drugs, seeking potential candidate for treating breast cancer effectively is a clinical problem that should be solved urgently. Natural products have attracted extensive attention, owing to their multi-target advantages and low toxicity. In the current study, the effects of XK-81, a novel bromophenol compound extracted from Leathesia nana, on breast cancer, and its underlying mechanisms, were explored. Firstly, data from in vitro experiments indicated that 4T-1, one of common mouse breast cancer cell lines, was a XK-81-susceptible cell line, and ferroptosis was the major death manner in response to XK-81 treatment, which was evidenced by increasing intracellular Fe2+ and ROS level with condensed mitochondrial membrane densities, as well as decreasing the protein expressions of SLC7A11 and GPX4. In vivo, XK-81 suppressed the growth of 4T-1 breast-tumor in both BALB/C mice and zebrafish. Obviously, XK-81 decreased the protein expression of SLC7A11 and GPX4 in tumor tissues, hinting at the occurrence of ferroptosis. Moreover, XK-81 increased CD8+ T cells and NK cells numbers and regulated M1/M2 macrophage ratio in tumor tissues, indicating XK-81's immunotherapeutic effect. Additionally, the secretions of immune-related cytokines, including TNF-α, IL-1ß, and IL-12, were elevated with XK-81 stimulation in RAW 264.7 cells. Intriguingly, compared with doxorubicin-induced heart damage, XK-81 demonstrated the therapeutic advantage of little cardiotoxicity on the heart. XK-81 demonstrated potential antitumor advantage by both directly inducing ferroptosis-mediated death of tumor cells and immunization.

The impact of Children's gender on Parent's mental health and cognition -- evidence from China.

With the growing and aging population round the world, it becomes increasingly important to understand what factors impact the mental health and cognition of the older generations in order to design effective interventions. In this paper, we investigate the effect of a child's gender on parental mental health and cognition in the context of one of the world's largest developing countries and the unique one-child policy, using China Family Panel Studies (CFPS). We exploit the exogeneity of the first child's gender and find that having a son has significant protective effects on parents' mathematics performance and memory functions in one-child families, but such effects are absent in multi-child families. Moreover, we find that the protective effect is more pronounced among one-child families in rural areas than urban areas. Our results suggest the existence of gender inequality in China and reveal the hidden long-term social cost of the one-child policy.

Aluminium nanoparticle modelling coupled with molecular dynamic simulation method to compare the effect of annealing rates on diethyl ether coating and oxidation behaviours.

This study was conducted to examine the influence of annealing rates on coating and oxidation performances of Aluminium (Al) nanoparticle (ANP) by molecular dynamic (MD) simulations. Four levels of cooling rates were utilized on melted ANP to obtain annealed ANP models with different microstructures. Then those nanoparticles were placed into pure diethyl ether or oxygen gas environments to perform coating and oxidation simulations respectively. It was revealed that there was a relatively optimal annealing condition for ANP models to recover the initial microstructure of themselves as much as possible. The ether coating behaviour of annealed ANP model under this condition was better than other models. In contrast, the oxidation of all different models was almost the same. So, the factor of the annealing rate had little effect on the oxidation results. Along with the growth of the oxide layer, the core of ANP still kept its annealed microstructure.

Economic Implications of Chinese Diagnosis-Related Group-Based Payment Systems for Critically Ill Patients in ICUs.

OBJECTIVES: To evaluate the economic implications of payments based on Chinese diagnosis-related groups for critically ill patients in ICUs in terms of total hospital expenditure, out-of-pocket payments, and length of stay. DESIGN: A pre-post comparison of patient cohorts admitted to ICUs 1 year before and 1 year after Chinese diagnosis-related group reform was undertaken. Demographic characteristics, clinical data, and medical expenditures were collated from a health insurance database. SETTING: Twenty-two public hospitals in Sanming, Southern China. PATIENTS: All patients admitted to ICUs from January 1, 2017, to December 31, 2018. INTERVENTION: The implementation of Chinese diagnosis-related group-based payments on January 1, 2018. MEASUREMENTS AND MAIN RESULTS: Economic variables (total expenditures, out-of-pocket payments, and length of stay) were calculated for each patient from the day of hospital admission to the day of hospital discharge. Adjusted mean out-of-pocket payment estimates were 29.46% (p < 0.001) lower following reform. Adjusted mean out-of-pocket payments fell by 41.32% for patients in neonatal ICU, whereas there were no significant decreases in out-of-pocket payments for patients in PICU and adult ICU. Furthermore, adjusted mean out-of-pocket payments decreased by 55.74% in secondary hospitals, but there was no significant change in tertiary hospitals after Chinese diagnosis-related group reform. No significant changes were found in total expenditures and length of stay. CONCLUSIONS: Chinese diagnosis-related group policy provided an opportunity for critically ill patients in ICUs to achieve at least short-term financial benefits in reducing out-of-pocket payments, without affecting the total expenditures and length of stay. Chinese diagnosis-related group-based payment significantly relieved financial burdens for patients with lower illness severities, such as patients in neonatal ICU. The results of this study can offer significant insights for policymakers in reducing the financial burden on critically ill patients, both in China and in other countries with similar systems.

A data set of global river networks and corresponding water resources zones divisions.

As basic data, the river networks and water resources zones (WRZ) are critical for planning, utilization, development, conservation and management of water resources. Currently, the river network and WRZ of world are most obtained based on digital elevation model data automatically, which are not accuracy enough, especially in plains. In addition, the WRZ code is inconsistent with the river network, hindering the efficiency of data in hydrology and water resources research. Based on the global 90-meter DEM data combined with a large number of auxiliary data, this paper proposed a series of methods for generating river network and water resources zones, and then obtained high-precision global river network and corresponding WRZs at level 1 to 4. The dataset provides generated rivers with high prevision and more accurate position, reasonable basin boundaries especially in inland and plain area, also the first set of global WRZ at level 1 to 4 with unified code. It can provide an important basis and support for reasonable use of water resources and sustainable social development in the world.