Can decreased cost-sharing reduce the vulnerability of sick families to poverty? An analysis of the multi-level social health insurance scheme in China.

In recent years, China has been increasing social health insurance benefits to alleviate poverty due to illness. In 2015, China introduced the Critical Illness Insurance for patients with high out-of-pocket expenses as supplementary to the social health insurance, which categorized patients with different medical expenses into different cost-sharing policies. We conducted a survey on households with high-cost patients in rural Shandong in 2019 and employed the instrumental variables estimation approach to determine how different cost-sharing measures affect households' poverty vulnerability. We found that cost-sharing reduction significantly decreases the vulnerability of sick families to poverty. Moreover, we found that the positive effect is attributed to a reduction in health burden and household livelihood capital shocks. The vulnerability to poverty is still exceptionally high owing to the heavy health burden in rural China and other developing countries. The results of our study provide insights into poverty alleviation by improving social health insurance in developing economies.

Single-component lipid nanoparticles for engineering SOCS1 gene-silenced dendritic cells to boost tumor immunotherapy.

Dendritic cells (DCs) that can prime antitumor responses show great potential in tumor immunotherapy, whereas the unsatisfactory effect which can be ascribed in part to the high expression of inhibitory cytokines, such as the suppressor of cytokine signaling 1 (SOCS1), restricts their application. Thus, silencing these genes in DCs is essential for DC-based therapy. However, safe and effective delivery of siRNA to DCs still faces challenges. Herein, we designed single-component lipid nanoparticles comprising a solely cationic lipid (OA2) for introducing siRNA into mouse DCs in order to inhibit the immunosuppressive gene and boost the effector responses of DC-based therapy. Compared to other multi-component lipid nanoparticles, single-component lipid nanoparticles are theoretically easy-to-control and detective, which is beneficial for future translation. We showed that the application of OA2 lipid nanoparticles significantly downregulated the expression of SOCS1 in DCs over 50%, compared with the commercial lipofectine2000. Besides, the treatment of OA2 lipid nanoparticles had no influence on the antigen capture of DCs. Thus, we fabricated a SOCS1-downregulated DC vaccine pulsed with Ova antigen and demonstrated that the antigen presentation and pro-inflammatory factor secretion ability of DCs were improved due to the SOCS1 downregulation, leading to an ameliorated immunosuppressive tumor microenvironment and finally exhibiting potent tumor prevention and suppression in B16-Ova tumor-bearing mice. Single-component lipid nanoparticles, which provide an available vector platform for siRNA delivery to primary DCs, appear to be a potent tool to engineer DCs and in turn boost DC-based tumor immunotherapy.

Intergenerational transmission of parental risky health behaviors in Chinese children: Are there socioeconomic status differences?

Background: Risky health behaviors in childhood, including smoking, alcohol consumption, and having a poor diet, are the major sources of non-communicable diseases in adulthood. This study aimed to examine how parents affect children's risky health behaviors and whether intergenerational transmission differs based on socioeconomic status (SES). Methods: Data were extracted from the 1991-2015 China Health and Nutrition Survey (CHNS). Smoking (n = 5,946), alcohol consumption (n = 7,821), and sugar-sweetened beverages (SSBs) consumption (n = 3,537) were used as proxies for risky health behaviors in children. A binary choice model for panel data with a random-effect specification was employed to examine whether risky health behaviors can be transmitted from parents to their children. Subsequently, we conducted a seemingly unrelated estimation test (SUEST) to explore the differences in parental transmission between the different SES groups. Results: We found strong intergenerational persistence of smoking, alcohol drinking, and SSBs drinking behaviors, except for the mothers' smoking behavior. Mothers had a greater influence on children's alcohol drinking and SSBs drinking behaviors than fathers both in urban and rural areas and in different SES groups. The intergenerational transmission of SSBs drinking behavior exhibited a decreasing trend with increasing SES for both urban and rural families. In urban areas, mothers' alcohol drinking behavior has a decreasing trend with increasing education level, occupation, and income; however, in rural areas, the influence of mothers' alcohol drinking behavior occurred in the same direction with increasing education level and occupation type. In rural areas, the influence of fathers' drinking and smoking behaviors on children appears to mostly increase with increasing SES. Meanwhile, the influence of such behaviors among urban fathers would decrease with increasing SES. Conclusion: Parents' behaviors and SES can influence the initiation of risky health behaviors in their offspring. Thus, to promote healthy behaviors, policymakers can introduce health education programs for parents, particularly for those living in rural areas and with a low SES.

Simultaneous blockage of contextual TGF-ß by cyto-pharmaceuticals to suppress breast cancer metastasis.

It remains challenging to treat tumor metastasis currently in the light of multiple cascade processes of tumor metastasis. Additionally, multiple clinical drugs for metastasis have quite limited therapeutic potential and even facilitate metastasis in preclinical models. Thus, potential metastasis targets and novel metastasis-directed drugs are urgently needed to be further developed. Herein, transforming growth factor-ß (TGF-ß) is verified to contribute to lung metastasis in a context-dependent manner in the 4T1 orthotopic tumor-bearing mice model, which induces epithelial-mesenchymal-transition (EMT) to promote tumor dissemination from the primary site and dampens the anti-tumor response of neutrophils to support tumor colonization at the metastatic niche. In view of neutrophils' superior tropism towards both inflammatory primary tumor and metastatic niche, SB525334, a TGF-ß receptor inhibitor, is loaded into cationic liposome (SBLP) which is subsequently incorporated into neutrophils to yield the cyto-pharmaceuticals (SBLP/NE). The systemically infused SBLP/NE can simultaneously migrate into both primary and metastatic sites, then release SB525334 in response to tumor stimuli, and contextually inhibit TGF-ß-mediated-EMT and phenotype reversal of infiltrated neutrophils, showing substantial metastasis suppression efficacy without causing any detectable toxicities. This project shifts the paradigm for metastasis suppression therapy by simultaneous blockage of contextual TGF-ß using metastatic-cascades-targeting neutrophil cyto-pharmaceuticals.

The development of tertiary amine cationic lipids for safe and efficient siRNA delivery.

Cationic liposomes have shown great potential in efficient siRNA delivery, and their positive charge is crucial for tight extracellular siRNA binding, effective intracellular siRNA disassembly and physiological toxicity. Thus, the development of novel cationic lipids with a suitable positive charge is desirable for safe and efficient siRNA delivery. Herein, we fabricated a library of 21 tertiary amine-derived cationic lipids (TA) to achieve a balance between effectiveness and safe siRNA delivery. The screened TA13 liposomes, which consisted of TA13 and helper lipid DOPE at a mole ratio of 1 : 1, readily condensed siRNA to form lipoplexes (TA13 LPs), achieving stronger gene silencing in diverse cells than the commercially available vector Lipo2000. Moreover, the TA13 LPs demonstrated effective in vivo gene silencing and good safety in normal mice. The improved gene silencing efficiency of the TA13 LPs is ascribed to their capability of sequentially conquering the barriers met by in vivo siRNA delivery. Notably, the TA13 LPs delivered ApoB-siRNA and obviously decreased ApoB mRNA expression in the liver and the total cholesterol and low-density lipoprotein in the serum of hypercholesterolemia mice, indicating a potential siRNA therapeutic for hypercholesterolemia treatment. It is anticipated that these novel tertiary amine-based liposomes can provide a simple and widely-used platform for the safe and effective delivery of siRNA, and their structure-activity relationships can aid in the further development of effective cationic lipids.