Is sub-national healthcare social protection sufficient for protecting rare disease patients? the case of China.

Background: Failing to provide social support to cover healthcare costs for rare diseases would lead to great financial distress for the patients and their families. People from countries without a well-developed health safety-net are particularly vulnerable. Existing literature on rare diseases in China focuses on the unmet needs for care of the patients and the difficulties of caregivers and physicians. Very few studies examine the state of social safety-net, the unresolved issues and whether the current localized arrangements are sufficient. This study aimed to gain in-depth knowledge of the current policy system and make sense of the local varieties, which would be essential for developing strategies for future policy changes. Methods: This systematic policy review focuses on the provincial level policies on subsidizing the healthcare costs for people with rare diseases in China. The cut-off point for the policies was March 19, 2022. The researchers coded the healthcare cost reimbursement policies and identified the different provincial level models based on the usage of reimbursement components in each provinces reimbursement arrangements. Results: 257 documents were collected. Five provincial level models (Process I, II, III, IV and V) have been identified with the five components across the country: Basic Medical Insurance for Outpatient Special Diseases (OSD), Catastrophic Medical Insurance for Rare Diseases (CMIRD), Medical Assistance for Rare Diseases (MARD), Special Fund for Rare Diseases (SFRD) and Mutual Medical Fund (MMF). The local health safety-net in each region is a combination of one or more of the five processes. Regions vary greatly in their rare diseases coverage and reimbursement policies. Conclusion: In China, the provincial health authorities have developed some level of social protection for rare disease patients. However, there are still gaps regarding coverage and regional inequality; and there is room for a more integrated healthcare safety-net for people suffering from rare diseases at the national level.

Ciclopirox targets cellular bioenergetics and activates ER stress to induce apoptosis in non-small cell lung cancer cells.

BACKGROUND: Lung cancer remains a major cause of cancer-related mortality throughout the world at present. Repositioning of existing drugs for other diseases is a promising strategy for cancer therapies, which may rapidly advance potentially promising agents into clinical trials and cut down the cost of drug development. Ciclopirox (CPX), an iron chelator commonly used to treat fungal infections, which has recently been shown to have antitumor activity against a variety of cancers including both solid tumors and hematological malignancies in vitro and in vivo. However, the effect of CPX on non-small cell lung cancer (NSCLC) and the underlying mechanism is still unclear. METHODS: CCK-8, clonal formation test and cell cycle detection were used to observe the effect of inhibitor on the proliferation ability of NSCLC cells. The effects of CPX on the metastasis ability of NSCLC cells were analyzed by Transwell assays. Apoptosis assay was used to observe the level of cells apoptosis. The role of CPX in energy metabolism of NSCLC cells was investigated by reactive oxygen species (ROS) detection, glucose uptake, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) experiments. Western blot was used to examine the protein changes. RESULTS: We report that CPX inhibits NSCLC cell migration and invasion abilities through inhibiting the epithelial-mesenchymal transition, impairing cellular bioenergetics, and promoting reactive oxygen species to activate endoplasmic reticulum (ER) stress-induced apoptotic cell death. Moreover, CPX intraperitoneal injection can significantly inhibit NSCLC growth in vivo in a xenograft model. CONCLUSIONS: Our study revealed that CPX targets cellular bioenergetics and activates unfolded protein response in ER to drive apoptosis in NSCLC cells, indicating that CPX may be a potential therapeutic drug for the treatment of NSCLC. Video Abstract.

Warming and Nitrogen Addition Change the Soil and Soil Microbial Biomass C:N:P Stoichiometry of a Meadow Steppe.

: Soil and soil microbial biomass (SMB) carbon: nitrogen: phosphorus (C:N:P) stoichiometry are important parameters to determine soil balance of nutrients and circulation of materials, but how soil and SMB C:N:P stoichiometry is affected by climate change remains unclear. Field experiments with warming and N addition had been implemented since April 2007. Infrared radiators were used to manipulate temperature, and aqueous ammonium nitrate (10 g m-2 yr-1) was added to simulate nitrogen deposition. We found that molar nutrient ratios in the soil averaged 60:11:1, warming and warming plus N addition reduced soil C:N by 14.1% and 20% (P < 0.01), and reduced soil C:P ratios by 14.5% and 14.8% (P < 0.01). N addition reduced soil C:N significantly by 17.6% (P < 0.001) (Figs. 2B, 2D). N addition and warming plus N addition increased soil N:P significantly by 24.6% and 7.7% (P < 0.01). The SMB C:N, C:P and N:P ratios increased significantly with warming, N addition and warming plus N addition. Warming and N addition increased the correlations between SOC and soil microbial biomass C (SMBC), soil total P and soil microbial biomass P (SMBP), warming increased the correlation between the soil total N and soil microbial biomass N (SMBN). After four years' treatment, our results demonstrated that the combined effects of warming and N fertilization could change the C, N, P cycling by affecting soil and SMB C:N:P ratios significantly and differently. At the same time, our results suggested SMB might have weak homeostasis in Sonnen Grassland and warming and N addition would ease N-limitation but aggravate P-limitation in northeastern China. Furthermore, these results further the current demonstration of the relationships between the soil and SMB C:N:P stoichiometry in response to global change in temperate grassland ecosystems.