Liver fibrosis, a major cause of morbidity and mortality worldwide, leads to liver damage, seriously threatening human health. In our previous study, we demonstrated that 14-kDa phosphohistidine phosphatase (PHP14) was upregulated in fibrotic liver tissue and involved in the migration and lamellipodia formation of hepatic stellate cells (HSCs). In this study, we evaluated PHP14 as a therapeutic target for liver fibrosis and investigated the mechanism by which it mediates liver fibrosis. AAV-shPhpt1 administration significantly attenuates CCl4-induced liver fibrosis in mice. In particular, fibrosis-associated inflammatory infiltration was significantly suppressed after PHP14 knockdown. Mechanistically, PHP14 regulated macrophage recruitment, infiltration and migration by affecting podosome formation of macrophages. Inhibition of PHP14 decreased the expression of the fibrogenic signature at the early stage of liver fibrogenesis and the activation of HSCs in vivo. Thus, PHP14 can be considered a potential therapeutic target for liver fibrosis.

Background There are about 7000 rare diseases worldwide, of which only 5% of the diseases can be treated with medicines, showing that it’s important to improve patient access to orphan drugs. Recently, China has actively worked to set up a national system for rare diseases to improve the diagnosis and treatment capabilities and ensure the accessibility of drugs. However, the benefits of the system have yet not to be measured. This study aimed to provide an overview of orphan drug access based on the Compendium of China’s First List of Rare Diseases and National Network to Collaborate on Diagnosis and Treatment of Rare Diseases, expecting to map a blueprint for orphan drug access in China. Methods Framework of China’s national system for rare diseases was summarized. We surveyed the availability and affordability of 79 approved orphan drugs based on the Compendium of China’s First List of Rare Diseases in 30 leading provincial institutions from 2017 to 2020. The availability was measured annually at 3 levels (market, hospital and drug), and affordability was reflected by comparing costs of daily defined dose with per capita income of urban and rural residents, with the National Basic Medical Insurance considered. Results The market availability of orphan drugs in China showed an upward trend. As of 2020, the median hospital-level availability was 41.1% (increased by 1.5 times), highly available drugs increased by 16.5%. There were 64/74 orphan drugs that were affordable to rural/urban residents with the National Basic Medical Insurance considered (an increase of 14.1%), and the urban–rural gap of affordability ratio was narrowed (down by 6.0%). Comprehensive analysis showed the proportions of drugs with better availability and affordability in urban and rural areas by 2020 were 39.4% and 32.3%, respectively, which had increased but were still at a low level. Conclusions China’s national system for rare diseases has made great progress in orphan drug access, indicating that it’s been functioning under the joint reformation of medical treatment, medical insurance and medicines supply. The list of rare diseases will be updated and collaboration in networks will be enhanced to further improve the system.

Loneliness has been reported to be associated with an increased risk of dementia; however, the extent of this relationship remains controversial. This study aimed to assess the strength of the relationship between loneliness and dementia using a meta-analysis approach. PubMed, EMBASE, and China National Knowledge Internet databases were systematically searched for potentially included studies from inception up to 17 February 2022. A meta-analysis was performed using a random-effects model to assess pooled relative risks (RRs) and 95% confidence intervals (CIs). A literature search identified 16 cohort studies (published in 15 articles), among which 4,625 dementia cases and 62,345 individuals were selected for further meta-analysis. Loneliness was associated with an increased risk of Alzheimer’s disease (AD) (RR: 1.72, 95% CI: 1.32–2.23; P < 0.001) and dementia (RR: 1.23, 95% CI: 1.16–1.31; P < 0.00001). However, no significant association between loneliness and risk of mild cognitive impairment (MCI) (RR: 1.34, 95% CI: 0.97–1.87; P = 0.080) or vascular dementia (VaD) (RR: 1.01, 95% CI: 0.51–1.99; P = 0.973) was observed. Results revealed that loneliness might increase the risk of Alzheimer’s disease and dementia. Early interventions that limit loneliness may reduce risk of dementia and Alzheimer’s disease.

The Zika virus (ZIKV) epidemic poses a significant threat to human health globally. Thus, there is an urgent need for developing effective anti-ZIKV agents. ZIKV non-structural protein 5 RNA-dependent RNA polymerase (RdRp), a viral enzyme for viral replication, has been considered an attractive drug target. In this work, we screened an anti-infection compound library and a natural product library by virtual screening to identify potential candidates targeting RdRp. Then, five selected candidates were further applied for RdRp enzymatic analysis, cytotoxicity, and binding examination by SPR. Finally, posaconazole (POS) was confirmed to effectively inhibit both RdRp activity with an IC50 of 4.29 μM and the ZIKV replication with an EC50 of 0.59 μM. Moreover, POS was shown to reduce RdRp activity by binding with the key amino acid D666 through molecular docking and site-directed mutation analysis. For the first time, our work found that POS could inhibit ZIKV replication with a stronger inhibitory activity than chloroquine. This work also demonstrated fast anti-ZIKV screening for inhibitors of RdRp and provided POS as a potential anti-ZIKV agent.