Potential impact of specific therapy on pregnant women with pulmonary arterial hypertension without cardiac shunt:a descriptive study in northern China

Background:Pregnancy in women with pulmonary arterial hypertension(PAH)is a fatal condition,despite the effectiveness of PAH-specific therapies.The coverage status and effect of specific therapies in pregnant patients with PAH without cardiac shunts in China remain unclear.To investigate this issue,we conducted a multicenter retrospective study in northern China.Methods:The study included 85 patients who were admitted to 4 clinical centers in Shandong Province between October 2010 and August 2020.Maternal endpoint events included(1)maternal death and/or(2)major adverse cardiac events,both occurring during pregnancy or within 6 weeks postpartum.Results:Although the overall mortality rate was encouraging(11.8%),the number of patients receiving PAH-specific therapies was extremely low(28.2%).Moreover,only 15.3%of patients received adequate duration of PAH-specific therapy(≥4 weeks)before delivery,and this subgroup showed the lowest major adverse cardiac events rate(7.7%)compared with that in the untreated(19.7%)and short-time treated groups(<4 weeks;54.5%).Conclusion:Pregnant patients with PAH without cardiac shunts face significantly increased mortality risks.Short-term PAH-specific therapy does not guarantee favorable maternal outcomes.Prepregnancy screening,early identification,and timely intervention are expected to improve maternal outcomes in pregnant women with PAH.

Peginterferon and ribavirin treatment for hepatitis C virus infection

Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.

Specific generation of nitric oxide in mitochondria of cancer cell for selective oncotherapy

Nitric oxide(NO)gas therapy,especially,L-arginine(L-Arg)-based NO treatment strategies have attracted extensive attention in the field of oncotherapy.However,current strategies are unable to differentiate well between normal cells and cancer cells,which may lead to unpredictable toxicity.Motivated by the fact that mitochondria of cancer cells can express excessive nitric oxide synthetase(NOS),herein,a nanozyme-based NO generator,cerium oxide(CeO_(2))-AT,is fabricated to specifically catalyze the production of NO in cancer cells for selective tumor treatment.In this system,after being endocytosed into cancer cells,the generator can produce a number of NO under the catalysis of NOS in mitochondria of cancer cells,which can disrupt the mitochondrial respiratory chain of tumor cells and further induce cell apoptosis.In addition,the generator with catalase(CAT)-like activity can catalyze H_(2)O_(2)to produce O_(2),which can promote the generation of NO and improve the performance of NO gas therapy.What is more,our system has no obvious impact on the viability of normal cells owing to the less production of NO.Our work paves a new way for the development of highly selective NO-based treatment particularly useful for the safe and specific cancer therapy.