Acute liver failure (ALF) is a rapidly progressing critical illness with a high mortality rate. Circulating inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), play a significant role in the pathophysiology of ALF through promoting hepatocellular apoptosis. Ginsenoside Rg1, the primary active ingredient in Panax ginseng (also termed Asian or Korean ginseng), has been reported to inhibit TNF-α production and has been shown to significantly attenuate liver fibrosis development. Here, we assessed ginsenoside Rg1's potential as a therapy for ALF by investigating the effect of ginsenoside Rg1 treatment on circulating inflammatory markers, hepatocellular apoptosis, and relevant apoptotic signaling pathways in a well-established murine ALF model. We found that ginsenoside Rg1 significantly reduces liver damage in a murine ALF model through inhibiting TNF-α-induced, caspase-dependent hepatocellular apoptosis. These results support the further investigation of ginsenoside Rg1 as a therapeutic candidate for ALF.

Hyperphosphatemia or even serum phosphate levels within the “normal laboratory range” are highly associated with increased cardiovascular disease risk and mortality in the general population and patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the development of hypertension, vascular calcification, cardiac valvular calcification, atherosclerosis, left ventricular hypertrophy and myocardial fibrosis by distinct mechanisms. Therefore, phosphate is considered as a promising therapeutic target to improve the cardiovascular outcome in CKD patients. The current therapeutic strategies are based on dietary and pharmacological reduction of serum phosphate levels to prevent hyperphosphatemia in CKD patients. Large randomized clinical trials with hard endpoints are urgently needed to establish a causal relationship between phosphate excess and cardiovascular disease (CVD) and to determine if lowering serum phosphate constitutes an effective intervention for the prevention and treatment of CVD.

Background There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir–ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19. Method In this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion. Results A total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81, p = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days ( p = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days ( p = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups. Conclusions and relevance rSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied. Key messages There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus. In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir–ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.

BackgroundFever of unknown origin (FUO) has always been a challenging problem for physicians since it was first reported half a century ago. This study aimed to investigate the clinical features of FUO and to compare the clinical significance of the classical diagnostic criteria and the Chinese revised diagnostic criteria of FUO.MethodsWe retrospectively collected a series of 140 patients admitted to our hospital between September 2011 and June 2013 because of prolonged febrile illnesses (lasting at least 2 weeks, temperature ≥38.5°C) without diagnosis and categorized them into two groups according to the Chinese revised diagnostic criteria (group A) and classical diagnostic criteria (group B) for FUO. The A group included patients presenting with fever persisting between 2 and 3 weeks with the diagnosis remaining uncertain after three outpatient visits or at least 3 days of hospital investigation. The B group included patients presenting with fever persisting for more than 3 weeks with no established diagnosis after 1 week of hospital investigation. The general conditions, etiologies, definite diagnosis times, and diagnostic methods of the two groups were compared.ResultsThere were no significant differences in the general conditions, etiologies, definite diagnosis times, and diagnostic methods between the Chinese revised diagnostic criteria and classical diagnostic criteria.ConclusionBoth the examined FUO diagnostic criteria are suitable for clinical practice in this region.

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