Efficacy and Safety of Huashi Baidu Granules in Treating Patients with SARS-CoV-2 Omicron Variant: A Single-Center Retrospective Cohort Study.

OBJECTIVE: To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. METHODS: A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users). RESULTS: The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%, P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8-11 days) vs. 11 days (IQR: 10.25-12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2-4 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days), P<0.01; 10 days (IQR: 8-11 days) vs. 11 days (IQR: 10-12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2-6 days) vs. 5 days (IQR: 4-7 days), P<0.01; 10.5 days (IQR: 8.75-11 days) vs. 11.0 days (IQR: 10.75-13 days); P<0.01]. No serious AEs were reported during the study. CONCLUSION: HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472).

Macrophage migration inhibitory factor triggers vascular smooth muscle cell dedifferentiation by a p68-serum response factor axis.

AIMS: Macrophage migration inhibitory factor (MIF) is an important proinflammatory mediator linked to arterial diseases. Although its inflammatory property such as macrophage recruitment is known for contributing to vascular pathogenesis, the direct effects of MIF on homeostasis and biological function of vascular smooth muscle cell (VSMC) that are crucial for development of arterial abnormalities, are poorly understood. METHODS AND RESULTS: We show that MIF is able to directly induce VSMC dedifferentiation, a pathophysiological process fundamental for progression of various arterial diseases. Mechanistically, MIF suppresses p68 protein, a crucial regulator of cell growth and organ differentiation, via activation of JNK and p38 MAPKs. siRNA targeting of p68 facilitated dedifferentiation state in VSMCs, whereas p68 overexpression blocked MIF-elicited transition. In addition, MIF decreased the expression of serum response factor (SRF) that governs VSMC differentiation marker genes transcription, through repression of p68 protein. Furthermore, we showed a previously uncharacterized molecular interaction between p68 and SRF by co-immunoprecipitation assay. p68 attenuated MIF-elicited suppression of SRF recruitment to VSMC-specific promoter. Finally, anti-MIF treatment could reverse VSMC dedifferentiation, preserve vascular function, and inhibit remodelling due to vascular injury. CONCLUSIONS: Our results demonstrate a novel mechanism for the regulation of VSMC differentiation by MIF involving p68 and SRF. Strategy for targeting of MIF could inhibit aberrant transition of VSMC in cardiovascular pathogenesis, and may be of therapeutic benefit in phenotype-related arterial remodelling.

A novel lipopolysaccharide-antagonizing aptamer protects mice against endotoxemia.

A growing number of researchers have recognized the importance of using lipopolysaccharide (LPS) as target for the prevention and treatment of sepsis. However, no drugs targeting LPS have been applied clinically. In this study, LPS-inhibiting aptamers were screened by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), and their therapeutic effects for experimental sepsis were observed. After 12 rounds of screening, 46 sequences were obtained. Primary structure analysis indicated that they had identical sequences, partly conserved sequences, or non-conserved sequences. Secondary structure analysis showed these sequences usually contained hairpin or stem-loop structures. Aptamer 19 significantly decreased NF-kappaB activation of monocytes challenged by LPS and reduced the IL-1 and TNF-alpha concentration in the media of LPS-challenged monocytes. Furthermore, aptamer 19 significantly increased the survival rate of mice with endotoxemia. The results suggest that a novel LPS antagonizing aptamer was obtained by SELEX, which successfully treated experimental sepsis.