The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens.
Abstract The human WW domain containing oxidoreductase ( WWOX ) gene has been identified as a tumor suppressor gene. However, recent reports have demonstrated its dominant role in autosomal recessive disorders of the central nervous system, especially in early onset epileptic encephalopathy. Here, we report a Chinese case with novel compound heterozygous mutation of WWOX gene (c.229_230+2del mutation originated from her mother and c.1065dup (p.Ala356Serfs*173) variation from her father), and compare them to previously reported 59 WWOX ‐related epileptic encephalopathy (WOREE). Early onset and frequent epileptic seizures in the postnatal period, hypsarrhythmia patterns in EEG background and retarded development are the most important characteristics of WOREE in infants. Although the seizures in our case can be controlled by phenobarbital and topiramate, the prognosis of WOREE is poor.
Skeletal muscle is a highly plastic organ that adapts to different metabolic states or functional demands. This study explored the impact of permanent glucose restriction (GR) on skeletal muscle composition and metabolism. Using
ABSTRACT Existing pharmacodynamic (PD) mathematical models for drug combinations discriminate antagonistic, additive, multiplicative, and synergistic effects, but fail to consider how concentration-dependent drug interaction effects may vary across an entire dose-response matrix. We developed a two-way pharmacodynamic (TWPD) model to capture the PD of two-drug combinations. TWPD captures interactions between upstream and downstream drugs that act on different stages of viral replication, by quantifying upstream drug efficacy and concentration-dependent effects on downstream drug pharmacodynamic parameters. We applied TWPD to previously published in vitro drug matrixes for repurposed potential anti-Ebola and anti-SARS-CoV-2 drug pairs. Depending on the drug pairing, the model recapitulated combined efficacies as or more accurately than existing models and can be used to infer efficacy at untested drug concentrations. TWPD fits the data slightly better in one direction for all drug pairs, meaning that we can tentatively infer the upstream drug. Based on its high accuracy, TWPD could be used in concert with PK models to estimate the therapeutic effects of drug pairs in vivo .
Xuezhikang (XZK), a red yeast rice extract with lipid-lowering effect, contains a family of naturally statins, such as lovastatin. In recent years, its effect beyond the regulation of lipids has also been received increasing attention. Therefore, the purpose of this study was to explore the protective effects and possible molecular mechanisms of XZK on brain injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), and to investigate whether it has a dose-dependent effect and the difference with lovastatin.Rats were treated with low-dose XZK (XZK-L, 20 mg/kg/d), high-dose XZK (XZK-H, 200 mg/kg/d) and lovastatin by gavage once daily for 2 weeks before CA. The levels of TNF-α, IL-6 and IL-1β were evaluated at 1, 4, and 72 h post-CA/CPR. The survival rate, neurological deficit score (NDS), and expression of TLR4, phosphorylated NF-κB and TNF-α in hippocampal tissues were evaluated at 72 h post-CA/CPR.CA/CPR induced a significant increase in serum TNF-α, IL-6 and IL-1β, as well as increased expressions of TLR4, phosphorylated NF-κB and TNF-α in the hippocampus. Both low-dose and high-dose XZK treatment inhibited the expression of these inflammatory cytokines. In addition, it reduced the number of defibrillations and shortened the duration of CPR required for return of spontaneous circulation (ROSC). XZK treatment also improved neurological function and 72-hour survival rate in rats. However, high-dose XZK was superior to lovastatin in the suppression of IL-1β mRNA level and TNF-α protein level in hippocampal tissue after CPR. There were no significant differences observed among high-dose XZK, low-dose XZK and lovastatin groups in other respects.These results indicated that XZK had a protective effect against brain injury post-CA/CPR. The mechanisms underlying the protective effects of XZK may be related to the suppressing of CA/CPR-induced inflammatory response through the inhibiting TLR4/NF-κB signaling pathway.
Background. In view of the global efforts to develop effective treatments for the current worldwide coronavirus 2019 (COVID-19) pandemic, Qingfei Paidu decoction (QPD), a novel traditional Chinese medicine (TCM) prescription, was formulated as an optimized combination of constituents of classic prescriptions used to treat numerous febrile and respiratory-related diseases. This prescription has been used to treat patients with COVID-19 pneumonia in Wuhan, China. Hypothesis/Purpose. We hypothesized that QPD would have beneficial effects on patients with COVID-19. We aimed to prove this hypothesis by evaluating the efficacy of QPD in patients with COVID-19 pneumonia. Methods. In this single-center, retrospective, observational study, we identified eligible participants who received a laboratory diagnosis of COVID-19 between January 15 and March 15, 2020, in the west campus of Union Hospital in Wuhan, China. QPD was supplied as an oral liquid packaged in 200-mL containers, and patients were orally administered one package twice daily 40 minutes after a meal. The primary outcome was death, which was compared between patients who did and did not receive QPD (QPD and NoQPD groups, respectively). Propensity score matching (PSM) was used to identify cohorts. Results. In total, 239 and 522 participants were enrolled in the QPD and NoQPD groups, respectively. After PSM at a 1 : 1 ratio, 446 patients meeting the criteria were included in the analysis with 223 in each arm. In the QPD and NoQPD groups, 7 (3.2%) and 29 (13.0%) patients died, and those in the QPD group had a significantly lower risk of death (hazard ratio (HR) 0.29, 95% CI: 0.13–0.67) than those in the NoQPD group ( p = 0.004). Furthermore, the survival time was significantly longer in the QPD group than in the NoQPD group ( p < 0.001). Conclusion. The use of QPD may reduce the risk of death in patients with COVID-19 pneumonia.
Clinical manifestation and neonatal outcomes of pregnant women with coronavirus disease 2019 (COVID-19) were unclear in Wuhan, China.We retrospectively analyzed clinical characteristics of pregnant and nonpregnant women with COVID-19 aged from 20 to 40, admitted between January 15 and March 15, 2020 at Union Hospital, Wuhan, and symptoms of pregnant women with COVID-19 and compared the clinical characteristics and symptoms to historic data previously reported for H1N1.Among 64 patients, 34 (53.13%) were pregnant, with higher proportion of exposure history (29.41% vs 6.67%) and more pulmonary infiltration on computed tomography test (50% vs 10%) compared to nonpregnant women. Of pregnant patients, 27 (79.41%) completed pregnancy, 5 (14.71%) had natural delivery, 18 (52.94%) had cesarean section, and 4 (11.76%) had abortion; 5 (14.71%) patients were asymptomatic. All 23 newborns had negative reverse-transcription polymerase chain results, and an average 1-minute Apgar score was 8-9 points. Pregnant and nonpregnant patients show differences in symptoms such as fever, expectoration, and fatigue and on laboratory tests such as neurophils, fibrinogen, D-dimer, and erythrocyte sedimentation rate. Pregnant patients with COVID-19 tend to have more milder symptoms than those with H1N1.Clinical characteristics of pregnant patients with COVID-19 are less serious than nonpregnant. No evidence indicated that pregnant women may have fetal infection through vertical transmission of COVID-19. Pregnant patients with H1N1 had more serious condition than those with COVID-19.
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