Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020

Exercise Ameliorates Atherosclerosis via Up-Regulating Serum β-Hydroxybutyrate Levels

Atherosclerosis, accompanied by inflammation and metabolic disorders, is the primary cause of clinical cardiovascular death. In recent years, unhealthy lifestyles (e.g., sedentary lifestyles) have contributed to a worldwide epidemic of atherosclerosis. Exercise is a known treatment of atherosclerosis, but the precise mechanisms are still unknown. Here, we show that 12 weeks of regular exercise training on a treadmill significantly decreased lipid accumulation and foam cell formation in ApoE−/− mice fed with a Western diet, which plays a critical role in the process of atherosclerosis. This was associated with an increase in β-hydroxybutyric acid (BHB) levels in the serum. We provide evidence that BHB treatment in vivo or in vitro increases the protein levels of cholesterol transporters, including ABCA1, ABCG1, and SR-BI, and is capable of reducing lipid accumulation. It also ameliorated autophagy in macrophages and atherosclerosis plaques, which play an important role in the step of cholesterol efflux. Altogether, an increase in serum BHB levels after regular exercise is an important mechanism of exercise inhibiting the development of atherosclerosis. This provides a novel treatment for atherosclerotic patients who are unable to undertake regular exercise for whatever reason. They will gain a benefit from receiving additional BHB

Exercise Ameliorates Atherosclerosis via Up-Regulating Serum β-Hydroxybutyrate Levels

Atherosclerosis, accompanied by inflammation and metabolic disorders, is the primary cause of clinical cardiovascular death. In recent years, unhealthy lifestyles (e.g., sedentary lifestyles) have contributed to a worldwide epidemic of atherosclerosis. Exercise is a known treatment of atherosclerosis, but the precise mechanisms are still unknown. Here, we show that 12 weeks of regular exercise training on a treadmill significantly decreased lipid accumulation and foam cell formation in ApoE−/− mice fed with a Western diet, which plays a critical role in the process of atherosclerosis. This was associated with an increase in β-hydroxybutyric acid (BHB) levels in the serum. We provide evidence that BHB treatment in vivo or in vitro increases the protein levels of cholesterol transporters, including ABCA1, ABCG1, and SR-BI, and is capable of reducing lipid accumulation. It also ameliorated autophagy in macrophages and atherosclerosis plaques, which play an important role in the step of cholesterol efflux. Altogether, an increase in serum BHB levels after regular exercise is an important mechanism of exercise inhibiting the development of atherosclerosis. This provides a novel treatment for atherosclerotic patients who are unable to undertake regular exercise for whatever reason. They will gain a benefit from receiving additional BHB

Childhood lichenoid granulomatous stomatitis: a case report and literature review

Objective To investigate the classification, clinical manifestations, diagnosis, differential diagnosis and treatment of oral lichenoid lesions and provide a reference for clinical practice. Methods Hospital ethical approval and patient informed consent were obtained. We report a case of oral lichenoid lesion in children and review the diagnosis and treatment of oral lichenoid damage in the literature. Results The patient experienced repeated rupture of the dorsal surface of the tongue with pain for more than 3 years. There was a large area of tongue back surface erosion with an irregular shape, surrounded by pearly-white lines. The left erosive area was accompanied by tissue hyperplasia, which was approximately 1.5 cm × 2.0 cm, with tough texture and broad masses. The pathological diagnosis of the patient was oral lichenoid lesion. After biopsy of the dorsal surface of the tongue, the pathological diagnosis of the patient was granulomatous inflammation. The final diagnosis of lichenoid granulomatous stomatitis was made on the basis of the patient's intraoral damage features, systemic history, medication history and histopathological findings. A review of the literature suggests that oral lichenoid lesions have an unknown etiology and need to be clinically differentiated from oral lichen planus, oral lichenoid drug reactions, oral lichenoid contact damage and chronic ulcerative stomatitis. The clinical treatment of oral lichen planus is based on the topical and/or systemic use of glucocorticoids. Conclusion There are still no uniform criteria for the classification and diagnosis of oral lichenoid lesions. They rely mainly on history taking, clinical manifestations and histopathological findings, and the treatment is mainly based on the topical and/or systemic use of glucocorticoids

Effect of Distiller's Grains Biochar Combined with

Aiming to clarify the effect of Lactobacillus plantarum combined with distiller's grains biochar on lead, cadmium and zinc complex contaminated soil, a pot experiment was conducted to investigate soil effective heavy metal concentration, plant growth, and heavy metal accumulation in the Sorghum hybrid sudangrass. The results revealed that single application of distiller's grains biochar, Lactobacillus plantarum thallus, Lactobacillus plantarum supernatant, and combined application of distiller's grain biochar and Lactobacillus plantarum thallus could significantly reduce the content of available Cd, Pb, and Zn in soil (P<0.05), and reduced the aboved metals content in the aerial parts and roots of Sorghum hybrid sudangrass to varying degrees. Compared with control group, high dosage of distiller's grain biochar and Lactobacillus plantarum thallus combined application treated Sorghum hybrid sudangrass with the lowest heavy metals content. The concentrations of Cd, Pb, and Zn decreased by 40.93%, 31.84%, and 40.25% in the aerial part, respectively, and decreased by 41.09%, 21.79%, and 29.62% in the root, respectively. The high dosage of distiller's grains biochar and the combination application of distiller's grains biochar and Lactobacillus plantarum thallus significantly increased the plant height and biomass of Sorghum hybrid sudangrass (P<0.05), and the overall promotion effect was better than other treatments

Signal “Off-On” Biosensor Based on Fluorescence Resonance Energy Transfer (FRET) for Detection of Sorghum Mosaic Virus

A fluorescence off-on method for the detection of Sorghum mosaic virus (SrMV) based on fluorescence resonance energy transfer (FRET) was developed in this study. The biosensor was realized by the adsorption of SrMV coat protein (CP) on gold nanoparticle (AuNP) and conjugation of anti-SrMV antibody (Ab) on cadmium telluride quantum dot (CdTe QD). The optimum quenching efficiency was about 50% obtained at a CdTe QD-Ab/AuNP-CP ratio of 1:7. Moreover, the feasibility of the developed biosensor was verified by the detection of purified CP and the limit of detection was estimated as 0.02 μg/mL. This strategy was also successfully applied to monitor SrMV CP in plant sap with a recovery rate between 97.7 and 107.4%. The developed biosensor is a simple, rapid, and efficient technique which does not need excessive washing and separation steps

Multidrug-resistant tuberculosis in middle ear: A case report

Background: Tuberculosis (TB) continues to be a common disease in developing countries, among which middle ear TB is rare. Furthermore, it is relatively difficult to make an early diagnosis and provide follow-up treatment for middle ear TB. So, it is necessary to report this case for reference and further discussion. Case presentation: We reported 1 case of multidrug-resistant tuberculosis otitis media. TB otitis media is rare in tuberculosis; multidrug-resistant TB otitis media is even more rare. Our paper analyzes the possible causes, imaging, molecular biology, pathology, and clinical manifestations of multidrug-resistant TB otitis media. Conclusion: PCR and DNA molecular biology techniques are highly recommended for the early diagnosis of multidrug-resistant TB otitis media. Early, effective anti-tuberculosis treatment is the guarantee for further recovery for patients with multidrug-resistant TB otitis media

Optimization of a Pilot Hydrocracking Unit To Improve the Yield and Quality of Jet Fuel Together with Heavy Naphtha and Tail Oil

Hydrocracking of vacuum gas oil (VGO) is a commonly used process to produce more high-quality transportation fuels and chemicals. In this work, effects of four different operation modes, i.e., SSOTP, FRTHT, FRTHC, and PRTHT, with different recycling modes of tail oil are comparatively studied on the performance of VGO hydrocracking. The FRTHT and FRTHC give rise to a higher yield and/or quality of jet fuel, heavy naphtha, and tail oil compared with that of the other two modes. Moreover, effects of the distillation–cutting scheme are also studied to further increase the yield and quality of jet fuel. It is found that all four of the operation modes show a much higher yield but a slightly higher smoke point for the jet fuel. The insights revealed here could shed new light on the optimization of VGO hydrocracking to produce more targeted products

Maggot Extract Inhibits Cell Migration and Tumor Growth by Targeting HSP90AB1 in Ovarian Cancer

Ovarian cancer is one of the most lethal gynecological malignancies, because of metastatic dissemination with poor late clinical therapy. Maggots have been used in traditional Chinese medicine, where they are also known as ‘Wu Gu Chong’. Previous studies have indicated that maggot extract (ME) was beneficial for the treatment of gastric cancer when combined with other drugs, but the effect on anti-ovarian cancer and the underlying mechanism remains unclear. The aim of this study was to investigate the effects of ME on suppressing the proliferation and migration of ovarian cancer cells, and to clarify the underlying mechanism. In this research, Cell Counting Kit-8 (CCK-8), colony formation assay, and luciferase-positive cell quantification assay were employed to identify the inhibitory effects of ME on cell proliferation. Then, the pro-apoptosis and anti-metastasis effects of ME were explored by Western blot, dual annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assay, immunofluorescent staining, and wound-healing assay. We further established a xenograft model by subcutaneously or intraperitoneally injecting BALB/c nude mice with SKOV3 cells stably expressing luciferase, and the mice were treated with ME. The results showed that ME therapy effectively restrained the growth and metastasis of ovarian tumors in vivo. Furthermore, the mRNA levels of cancer factors including heat shock protein 90 alpha family class B member 1 (HSP90AB1), MYC, and insulin like growth factor 1 receptor (IGF1R) were analyzed by quantitative real-time PCR assay to explore the possible antitumor mechanisms of ME. Next, HSP90 ATPase activity was inhibited by geldanamycin in A2780, and the cell viability was shown to be dramatically reduced, decreasing further with the combination of ME and cisplatin. In turn, HSP90AB1 overexpression effectively inhibited the effect of ME in suppressing capability for cell viability and migration. In addition, HSP90AB1 overexpression limited the ability of ME to inhibit expression of MYC and IGF1R, while the opposite effect was observed for expression of pro-apoptosis protein caspase3 and BAX. Therefore, this study confirmed the potential roles and mechanisms of ME in inhibiting the growth and metastasis of ovarian tumors and promoting apoptosis of ovarian cancer cells by inhibiting overexpression of HSP90AB1