No effective treatment for COVID-19 has been well established yet. Nafamostat, known as anticoagulant, has potential anti-inflammatory and anti-viral activities against COVID-19. We report three cases of COVID-19 pneumonia who progressed while using antiviral drugs and needed supplementary oxygen therapy, improved after treatment with nafamostat. These preliminary findings show the possibility that Nafamostat can be considered to be used in elderly patients with COVID-19 pneumonia who need oxygen therapy. The effectiveness of nafamostat should be evaluated in further studies.COVID-19 associated cytokine storm could induce ARDS rapidly and the patients would require the support of mechanic ventilation. However, the prognosis was not that optimistic. The outcome might be changed if the intervention of EBP was performed timely. We present a case of severe SARS-CoV-2 infection who recovered from cytokine storm.Endocarditis due to Lactobacillus species is extremely rare. We report an uncommon case of Lactobacillus plantarum bioprosthetic aortic valve endocarditis, presenting with severe aortic steno-regurgitation, which responded to conventional medical and surgical treatment. This case provides a better understanding of the disease process of L. plantarum and highlights the role of transesophageal echocardiography in following the entire course of endocarditis.Pneumonia can be stopped while fight against the SARS-COV-2 outbreak.•Pneumonia cases (except COVID-19 cases) were dramatically decreased since the control measures were onset.•Other respiratory infection diseases may also to some extent be stopped while fighting against the pandemic of COVID-19.Inorganic dietary nitrate plays vital roles in biological functions via the exogenous NO3-/NO2-/NO pathway under hypoxia and ischemia. We previously verified the antioxidative effects of inorganic nitrate in a mouse model of total body irradiation (TBI). Accordingly, in this study, we evaluated the effects of inorganic nitrate on prevention of TBI-induced colon injury and dysbiosis of the gut microbiome. Nitrate significantly rescued the abnormal biological indexes (body weight, white blood cell, red blood cell, platelet, hemoglobin level and intestinal canal lengths) induced by TBI. Then, we detected oxidative stress and DNA damage indexes (phospho-histone H2AX and p53 binding protein 1), which were both increased by irradiation (IR) and alleviated by nitrate. IR-induced apoptosis and senescence were ameliorated by inorganic nitrate. The distribution of the gut microbiome differed for mice with TBI and those receiving inorganic nitrate. The average abundance of Lactobacillus significantly increased, and that of Bacteroidales decreased at the genus level in the nitrate group compared with that in the IR alone group. At 30 days after TBI, the abundances of Bacteroides and Faecalibaculum decreased, whereas that of Lactobacillus increased in the IR + nitrate group compared with that in the IR alone group. Inorganic nitrate efficiently prevents TBI-induced colon epithelium injury and maintains the homeostasis of the gut microbiome. Thus, our results showed that inorganic nitrate might be a promising treatment for TBI induced colon injury.Objective This study investigated whether melatonin alleviates intervertebral disc degeneration (IVDD) by promoting autophagy through inhibiting the NF-κB signaling pathway. Methods Magnetic resonance imaging (MRI), hematoxylin and eosin (H&E) staining and Safranin-O staining were used to measure disc degeneration in rat needle puncture IVDD models, and melatonin was injected intraperitoneally in the treated group to test its function. The expression of autophagy and extracellular matrix (ECM) degeneration related-markers were measured in the discs using immunohistochemistry. Transmission electron microscopy was used to evaluate the activation of autophagy in human nucleus pulposus (NP) tissues with different degenerated statuses. The expression of autophagy and disc degeneration related-markers were detected in NP cells by Western blot, RT-qPCR, and immunofluorescence analyses. https://www.selleckchem.com/products/triparanol-mer-29.html NF-κB signaling pathway involvement was studied by lentivirus-mediated knockdown, Western blotting, and immunohistochemistry and immunofluorescence staining. Results Melatonin prevented IVDD development in vivo and in vitro. Compared to non-degenerated disc tissues, degenerated human NP tissues showed a decrease in the autophagy-specific marker LC3B and the numbers of autophagosomes and autolysosomes, whereas the p62 level was increased; similar results were observed in rat IVDD models, indicating a negative correlation between autophagy and IVDD. Furthermore, both in vivo and in vitro studies found that melatonin application induced autophagy and reduced ECM disc degradation. Melatonin was also shown to regulate autophagy by inhibiting the NF-κB signaling pathway in vivo and vitro. Conclusion This study indicates that melatonin prevents IVDD by promoting autophagy, indicating its possible therapeutic potential for controlling the progression of IVDD.Objectives Subchondral bone may contribute to knee osteoarthritis (OA) pain. Nerve growth factor (NGF) can stimulate nerve growth through TrkA. We aimed to identify how sensory nerve growth at the osteochondral junction in human and rat knees associates with OA pain. Methods Eleven symptomatic chondropathy cases were selected from people undergoing total knee replacement for OA. Twelve asymptomatic chondropathy cases who had not presented with knee pain were selected post-mortem. OA was induced in rat knees by meniscal transection (MNX) and sham-operated rats were used as controls. Twice-daily oral doses (30 mg/kg) of TrkA inhibitor (AR786) or vehicle were administered from before and up to 28 days after OA induction. Joints were analysed for macroscopic appearances of articular surfaces, OA histopathology and calcitonin gene-related peptide-immunoreactive (CGRP-IR) sensory nerves in medial tibial plateaux, and rats were assessed for pain behaviors. Results The percentage of osteochondral channels containing CGRP-IR nerves in symptomatic chondropathy was higher than in asymptomatic chondropathy (difference 2.5% [95% CI 1.1-3.7]), and in MNX-than in sham-operated rat knees (difference 7.8% [95%CI 1.7-15.0]). Osteochondral CGRP-IR innervation was significantly associated with pain behavior in rats. Treatment with AR786 prevented the increase in CGRP-IR nerves in osteochondral channels and reduced pain behavior in MNX-operated rats. Structural OA was not significantly affected by AR786 treatment. Conclusions CGRP-IR sensory nerves within osteochondral channels are associated with pain in human and rat knee OA. Reduced pathological innervation of the osteochondral junction might contribute to analgesic effects of reduced NGF activity achieved by blocking TrkA.