Objective: To survey the health-related quality of life (HRQoL) and its influencing factors among patients with COVID-19 in their first medical follow up. Methods: All patients diagnosed with COVID-19 were discharged from 12 hospitals in Wenzhou, Zhejiang from Jan 17, 2020 to Mar 20, 2020. Prospectively collected and analyzed data included demographics, clinical symptoms, comorbidity, and chest CT imaging features at the first follow up, 1 month after discharge. All patients underwent the HRQoL evaluation with the Chinese version of Short-Form 36-item questionnaire (SF-36) as well as a general condition questionnaire. Factors associated with SF-36 were constructed using linear regression. Predictors of impaired physical component summary (PCS) and a mental component summary (MCS) were identified by logistic regression. Results: SF-36 demonstrated a significant difference in HRQoL in patients with COVID-19, except in physical function (PF), when compared to the general Chinese population (p<0.05). The multiple linear regressions demonstrated that age was negatively associated with PF, role physical (RP), but positively associated with vitality (VT) (p<0.05). PF, bodily pain (BP), and role-emotional (RE) were negatively associated with the female sex (p<0.05). For mental health, the clinical subtypes were significant associated factors (p < 0.05). Length of stay (LOS) was strongly negatively associated with RE and RP, and positively associated with VT (p< 0.05). Logistical regression revealed that non-obese overweight (OR 3.71) and obesity (OR 3.94) were risk factors for a low PCS and female sex (OR 2.22) was a risk factor for a low MCS. Conclusions: Health-related quality of life was poor among COVID-19 patients at the 1 month follow-up. Patients suffered from significant physical and psychological impairment. Therefore, prospective monitoring of individuals exposed to SARS-CoV-2 is needed in order to fully understand the long-term impact of COVID-19, as well as to inform prompt and efficient interventions to alleviate suffering.
Acidic fibroblast growth factor (aFGF) exerts a protective effect on spinal cord injury (SCI) but is limited by the lack of physicochemical stability and the ability to cross the blood spinal cord barrier (BSCB). As promising biomaterials, hydrogels contain substantial amounts of water and a three-dimensional porous structure and are commonly used to load and deliver growth factors. Heparin can not only enhance growth factor loading onto hydrogels but also can stabilize the structure and control the release behavior. Herein, a novel aFGF-loaded thermosensitive heparin-poloxamer (aFGF-HP) hydrogel was developed and applied to provide protection and regeneration after SCI. To assess the effects of the aFGF-HP hydrogel, BSCB restoration, neuron and axonal rehabilitation, glial scar inhibition, inflammatory response suppression, and motor recovery were studied both in vivo and in vitro. The aFGF-HP hydrogels exhibited sustained release of aFGF and protected the bioactivity of aFGF in vitro. Compared to groups intravenously administered either drug-free HP hydrogel or aFGF alone, the aFGF-HP hydrogel group revealed prominent and attenuated disruption of the BSCB, reduced neuronal apoptosis, reactive astrogliosis, and increased neuron and axonal rehabilitation both in vivo and in vitro. This work provides an effective approach to enhance recovery after SCI and provide a successful strategy for SCI protection.
As coronavirus disease 2019 (COVID-19) outbreak, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started in China in January, 2020, repurposing approved drugs is emerging as important therapeutic options. We reported here the first clinical study using hepatitis C virus (HCV) protease inhibitor, danoprevir, to treat COVID-19 patients. Danoprevir (Ganovo) is a potent HCV protease (NS3/4A) inhibitor (IC50 = 0.29 nM), which was approved and marketed in China since 2018 to treat chronic hepatitis C patients. Ritonavir is a CYP3A4 inhibitor to enhance plasma concentration of danoprevir while it also acts as a human immunodeficiency virus (HIV) protease inhibitor at high doses. The chymotrypsin-like protease of SARS-CoV-2 shares structure similarity with HCV and HIV proteases. In the current clinical study (NCT04291729) conducted at the Nineth Hospital of Nanchang, we evaluated therapeutic effects of danoprevir, boosted by ritonavir, on treatment naive and experienced COVID-19 patients. The data from this small-sample clinical study showed that danoprevir boosted by ritonavir is safe and well tolerated in all patients. After 4 to 12-day treatment of danoprevir boosted by ritonavir, all eleven patients enrolled, two naive and nine experienced, were discharged from the hospital as they met all four conditions as follows: (1) normal body temperature for at least 3 days; (2) significantly improved respiratory symptoms; (3) lung imaging shows obvious absorption and recovery of acute exudative lesion; and (4) two consecutive RT-PCR negative tests of SARS-CoV-2 nucleotide acid (respiratory track sampling with interval at least one day). Our findings suggest that repurposing danoprevir for COVID-19 is a promising therapeutic option.
The COVID-19 caused by a novel strain of coronavirus has been spreading rapidly since its onset in Wuhan, the capital city of central China's Hubei Province, in December 2019. It is highly communicable through human-to-human transmission. China has been making unprecedented efforts in treating the confirmed cases, identifying and isolating their close contacts and suspected cases to control the source of infection and cut the route of transmission. China's devotion in handling this epidemic has effectively and efficiently curbed communication domestically and across the border. Representative measures adopted by Wenzhou, the worst hit city out of Hubei Province, are examined to elucidate those massive undertakings with the aim of enhancing international understanding and building global rapport in fighting this evolving epidemic situation.
The aim of the present study is to explore the molecular mechanism of fibroblast growth factor 21 (FGF21) in protecting against diabetic cardiomyopathy (DCM). Streptozotocin/high-fat diet (STZ/HFD) was used to induced diabetes in FGF21-deficient mice and their wild-type littermates, followed by evaluation of the difference in DCM between the two genotypes. Primary cultured cardiomyocytes were also used to explore the potential molecular mechanism of FGF21 in the protection of high glucose (HG)-induced cardiomyocyte injury. STZ/HFD-induced cardiomyopathy was exacerbated in FGF21 knockout mice, which was accompanied by a significant reduction in cardiac AMP-activated protein kinase (AMPK) activity and paraoxonase 1 (PON1) expression. By contrast, adeno-associated virus (AAV)-mediated overexpression of FGF21 in STZ/HFD-induced diabetic mice significantly enhanced cardiac AMPK activity, PON1 expression and its biological activity, resulting in alleviated DCM. In cultured cardiomyocytes, treatment with recombinant mouse FGF21 (rmFGF21) counteracted HG-induced oxidative stress, mitochondrial dysfunction, and inflammatory responses, leading to increased AMPK activity and PON1 expression. However, these beneficial effects of FGF21 were markedly weakened by genetic blockage of AMPK or PON1. Furthermore, inactivation of AMPK also markedly blunted FGF21-induced PON1 expression but significantly increased HG-induced cytotoxicity in cardiomyocytes, the latter of which was largely reversed by adenovirus-mediated PON1 overexpression. These findings suggest that FGF21 ameliorates DCM in part by activation of the AMPK-PON1 axis.
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