Brain Network Homeostasis and Plasticity of Salidroside for Achieving Neuroprotection and Treating Psychiatric Sequelae Stemming from Stress (preprint)

The coronavirus disease 2019 (COVID-19) pandemic has affected the mental health of individuals worldwide, and the risk of psychiatric sequelae and consequent mental disorders has increased among the general population, health care workers and patients with COVID-19. Achieving effective and widespread prevention of pandemic-related psychiatric sequelae to protect the mental health of the global population is a serious challenge. Salidroside, as a natural agent, has substantial pharmacological activity and health effects, exerts obvious neuroprotective effects, and may be effective in preventing and treating psychiatric sequelae and mental disorders resulting from stress stemming from the COVID-19 pandemic. Herein, we systematically summarise, analyse and discuss the therapeutic effects of salidroside in the prevention and treatment of psychiatric sequelae as well as its roles in preventing the progression of mental disorders, and fully clarify the potential of salidroside as a widely applicable agent for preventing mental disorders caused by stress; the mechanisms underlying the potential protective effects of salidroside are involved in the regulation of the oxidative stress, neuroinflammation, neural regeneration and cell apoptosis in the brain, the network homeostasis of neurotransmission, HPA axis and cholinergic system, and the improvement of synaptic plasticity. Notably, this review innovatively proposes that salidroside is a potential agent for treating stress-induced health issues during the COVID-19 pandemic and provides scientific evidence and a theoretical basis for the use of natural products to combat the current mental health crisis.

Integrated network pharmacology analysis, molecular docking, LC-MS analysis and bioassays revealed the potential active ingredients and underlying mechanism of Scutellariae radix for COVID-19

Scutellariae radix (“Huang-Qin” in Chinese) is a well-known traditional herbal medicine and popular dietary supplement in the world, extensively used in prescriptions of TCMs as adjuvant treatments for coronavirus pneumonia 2019 (COVID-19) patients in China. According to the differences in its appearance, Scutellariae radix can be classified into two kinds: ZiQin (1∼3 year-old Scutellariae baicalensis with hard roots) and KuQin (more than 3 year-old S. baicalensis with withered pithy roots). In accordance with the clinical theory of TCM, KuQin is superior to ZiQin in cooling down the heat in the lung. However, the potential active ingredients and underlying mechanisms of Scutellariae radix for the treatment of COVID-19 remain largely unexplored. It is still not clear whether there is a difference in the curative effect of ZiQin and KuQin for the treatment of COVID-19. In this research, network pharmacology, LC-MS based plant metabolomics, and in vitro bioassays were integrated to explore both the potential active components and mechanism of Scutellariae radix for the treatment of COVID-19. As the results, network pharmacology combined with molecular docking analysis indicated that Scutellariae radix primarily regulates the MAPK and NF-κB signaling pathways via active components such as baicalein and scutellarin, and blocks SARS-CoV-2 spike binding to human ACE2 receptors. In vitro bioassays showed that baicalein and scutellarein exhibited more potent anti-inflammatory and anti-infectious effects than baicalin, the component with the highest content in Scutellariae radix. Moreover, baicalein inhibited SARS-CoV-2’s entry into Vero E6 cells with an IC50 value of 142.50 μM in a plaque formation assay. Taken together, baicalein was considered to be the most crucial active component of Scutellariae radix for the treatment of COVID-19 by integrative analysis. In addition, our bioassay study revealed that KuQin outperforms ZiQin in the treatment of COVID-19. Meanwhile, plant metabolomics revealed that baicalein was the compound with the most significant increase in KuQin compared to ZiQin, implying the primary reason for the superiority of KuQin over ZiQin in the treatment of COVID-19.

Impact of the COVID-19 pandemic on congenital diaphragmatic hernia patients: a single-center retrospective study (preprint)

Purpose To investigate the impact of COVID-19 on the treatment of children with congenital diaphragmatic hernia (CDH).Methods We retrospectively collected and compared the data of patients with CDH admitted between January 1, 2020 and December 31, 2021 with the CDH patients admitted before the pandemic between January 1, 2018 and December 31, 2019 (control group).Results During the pandemic, 41 patients with CDH diagnosed prenatally were transferred to our hospital, and 40 underwent surgical repair. The number of patients treated in our hospital increased by 24.2% compared with that before the pandemic. During the pandemic, the overall survival rate, postoperative survival rate and recurrence rate were 85.4%, 87.5% and 7.3%, respectively, and there were no significant differences compared with the control group. The average length of hospital stay in patients admitted during the pandemic was longer than that in the control group, and the incidence of nosocomial infection was higher than that in the control group.Conclusions CDH patients confirmed to be SARS-CoV-2 infection-free can receive routine treatment. Our data indicate that the implementation of protective measures during the COVID-19 pandemic, along with appropriate screening and case evaluation, do not have a negative impact on the prognosis of children.

CONUT score is associated with mortality in patients with COVID-19: a retrospective study in Wuhan (preprint)

Background The coronavirus disease 2019 (COVID-19) pneumonia, outbreak in Wuhan, China, has led to a global pandemic. The high mortality of COVID-19 patients makes it significant to evaluate possible disease progression. This study was designed to explore the prognostic value of Controlling Nutritional Status (CONUT) score in patients with COVID-19.Methods Patients diagnosed with COVID-19 of a single center in Wuhan, China from January 2020 to February 2020 were enrolled in this study. Logistic regression analysis was performed to find independent risk factor of mortality. Receiver operating characteristics (ROC) curve was drawn to evaluate the prognostic value of CONUT score.Results Among 442 included patients, there were 79 non-survivors with mortality of 17.9%. Compared with survivors, the median age (p < 0.001) and male ratio (p = 0.042) were higher in non-survivors. Non-survivors had higher incidence of comorbidities including hypertension (p < 0.001), chronic lung disease (p = 0.001) and cardiovascular disease (p = 0.005). Complications such as respiratory failure(p < 0.001), acute kidney injury (AKI) (p < 0.001) occurred more frequently in non-survivors. Multivariate logistic regression analysis showed that CONUT (p = 0.002), lactate dehydrogenase (LDH) (p < 0.001), C-reactive protein (CRP) (p = 0.020) were risk factor of mortality in COVID-19 patients. Area under the ROC curve (AUC) of CONUT and Nutrition risk screening 2002 (NRS2002) score were 0.813 and 0.795, respectively. Comprised of CONUT, LDH, CRP, the constructed prognostic model had higher AUC of 0.923 (Z = 3.5210, p < 0.001).Conclusion CONUT is an independent risk factor of mortality in COVID-19 patients. Evaluating CONUT is beneficial for clinicians to predict the progression of COVID-19 patients and strengthen monitoring and management to improve prognosis.

Clinical characteristics of 82 death cases with COVID-19 (preprint)

Background A recently developing pneumonia caused by SARS-CoV-2 was originated in Wuhan, China, and has quickly spread across the world. We reported the clinical characteristics of 82 death cases with COVID-19 in a single center. Methods Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital's electronic medical records according to previously designed standardized data collection forms. Findings All patients were local residents of Wuhan, and the great proportion of them were diagnosed as severe illness when admitted. Most of the death cases were male (65.9%). More than half of dead patients were older than 60 years (80.5%) and the median age was 72.5 years. The bulk of death cases had comorbidity (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), following by sepsis syndrome/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhage, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On the admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), increased C-reactive protein level (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%). A high level of IL-6 (>10 pg/ml) was observed in all detected patients. Median time from initial symptom to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p=0.002), alanine aminotransferase (p=0.037) and time from initial symptom to death were interestingly observed. Conclusion Older males with comorbidities are more likely to develop severe disease, even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but either virus itself or cytokine release storm mediated damage to other organ including cardiac, renal, hepatic, and hemorrhage should be taken seriously as well.