Ultrasound combined with glial cell line-derived neurotrophic factor-loaded microbubbles for the targeted treatment of drug addiction.

Drug addiction is a serious problem globally, recently exacerbated by the COVID-19 pandemic. Glial cell-derived neurotrophic factor (GDNF) is considered a potentially effective strategy for the treatment of addiction. Previous animal experiments have proven that GDNF has a good therapeutic effect on drug addiction, but its clinical application is limited due to its poor blood-brain barrier (BBB) permeability. Low-frequency focused ultrasound, combined with microbubbles, is a non-invasive and reversible technique for locally-targeted BBB opening. In the present study, magnetic resonance imaging-guided low-frequency focused ultrasound, combined with GDNF microbubbles, was used to target BBB opening in the ventral tegmental area (VTA) region. The effects of GDNF on morphine-induced conditioned place preference (CPP) and acute withdrawal symptoms in rats after a partially opened BBB were evaluated by behavioral observation. Western blot was used to detect changes in tyrosine hydroxylase (TH) expression levels in the VTA region after different treatments, and high performance liquid chromatography was used to detect the changes in monoamine neurotransmitter content. The results showed that ultrasound combined with GDNF microbubbles targeted and opened the BBB in the VTA region, and significantly increased GDNF content, destroyed morphine-induced CPP, and reduced the withdrawal symptoms of morphine addiction in rats. Furthermore, the up-regulation of TH expression and the increase of norepinephrine and dopamine content induced by morphine were significantly reversed, and the increase of 5-hydroxytryptamine content was partially reversed. Therefore, ultrasound combined with GDNF microbubbles to target and open the BBB can effectively increase the content of central GDNF, thus playing a therapeutic role in morphine addiction. Our study provides a new approach to locally open the BBB and target delivery of neurotrophic factors, such as GDNF, to treat brain diseases like addiction.

More Aggressive Cancer Behaviour in Thyroid Cancer Patients in the Post-COVID-19 Pandemic Era: A Retrospective Study.

PURPOSE: Many thyroid cancer patients have suffered from treatment delays caused by the coronavirus disease 2019 pandemic. Although there have been many reviews, recommendations, or clinical experiences, clinical evidence that evaluates patient disease status is lacking. The aim of our research was to evaluate thyroid cancer behaviour in the post-COVID-19 era. PATIENTS AND METHODS: A retrospective study was conducted and thyroid cancer patient data from February 1, 2017 to September 15, 2020 were pooled for analysis. The demographic, ultrasound and pathological data of the pre- and post-COVID-19 groups were compared. Lymph node metastases, tumour size, extrathyroidal extension, and multifocality were compared year-by-year to evaluate annual changes in patient characteristics. Regression analyses were adopted to reveal cancer behaviour along with the admission date interval and to reveal risk factors for lymph node metastasis. Patient ultrasound data were compared before and after the lockdown to assess tumour progression. The outcomes of delays in treatment ≤180 days were then studied. RESULTS: The post-lockdown patients were more likely to have multiple lesions (31.2% vs 36.5%, p = 0.040), extrathyroidal extension (65.5% vs 72.2%, p = 0.011) and lymph node metastases (37.7% vs 45.0%, p = 0.007), while tumour size remained stable (1.01cm vs.1.02cm, p = 0.758). The lymph node metastasis rate increased by year (p < 0.001). The tumour size correlated negatively with the post-lockdown admission date (p = 0.002). No significant difference in tumour size, multifocality or lymph node metastasis on ultrasound was revealed between the pre- and post-lockdown group. No significant difference in tumour size, multifocality, extrathyroidal extension or lymph node metastasis was revealed among patients with a delayed treatment time ≤180 days. CONCLUSION: Patients with a COVID-19-induced treatment delay had more aggressive cancer behaviour. Rebound medical visits and annually increasing aggressiveness may be potential reasons for this observation, as individual patient tumour did not progress during the delay.

Association of administration of IFN-α with mortality among patients hospitalized with coronavirus disease 2019

Aim: Recent studies on coronavirus disease 2019 (COVID-19) have not offered sufficient clinical evidence to support whether IFN-α can decrease the mortality of patients with COVID-19. Method: In this retrospective study, 103 of 1555 hospitalized COVID-19 patients were treated with IFN-α, and the others matched through propensity score matching. Cox regression model, logistics analysis and Kaplan–Meier statistics depicted the survival curve. Results & conclusion: Single factor analysis demonstrated that fewer deaths occurred in patients treated with IFN-α compared with patients treated without IFN-α (p = 0.000). Logistics analysis showed that patients treated with IFN-α had an all-cause mortality odds ratio = 0.01 (95% CI: 0.001–0.110;p = 0.000). The Cox regression model was utilized to determine an all-cause mortality with a hazard ratio of 0.102 (95% CI: 0.030–0.351;p = 0.000). IFN-α can alleviate disease severity and decrease all-cause mortality, especially in critical patients. IFN-α could effectively treat patients with COVID-19.

Effects of a Serum Heating Procedure for Inactivating COVID-19 on Common Biochemical Tests.

BACKGROUND: COVID-19 has recently been declared an epidemic by the WHO, and there is an urgent need for affected countries and laboratories to assess and treat people at risk of COVID-19. A heat procedure has been suggested for specimen inactivation. This study was designed to evaluate the effect of serum heating on biochemical indexes, and providing a basis for accurate detection results of the COVID-19 patients. METHODS: We collected 29 normal cases of two tubes of 5 mL whole blood. One tube was analyzed directly, and the other was analyzed after heating at 56°C 30 minutes. RESULTS: A total of 34 serum biochemical index quantitative results were obtained, 28/34 indexes were not significantly affected by the heat inactivation and remained clinically interpretable. As the thermal inactivation for these indexes showed good correlation, ALB (p = 0.04, Pearson R = 0.91, 2.6% mean increase), CysC (p = 0.03, Pearson R = 0.98, 9.9% mean increase), CO2CP (p < 0.001, Pearson R = 0.96, 13% mean decrease), they were still inter-pretable. Four biochemical indexes ALP, CK, CK-MB, and insulin were inactivated and showed significant statistical differences (p < 0.001). CONCLUSIONS: Our study showed CK, CK-MB, ALP, and insulin were sensitive to heat and will be inhibited or degrade after heating, indicating that the rapid decrease of this indexes in the COVID-19 patients may be caused by sample heat inactivation. For safety and diagnostic accuracy, we recommend the use of a point-of-care device for blood gases, electrolytes, troponin, and liver and renal function tests within a ISL 2 or above biosafety cabinet with level 3 or above biosafety laboratory practice.

Clinical characteristics and impacts of traditional Chinese medicine treatment on the convalescents of COVID-19.

Objectives: A significant proportion of discharged COVID-19 patients still have some symptoms. Traditional Chinese medicine (TCM) has played an important role in the treatment of COVID-19, but whether it is helpful for discharged patients is still unknown. The aim of this study was to retrospectively analyze the impacts of TCM treatment on the convalescents of COVID-19. Methods: A total of 372 COVID-19 convalescents from February 21 to May 3 in Shenzhen, China were retrospectively analyzed, 291 of them accepted clinically examined at least once and 191 convalescents accepted TCM. Results: After retrospective analysis of the clinical data of convalescents accepted TCM treatment or not, we found that the white blood cell count, as well as serum interleukin-6 and procalcitonin decreased in TCM group. Serum γ-glutamyl transpeptidase was significantly decreased, while prealbumin and albumin increased in TCM group. Red blood cell, hemoglobin, and platelet count increased in TCM group. The mechanisms of TCM treatment might be the overall regulations, including balanced immune response, improved hematopoiesis and coagulation systems, enhanced functions of liver and heart, increased nutrient intake and lipid metabolism. Conclusions: This study suggested that TCM treatment would be beneficial for discharged COVID-19 patients. However, long-term medical observation and further study with randomized trial should be done to confirm this result. Besides, the potential molecular mechanisms of TCM treatment should be further revealed.

Liver function recovery of COVID-19 patients after discharge, a follow-up study.

Objective: The aim of this study was to observe the liver function recovery of COVID-19 patients after discharge. Patients and Methods: A total of 253 discharged COVID-19 patients in Shenzhen city, China were selected. The clinical characteristics of these patients were assessed. A 2-month follow-up and laboratory hematology test were performed to examine the status of patients' liver function. Results: Patients combined with liver diseases, especially fatty liver, are more likely to progress to severe condition (P<0.05). Patients in severe condition and those with liver diseases have higher rates of liver injuries during hospitalization, characterized by a significant increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P<0.01). The ALT, AST/ALT, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), and A/G levels showed significant differences in comparison with the control group (P<0.05, and P<0.001); and the outlier ratio of A/G, ALT, GGT and ALP of patients remained abnormal higher within 14 days after discharge (P<0.001). Liver injuries of COVID-19 patients may be related to the epidemiological characteristics, clinical indexes, basic diseases, symptoms, drug treatment during hospitalization and the complications. Indicators of liver function were correlated with cardiac function, renal function, thyroid function, lipid metabolism, glucose metabolism, immune index, leukocyte, erythrocyte, hemoglobin and platelet related indexes. The outlier ratio of TP, ALB and GLB remained extremely low throughout the follow-up period; the outlier ratio of ALT, AST and GGT decreased below 10% from a high level at 40 days after discharged. However, the outlier ratio of A/G, AST/ALT and ALP remained high during the follow-up period. Conclusions: Abnormal liver function might indicate worse recovery of COVID-19 patients. Changes in liver function should be emphasized during long-term follow-up of COVID-19 patients after hospital discharge; the necessity of employing appropriate interventions for liver function repair should be emphasized.

The effect of anticancer treatment on cancer patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: The relationship between cancer and COVID-19 has been revealed during the pandemic. Some anticancer treatments have been reported to have negative influences on COVID-19-infected patients while other studies did not support this hypothesis. METHODS: A literature search was conducted in WOS, PubMed, Embase, Cochrane Library, CNKI and VIP between Dec 1, 2019 and Sept 23, 2020 for studies on anticancer treatments in patients with COVID-19. Cohort studies involving over 20 patients with cancer were included. The characteristics of the patients and studies, treatment types, mortality, and other additional outcomes were extracted and pooled for synthesis. RRs and forest plots were adopted to present the results. The literature quality and publication bias were assessed using NOS and Egger's test, respectively. RESULTS: We analyzed the data from 29 studies, with 5121 cancer patients with COVID-19 meeting the inclusion criteria. There were no significant differences in mortality between patients receiving anticancer treatment and those not (RR 1.17, 95%CI: 0.96-1.43, I2 =66%, p = 0.12). Importantly, in patients with hematological malignancies, chemotherapy could markedly increase the mortality (RR 2.68, 95% CI: 1.90-3.78, I2 =0%, p < 0.00001). In patients with solid tumors, no significant differences in mortality were observed (RR 1.16, 95% CI: 0.57-2.36, I2 =72%, p = 0.67). In addition, our analysis revealed that anticancer therapies had no effects on the ICU admission rate (RR 0.87, 95% CI: 0.70-1.09, I2 =25%, p = 0.23), the severe rate (RR 1.04, 95% CI: 0.95-1.13, I2 =31%, p = 0.42), or respiratory support rate (RR 0.92, 95% CI: 0.70-1.21, I2 =32%, p = 0.55) in COVID-19-infected patients with cancer. Notably, patients receiving surgery had a higher rate of respiratory support than those without any antitumor treatment (RR 1.87, 95%CI: 1.02-3.46, I2 =0%, p = 0.04). CONCLUSIONS: No significant difference was seen in any anticancer treatments in the solid tumor subgroup. Chemotherapy, however, will lead to higher mortality in patients with hematological malignancies. Multicenter, prospective studies are needed to re-evaluate the results.

Clinical characteristics and follow-up analysis of 324 discharged COVID-19 patients in Shenzhen during the recovery period.

Objectives: Research on recovering COVID-19 patients could be helpful for containing the pandemic and developing vaccines, but we still do not know much about the clinical features, recovery process, and antibody reactions during the recovery period. Methods: We retrospectively analysed the epidemiological information, discharge summaries, and laboratory results of 324 patients. Results: In all, 15 (8.62%) patients experienced chest distress/breath shortness, where 8 of the 15 were severely ill. This means severely ill patients need an extended amount of time to recover after discharge; next, 20 (11.49%) patients experienced anxiety and 21 (12.07%) had headache/insomnia and a small fraction of them complained of anosmia/ageusia, indicating that these patients need treatment for mental and psychological health issues. Regarding the re-positive patients, their CT and laboratory test results showed no obvious evidence of illness progress or infectivity but a high anti-SARS-CoV-2 antibody expression. Conclusion: Recovered COVID-19 patients need psychological and physiological care and treatment, re-positivity can occur in any person, but juveniles, females, and patients with mild/moderate existing symptoms have higher rates of re-positivity, While there is no evidence that turning re-positive has an impact on their infectivity, but it still alerted us that we need differentiate them in the following managements.

Recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients during medical isolation observation.

Recently, the recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients is receiving more attention. Herein we report a cohort study on the follow-up of 182 recovered patients under medical isolation observation. Twenty (10.99%) patients out of the 182 were detected to be SARS-CoV-2 RNA positive (re-positives), although none showed any clinical symptomatic recurrence, indicating that COVID-19 responds well to treatment. Patients aged under 18 years had higher re-positive rates than average, and none of the severely ill patients re-tested positive. There were no significant differences in sex between re-positives and non-re-positives. Notably, most of the re-positives turned negative in the following tests, and all of them carried antibodies against SARS-CoV-2. This indicates that they might not be infectious, although it is still important to perform regular SARS-CoV-2 RNA testing and follow-up for assessment of infectivity. The findings of this study provide information for improving the management of recovered patients, and for differentiating the follow-up of recovered patients with different risk levels.

Correlation between immune response and self-reported depression during convalescence from COVID-19.

Self-reported depression has been observed in coronavirus disease-2019 (COVID-19) patients, infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during discharge from the hospital. However, the cause of this self-reported depression during the convalescent period remains unclear. Here, we report the mental health status of 96 convalescent COVID-19 patients who were surveyed using an online questionnaire at the Shenzhen Samii Medical Center from March 2 to March 12, 2020 in Shenzhen, China. After obtaining their informed consent, we retrospectively analyzed the clinical characteristics of patients, including routine blood and biochemical data. The results suggested that patients with self-reported depression exhibited increased immune response, as indicated by increased white blood cell and neutrophil counts, as well as neutrophil-to-lymphocyte ratio. However, the mechanism linking self-reported depression to these cellular changes needs further study. In conclusion, self-reported depression occurred at an early stage in convalescent COVID-19 patients, and changes in immune function were apparent during short-term follow-up of these patients after discharge. Appropriate psychological interventions are necessary, and changes in immune function should be emphasized during long-term follow up of these patients.