Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic in only 3 months. In addition to major respiratory distress, characteristic neurological manifestations are also described, indicating that SARS-CoV-2 may be an underestimated opportunistic pathogen of the brain. Based on previous studies of neuroinvasive human respiratory coronaviruses, it is proposed that after physical contact with the nasal mucosa, laryngopharynx, trachea, lower respiratory tract, alveoli epithelium, or gastrointestinal mucosa, SARS-CoV-2 can induce intrinsic and innate immune responses in the host involving increased cytokine release, tissue damage, and high neurosusceptibility to COVID-19, especially in the hypoxic conditions caused by lung injury. In some immunecompromised individuals, the virus may invade the brain through multiple routes, such as the vasculature and peripheral nerves. Therefore, in addition to drug treatments, such as pharmaceuticals and traditional Chinese medicine, non-pharmaceutical precautions, including facemasks and hand hygiene, are critically important.

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Cancer-induced bone pain (CIBP) is a common clinical problem in breast cancer patients with bone metastasis. Recent studies shows chemokines are novel targets for treatment of CIBP. In this study, we intra-tibial inoculated with Walker 256 rat mammary gland carcinoma cells into rat bone to established metastatic breast cancer. Then we measured the expression of CXCL10 in the spinal cord of metastatic bone cancer rats, investigated the role of CXCL10 in the development of CIBP, and the underlying mechanism. Results revealed that after intra-tibial inoculation with Walker 256 cells, rats showed up-regulation of CXCL10 and its receptor CXCR3 in the spinal cord. Interestingly, intrathecally injection of recombinant CXCL10 protein induced mechanical allodynia in naïve rats. Blocking the function of CXCL10/CXCR3 pathway via anti-CXCL10 antibody or CXCR3 antagonist prevented the development of CIBP and microglial activation. Moreover, CXCL10-induced mechanical allodynia was rescued by minocycline treatment during the late-stage of CIBP, days 10-14. The regulation of CXCL10 expression involved microglial activation in a manner of autocrine positive feedback. These results suggest that CXCL10 may be a necessary algogenic molecule, especially in the development of CIBP. Its function was partly mediated via spinal microglial activation. This study provides a novel insight into the biological function of chemokine CXCL10 in the molecular mechanism underlying cancer pain. It also provides new target for clinical treatment of metastatic breast cancer-induced bone pain in future.

Endothelial dysfunction exists in HT patients with euthyroidism. Autoimmune reactivity and an elevated Lp(a) level might be responsible for the endothelial dysfunction.

BACKGROUND After the initial surge in COVID-19 cases, large numbers of patients were discharged from a hospital without assessment of recovery. Now, an increasing number of patients report postacute neurological sequelae, known as “long COVID” — even those without specific neurological manifestations in the acute phase. METHODS Dynamic brain changes are crucial for a better understanding and early prevention of “long COVID.” Here, we explored the cross-sectional and longitudinal consequences of COVID-19 on the brain in 34 discharged patients without neurological manifestations. Gray matter morphology, cerebral blood flow (CBF), and volumes of white matter tracts were investigated using advanced magnetic resonance imaging techniques to explore dynamic brain changes from 3 to 10 months after discharge. RESULTS Overall, the differences of cortical thickness were dynamic and finally returned to the baseline. For cortical CBF, hypoperfusion in severe cases observed at 3 months tended to recover at 10 months. Subcortical nuclei and white matter differences between groups and within subjects showed various trends, including recoverable and long-term unrecovered differences. After a 10-month recovery period, a reduced volume of nuclei in severe cases was still more extensive and profound than that in mild cases. CONCLUSION Our study provides objective neuroimaging evidence for the coexistence of recoverable and long-term unrecovered changes in 10-month effects of COVID-19 on the brain. The remaining potential abnormalities still deserve public attention, which is critically important for a better understanding of “long COVID” and early clinical guidance toward complete recovery. FUNDING National Natural Science Foundation of China.

The mechanism behind itching is not well understood. Proton nuclear magnetic resonance (H-NMR) spectroscopic analysis of spinal cord extracts provides a quick modality for evaluating the specific metabolic activity of α-Me-5-HT-evoked pruritus mice. In the current study, four groups of young adult male C57Bl/6 mice were investigated; one group treated with saline, while the other groups intradermally injected with α-Me-5-HT (histamine independent pruritogen), histamine (histamine dependent pruritogen) and capsaicin (algogenic substance), respectively. The intradermal microinjection of α-Me-5-HT and histamine resulted in a dramatic increase in the itch behavior. Furthermore, the results of NMR studies of the spinal cord extracts revealed that the metabolites show very different patterns for these different drugs, especially when comparing α-Me-5-HT and capsaicin. All the animals in the groups of α-Me-5-HT and capsaicin were completely separated using the metabolite parameters and principal component analysis. For α-Me-5-HT, the concentrations of glutamate, GABA, glycine and aspartate increased significantly, especially for GABA (increased 17.2%, p=0.008). Furthermore, the concentration of NAA increased, but there was no significant difference (increased 11.3%, p=0.191) compared to capsaicin (decreased 29.1%, p=0.002). Thus the application of magnetic resonance spectroscopy technique, coupled with statistical analysis, could further explain the mechanism behind itching evoked by α-Me-5-HT or other drugs. It can thus improve our understanding of itch pathophysiology and pharmacological therapies which may contribute to itch relief.

Our study showed decreased percent change in diameter of the brachial artery induced by reactive hyperemia in patients with history of Kawasaki disease compared with the healthy children, indicating that systemic endothelial dysfunction exits after Kawasaki disease. Although such systemic endothelial dysfunction after Kawasaki disease is not influenced by early treatment with high dose gamma-globulin in the acute stage of Kawasaki disease, it can be restored by the acute intravenous administration of vitamin C.

Morphine is a potent agonist of μ-opioid receptor and is widely used to relieve severe pain, including cancer pain. Some chemokines, for example, CX3CL1 and CCL2, participate in the regulation of opioid santinociception. In our previous study, we found overexpression of chemokine CXCL10/CXCR3 in spinal cord participated in the development of cancer-induced bone pain, so we supposed that CXCL10 may have influence in morphine analgesia in cancer pain relief. In this study, we found that a single dose of morphine could transiently increase the expression of CXCL10 in spinal cord. Blocking the function of CXCL10 enhanced morphine antinociception in cancer-induced bone pain rats. However, overexpression of CXCL10 induced acute algesia and decreased the analgesic effect of morphine in normal mice. The algesic effect of CXCL10 was blocked by inhibition of CXCR3 and Gi protein. These results suggested that CXCL10 in spinal cord serves as a novel negative regulator of morphine analgesia and provided evidence that activation of CXCL10/CXCR3 in spinal cord may attenuate antinociceptive potency of morphine in cancer pain relief.