Survival Outcome and Prognostic Factors of Primary Spinal Cord Lymphoma.

AIM: To identify the predictive factors associated with the survival of patients with a diagnosis of primary spinal cord lymphoma (PSCL). MATERIAL AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used in this study, which involved 254 patients with PSCL. Data on the patients' age, sex, race, pathology, Ann Arbor stage, adjuvant therapy, and year of diagnosis were collected. Univariate and multivariate Cox regression models were conducted to detect the predictive variables. RESULTS: Of the 254 patients, 67 (26.4%) die from lymphoma at the time of data collection. Cancer-specific survival at 1, 3, and 5 years was 81.0%, 74.6%, and 74.1%, respectively. Diffuse large B-cell lymphoma (DLBL) was the highest prevalent histotype (n=140, 55.1%). The multivariate Cox regression models revealed that chemotherapy (hazard ratio (HR): 0.47; 95% confidence interval (CI), 0.16-0.82; p=0.040) and radiochemotherapy (HR: 0.43; 95% CI, 0.10-0.57; p=0.045) were independent predictors of favorable cancer-specific survival, whereas age - 80 years (HR: 6.51; 95% CI, 1.65-25.64; p=0.003) and DLBL (HR:1.71; 95% CI, 1.02-2.88; p=0.030) were independently associated with poor cancer-specific survival. CONCLUSION: The survival outcome of PSCL is favorable in the current treatment strategy. Chemotherapy and radiochemotherapy were predictors of favorable outcomes, whereas older age and DLBL were associated with poor prognosis.

Low-dose ketamine attenuates microcirculatory deficits after traumatic brain injury in mice via microglial NF-κB/iNOS pathway / 中华神经医学杂志

Objective:To investigate the effect of low-dose ketamine on neuroinflammation and microcirculation in mice with traumatic brain injury (TBI).Methods:Sixty adult male C57BL/6 mice, weighing 22-28 g, were randomly divided into sham-operated group, TBI group, Sham+ketamine group, and TBI+ketamine group ( n=15). A controlled cortical impingement (CCI) method was used to establish TBI models in the later 2 groups. Sham+ketamine group and TBI+ketamine group were intraperitoneally injected with 30 mg/kg ketamine once daily for 3 d at 30 min after TBI; sham-operated group and TBI group were intraperitoneally injected same amount of saline at the same time points. Cerebral cortical blood flow in 6 mice from each group was measured by laser speckle contrast imaging (LSCI) before, immediately after, 30 min after, 1 d after and 3 d after modeling, respectively. Three d after modeling, immunohistochemical staining and immunofluorescent double label staining were used to detect the nuclear translocation of microglia markers, ionized calcin-antibody-1 (Iba-1) and nuclear factor (NF)-κB p65 in damaged cortical brain tissues in 6 mice from each group. The remaining 3 mice in each group were sacrificed and tissue plasma was extracted 3 d after modeling; levels of NF-κB p65, phosphorylated (p)-NF-κB p65, p-IκB and inducible nitric oxide synthase (iNOS) in cortical brain tissues were detected by Western blotting. Expressions of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β) and interleukin-6 (IL-6), iNOS, reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cortical brain tissues were detected by ELISA. Results:LSCI indicated that, 3 d after modeling, relative blood flow in local cerebral microcirculation of TBI+ketamine group was significantly increased compared with that of TBI group ( P<0.05). Immunohistochemical staining indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased number of Iba-1 positive cells in the cerebral cortex ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased number of Iba-1 positive cells ( P<0.05). ELISA indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ ketamine group had significantly decreased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05). Immunofluorescent double label staining indicated obviously inhibited NF-κB p65 nuclear translocation in TBI+ketamine group when it was compared with TBI group. Western blotting indicated that compared with the sham-operated group and Sham+ketamine group, the TBI+ketamine group had significantly increased iNOS, NF-κB p65, p-NF-κB p65 and P-IκB protein expressions in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased protein expressions of iNOS, NF-κB p65, p-NF-κB p65 and p-IκB in damaged cortical brain tissues ( P<0.05). Conclusion:Low-dose ketamine reduces neuroinflammation and improves cerebral microcirculatory blood flow after open TBI, whose mechanism may be related to inhibition of microglia NF-κB/iNOS pathway.

A novel viral protein translation mechanism reveals mitochondria as a target for antiviral drug development

The ongoing Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) pandemic has acutely highlighted the need to identify new treatment strategies for viral infections. Here we present a pivotal molecular mechanism of viral protein translation that relies on the mitochondrial translation machinery. We found that rare codons such as Leu-TTA are highly enriched in many viruses, including SARS-CoV-2, and these codons are essential for the regulation of viral protein expression. SARS-CoV-2 controls the translation of its spike gene by hijacking host mitochondria through 5 leader and 3UTR sequences that contain mitochondrial localization signals and activate the EGR1 pathway. Mitochondrial-targeted drugs such as lonidamine and polydatin significantly repress rare codon-driven gene expression and viral replication. This study identifies an unreported viral protein translation mechanism and opens up a novel avenue for developing antiviral drugs. One Sentence SummaryMitochondria are a potential target for antiviral therapy

An effective, safe and cost-effective cell-based chimeric vaccine against SARS-CoV2

More than one hundred vaccines against SARS-CoV-2 have been developed and some of them have entered clinical trials, but the latest results revealed that these vaccines still face great challenges. Here, we developed a novel cell-based gp96-Ig-secreting chimeric vaccine which is composed of two viral antigens, the RBD of spike protein, and a truncated nucleocapsid protein that could induce epitope-specific cytotoxic T lymphocytes but low antibody response. Syrian hamsters immunized with the cell-based vaccine produced high level of SARS-CoV-2 specific NAbs and specific T cell immunity which could eliminate RBD-truncated N-expressing cells, without the induction of antibody against N protein and other observed toxicity. This study provides a proof of concept for clinical testing of this safe, effective and cost-effective vaccine against SARS-CoV2 infection.

Effects of sevoflurane on microglial polarization after traumatic brain injury in rats / 中华麻醉学杂志

Objective@#To evaluate the effects of sevoflurane on microglial polarization after traumatic brain injury (TBI) in rats.@*Methods@#Seventy-two healthy adult male Sprague-Dawley rats, weighing 230-250 g, were divided into 3 groups (n=24 each) using a random number table method: sham operation group (group Sham), group TBI, and TBI plus sevoflurane anesthesia group (group TBI+ Sevo). TBI models were established by using Feeney′s method in TBI and TBI+ Sevo groups, 30 min later 2.4% sevoflurane was inhaled for 1 h once a day for 3 consecutive days in TBI+ Sevo group, while pure oxygen was inhaled instead in Sham and TBI groups.At 1, 3, 7 and 14 days after establishing the model, 6 rats were selected, the neurological function was evaluated with the modified neurologic severity score (mNSS), and tail venous blood samples were taken for determination of tumor necrosis factor-a (TNF-α), interleukin-1beta (IL-1β) and IL-6 concentrations by enzyme-linked immunosorbent assay.The rats were then sacrificed, the limbic cortical tissues of brain contusion lesion were taken for determination of cell apoptosis (by TUNEL) and expression of microglial marker Iba-1, microglial M1 phenotypic marker CD86 and microglial M2 phenotypic marker CD206 (by Western blot).@*Results@#Compared with group Sham, the mNSS score, apoptosis rate of cortical cells, expression of Iba-1, CD86 and CD206, and concentrations of serum TNF-α, IL-1β and IL-6 were significantly increased in TBI and TBI+ Sevo groups (P<0.05). Compared with TBI group, the mNSS score, apoptosis rate of cortical cells, expression of Iba-1 and CD86 and concentrations of serum TNF-α, IL-1β and IL-6 were significantly decreased, and the expression of CD206 was up-regulated in TBI+ Sevo group (P<0.05).@*Conclusion@#The mechanism by which sevoflurane anesthesia reduces TBI may be related to promoting microglial polarization and inhibiting systemic inflammatory response in rats.