Micronutrient Level Is Negatively Correlated with the Neutrophil-Lymphocyte Ratio in Patients with Severe COVID-19.

Aim: To explore the potential relationship between NLR and micronutrient deficiency in patients with severe COVID-19 infection. Methods: Sixteen patients were categorized into the mild group (mild COVID-19) and severe group (severe COVID-19) based on the guideline of the management of COVID-19. The lactate dehydrogenase (LDH); superoxide dismutase (SOD), the inflammatory markers (neutrophil lymphocyte ratio (NLR)), erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), selenium (Se), iron (Fe), zinc (Zn), nickel (Ni), copper (Cu), chromium (Cr), cadmium (Cd), arsenic (As), and manganese (Mn) were measured in the blood. Results: Compared to the mild group, the NLR (P < 0.05) and the level of Se (P < 0.01), Fe (P < 0.05), and Zn (P < 0.05) were significantly decreased in the severe group. The level of Se, Fe, and Zn was significantly correlated to NLR levels. Furthermore, close positive correlation was found between NLR and severity of COVID-19. Conclusion: The micronutrient deficiency in the blood is associated with NLR in the severity of COVID-19 patients.

An epigenome-wide DNA methylation study of patients with COVID-19.

In the early 2000s, emerging SARS-CoV-2, which is highly pathogenic, posed a great threat to public health. During COVID-19, epigenetic regulation is deemed to be an important part of the pathophysiology and illness severity. Using the Illumina Infinium Methylation EPIC BeadChip (850 K), we investigated genome-wide differences in DNA methylation between healthy subjects and COVID-19 patients with different disease severities. We conducted a combined analysis and selected 35 "marker" genes that could indicate a SARS-CoV-2 infection, including 12 (ATHL1, CHN2, CHST15, CPLX2, CRHR2, DCAKD, GNAI2, HECW1, HYAL1, MIR510, PDE11A, and SMG6) situated in the promoter region. The functions and pathways of differentially methylated genes were enriched in biological processes, signal transduction, and the immune system. In the "Severe versus Mild" group, differentially methylated genes, after eliminating duplicates, were used for PPI analyses. The four hub genes (GNG7, GNAS, PRKCZ, and PRKAG2) that had the highest degree of nodes were identified and among them, GNG7 and GNAS genes expressions were also downregulated in the severe group in sequencing results. Above all, the results suggest that GNG7 and GNAS may play a non-ignorable role in the progression of COVID-19. In conclusion, the identified key genes and related pathways in the current study can be used to study the molecular mechanisms of COVID-19 and may provide possibilities for specific treatments.

Thrombin promotes proliferation of human lung fibroblasts via protease activated receptor-1-dependent and NF-κB-independent pathways.

Acute and chronic respiratory diseases are associated with abnormal coagulation regulation and fibrolysis. However, the detailed mechanism by which coagulation regulation and fibrolysis affect the occurrence and development of lung diseases remain to be elucidated. Protease activated receptor-1 (PAR-1), a major high-affinity thrombin receptor, and nuclear factor kappa B (NF-κB), a transcription factor, are involved in cell survival, differentiation, and proliferation. We have investigated the potential mechanism of thrombin-induced fibroblast proliferation and roles of PAR-1 and NF-κB signalling in this process. The effect of thrombin on proliferation of human pulmonary fibroblasts (HPF) was assessed by 5-bromo-2-deoxyuridine (BrdU) incorporation assay. The expression of PAR1 and NF-κB subunit p65 protein was detected by Western blot. Nuclear translocation of p65 was examined by laser scanning confocal microscopy. We show that thrombin significantly increased proliferation of HPF as determined by induction of BrdU-positive incorporation ratio. Induced PAR1 protein expression was also seen in HPF cells treated with thrombin. However, thrombin had no significant effect on expression and translocation of NF-κB p65 in HPF cells. The results indicate that, by increasing protein expression and interacting with PAR1, thrombin promotes HPF proliferation. NF-κB signalling appears to play no role in this process.

Novel insights into molecular patterns of ROS1 fusions in a large Chinese NSCLC cohort: a multicenter study.

ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) rearrangements are a crucial therapeutic target in non-small cell lung cancer (NSCLC). However, there is limited comprehensive analysis of the molecular patterns of ROS1 fusions. This study aimed to address this gap by analysing 135 ROS1 fusions from 134 Chinese NSCLC patients using next-generation sequencing (NGS). The fusions were categorized into common and uncommon based on their incidence. Our study revealed, for the first time, a unique distribution preference of breakpoints within ROS1, with common fusions occurring in introns 31-33 and uncommon fusions occurring in introns 34 and 35. Additionally, we identified previously unknown breakpoints within intron 28 of ROS1. Furthermore, we identified a close association between the distribution patterns of fusion partners and breakpoints on ROS1, providing important insights into the molecular landscape of ROS1 fusions. We also confirmed the presence of inconsistent breakpoints in ROS1 fusions between DNA-based NGS and RNA-based NGS through rigorous validation methods. These inconsistencies were attributed to alternative splicing resulting in out-of-frame or exonic ROS1 fusions. These findings significantly contribute to our understanding of the molecular characteristics of ROS1 fusions, which have implications for panel design and the treatment of NSCLC patients with ROS1 rearrangements.

[Influence of Aconiti Lateralis Radix Praeparata on asthenia cold syndrome rats with whole genome gene expression of liver by gene chip technique].

OBJECTIVE: To study the influence of Aconiti Lateralis Radix Praeparata on asthenia cold syndrome rats with whole genome gene expression of liver by gene chip technique. METHOD: The asthenia cold syndrome rat models were established by administering traditional Chinese medicine raw Gypsum Fibrosum, Gentianae Radix, Phellodendri Chinensis Cortex and Anemarrhenae Rhizoma. After treated with Aconiti Lateralis Radix Praeparata, the rats' liver gene expressions were detected using gene chip. Differential expression genes were screened for gene function annotation, and some genes were selected to check the accuracy of the results by RT-PCR. RESULT: Compared with the asthenia cold model group, the asthenia cold treatment group showed 212 differential expression genes, mainly involving function of immune response and oxidoreductase activity. CONCLUSION: Aconiti Lateralis Radix Praeparata is proved to have an effect on up-regulating immune response-related genes and oxidizing oxidoreductase activity-related genes of asthenia cold syndrome rats and may be a molecular mechanism for classical warm-nature medicine Aconiti Lateralis Radix Praeparata in warming meridians and dissipating cold.

CXCL8 chemokine in ulcerative colitis.

Ulcerative colitis (UC) is a major type of inflammatory bowel disease (IBD), which is characterized by diffuse inflammation of the mucosa of the colon and rectum. Abdominal pain, diarrhea, and hematochezia are UC's main clinical manifestations. Pathogenesis of UC has not yet been clearly elucidated, but it is considered to result from dysregulated expressions of molecules engaged in proinflammatory and anti-inflammatory processes. CXCL8 is one of the most important proinflammatory factors which play a vital role in many inflammatory diseases including UC. The CXCL8-CXCR1/2 axis participates in the pathogenesis of UC through multiple signaling pathways, including PI3k/Akt, MAPKs and NF-κB signaling pathways. Meanwhile, more and more studies in recent years have shown that UC patients have specific non-coding RNA (ncRNA) expression profiles, which may be involved in the occurrence and development of inflammation. In this article, we analyzed the CXCL8-CXCR1/2 axis related signaling pathways and ncRNAs in UC, as well as recent advances in our understanding of the CXCL8-CXCR1/2 axis inhibition as a therapeutic strategy against UC.

Clinical Features for Severely and Critically Ill Patients with COVID-19 in Shandong: A Retrospective Cohort Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel pathogen, has caused an outbreak of coronavirus disease 2019 (COVID-19) that has spread rapidly around the world. Determining the risk factors for death and the differences in clinical features between severely ill and critically ill patients with SARS-CoV-2 pneumonia has become increasingly important. AIM: This study was intended to provide insight into the difference between severely ill and critically ill patients with SARS-CoV-2 pneumonia. METHODS: In this retrospective, multicenter cohort study, we enrolled 62 seriously ill patients with SARS-CoV-2 pneumonia who had been diagnosed by March 12, 2020. Clinical data, laboratory indexes, chest images, and treatment strategies collected from routine medical records were compared between severely ill and critically ill patients. Univariate and multivariate logistic regression analyses were also conducted to identify the risk factors associated with the progression of patients with severe COVID-19. RESULTS: Of the 62 patients with severe or critical illness, including 7 who died, 30 (48%) patients had underlying diseases, of which the most common was cardiovascular disease (hypertension, 34%, and coronary heart disease, 5%). Compared to patients with severe disease, those with critical disease had distinctly higher white blood cell counts, procalcitonin levels, and D-dimer levels, and lower hemoglobin levels and lymphocyte counts. Multivariate regression showed that a lymphocyte count less than 109/L (odds ratio 20.92, 95% CI 1.76-248.18; p=0.02) at admission increased the risk of developing a critical illness. CONCLUSION: Based on multivariate regression analysis, a lower lymphocyte count (<109/L) on admission is the most critical independent factor that is closely associated with an increased risk of progression to critical illness. Age, underlying diseases, especially hypertension and coronary heart disease, elevated D-dimer, decreased hemoglobin, and SOFA score, and APACH score also need to be taken into account for predicting disease progression. Blood cell counts and procalcitonin levels for the later secondary bacterial infection have a certain reference values.

LncRNA LINC00511 plays an oncogenic role in lung adenocarcinoma by regulating PKM2 expression via sponging miR-625-5p.

BACKGROUND: Lung adenocarcinoma (LAC) is the most prominent histological subtype of non-small cell lung cancer (NSCLC) with a high rate of mortality and metastasis. Accumulating evidence has shown that long non-coding RNAs (lncRNAs) play malfunctioning roles in the development of human tumors. Hence, this study aimed to determine the biological function of LINC00511 in LAC and to provide a novel diagnostic and therapeutic target for it. METHODS: LINC00511 expression in LAC tissues and cell lines (H1299 and A549) were detected by real time-polymerase chain reaction (RT-qPCR). Cell counting kit-8 (CCK-8) assay was employed to analyze cell proliferative ability. Cell metastasis change was measured using transwell assay. Moreover, we revealed a novel target gene of LINC00511 and elucidated the underlying competitive endogenous RNA regulatory mechanism in LAC cells. RESULTS: Data from our study demonstrated that LINC00511 expression was increased in LAC tissues and cells in comparison to their corresponding controls. Moreover, overexpression of LINC00511 indicated the poor prognosis of LAC patients. Overexpression of LINC00511 promoted proliferation, invasion and migration capacities of LAC cells. Moreover, LINC00511 promoted LAC progression via serving as a sponge of miR-625-5p and regulating PKM2 expression. CONCLUSIONS: The present study showed that LINC00511 was involved in LAC progression by targeting miR-625-5p/PKM2, indicating that LINC00511/miR-625-5p/PKM2 may function as promising therapeutic targets for LAC.

[The locus coeruleus modulates the inspiratory inhibition induced by electrical stimulation of the Bötzinger complex].

Experiments were done on urethane anesthetized adult rabbits. Long-train electrical stimulation was delivered to the Bötzinger complex (Böt.C) to observe the changes in the peak amplitude of integrated phrenic nerve activity. Then, a long-train electrical stimulation was delivered to the locus coeruleus (LC) or monosodium glutamate was microinjected into the LC . Within a certain period of time, another long-train electrical stimulation was delivered to the Böt.C to observe the responses of phrenic nerve activity. We investigated whether the LC could modulate the inspiratory inhibition induced by electrical stimulation of the Böt.C. The results are as follows: (1) Within a certain period of time after a long-train electrical stimulation applied at the LC, the inspiratory inhibition produced by electrical stimulation at the Böt.C was significantly attenuated. Comparing with the control stimulation that was only delivered at Böt.C without pre-stimulation of the LC, the inspiratory inhibition was decreased by (28.78+/-19.49)%. (2) Similarly, after chemical stimulation of the LC with microinjection of monosodium glutamate, the inspiratory inhibition produced by electrical stimulation of Böt.C was also significantly attenuated [decreased by (19.18+/-8.06)%]. The results obtained suggest that the LC plays a role in the modulation of the inspiratory inhibition of Böt.C stimulation.

[Sustained electrical stimulation of Bötzinger complex on phrenic nerve discharges in rabbits].

AIM: To observe the effects of sustained electrical stimulation at Bötzinger complex (Böt. c) on phrenic nerve discharges. METHODS: Sustained electrical stimulation (10--50 microA, 40-100 Hz, 0.3 ms, for 15-30 s) of Böt. C on 30 urethane anaesthetized, vagotomized, paralyzed and artificially ventilated rabbits. RESULTS: Sustained electrical stimulation of Bot. C produced the inhibition or "inspiratory off-switch" of phrenic discharge during the stimulation. The inhibition of the phrenic discharges showed intensity and frequency dependence. Habituation was shown during the stimulation, showing the magnitude of the phrenic nerve discharge increased gradually. Post-stimulus rebound exhibited upon the cessation of the stimulation, showing the magnitude of the phrenic activity increased significantly. Short-term memory was shown in the habituation of the phrenic activity. CONCLUSION: Non-associative learning is involved in the central control of respiratory modulation in the Böt. C and synaptic plasticity may exist in the respiratory neurons of Böt. C.