Computational exploration of the significance of COPS6 in cancer: Functional and clinical relevance across tumor types.

BACKGROUND: The COP9 signalosome subunit 6 (COPS6) has been implicated in cancer progression, while its precise role in most types of cancer remains elusive. AIM: To investigate the functional and clinical relevance of COPS6 across various tumor types using publicly available databases. METHODS: We used R software and online analysis databases to analyze the differential expression, prognosis, mutation and related functions of COPS6 in pan-cancer. RESULTS: Differential expression analysis and survival analysis demonstrated that COPS6 was highly expressed and associated with high-risk profiles in the majority of cancer types. Possible associations between COPS6 expression level and prognostic outcomes were found using data from public databases. Mutational analysis revealed that missense mutations were the predominant type of COPS6 mutation. Additionally, positive correlations were identified between COPS6 expression level and tumor mutational burden and microsatellite instability in most types of cancer. Immune infiltration analysis demonstrated a negative correlation between COPS6 expression level and CD8+ T cell infiltration in certain types of cancer. The correlation between COPS6 expression level and cancer-associated fibroblast infiltration exhibited heterogeneity, in which a positive correlation was found in head and neck squamous cell carcinoma and tenosynovial giant cell tumor, and a negative correlation was identified in diffuse large B-cell lymphoma and thymoma. The correlation between COPS6 expression level and macrophage infiltration was closely related to macrophage type. Gene co-expression and enrichment analysis highlighted transcription elongation factor B polypeptide 2 and G protein pathway suppressor 1 were significantly and positively associated with COPS6 expression level. These genes were predominantly involved in processes, such as ubiquitin-mediated proteolysis and human immunodeficiency virus 1 infection. CONCLUSION: In conclusion, this study systematically explored the significance of COPS6 across different tumor types, providing a solid foundation for considering COPS6 as a novel biomarker in cancer research.

Network pharmacology study of Citrus reticulata and Pinellia ternata in the treatment of non-small cell lung cancer.

It has been recognized that Citrus reticulata and Pinellia ternata have a good therapeutic effect on NSCLC. However, the potential mechanism of C. reticulata and P. ternata in the treatment of NSCLC based on network pharmacology analysis is not clear. The "Drug-Component-Target-Disease" network was constructed by Cytoscape, and the protein interaction (PPI) network was constructed by STRING. Our study indicated that 18 active ingredients of C. reticulata and P. Ternata were screened from the TCMSP database, and 56 target genes of C. reticulata and P. Ternata for the treatment of NSCLC were identified, and we constructed the "Drug-Component-Target-Disease" network. In this study, we screened 56 PPI core genes to establish a PPI network. We concluded that the network pharmacology mechanism of the effect of C. reticulata and P. Ternata  on NSCLC may be closely related to the protein expressed by TP53, ESR1, FOS, NCOA3 and MAPK8, and these may play the therapeutic roles by regulating the IL-17 signaling pathway, antigen processing and presentation, microRNAs in cancer and endocrine resistance.

COVID-19 and Cancer: Discovery of Difference in Clinical Immune Indexes.

OBJECTIVE: This study explored the consistency and differences in the immune cells and cytokines between patients with COVID-19 or cancer. We further analyzed the correlations between the acute inflammation and cancer-related immune disorder. METHODS: This retrospective study involved 167 COVID-19 patients and 218 cancer patients. COVID-19 and cancer were each further divided into two subgroups. Quantitative and qualitative variables were measured by one-way ANOVA and chi-square test, respectively. Herein, we carried out a correlation analysis between immune cells and cytokines and used receiver operating characteristic (ROC) curves to discover the optimal diagnostic index. RESULTS: COVID-19 and cancers were associated with lymphopenia and high levels of monocytes, neutrophils, IL-6, and IL-10. IL-2 was the optimal indicator to differentiate the two diseases. Compared with respiratory cancer patients, COVID-19 patients had lower levels of IL-2 and higher levels of CD3+CD4+ T cells and CD19+ B cells. In the subgroup analysis, IL-6 was the optimal differential diagnostic parameter that had the ability to identify if COVID-19 patients would be severely affected, and severe COVID-19 patients had lower levels of lymphocyte subsets (CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+T cells, and CD19+ B cells) and CD16+CD56+ NK cells and higher level of neutrophils. There were significant differences in the levels of CD3+CD4+ T cells and CD19+ B cells between T1-2 and T3-4 stages as well as IL-2 and CD19+ B cells between N0-1 and N2-3 stages while no significant differences between the metastatic and nonmetastatic cancer patients. Additionally, there were higher correlations between IL-2 and IL-4, TNF-α and IL-2, TNF-α and IL-4, TNF-α and IFN-γ, and CD16+CD56+NK cells and various subsets of T cells in COVID-19 patients. There was a higher correlation between CD3+CD4+ T cells and CD19+ B cells in cancer patients. CONCLUSION: Inflammation associated with COVID-19 or cancer had effects on patients' outcomes. Accompanied by changes in immune cells and cytokines, there were consistencies, differences, and satisfactory correlations between patients with COVID-19 and those with cancers.

SARS-CoV-2-specific immune response in COVID-19 convalescent individuals.

We collected blood from coronavirus disease 2019 (COVID-19) convalescent individuals and investigated SARS-CoV-2-specific humoral and cellular immunity in these discharged patients. Follow-up analysis in a cohort of 171 patients at 4-11 months after the onset revealed high levels of IgG antibodies. A total of 78.1% (164/210) of the specimens tested positive for neutralizing antibody (NAb). SARS-CoV-2 antigen peptide pools-stimulated-IL-2 and -IFN-γ response can distinguish COVID-19 convalescent individuals from healthy donors. Interestingly, NAb survival was significantly affected by the antigen peptide pools-stimulated-IL-2 response, -IL-8 response, and -IFN-γ response. The antigen peptide pools-activated CD8+ T cell counts were correlated with NAb. The antigen peptide pools-activated natural killer (NK) cell counts in convalescent individuals were correlated with NAb and disease severity. Our data suggested that the development of NAb is associated with the activation of T cells and NK cells. Our work provides a basis for further analysis of the protective immunity to SARS-CoV-2 and for understanding the pathogenesis of COVID-19. It also has implications for the development of an effective vaccine for SARS-CoV-2 infection.

Analysis of Lymphocyte Subpopulations and Cytokines in COVID-19-Associated Pneumonia and Community-Acquired Pneumonia.

BACKGROUND: The 2019 novel coronavirus SARS-CoV-2 caused large outbreaks of COVID-19 worldwide. COVID-19 resembles community-acquired pneumonia (CAP). Our aim was to identify lymphocyte subpopulations to distinguish between COVID-19 and CAP. METHODS: We compared the peripheral blood lymphocytes and their subsets in 296 patients with COVID-19 and 130 patients with CAP. Parameters for independent prediction of COVID-19 were calculated by logistic regression. RESULTS: The main lymphocyte subpopulations (CD3+CD4+, CD16+CD56+, and CD4+/CD8+ ratio) and cytokines (TNF-α and IFN-γ) of COVID-19 patients were significantly different from that of CAP patients. CD16+CD56+%, CD4+/CD8+ratio, CD19+, and CD3+CD4+ were identified as predictors of COVID-19 diagnosis by logistic regression. In addition, the CD3+CD4+counts, CD3+CD8+ counts, andTNF-α are independent predictors of disease severity in patients. CONCLUSIONS: Lymphopenia is an important part of SARS-CoV-2 infection, and lymphocyte subsets and cytokines may be useful to predict the severity and clinical outcomes of the disease.

Immune checkpoint: The novel target for antitumor therapy.

Inhibitory checkpoint molecules include programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), human endogenous retrovirus-H Long terminal repeat-associating 2 (HHLA2), B7 homolog 4 protein (B7-H4), T cell membrane protein-3 (TIM-3) and Lymphocyte-activation gene 3 (LAG-3), which are up-regulated during tumorigenesis. These pathways are essential to down-regulate the immune system by blocking the activation of T cells. In recent years, immune checkpoint blockers (ICBs) against PD-1, PD-L1, CTLA-4 or TIM-3 has made remarkable progress in the clinical application, revolutionizing the treatment of malignant tumors and improving patients' overall survival. However, the efficacy of ICBs in some patients does not seem to be good enough, and more immune-related adverse events (irAEs) will inevitably occur. Therefore, biomarkers research provides practical guidance for clinicians to identify patients who are most likely to benefit from or exhibit resistance to particular types of immune checkpoint therapy. There are two points in general. On the one hand, given the spatial and temporal differential expression of immune checkpoint molecules during immunosuppression process, it is essential to understand their mechanisms to design the most effective individualized therapy. On the other hand, due to the lack of potent immune checkpoints, it is necessary to combine them with novel biomarkers (such as exosomes and ctDNA) and other anticancer modalities (such as chemotherapy and radiotherapy).

Can routine laboratory tests discriminate SARS-CoV-2-infected pneumonia from other causes of community-acquired pneumonia?

BACKGROUND: The clinical presentation of SARS-CoV-2-infected pneumonia (COVID-19) resembles that of other etiologies of community-acquired pneumonia (CAP). We aimed to identify clinical laboratory features to distinguish COVID-19 from CAP. METHODS: We compared the hematological and biochemical features of 84 patients with COVID-19 at hospital admission and 221 patients with CAP. Parameters independently predictive of COVID-19 were calculated by multivariate logistic regression. The receiver operating characteristic (ROC) curves were generated and the area under the ROC curve (AUC) was measured to evaluate the discriminative ability. RESULTS: Most hematological and biochemical indexes of patients with COVID-19 were significantly different from patients with CAP. Nine laboratory parameters were identified to be predictive of a diagnosis of COVID-19. The AUCs demonstrated good discriminatory ability for red cell distribution width (RDW) with an AUC of 0.87 and hemoglobin with an AUC of 0.81. Red blood cell, albumin, eosinophil, hematocrit, alkaline phosphatase, and mean platelet volume had fair discriminatory ability. Combinations of any two parameters performed better than did the RDW alone. CONCLUSIONS: Routine laboratory examinations may be helpful for the diagnosis of COVID-19. Application of laboratory tests may help to optimize the use of isolation rooms for patients when they present with unexplained febrile respiratory illnesses.

[Relationship between effect of lamivudine in the treatment of cirrhotic patients with uncompensated hepatitis B with HBV genotypes and cytotoxic T lymphocyte].

OBJECTIVE: To explore relationship between effect of Lamivudine in the treatment of cirrhotic patients with uncompensated hepatitis B with hepatitis B virus (HBV)genotypes and HBV specific cytotoxic T lymphocytes (CTL). METHODS: 80 cases of uncompensated cirrhotic hepatitis B (40 cases with genotype B and 40 with genotype C), HBV DNA positive, HBeAg positive and human leukocyte antigen (HLA)-A2 positive,were treated with Lamivudine 100 mg/d, one year later, its effect and relationship with HBV genotypes and HBV specific CTL were observed. RESULTS: HBV DNA turned negative:40 cases with genotype B turned negative (100%). In the 9th and 10th month of treatment, there was one case with genotype C had YMDD variation respectively and Adefovir dipivoxil was used for treatment, of the rest 38 cases, HBV DNA of 26 cases (68.42%) turned negative,HBV DNA negative rate of patients with genotype is lower than that of patients with genotype B, chi2 = 14.91, P < 0.01. HBeAg turned negative: 18 cases with genotype B (45%) turned negative, more than that of patients with genotype C (7 cases, 18.42%), chi2 = 6.32, P < 0.05. Peripheral blood HBV specific CTL level: before treatment, it was (0.33 +/- 0.03)% of patients with genotype B,higher than that of patients with genotype C [(0.11 +/- 0.02)%], t = 8.12, P < 0.001. 1 year after treatment: it was (0.44 +/- 0.04)% of patients with genotype B, higher than that before treatment, t = 4.01, P < 0.001, it was also higher than that of patients with genotype C 1 year after treatment [(0.23 +/- 0.03)%], t = 5.63, P < 0.01, alanine amino-transferase (ALT) returned to normal: 38 cases with genotype B (95%) returned to normal, more than that of patients with genotype C (28 cases, 73.68%), X2 = 6.79, P < 0.01. CONCLUSION: Effect of Lamivudinein the treatment of cirrhotic patients with uncompensated hepatitis B is better in patients with genotype B than patients with genotype C, its mechanism may be related to lower level of HBV specific CTL in patients with genotype C than patients with genotype B.

[Study on effects of kurarinol combined with glycyrrhizic acid on cellular immunity of patients with chronic hepatitis B].

OBJECTIVE: To explore effects of kurarinol combined with Diammonium Glycyrrhizinate on specific cellular immunity of patients with chronic hepatitis B (CHB). METHODS: Sixty-three CHB patients were randomly divided into two groups, 32 cases in group of kurarinol combined with Diammonium Glycyrrhizinate group (combined therapy group) were treated with 600 mg kurarinol glucose injection intravenously, once a day for one month, then 200 mg kurarinol capsule was used orally, three times a day for two months. 150 mg Diammonium Glycyrrhizinate for Injection was added to 250 ml 10% glucose injection for intravenous drip, once a day for one month, then 150 mg Diammonium Glycyrrhizinate capsule was used orally, three times a day for two months; 31 case in kurarinol group (single drug group) only used kurarinol, methods and dosage were the same as those of treatment group. HBV specific CTL, T cell subgroups, change of Th1 and Th2 level, HBV-DNA and HBeAg negative rate of the two groups were compared. RESULTS: Three months after treatment, HBV specific CTL, CD4 + and Th1 of combined therapy group were higher than those before treatment, and higher than those of single drug group after treatment (P < 0.01). CONCLUSION: HBV-DNA and HBeAg negative rate between the two groups had no statistic significance (P > 0.05). CONCLUSION: Kurarinol combined with Diammonium Glycyrrhizinate can further increase HBV specific CTL, CD4+ and Th1 level of CHB patients.

[A study on the treatment of chronic hepatitis B with YMDD mutation].

OBJECTIVE: To explore the strategy for the treatment of chronic hepatitis B with YMDD mutation. METHODS: A total of 120 chronic hepatitis B patients with YMDD mutation were randomly assigned into four groups. In group A, patients received adefovir dipivoxil for 48 weeks. In group B, patients received adefovir dipivoxil in combination with lamivudine during the first 12 weeks and adefovir dipivoxil only for the following 36 weeks. In group C, patients received adefovir dipivoxil in combination with lamivudine for 48 weeks. In group D, patients received entecavir for 48 weeks. RESULTS: The rate of rebound of alanine aminotransferase (ALT) was 30.0% (9/30), 10.0% (3/30), 6.7% (2/30), 10.0% (3/30) (P < 0.05) during the first 12 weeks, and one patient with severe hepatitis was found in group A. The positive rate of YMDD mutation was 17.9%, 0, 0, 0 at week 12. There was no significant difference in the level of ALT and the rate of HBeAg seroconversion after 48-week treatment (P > 0.05). At week 48, there was significant difference in the ALT normalization rate and undetectable HBV DNA rate between group C and group A, and also between group D and group A, and the rate of drug resistant genotype was 6.9%, 6.7%, 0, 0. Two patients had rtN236T mutation in group A, and one patient had rtN236T mutation and another one had rtA181V mutation in group B. CONCLUSION: Adefovir dipivoxil in combination with lamivudine or entecavir are safe and effective therapies for chronic hepatitis B patients with YMDD mutation.