Jinya Ding

Metabolomics analysis revealed the metabolic heterogeneity of cervical cancer (CC) cell lines C33A and CaSki, and their molecular mechanisms were explored. Using the modified Bligh-Dyer method, the endogenous metabolites of C33A and CaSki cells were divided into polar and nonpolar fractions. The metabolites were analysed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Then, the differential metabolites were screened by combining multivariate statistical analysis and volcano maps, and functional enrichment and pathway analysis of the differential metabolites were performed. Finally, association analysis was carried out in combination with transcriptomics, and the important differential metabolisms were experimentally verified by real-time PCR (RT−qPCR) and oil red staining. The results showed that between the C33A and CaSki cell lines, there were significant differences in amino acids, nucleotides and lipids, such as in threonine, arachidonic acid and hypoxanthine, in the metabolic pathways. These compounds could be used as markers of differences in cellular metabolism. The heterogeneity of lipid metabolism accounted for 87.8%, among which C33A cells exhibited higher contents of fatty acid polar derivatives, while CaSki cells showed higher contents of free fatty acids and glycerides. Based on correlation analysis of the above metabolic differences in HPV pathways as well as lipid metabolism-related genes, p53 and the genes involved in lipid metabolism pathways, such as Peroxisome Proliferator Activated Receptor Gamma(PPARG) and stearoyl-CoA desaturase (SCD), are relevant to the metabolic heterogeneity of the cells. The differential expression of some genes was validated by RT−qPCR. CaSki cells showed significantly higher glyceride levels than that of C33A cells, as verified by oil red O staining and glyceride assays. The above results showed that the metabolomic differences between C33A and CaSki cells were relatively obvious, especially in lipid metabolism, which might be related to the decreased expression of PPARG and p53 caused by HPV E6. Further studies on the molecular mechanism of lipid metabolism heterogeneity in cervical cancer cell lines with or without HPV could provide a new reference for the development of CC and individualized treatments of tumour patients.

Background Clinical features and the dynamic changes of the immune response in coronavirus disease-2019 (COVID-19) patients play essential roles in the disease courses. We hypothesized that clinical features and longitudinal dynamic immune response of COVID-19 patients might be associated with viral shedding duration. Methods In this retrospective study, we documented 413 adult patients with laboratory-confirmed COVID-19 from Wuhan Huoshenshan Hospital. Demographic, clinical, and laboratory data were extracted from electronic medical records. Risk factors associated with viral shedding duration were examined using odds ratios (ORs) and 95% confidence intervals (CIs) in the multivariable logistic regression models. Results The median duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding was 48 days (interquartile range, 40–58 days) among all patients. Fever symptom (OR, 2.23; 95% CI, 1.46–3.44), delayed admission after symptom onset (OR, 15.33; 95% CI, 9.14–26.65), CD8⁺ T cells (OR, 1.93; 95% CI, 1.10–3.44) were associated with prolonged viral shedding. In contrast, shorter viral shedding was associated with CD4⁺ T cells (OR, 0.38; 95% CI, 0.16–0.88), the ratios of CD4⁺ T cells to CD8⁺ T cells (OR, 0.79; 95% CI, 0.63–0.98). Longitudinal dynamic analyses demonstrate that sustained monocyte level was associated with shorter viral shedding (OR, 0.41; 95% CI, 0.22–0.76). More importantly, the associations of CD4⁺ T cells, CD8⁺ T cells, the ratio of CD4⁺ T cells to CD8⁺ T cells, and sustained monocyte level were confined to male patients. Conclusions Higher CD4⁺ T cells, sustained monocyte level, and lower CD8⁺ T cells might shorten the disease course. The male-specific associations supported the contribution of sex-dependent immune responses to the disease courses.

[Abstract]: Objective: Coronavirus disease 2019 (COVID-19) has become pandemic in the world. The need for IgG-IgM combined antibody test is booming, but data on diagnostic indexes evaluation was inadequate. The aim of this study was to evaluate diagnostic indexes of a rapid IgG-IgM combined antibody test for SARS-CoV-2. Methods: A total of 179 patients were enrolled. Serum were collected for IgG-IgM combined antibody test and corresponding nasal and pharyngeal swab specimens were collected for SARS-CoV-2 RT-PCR. According to SARS-CoV-2 RT-PCR results, patients under study were categorized as PCR positive group in 90 patients and PCR negative group in 89 patients. Results: 1. Of the 90 PCR positive samples, 77 were tested positive by SARS-CoV-2 IgG-IgM test kit, yielding a sensitivity of 85.6%. Meanwhile, of the 89 PCR negative sample, 8 samples were detected positive, resulting in a specificity of 91%. Positive predictive value, negative predictive value and accuracy of this test kit was 95.1%, 82.7%, and 88.3%, respectively. Kappa efficiency between IgG/IgM test kit and RT-PCR were 0.75. 2. Accuracy in mild/common and severe/critical subgroup were 73.9% and 97.7%, respectively. Accuracy in clinical confirmed, suspected cases and other disease subgroups were 70%, 60%, and 100%, respectively. 3. Patients were further divided into ‘0 - 7’, ‘8 - 15’ and ‘>= 16’ groups according to the time from illness onset to sample collection. Sensitivity, specificity and accuracy in these three groups were 18.8%, 77.8% and 40%; 100%, 50% and 87.5%; 100%, 64.3%, and 93.9, respectively. Conclusion: The sensitivity and specificity of this ease-of-use IgG/IgM combined test kit were adequate, plus short turnaround time, no specific requirements for additional equipment or skilled technicians, all of these collectively contributed to its competence for mass testing. At the current stage, it cannot take the place of SARA-CoV-2 nucleic acid RT-PCR, but can be served as a complementary option for RT-PCR. The combination of RT-PCR and IgG-IgM combined test kit could provide further insight into SARS-CoV-2 infection diagnosis.

Background: Although the SARS-CoV-2 viral load detection of respiratory specimen has been widely used for novel coronavirus disease (COVID-19) diagnosis, it is undeniable that serum SARS-CoV-2 nucleic acid (RNAaemia) could be detected in a fraction of the COVID-19 patients. However, it is not clear that if the incidence of RNAaemia could be correlated with the occurrence of cytokine storm or with the specific class of patients. Methods: This study enrolled 48 patients with COVID-19 admitted to the General Hospital of Central Theater Command, PLA, a designated hospital in Wuhan, China. The patients were divided into three groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (version 6) published by the National Health Commission of China. The clinical and laboratory data were collected. The serum viral load detection and serum IL-6 levels were determined. Except for routine statistical analysis, Generalized Linear Models (GLMs) analysis was used to establish a patient status prediction model based on real-time RT-PCR Ct value. Findings: The Result showed that cases with RNAaemia were exclusively confirmed in critically ill patients group and appeared to reflect the illness severity. Further more, the inflammatory cytokine IL-6 levels were significantly elevated in critically ill patients, which is almost 10-folds higher than those in other patients. More importantly, the extremely high IL-6 level was closely correlated with the incidence of RNAaemia (R=0.902) and the vital signs of COVID-19 patients (R= −0.682). Interpretation: Serum SARS-CoV-2 viral load (RNAaemia) is strongly associated with cytokine storm and can be used to predict the poor prognosis of COVID-19 patients. Moreover, our results strongly suggest that cytokine IL-6 should be considered as a therapeutic target in critically ill patients with excessive inflammatory response.

Multiple myeloma (MM), a type of malignant tumor, is characterized by dysplasia of clonal plasma cells in the bone marrow. People with multiple myeloma will have damaged organs or tissues due to secreting of large amounts of monoclonal immunoglobulin or fragments (M protein). In spite of improved survivability by novel treatment strategies over the last decade, MM is still incurable by current therapy. Long non-conding RNA (lncRNA), with length of more than 200 nucleotides, has been reported to act as important regulators in many diseases, including multiple myeloma. Recent studies have reported aberrant lncRNA expression in MM, these dysregulated lncRNAs can play oncogenic and/or tumor suppressive roles in the development and progression of MM. In this paper, we present a general overview on the role of lncRNA in MM pathogenesis, and discuss their potential as prognostic biomarkers and targets for treatment.