The impact of the COVID-19 pandemic on SLE.

Little is known about the association between coronavirus disease 2019 (COVID-19) and autoimmune diseases, especially in the case of systemic lupus erythematosus (SLE). SLE patients met with many questions during the pandemic in COVID-19, such as how to minimize risk of infection, the complex pathological features and cytokine profiles, diagnosis and treatment, rational choice of drugs and vaccine, good nursing, psychological supervision, and so on. In this study, we review and discuss the multifaceted effects of the COVID-19 pandemic on patients living with SLE using the available literature. Cross-talk in implicated inflammatory pathways/mechanisms exists between SLE and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and SARS-CoV-2 displays similar clinical characteristics and immuno-inflammatory responses to SLE. Current epidemiological data inadequately assess the risk and severity of COVID-19 infection in patients with SLE. More evidence has shown that hydroxychloroquine and chloroquine cannot prevent COVID-19. During the pandemic, patients with SLE had a higher rate of hospitalization. Vaccination helps to reduce the risk of infection. Several therapies for patients with SLE infected with COVID-19 are discussed. The cases in the study can provide meaningful information for clinical diagnosis and management. Our main aim is to help preventing infection and highlight treatment options for patients with SLE infected with COVID-19.

The tumor immune microenvironment remodeling and response to HER2-targeted therapy in HER2-positive advanced gastric cancer.

Combination therapy with anti-HER2 agents and immunotherapy has demonstrated significant clinical benefits in gastric cancer (GC), but the underlying mechanism remains unclear. In this study, we used multiplex immunohistochemistry to assess the changes of the tumor microenvironment in 47 advanced GC patients receiving anti-HER2 therapy. Additionally, we performed single-cell transcriptional sequencing to investigate potential cell-to-cell communication and molecular mechanisms in four HER2-positive GC baseline samples. We observed that post-treated the infiltration of NK cells, CD8+ T cells, and B lymphocytes were significantly higher in patients who benefited from anti-HER2 treatment than baseline. Further spatial distribution analysis demonstrated that the interaction scores between NK cells and CD8+ T cells, B lymphocytes and M2 macrophages, B lymphocytes and Tregs were also significantly higher in benefited patients. Cell-cell communication analysis from scRNA sequencing showed that NK cells utilized CCL3/CCL4-CCR5 to recruit CD8+ T cell infiltration. B lymphocytes employed CD74-APP/COPA/MIF to interact with M2 macrophages, and utilized TNF-FAS/ICOS/TNFRSR1B to interact with Tregs. These cell-cell interactions contribute to inhibit the immune resistance of M2 macrophages and Tregs. Our research provides potential guidance for the use of anti-HER2 therapy in combination with immune therapy.

Featured immune characteristics of COVID-19 and systemic lupus erythematosus revealed by multidimensional integrated analyses.

BACKGROUND: Coronavirus disease 2019 (COVID-19) shares similar immune characteristics with autoimmune diseases like systemic lupus erythematosus (SLE). However, such associations have not yet been investigated at the single-cell level. METHODS: We integrated and analyzed RNA sequencing results from different patients and normal controls from the GEO database and identified subsets of immune cells that might involve in the pathogenesis of SLE and COVID- 19. We also disentangled the characteristic alterations in cell and molecular subset proportions as well as gene expression patterns in SLE patients compared with COVID-19 patients. RESULTS: Key immune characteristic genes (such as CXCL10 and RACK1) and multiple immune-related pathways (such as the coronavirus disease-COVID-19, T-cell receptor signaling, and MIF-related signaling pathways) were identified. We also highlighted the differences in peripheral blood mononuclear cells (PBMCs) between SLE and COVID-19 patients. Moreover, we provided an opportunity to comprehensively probe underlying B-cell‒cell communication with multiple ligand-receptor pairs (MIF-CD74+CXCR4, MIF-CD74+CD44) and the differentiation trajectory of B-cell clusters that is deemed to promote cell state transitions in COVID-19 and SLE. CONCLUSIONS: Our results demonstrate the immune response differences and immune characteristic similarities, such as the cytokine storm, between COVID-19 and SLE, which might pivotally function in the pathogenesis of the two diseases and provide potential intervention targets for both diseases.

Neutrophil extracellular traps induced by the hypoxic microenvironment in gastric cancer augment tumour growth.

BACKGROUND: Inflammation-related predisposition to cancer plays an essential role in cancer progression and is associated with poor prognosis. A hypoxic microenvironment and neutrophil infiltration are commonly present in solid tumours, including gastric cancer (GC). Neutrophil extracellular traps (NETs) have also been demonstrated in the tumour immune microenvironment (TIME), but how NETs affect GC progression remains unknown. Here, we investigated the role of NET formation in the TIME and further explored the underlying mechanism of NETs in GC tumour growth. METHODS: Hypoxia-induced factor-1α (HIF-1α), citrulline histone 3 (citH3) and CD66b expression in tumour and adjacent nontumor tissue samples was evaluated by western blotting, immunofluorescence and immunohistochemical staining. The expression of neutrophil-attracting chemokines in GC cells and their hypoxic-CM was measured by qRT‒PCR and ELISA. Neutrophil migration under hypoxic conditions was evaluated by a Transwell assay. Pathway activation in neutrophils in a hypoxic microenvironment were analysed by western blotting. NET formation was measured in vitro by immunofluorescence staining. The protumour effect of NETs on GC cells was identified by Transwell, wound healing and cell proliferation assays. In vivo, an lipopolysaccharide (LPS)-induced NET model and subcutaneous tumour model were established in BALB/c nude mice to explore the mechanism of NETs in tumour growth. RESULTS: GC generates a hypoxic microenvironment that recruits neutrophils and induces NET formation. High mobility group box 1 (HMGB1) was translocated to the cytoplasm from the nucleus of GC cells in the hypoxic microenvironment and mediated the formation of NETs via the toll-like receptor 4 (TLR4)/p38 MAPK signalling pathway in neutrophils. HMGB1/TLR4/p38 MAPK pathway inhibition abrogated hypoxia-induced neutrophil activation and NET formation. NETs directly induced GC cell invasion and migration but not proliferation and accelerated the augmentation of GC growth by increasing angiogenesis. This rapid tumour growth was abolished by treatment with the NET inhibitor deoxyribonuclease I (DNase I) or a p38 MAPK signalling pathway inhibitor. CONCLUSIONS: Hypoxia triggers an inflammatory response and NET formation in the GC TIME to augment tumour growth. Targeting NETs with DNase I or HMGB1/TLR4/p38 MAPK pathway inhibitors is a potential therapeutic strategy to inhibit GC progression. Video Abstract.

Improved BDS-2/3 Satellite Ultra-Fast Clock Bias Prediction Based with the SSA-ELM Model.

Ultra-fast satellite clock bias (SCB) products play an important role in real-time precise point positioning. Considering the low accuracy of ultra-fast SCB, which is unable to meet the requirements of precise point position, in this paper, we propose a sparrow search algorithm to optimize the extreme learning machine (SSA-ELM) algorithm in order to improve the performance of SCB prediction in the Beidou satellite navigation system (BDS). By using the sparrow search algorithm's strong global search and fast convergence ability, we further improve the prediction accuracy of SCB of the extreme learning machine. This study uses ultra-fast SCB data from the international GNSS monitoring assessment system (iGMAS) to perform experiments. First, the second difference method is used to evaluate the accuracy and stability of the used data, demonstrating that the accuracy between observed data (ISUO) and predicted data (ISUP) of the ultra-fast clock (ISU) products is optimal. Moreover, the accuracy and stability of the new rubidium (Rb-II) clock and hydrogen (PHM) clock onboard BDS-3 are superior to those of BDS-2, and the choice of different reference clocks affects the accuracy of SCB. Then, SSA-ELM, quadratic polynomial (QP), and a grey model (GM) are used for SCB prediction, and the results are compared with ISUP data. The results show that when predicting 3 and 6 h based on 12 h of SCB data, the SSA-ELM model improves the prediction model by ~60.42%, 5.46%, and 57.59% and 72.27%, 44.65%, and 62.96% as compared with the ISUP, QP, and GM models, respectively. When predicting 6 h based on 12 h of SCB data, the SSA-ELM model improves the prediction model by ~53.16% and 52.09% and by 40.66% and 46.38% compared to the QP and GM models, respectively. Finally, multiday data are used for 6 h SCB prediction. The results show that the SSA-ELM model improves the prediction model by more than 25% compared to the ISUP, QP, and GM models. In addition, the prediction accuracy of the BDS-3 satellite is better than that of the BDS-2 satellite.

Circular RNA circLOC101928570 suppresses systemic lupus erythematosus progression by targeting the miR-150-5p/c-myb axis.

BACKGROUND: Accumulating evidence supports the implication of circular RNAs (circRNAs) in systemic lupus erythematosus (SLE). However, little is known about the detailed mechanisms and roles of circRNAs in the pathogenesis of SLE. METHODS: Quantitative real-time PCR was used to determine the levels of circLOC101928570 and miR-150-5p in peripheral blood mononuclear cells of SLE. Overexpression and knockdown experiments were conducted to assess the effects of circLOC101928570. Fluorescence in situ hybridization, RNA immunoprecipitation, luciferase reporter assays, Western blot, flow cytometry analysis and enzyme-linked immunosorbent assay were used to investigate the molecular mechanisms underlying the function of circLOC101928570. RESULTS: The results showed that the level of circLOC101928570 was significantly downregulated in SLE and correlated with the systemic lupus erythematosus disease activity index. Functionally, circLOC101928570 acted as a miR-150-5p sponge to relieve the repressive effect on its target c-myb, which modulates the activation of immune inflammatory responses. CircLOC101928570 knockdown enhanced apoptosis. Moreover, circLOC101928570 promoted the transcriptional level of IL2RA by directly regulating the miR-150-5p/c-myb axis. CONCLUSION: Overall, our findings demonstrated that circLOC101928570 played a critical role in SLE. The downregulation of circLOC101928570 suppressed SLE progression through the miR-150-5p/c-myb/IL2RA axis. Our findings identified that circLOC101928570 serves as a potential biomarker for the diagnosis and therapy of SLE.

SIRT1 enhances oxaliplatin resistance in colorectal cancer through microRNA-20b-3p/DEPDC1 axis.

Oxaliplatin (L-OHP) is a standard treatment drug for colorectal cancer (CRC), but acquired drug resistance limits the outcome of patients. We investigated the involvement of sirtuin 1 (SIRT1) in L-OHP resistance in the setting of CRC via microRNA-20b-3p/DEP domain containing 1 (miR-20b-3p/DEPDC1) axis. CRC tissues that were resistant or sensitive to L-OHP were harvested, in which SIRT1, miR-20b-3p, and DEPDC1 levels were tested. L-OHP-resistant-resistant CRC cells were transfected, subsequently, cellular proliferation, invasion, migration, and apoptosis were tested, and tumor resistance to L-OHP was observed. The binding of SIRT1 to miR-20b-3p promoter and the targeting relationship between miR-20b-3p and DEPDC1 were verified. An aberrant elevation in SIRT1 expression was seen in L-OHP-resistant CRC tissues and cells. Knockdown of SIRT1 sensitized CRC cells and xenografted CRC tumors to L-OHP. SIRT1 bound with miR-20b-3p promoter to regulate DEPDC1. Reducing miR-20b-3p or raising DEPDC1 levels weakened the effect of SIRT1 knockdown on L-OHP-resistant-CRC cells. SIRT1 enhances L-OHP resistance in CRC by mediating miR-20b-3p/DEPDC1 axis.

Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment.

A single biomarker is not adequate to identify patients with gastric cancer (GC) who have the potential to benefit from anti-PD-1/PD-L1 therapy, presumably owing to the complexity of the tumour microenvironment. The predictive value of tumour-infiltrating immune cells (TIICs) has not been definitively established with regard to their density and spatial organisation. Here, multiplex immunohistochemistry is used to quantify in situ biomarkers at sub-cellular resolution in 80 patients with GC. To predict the response to immunotherapy, we establish a multi-dimensional TIIC signature by considering the density of CD4+FoxP3-PD-L1+, CD8+PD-1-LAG3-, and CD68+STING+ cells and the spatial organisation of CD8+PD-1+LAG3- T cells. The TIIC signature enables prediction of the response of patients with GC to anti-PD-1/PD-L1 immunotherapy and patient survival. Our findings demonstrate that a multi-dimensional TIIC signature may be relevant for the selection of patients who could benefit the most from anti-PD-1/PD-L1 immunotherapy.

The Association between Blood Indexes and Immune Cell Concentrations in the Primary Tumor Microenvironment Predicting Survival of Immunotherapy in Gastric Cancer.

The tumor microenvironment plays a vital role in tumor progression and treatment response. However, the association between immune cell concentrations in primary tumor and blood indexes remains unknown. Thus, we enrolled patients with gastric cancer (GC) in two cohorts. We used multiplexed immunohistochemistry to quantify in situ proteins covering rare cell types at sub-cellular resolution in 80 patients with GC in the first cohort. A high correlation between the LMR (lymphocyte-to-monocyte ratio)/NLR (neutrophil-to-lymphocyte ratio) and tumor immune microenvironment was found. The density of exhausted CD8 T cells including CD8+PD1−TIM3+, CD8+LAG3+PD1+, CD8+LAG3+PD1−, CD8+LAG3+PD1+TIM3− was negatively associated with LMR and positively associated with NLR (p < 0.05). Additionally, the higher density of macrophages in tumor core was associated with a higher platelet-to-lymphocyte ratio and systemic immune-inflammation index. Furthermore, we validated the prognostic value of LMR and NLR in an independent cohort of 357 gastric cancer patients receiving immunotherapy. Higher LMR at baseline was significantly associated with superior immune-related PFS (irPFS) and a trend of superior immune-related OS (irOS). Higher NLR was associated with inferior irOS. In conclusion, blood indexes were associated with immune cells infiltrating in primary tumors of GC. NLR and LMR are associated with the density of exhausted CD8+ T immune cells, which leads to prognostic values of immunotherapy.

Airborne transmission of COVID-19 virus in enclosed spaces: An overview of research methods.

Since the outbreak of COVID-19 in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has spread worldwide. This study summarized the transmission mechanisms of COVID-19 and their main influencing factors, such as airflow patterns, air temperature, relative humidity, and social distancing. The transmission characteristics in existing cases are providing more and more evidence that SARS CoV-2 can be transmitted through the air. This investigation reviewed probabilistic and deterministic research methods, such as the Wells-Riley equation, the dose-response model, the Monte-Carlo model, computational fluid dynamics (CFD) with the Eulerian method, CFD with the Lagrangian method, and the experimental approach, that have been used for studying the airborne transmission mechanism. The Wells-Riley equation and dose-response model are typically used for the assessment of the average infection risk. Only in combination with the Eulerian method or the Lagrangian method can these two methods obtain the spatial distribution of airborne particles' concentration and infection risk. In contrast with the Eulerian and Lagrangian methods, the Monte-Carlo model is suitable for studying the infection risk when the behavior of individuals is highly random. Although researchers tend to use numerical methods to study the airborne transmission mechanism of COVID-19, an experimental approach could often provide stronger evidence to prove the possibility of airborne transmission than a simple numerical model. All in all, the reviewed methods are helpful in the study of the airborne transmission mechanism of COVID-19 and epidemic prevention and control.

Correlation between the accumulation of skin glycosylation end products and the development of type 2 diabetic peripheral neuropathy.

BACKGROUND: The accumulation of advanced glycation end products (AGEs) occurring in skin tissues can be measured by AGE Reader. Here, we assessed the correlation between AGEs values and the development of type 2 diabetic peripheral neuropathy (DPN). METHODS: The basic clinical information of 560 patients with T2DM was collected through an electronic system. AGEs and diabetic complication risk score was measured by AGE Reader, a non-invasive optical signal detector. All of the participants were classified into 4 groups based on Dyck criteria: grade 0 (non-DPN group), grade 1 (early stage group), grade 2 (middle stage group) and grade 3 (advanced group). Pearson correlation analysis and Spearman correlation analysis were used to evaluate the correlation between AGEs and other indexes. The sensitivity and specificity of glycosylated products were evaluated by ROC curve. RESULTS: With the increase of DPN severity, the accumulative AGEs showed an increasing trend. Significant differences (P = 0.000) of AGEs were found among grades 0, 1, 2, and 3 of DPN, and significant differences (P = 0.000) of AGEs were found between grades 1 and 3. There were significant differences in DPN risk score between grades 0, 1, 2, and 3, between grades 1, 2, and 3, and between grades 2 and 3 (P < 0.01 or P < 0.05). AGEs were positively correlated with age, blood uric acid, disease course, systolic blood pressure, the risk scores of the four major complications of diabetes, renal function indicators (serum creatinine, Cystatin C, homocysteine, the ratio of urinary albumin and creatinine, urinary microalbumin, α-microglobulin, urinary transferrin, urinary immunoglobulin), inflammatory indicators (white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, C-reactive protein), and TCSS score. However, it was negatively correlated with BMI,fasting insulin, insulin 1-3 h postprandial, lymphocyte count, HOMA insulin resistance index and estimated glomerular filtration rate. The area under the AGEs cumulant and neuropathy risk score curve was 0.769 and 0.743, respectively. The confidence intervals were (71.2-82.6%) and (68.8-79.9%), respectively. The maximum Youden's index of AGEs cumulant was 0.440, and the corresponding AGEs cumulant value was 77.65. The corresponding sensitivity and specificity were 0.731 and 0.709, respectively. Furthermore, the maximum Youden's index of neuropathy risk score was 0.385, and the corresponding neuropathy risk score was 66.25. The corresponding sensitivity and the specificity were 0.676 and 0.709, respectively. CONCLUSION: The cumulative amount of skin AGEs can be used as the diagnostic index and the prediction and evaluation index of DPN severity. Moreover, the diabetic peripheral neuropathy risk score can predict the risk of DPN in patients with T2DM.

N6-methyladenosine-dependent modification of circGARS acts as a new player that promotes SLE progression through the NF-κB/A20 axis.

BACKGROUND: Certain circRNAs could be used as biomarkers to determine the risk of development and/or severity of systemic lupus erythematosus, and their new function in the regulation of gene expression has motivated us to investigate their role in SLE METHODS: Experimental methods including qRT-PCR, RNA immunoprecipitation (RIP), pulldown, dual luciferase reporter assay, RNA interference and cell transfection, RNA fluorescence in situ hybridization, western blotting, and mass spectrometry were used to assessed circGARS (hsa_circRNA_0009000) for immune functions and defined mechanisms by which circGARS promotes the progression in SLE. RESULTS: Our results demonstrated that the levels of circGARS was remarkably upregulated in SLE and correlated with clinicopathological features. CircGARS directly combined with microRNA-19a (miR-19a). Functionally, circGARS downregulated the expression of TNFAIP3 (A20, tumor necrosis factor alpha-induced protein 3) to mediate the activation of immune responses that were regulated by the nuclear factor-κB (NF-κB) pathway as a negative feedback mechanism. In addition, miR-19a regulated A20 (TNFAIP3) degradation by downregulating the expression of YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2). CONCLUSIONS: The circGARS sponges miR-19a to regulate YTHDF2 expression to promote SLE progression through the A20/NF-κB axis and may act as an independent biomarker to help the treatment of SLE patients.

Evaluation of airborne particle exposure for riding elevators.

Social distancing is a key factor for health during the COVID-19 pandemic. In many indoor spaces, such as elevators, it is difficult to maintain social distancing. This investigation used computational-fluid-dynamics (CFD) to study airborne particle exposure in riding an elevator in a typical building with 35 floors. The elevator traveled from the ground floor to the 35th floor with two stops on floor 10 and floor 20, comprising 114 s. The CFD simulated the dispersion of the aerosolized particles exhaled by an index person while breathing in both lobby and elevator areas. The study calculated the accumulated dose of susceptible riders riding in elevators with the index person under different conditions including different ventilation rates, air supply methods, and elevator cab geometries. This investigation also studied a case with a single cough from the index person as the person entered the elevator. The results show that, due to the short duration of the average elevator ride, the number of particles inhaled by a susceptible rider was low. For the reference case with a 72 ACH (air changes per hour) ventilation rate, the highest accumulated particle dose by a susceptible passenger close to the index person was only 1.59. The cough would cause other riders to inhale approximately 8 orders of magnitude higher particle mass than from continuous breathing by the index person for the whole duration of the ride.

Increased Frequency of Circulating Classical Monocytes in Patients with Rosacea.

PURPOSE: Monocyte subsets, including classical, intermediate and non-classical monocytes, are involved in the pathogenesis of inflammatory or autoimmune diseases. The pathogenic role of monocytes in the peripheral blood mononuclear cells (PBMCs) of patients with rosacea remains unclear. This study aimed to assess frequencies of monocyte subsets in PBMCs from rosacea patients before and after clinical treatment. PATIENTS AND METHODS: We applied flow cytometry to examine frequencies of monocyte subsets in 116 patients with rosacea, while patients with 26 systemic lupus erythematosus (SLE), 28 acne and 42 normal healthy subjects without skin problems (HC) were recruited as controls. Expression of C-C chemokine receptor 2 (CCR2) on monocytes and plasma levels of CC-chemokine ligand 2 (CCL2), high mobility group box-1 (HMGB-1), interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) were measured in HC and rosacea patients before and after treatment. RESULTS: The frequency of classical monocytes, but not intermediate or non-classical monocytes, was higher in rosacea as compared with HC, which decreased after treatment. Frequencies of monocyte subsets showed no gender difference, while increased with age in patients but not in HC. Frequencies of classical monocytes in patients with erythematotelangiectatic rosacea (ETR) and ETR-papulopustular rosacea (PPR) overlap were significantly higher than HC or patients with only PPR or phymatous rosacea (PhR). There was a significant higher expression of CCR2 in classical monocytes, with higher plasma levels of CCL2, HMGB-1, IL-1ß and TNF-α in patients than in HC, which all significantly decreased after treatment. CONCLUSION: Our data indicated a possible association between abnormal classical monocytes frequencies and rosacea.

Effective ventilation and air disinfection system for reducing coronavirus disease 2019 (COVID-19) infection risk in office buildings.

During the COVID-19 pandemic, an increasing amount of evidence has suggested that the virus can be transmitted through the air inside buildings. The ventilation system used to create the indoor environment would facilitate the transmission of the airborne infectious diseases. However, the existing ventilation systems in most buildings cannot supply sufficient clean outdoor air for diluting the virus concentration. To reduce the airborne infection risk and minimize energy consumption, especially in existing buildings with well-mixed ventilation systems, this investigation used an ultraviolet-C (UV-C) air disinfection device (Rheem's third generation products, RM3) with 99.9% disinfection efficiency to clean air carrying the COVID-19 virus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) which could help promote environmental sustainability and create healthy cities. This investigation assessed the impact of the RM3 UV-C units on the infection risk, the number of RM3 UV-C units required, and the strategy for decreasing the infection risk, with the use of computational-fluid-dynamics (CFD) numerical simulations. An actual office building with a combination of individual offices and workstations was selected as an example for the research. According to the numerical results, the best strategy would be to use a combination of 100% outside air and UV-C in heating, ventilation and air-conditioning (HVAC) ducts with air disinfected by the RM3 UV-C units. The infection risk in the office building could thus be reduced to a negligible level. These findings could provide theoretical basis and engineering application basis for COVID-19 epidemic prevention and control.

Integrated Transcriptome Profiling Revealed That Elevated Long Non-Coding RNA-AC007278.2 Expression Repressed CCR7 Transcription in Systemic Lupus Erythematosus.

Purpose: Systemic lupus erythematosus (SLE) is a serious autoimmune disease. Its molecular pathogenesis, especially the long non-coding RNA (lncRNA) function, remains unclear. We want to investigate the lncRNA dysregulation profile and their molecular mechanisms in SLE. Methods: In this study, we analyzed the transcriptome profiles (RNA-seq) of peripheral blood mononuclear cells (PBMCs) from SLE patients and two published transcriptome datasets to explore lncRNA profiles. The differentially expressed lncRNAs were confirmed by quantitative real-time PCR in another set of female patients. We constructed the lncRNA-mRNA regulatory networks by performing weighted gene co-expression network analysis (WGCNA). Dysregulated lncRNA AC007278.2 was repressed by short hairpin RNA (shRNA) in Jurkat cells. Dual-luciferase reporter gene assay was performed to investigate the regulatory mechanism of AC007278.2 on target gene CCR7. Results: We observed dominant up-regulation of transcripts, including mRNAs and lncRNAs, in SLE patients. By WGCNA method, we identified three modules that were highly related to SLE. We then focused on one lncRNA, AC007278.2, with a T-helper 1 lineage-specific expression pattern. We observed consistently higher AC007278.2 expression in SLE patients. Co-expression network revealed that AC007278.2 participated in the innate immune response and inflammatory bowel disease pathways. By knocking down AC007278.2 expression, we found that AC007278.2 could regulate the expression of inflammatory and cytokine stimulus response-related genes, including CCR7, AZU1, and TNIP3. AC007278.2 inhibits the functional CCR7 promoter to repress its transcription, thereby regulating autoimmunity and follicular T-helper cell differentiation. Conclusion: In summary, our study indicated the important regulatory role of lncRNAs in SLE. AC007278.2 may be treated as a novel biomarker for SLE diagnosis and treatment.

Association of CYP24A1 gene polymorphism with colorectal cancer in the Jiamusi population.

BACKGROUND: The population in Jiamusi has been reported to have the highest prevalence of colorectal cancer (CRC) in China. The genetic causal-effect for this occurrence among the residents remains unclear. Given the long cold seasons with people wearing more clothes and reduced UV exposure, we aimed to study the association between the vitamin D metabolism-related gene CYP24A1 polymorphism and CRC susceptibility. METHOD: A case-control study was conducted that included 168 patients with CRC and 710 age-matched healthy individuals as the control group. Plausible susceptible variations were sought and clinical phenotypic-genotype association analysis was performed. RESULTS: Overall, two CYP24A1 polymorphisms, rs6013905 AX (P = 0.02, OR = 1.89, 95%CI: 1.09-3.29) and rs2762939 GX (P = 0.02, OR = 1.52, 95%CI: 1.08-2.13) were significantly associated with CRC in the Jiamusi population. In the female group, three CYP24A1 polymorphisms, rs6013905 AX (P = 0.04, OR = 2.59, 95%CI: 1.03-6.49), rs2762939 GX (P = 0.01, OR = 2.35, 95%CI: 1.25-4.42), and rs6068816 GG (P = 0.05, OR = 1.89, 95%CI: 0.99-3.59) carriers were significantly associated with CRC. In clinical phenotypic-genotype analysis, rs6013905 GG (P = 0.05, OR = 4.00, 95%CI: 0.92-17.48) and rs2762939 GX (P = 0.03, OR = 4.87, 95%CI: 1.00-23.69) carriers were significantly associated with poorly differentiated CRC, while CYP24A1 rs6068816 AX was significantly associated with the tumor type (P = 0.02, OR = 2.08, 95%CI: 1.10-3.96) and location (P = 0.04, OR = 2.24, 95%CI: 1.05-4.77). CONCLUSION: CYP24A1 gene polymorphism may be a genetic risk factor attributable to the highest prevalence of CRC in Jiamusi people. Individuals with CYP24A1 gene polymorphism may have an increased barrier for vitamin D absorption, thus contributing to the risk of CRC development.

Skin autofluorescence and the complexity of complications in patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: The accumulation of advanced glycation end products (AGEs) occurring in skin tissues can be measured as skin autofluorescence (SAF). Here, we assessed the correlation between SAF values and the complexity and severity of type 2 diabetes mellitus (T2DM) complications. METHODS: The basic clinical information of 825 patients with T2DM was collected through an electronic system, and SAF was measured by adapting a DM-Scan, a non-invasive optical signal detector. Diabetic complications were diagnosed based on clinical criteria by experienced doctors. Linear regression analysis was used to evaluate the independent determinants of SAF, and multiple logistic regression analysis was performed to assess independent determinants that influence the severity of the complications. RESULTS: SAF was significantly associated with the complexity of T2DM complications. Similarly, independent relationships between SAF and age (ß = 0.389, P <  0.001), sex (ß = - 2.221, P = 0.004), 2-h C-peptide (ß = - 0.182, P = 0.017), aminotransferase (ALT, ß = - 0.158, P = 0.041), blood creatinine (BCr, ß = 0.206, P = 0.009), and fatty liver (ß = 0.161, P = 0.026) were observed. With the increasing number of complications, the SAF values increased significantly after adjusting for related risk factors. The SAF values correlated with diabetic retinopathy, diabetic kidney diseases, cardiovascular disease, and diabetic peripheral neuropathy when compared with patients without any T2DM-associated complications. Moreover, the AGE-based diabetic complication risk score for each complication demonstrated a relationship with the presence or absence of certain complications. CONCLUSION: SAF is an independent marker for diabetic retinopathy, diabetic kidney diseases, cardiovascular disease, and diabetic peripheral neuropathy, and it is also a predictor of the complexity of T2DM complications. Moreover, the diabetic complication risk score is capable of predicting the risk of diabetic complications in patients with T2DM.

EIF2AK2 selectively regulates the gene transcription in immune response and histones associated with systemic lupus erythematosus.

PKR, also known as EIF2AK2, is an IFN-stimulated gene (ISG) and shows a higher expression in probands with systemic lupus erythematosus (SLE), which is likely responsible for the impaired translational and proliferative responses to mitogens in T cells from SLE patients. In this study, we overexpressed EIF2AK2 in HeLa cells to study EIF2AK2-regulated genes using RNA-seq technology, followed by bioinformatic analysis of target genes of EIF2AK2-regulated transcriptional factors (TFs). Overexpression of EIF2AK2 promotes HeLa cell apoptosis. EIF2AK2 selectively represses the transcription of histone protein genes associated with SLE, immune response genes and TF genes, which was validated by RT-qPCR experiments. Analysis of motifs overrepresented in the promoter regions of EIF2AK2-regulated genes revealed eighteen EIF2AK2-regulated TFs involved in establishing the EIF2AK2 network. Eight out of these predicted EIF2AK2-regulated TFs were further verified by RT-qPCR selectively in both HeLa and Jurkat cells, and most such as HEY2, TFEC, BATF2, GATA3 and ATF3 and FOXO6 are known to regulate immune response. Our results suggest that the dsRNA-dependent kinase EIF2AK2 selectively regulates the transcription of immune response and SLE-associated histone protein genes, and such a selectivity is likely to be operated by EIF2AK2-targeted TFs. The EIF2AK2-TFs axis potentially offers new therapeutic targets for counteracting immunological disease in the future.